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Title:
Cell Death, Damage-Associated Molecular Patterns, and Sterile Inflammation in Cardiovascular Disease
Abstract:
Cell death and inflammation are ancient processes of fundamental biological importance in both normal physiology and pathology.
This is evidenced by the profound conservation of mediators, with ancestral homologues identified from plants to humans, and the number of diseases driven by aberrant control of either process.
Apoptosis is the most well-studied cell death, but many forms exist, including autophagy, necrosis, pyroptosis, paraptosis, and the obscure dark cell death.
Cell death occurs throughout the cardiovascular system, from initial shaping of the heart and vasculature during development to involvement in pathologies, including atherosclerosis, aneurysm, cardiomyopathy, restenosis, and vascular graft rejection.
However, determining whether cell death primarily drives pathology or is a secondary bystander effect is difficult.
Inflammation, the primary response of innate immunity, is considered essential in initiating and driving vascular diseases.
Cell death and inflammation are inextricably linked with their effectors modulating the other process.
Indeed, an evolutionary link between cell death and inflammation occurs at caspase-1 (which activates interleukin-1β), which can induce death by pyroptosis, and is a member of the caspase family vital for apoptosis.
This review examines cell death in vascular disease, how it can induce inflammation, and finally the emergence of inflammasomes in vascular pathology. | 6,917 |
Title:
Identification and purification of an aspartic proteinase from human semen
Abstract:
To purify and evaluate the molecular changes associated with an aspartic protease (Cathepsin D) in human semen from infertile subjects.
Cathepsin D was purified from normo-, oligo- and azoospermic semen, by a procedure involving detergent solubilisation, affinity chromatography and gel filtration chromatography.
The enzyme from normo-, oligo- and azoospermic samples was purified 86, 60 and 44 fold respectively.
The purified enzyme appeared as a single band on SDS as well as on native PAGE irrespective of the pathological conditions.
The molecular weight of Cathepsin D from oligospermic and normospermic samples was 40 kDa while that of azoospermic sample was found to be 43 kDa.
The enzyme was inhibited by pepstatin while other proteinase inhibitors and metal ions did not have any effect.
Purified Cathepsin D from azoospermic sample differs from normospermia and oligospermia. | 6,968 |
Title:
An asymmetric PAN3 dimer recruits a single PAN2 exonuclease to mediate mRNA deadenylation and decay
Abstract:
The PAN2-PAN3 complex functions in general and microRNA-mediated mRNA deadenylation.
However, mechanistic insight into PAN2 and its complex with the asymmetric PAN3 dimer is lacking.
Here, we describe crystal structures that show that Neurospora crassa PAN2 comprises two independent structural units: a C-terminal catalytic unit and an N-terminal assembly unit that engages in a bipartite interaction with PAN3 dimers.
The catalytic unit contains the exonuclease domain in an intimate complex with a potentially modulatory ubiquitin-protease-like domain.
The assembly unit contains a WD40 propeller connected to an adaptable linker.
The propeller contacts the PAN3 C-terminal domain, whereas the linker reinforces the asymmetry of the PAN3 dimer and prevents the recruitment of a second PAN2 molecule.
Functional data indicate an essential role for PAN3 in coordinating PAN2-mediated deadenylation with subsequent steps in mRNA decay, which lead to complete mRNA degradation. | 7,083 |
Title:
An updated review of the clinical development of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin
Abstract:
Several authors have demonstrated that coumarin (1,2-benzopyrone) in combination with cimetidine can produce objective antitumor responses in some patients with advanced renal cell carcinoma.
The purpose of this report is to review the clinical development of coumarin, with or without cimetidine, with special reference to renal cell carcinoma (RCC).
Previously unpublished data concerning the survival of a population of patients with RCC, who were treated on a phase I trial of coumarin and cimetidine, are presented.
The rationale and study design of an active randomized, double-blinded, placebo-controlled trial of coumarin for RCC are discussed.
A progress report is given for an ongoing phase I trial of oral 7-hydroxycoumarin, the major human metabolite of coumarin. | 7,091 |
Title:
The Rat Genome Database curation tool suite: a set of optimized software tools enabling efficient acquisition, organization, and presentation of biological data
Abstract:
The Rat Genome Database (RGD) is the premier repository of rat genomic and genetic data and currently houses over 40 000 rat gene records as well as human and mouse orthologs, 1771 rat and 1911 human quantitative trait loci (QTLs) and 2209 rat strains.
Biological information curated for these data objects includes disease associations, phenotypes, pathways, molecular functions, biological processes and cellular components.
A suite of tools has been developed to aid curators in acquiring and validating data objects, assigning nomenclature, attaching biological information to objects and making connections among data types.
The software used to assign nomenclature, to create and edit objects and to make annotations to the data objects has been specifically designed to make the curation process as fast and efficient as possible.
The user interfaces have been adapted to the work routines of the curators, creating a suite of tools that is intuitive and powerful. ::: ::: Database URL: http://rgd.mcw.edu | 7,101 |
Title:
Attentional demand influences strategies for encoding into visual working memory
Abstract:
Visual selective attention and visual working memory (WM) share the same capacity-limited resources.
We investigated whether and how participants can cope with a task in which these 2 mechanisms interfere.
The task required participants to scan an array of 9 objects in order to select the target locations and to encode the items presented at these locations into WM (1 to 5 shapes).
Determination of the target locations required either few attentional resources (“popout condition”) or an attention-demanding serial search (“non pop-out condition”).
Participants were able to achieve high memory performance in all stimulation conditions but, in the non popout conditions, this came at the cost of additional processing time.
Both empirical evidence and subjective reports suggest that participants invested the additional time in memorizing the locations of all target objects prior to the encoding of their shapes into WM.
Thus, they seemed to be unable to interleave the steps of search with those of encoding.
We propose that the memory for target locations substitutes for perceptual pop-out and thus may be the key component that allows for flexible coping with the common processing limitations of visual WM and attention.
The findings have implications for understanding how we cope with real-life situations in which the demands on visual attention and WM occur simultaneously. | 7,104 |
Title:
Delivering Genetic Education and Genetic Counseling for Rare Diseases in Rural Brazil
Abstract:
Brazil is the largest country in Latin America, with an ethnically diverse, Portuguese-speaking and predominantly Roman Catholic population of some 194 million.
Universal health care is provided under the Federal Unified Health System (Sistema Único de Saúde) but, as in many other middle and low income countries, access to medical genetics services is limited in rural and remote regions of the country.
Since there is no formally recognized Genetic Counseling profession, genetic counseling is provided by physicians, trained either in medical genetics or a related clinical discipline.
A comprehensive medical genetics program has been established in Monte Santo, an inland rural community located in the state of Bahia in Northeast Brazil, with high prevalences of a number of autosomal recessive genetic disorders, including non-syndromic deafness, phenyketonuria, congenital hypothyroidism and mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).
Genetic education, counseling and treatment are locally provided, with a neonatal screening program for MPSVI currently under trial. | 7,199 |
Title:
Associations between patterns of active commuting and socioeconomic factors in women with fibromyalgia: the al-Ándalus project.
Abstract:
OBJECTIVES ::: The aims of this study were to know whether active commuting behaviour differs between fibromyalgia patients and controls, and to test whether active commuting is associated with socioeconomic factors in this population. ::: ::: ::: METHODS ::: This cross-sectional study included 459 women with fibromyalgia (52.2 years) and 214 female control participants (51.3 years) from Andalusia (southern Spain).
Participants reported patterns of active commuting and socioeconomic factors (civil status, accompaniment at home, living with, educational level, and current occupational and professional status). ::: ::: ::: RRESULTS ::: On the age group <51 years, women with fibromyalgia revealed a significant higher percentage of active commuting for the variable active worker commuters than control group (p<0.05).
On the age group ≥51 years, control group displayed a significant higher percentage of active commuting for commuting to local shops, super-market and active commuters variables (all, p<0.05).
Women with fibromyalgia who lived alone were more active commuters in comparison to either those living accompanied, or living with both partner and children, only partner and only children (all, p<0.05). ::: ::: ::: CONCLUSIONS ::: The prevalence of active commuting was similar in women with fibromyalgia and controls aged <51 years.
However, fibromyalgia participants aged ≥51 years displayed differences: fibromyalgia women who lived alone were more active commuters than those living accompanied; family demands were inversely associated with commuting patterns.
Policies focused on reducing family demands for fibromyalgia patients (i.e. social help on housework, childcare or overprotection) might facilitate the inclusion of daily active behaviours. | 7,200 |
Title:
Health literacy and warfarin therapy at two anticoagulation clinics in Brazil
Abstract:
Objective Health literacy has been related to health-related conditions and health outcomes.
Studies examining the association of health literacy and anticoagulation have had variable results.
We sought to investigate the relations of health literacy and percentage of time in therapeutic range (TTR) in a vulnerable Brazilian cohort at two hospital-based anticoagulation clinics.
Methods We measured health literacy with the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA-18) in 2015–2016.
We identified the demographic and clinical characteristics associated with health literacy and related health literacy to TTR.
Results We enrolled 422 adults prescribed chronic warfarin therapy in our observational study (median age 62.1 years; 58.8% women; monthly income $200.00).
The prevalence of inadequate health literacy (score 0–14 points) was 72.3% with a median score of 12 (quartiles, Q1=10; Q3=15) on the SAHLPA-18.
The median TTR was 66.1%.
In the multivariable logistic analysis, cognitive impairment and assistance with taking warfarin were associated with inadequate health literacy.
Prosthetic heart valves and more school years were associated with adequate health literacy.
Our analyses showed no significant relation between health literacy and TTR, analysing health literacy as a categorical (adjusted OR 1.05; 95% CI 0.65 to 1.70) or continuous variable (Spearman’s coefficient 0.02; p=0.70).
Conclusions Inadequate health literacy was highly prevalent in this impoverished Brazilian cohort receiving anticoagulation with warfarin.
However, we did not identify an association between health literacy and TTR.
Future investigations may consider the systemic factors that contribute towards successful anticoagulation outcomes for vulnerable patient cohorts with inadequate health literacy. | 7,415 |
Title:
Extracellular electrical recording of pH-triggered bursts in C6 glioma cell populations
Abstract:
Glioma patients often suffer from epileptic seizures because of the tumor’s impact on the brain physiology.
Using the rat glioma cell line C6 as a model system, we performed long-term live recordings of the electrical activity of glioma populations in an ultrasensitive detection method.
The transducer exploits large-area electrodes that maximize double-layer capacitance, thus increasing the sensitivity.
This strategy allowed us to record glioma electrical activity.
We show that although glioma cells are nonelectrogenic, they display a remarkable electrical burst activity in time.
The low-frequency current noise after cell adhesion is dominated by the flow of Na+ ions through voltage-gated ion channels.
However, after an incubation period of many hours, the current noise markedly increased.
This electric bursting phenomenon was not associated with apoptosis because the cells were viable and proliferative during the period of increased electric activity.
We detected a rapid cell culture medium acidification accompanying this event.
By using specific inhibitors, we showed that the electrical bursting activity was prompted by extracellular pH changes, which enhanced Na+ ion flux through the psalmotoxin 1–sensitive acid-sensing ion channels.
Our model of pH-triggered bursting was unambiguously supported by deliberate, external acidification of the cell culture medium.
This unexpected, acidosis-driven electrical activity is likely to directly perturb, in vivo, the functionality of the healthy neuronal network in the vicinity of the tumor bulk and may contribute to seizures in glioma patients. | 7,479 |
Title:
Host Range and Specificity of the Drosophila C Virus
Abstract:
BACKGROUND ::: The Drosophila C virus (DCV) is a common and well-studied Drosophila pathogen.
Although natural infections are known from Drosophila melanogaster and D. simulans, and artificial infections have been reported from several Drosophila species and other insects, it remains unclear to date whether DCV infections also occur naturally in other Drosophila species. ::: ::: ::: METHODS/PRINCIPAL FINDINGS ::: Using reverse transcription PCR, we detected natural infections in six Drosophila species, which have not been previously known as natural hosts.
By subsequent Sanger sequencing we compared DCV haplotypes among eight Drosophila host species.
Our data suggest that cross-infections might be frequent both within and among species within the laboratory environment.
Moreover, we find that some lines exhibit multiple infections with distinct DCV haplotypes. ::: ::: ::: CONCLUSIONS ::: Our results suggest that the natural host range of DCV is much broader than previously assumed and that cross-infections might be a common phenomenon in the laboratory, even among different Drosophila hosts. | 7,484 |
Title:
Outcome of Observing the N0 Neck Using Ultrasonographic-Guided Cytology for Follow-up
Abstract:
OBJECTIVE ::: To assess the outcome of patients who underwent transoral tumor excision and a wait-and-see policy for the NO neck, using ultrasonographic-guided fine-needle aspiration cytology (US-FNAC) of the neck for both selecting patients for neck treatment or observation and for follow-up. ::: ::: ::: DESIGN ::: Retrospective outcome analysis of a patient cohort without palpable or US-FNAC detectable nodal metastases undergoing transoral tumor excisions.
Patients were followed up for 1 to 4 years using palpation and US-FNAC. ::: ::: ::: SETTING ::: Academic center. ::: ::: ::: PATIENTS ::: A consecutive sample of 77 patients mainly with oral carcinomas.
Excluded were patients who had neck dissections, radiotherapy, or no US-FNAC during follow-up. ::: ::: ::: INTERVENTION ::: Transoral tumor excision.
Neck dissection with radiotherapy for regional failure. ::: ::: ::: OUTCOME MEASURE ::: The recurrence rate in the neck, without failure at the primary site and the salvage rate of these neck recurrences were the most important measures.
Treatment delay and histopathologic findings were assessed as well. ::: ::: ::: RESULTS ::: Fourteen patients (18%) had occult lymph node metastases and neck failures.
Of the 14 neck failures, 9 were detected within 7 months of which 6 were not palpable.
Ten (71%) of these 14 patients were successfully salvaged, and 4 died of uncontrolled disease.
Three of the 4 patients also had distant metastases. ::: ::: ::: CONCLUSIONS ::: The low recurrence rate (18%) can be attributed to the initial US-FNAC.
The high salvage rate (71%) indicates that strict US-FNAC follow-up enables early detection of recurrence in the neck.
A wait-and-see policy thus seems warranted, provided regular US-FNAC examinations during follow-up can be guaranteed. | 7,599 |
Title:
Oxidized LDL and Lysophosphatidylcholine Stimulate Plasminogen Activator Inhibitor-1 Expression in Vascular Smooth Muscle Cells
Abstract:
Plasminogen activator inhibitor-1 (PAI-1) functions as an important regulator of fibrinolysis by inhibiting both tissue-type and urokinase-type plasminogen activator.
PAI-1 is produced by smooth muscle cells (SMCs) in atherosclerotic arteries, but the mechanisms responsible for induction of PAI-1 in SMCs are less well understood.
In cultured human aortic SMCs, PAI-1 mRNA expression and protein secretion were increased after incubation with oxidized low-density lipoprotein (LDL) and the lipid peroxidation product lysophosphatidylcholine, whereas the effects of native LDL on PAI-1 production and release were more variable and did not reach statistical significance.
The effect of LDL on arterial expression of PAI-1 in vivo was also studied in an animal model.
Intravenous injection of human LDL in Sprague-Dawley rats resulted in accumulation of apolipoprotein B in the aorta within 12 hours as assessed by immunohistochemical testing.
Epitopes specific for oxidized LDL began to develop in the aorta 12 hours after injection of LDL and peaked at 24 hours; this peak was accompanied by intense expression of PAI-1 immunoreactivity in the media.
Also, increased aortic expression of PAI-1 mRNA after LDL injection was detected by using in situ hybridization.
The transcription factor activator protein-1, which is known to bind to the promoter of the PAI-1 gene, was activated in the aortic wall 24 hours after LDL injection as assessed by electrophoretic mobility shift assay.
Pretreatment of LDL with the antioxidant probucol decreased expression of oxidized LDL and PAI-1 immunoreactivity and activator protein-1 induction in the aorta but did not affect expression of apolipoprotein B immunoreactivity.
These findings demonstrate that LDL oxidation enhances secretion of PAI-1 from cultured SMCs and that a similar mechanism may be involved in vascular expression of PAI-1. | 7,608 |
Title:
Significance of pulmonary artery pressure in emphysema patients with mild-to-moderate hypoxemia.
Abstract:
The guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) do not recommend the measurement of pulmonary artery pressure in patients with chronic obstructive pulmonary disease (COPD).
This is on the basis that the mean pulmonary artery pressure (mPAP) does not provide more clinical information than measurement of the oxygen tension in arterial blood (PaO2).
The mPAP correlates well with PaO2 in emphysema patients with severe hypoxemia (PaO2 < or = 7.3 kPa (55 mmHg)).
However, the occurrence and significance of mPAP is unclear in patients without severe hypoxemia (PaO2 > 7.3 kPa (55 mmHg)).
In order to evaluate the usefulness of measurement of mPAP in emphysema patients without severe hypoxemia, we performed right heart catheterization and investigated the pulmonary hemodynamics of 53 patients without severe hypoxemia.
In addition, we identified long-term prognostic factors with a mean follow-up term of 77 months after right heart catheterization.
Seventeen of 27 patients with mild-to-moderate hypoxemia exhibited pulmonary hypertension (mPAP > or = 2.7 kPa (20 mmHg)) and the classification according to severity in GOLD exhibited a greater correlation to mPAP than PaO2.
Moreover, only mPAP was found to be a significant prognostic factor according to multivariate proportional hazards analysis (P = 0.01).
We conclude that mPAP is more informative about the severity of emphysema than PaO2 in patients with mild-to-moderate hypoxemia. | 7,658 |
Title:
Diagnosis of a variant of Mayer–Rokitansky–Kuster–Hauser syndrome: useful MRI findings
Abstract:
Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome consists of vaginal aplasia associated with other mullerian duct abnormalities.
Its penetrance varies, as does the involvement of other organ systems.
Type I MRKU syndrome is characterized by an isolated absence of the proximal two thirds of the vagina, whereas type II is marked by other malformations which include vertebral, cardiac, urologic (upper tract), and otologic anomalies.
In both types, the extent of vaginal aplasia varies, ranging from virtually absent to a length much more inferior than the normal one (2–5 cm).
MRKU syndrome usually remains undetected until the patient presents with primary amenorrhea despite normal female sexual development.
It is important to underline the fact that this syndrome is the second most common cause of primary amenorrhea.
Although this condition has psychologically devastating consequences, its anatomical defects can be surgically treated.
In fact, following diagnosis, surgery allows patients to have normal sexual function while reproduction may be possible if assisted techniques are performed. | 7,679 |
Title:
Shape encoding consistency across colors in primate V4.
Abstract:
Neurons in primate cortical area V4 are sensitive to the form and color of visual stimuli.
To determine whether form selectivity remains consistent across colors, we studied the responses of single V4 neurons in awake monkeys to a set of two-dimensional shapes presented in two different colors.
For each neuron, we chose two colors that were visually distinct and that evoked reliable and different responses.
Across neurons, the correlation coefficient between responses in the two colors ranged from −0.03 to 0.93 (median 0.54).
Neurons with highly consistent shape responses, i.e., high correlation coefficients, showed greater dispersion in their responses to the different shapes, i.e., greater shape selectivity, and also tended to have less eccentric receptive field locations; among shape-selective neurons, shape consistency ranged from 0.16 to 0.93 (median 0.63).
Consistency of shape responses was independent of the physical difference between the stimulus colors used and the strength of neuronal color tuning.
Finally, we found that our measurement of shape response consistency was strongly influenced by the number of stimulus repeats: consistency estimates based on fewer than 10 repeats were substantially underestimated.
In conclusion, our results suggest that neurons that are likely to contribute to shape perception and discrimination exhibit shape responses that are largely consistent across colors, facilitating the use of simpler algorithms for decoding shape information from V4 neuronal populations. | 7,692 |
Title:
Lipoprotein (a), thrombophilia and inflammatory bowel disease.
Abstract:
Thrombophilia in inflammatory bowel disease may be due to several risk factors, such as a dysbalanced haemostasis with a hypercoagulative state, thrombocytosis, hyperfibrinogenaemia and hyperhomocysteinaemia.
In addition, increased concentrations of lipoprotein (a), a modified form of low-density lipoprotein particles, have been associated with a higher risk of thrombotic vascular disease, probably due to inhibition of (local and endothelial) fibrinolysis.
The mechanisms regulating the plasma concentration of lipoprotein (a) have not yet been elucidated completely, but genetic factors are involved.
Dietary factors seem to play a minor role.
In this issue of the journal, Koutroubakis et al. report that lipoprotein (a) concentration is elevated in patients with Crohn's disease, but not in patients with ulcerative colitis.
Several other (apo)lipoproteins have a different pattern in patients with inflammatory bowel disease than in a control population of healthy subjects from Crete.
These findings add up to the multifactorial nature of thrombophilia in inflammatory bowel disease patients, especially in patients with Crohn's disease, and give rise to speculations about the clinical significance of the observed different lipoprotein metabolism in patients with inflammatory bowel disease. | 7,892 |
Title:
Water ingestion decreases cardiac workload time-dependent in healthy adults with no effect of gender
Abstract:
Ingestion of water entails a variety of cardiovascular responses.
However, the precise effect remains elusive.
We aimed to determine in healthy adults the effect of water on cardiac workload and to investigate potential gender differences.
We pooled data from two controlled studies where blood pressure (BP) and heart rate (HR) were continuously recorded before and after the ingestion of 355 mL of tap water.
Additionally, we calculated double product by multiplying systolic BP with HR and evaluated spectral parameters referring to vagal tone.
All parameters were investigated for potential differences based on gender.
In response to water, HR, systolic BP, and double product decreased significantly during the first 30 min.
However, these effects were attenuated for HR and double product and even abolished for systolic BP over the subsequent 30 min.
Over the entire post-drink period (60 min), decreases in HR and double product (all P < 0.05) were observed.
Spectral markers for vagal tone increased with the on-set of the water drink and remained elevated until the end (P < 0.005).
No significant gender difference in cardiac workload parameters was observed.
We provide evidence that drinking water decreases, in a time-dependent fashion, cardiac workload and that these responses appear not to be influenced by gender. | 7,896 |
Title:
BC1 RNA, the transcript from a master gene for ID element amplification, is able to prime its own reverse transcription.
Abstract:
ID elements are short interspersed elements (SINEs) found in high copy number in many rodent genomes.
BC1 RNA, an ID-related transcript, is derived from the single copy BC1 RNA gene.
The BC1 RNA gene has been shown to be a master gene for ID element amplification in rodent genomes.
ID elements are dispersed through a process termed retroposition.
The retroposition process involves a number of potential regulatory steps.
These regulatory steps may include transcription in the appropriate tissue, transcript stability, priming of the RNA transcript for reverse transcription and integration.
This study focuses on priming of the RNA transcript for reverse transcription.
BC1 RNA gene transcripts are shown to be able to prime their own reverse transcription in an efficient intramolecular and site-specific fashion.
This self-priming ability is a consequence of the secondary structure of the 3'-unique region.
The observation that a gene actively amplified throughout rodent evolution makes a RNA capable of efficient self-primed reverse transcription strongly suggests that self-priming is at least one feature establishing the BC1 RNA gene as a master gene for amplification of ID elements. | 7,912 |
Title:
An Alternative to Domain-general or Domain-specific Frameworks for Theorizing about Human Evolution and Ontogenesis
Abstract:
This paper maintains that neither a domain-general nor a domain-specific framework is appropriate for furthering our understanding of human evolution and ontogenesis.
Rather, as we learn increasingly more about the dynamics of gene-environment interaction and gene expression, theorists should consider a third alternative: a domain-relevant approach, which argues that the infant brain comes equipped with biases that are relevant to, but not initially specific to, processing different kinds of input.
The hypothesis developed here is that domain-specific core knowledge/specialized functions do not constitute the start state; rather, functional specialization emerges progressively through neuronal competition over developmental time.
Thus, the existence of category-specific deficits in brain-damaged adults cannot be used to bolster claims that category-specific or domain-specific modules underpin early development, because neural specificity in the adult brain is likely to have been the emergent property over time of a developing, self-structuring system in interaction with the environment. | 7,962 |
Title:
Isolation of bacteria producing siderophores under alkaline conditions
Abstract:
SummaryThe isolation of bacteria producing siderophores under alkaline conditions is reported.
Enrichment cultures initiated with samples from a number of alkaline environmental sources yielded 80 isolates.
From this group selections were made on the basis of growth at high pH and the gallium-binding capacity of the siderophores.
It was found that some isolates grew well and high concentrations of siderophore were detected whereas others grew well in the presence of much lower concentrations of siderophore.
The effect of iron, gallium and aluminium on growth and siderophore production in batch culture was investigated for six isolates.
The presence of iron greatly decreased the siderophore concentration in these cultures, whereas the response to added gallium or aluminium was dependent upon the isolate. | 7,971 |
Title:
Combined liver and kidney transplantation with particular reference to positive cytotoxic crossmatches
Abstract:
Nine patients were provided with 10 livers and 10 kidneys.
Nine of the paired allografts were from the same donors.
Seven of the 9 recipients are alive after 6 to 26 months.
At least 3 and possibly as many as 5 of the paired transplantations were to patients whose sera possessed preformed antigraft cytotoxic antibodies.
Only one of the livers seemed harmed by the antibodies, and the kidneys that were transplanted after the livers were in place were thereby seemingly protected from antibody injury in 2 of the 3 unequivocal cases.
These observations may provide a clue for the development of new methods to prevent hyperacute renal rejection. | 8,045 |
Title:
Head-to-head comparison of a 2-day myocardial perfusion gated SPECT protocol and cardiac magnetic resonance late gadolinium enhancement for the detection of myocardial infarction
Abstract:
BACKGROUND ::: The aim was to determine the sensitivity and specificity of gated myocardial perfusion SPECT (MPS) with a technetium-labelled (Tc) perfusion tracer to detect myocardial infarction (MI) in a clinical population referred for assessment of stress-induced ischemia using late gadolinium enhancement cardiac magnetic resonance (CMR) as reference method. ::: ::: ::: METHODS ::: 119 patients referred for evaluation of stress-induced ischemia with MPS were included.
108 patients (age 62 ± 10 years, 39% females) completed MPS and CMR.
A 2-day protocol for MPS was used for most patients (n = 105). ::: ::: ::: RESULTS ::: MI was found in 31 patients (29%) using MPS and in 30 patients using CMR (28%).
The sensitivity and specificity on a patient basis were 93% and 96%, respectively.
Positive predictive value (PPV) was 90% and negative predictive value (NPV) was 97%.
Per territory, the sensitivity and specificity for LAD infarcts were 83% and 97%, respectively.
PPV was 77% and NPV was 98% for LAD infarcts.
The sensitivity and specificity for RCA/LCx infarcts were 95% and 95%, respectively.
PPV was 84% and NPV was 99% for RCA/LCx infarcts.
The MI size on CMR was 12.0 ± 7.3% of the LV and mean transmurality was 66.3 ± 12.0%.
All MI > 3% were detected on gated SPECT.
::: ::: ::: CONCLUSION ::: This study has demonstrated high sensitivity and specificity for gated Tc-MPS detecting subendocardial and transmural MI. | 8,049 |
Title:
Nanog Predicts Poor Prognosis in Human Pancreatic Cancer and Is Downregulated by QingyihuaJi Formula in Pancreatic Cancer Stem Cells
Abstract:
Qingyihuaji formula (QYHJ), confirmed efficacious in a series of clinical trials, has been applied to human pancreatic carcinoma treatment in Shanghai Cancer Center for years.
Recent evidence highlighted that pluripotent stem cells transcription factor Nanog plays a pivotal role in carcinogenesis.
However, there is little published information regarding the underlying clinical significance and mechanisms of transcription factor Nanog in pancreatic cancer.
In this study, our results indicated that Nanog is overexpressed in human pancreatic cancer stem cells and downregulated by QYHJ, which may contribute to explain the clinical effectiveness of QYHJ and provide advanced pancreatic cancer patients with a new therapeutic option, supporting our hypothesis that the degradation pathway is another mechanism by which QYHJ affects Nanog expression. | 8,090 |
Title:
Seasonal availability of resources and habitat degradation for the western tree-hole mosquito, Aedes sierrensis
Abstract:
The nutrient base of aquatic tree-hole communities is derived from leaf litter, benthic detritus, and water flowing down the tree trunk (stemflow water).
Previous studies in eastern North America with the mosquito, Aedes triseriatus, have identified leaf litter as a major and stemflow water as a minor source of mosquito nutrition, but did not consider the role of the benthic detritus or how the aggregate or relative contribution of these sources of mosquito nutrition changed during the year.
We use the leaf litter, benthic detritus, and stemflow water from tree holes in western Oregon (USA) to determine how these substrates affect mass at metamorphosis, biomass yield, and fitness (cohort replacement rate; R 0) of the mosquito, Aedes sierrensis, through both natural and simulated winters, the normal growing season for larvae in tree holes.
We found that fresh leaf litter constitutes the major determinant of mosquito fitness by a factor of >15:1 over any other substrate taken directly from tree holes in nature.
The other substrates, including the benthic detritus, individually make only a meager contribution to mosquito fitness but, when added to the leaf litter, can sustain yield and improve fitness at high, limiting larval densities.
Nutritional quality of tree-hole substrates declines by >90% from early (fall) to late (spring) in the larval growing season.
At both times of year, the coarse or fine detritus provide minor resources, and stemflow water provides no detectable contribution to mosquito nutrition.
The resources in the litter are not transported during the year to the benthic detritus; rather, these resources are either exploited by mosquitoes when they first become available, or they deteriorate and become progressively more unavailable to them.
Growth and development of A. sierrensis feeding on dried and reconstituted tree-hole contents during a 6-month simulated winter in the laboratory showed: (1) the same relative contributions of leaf litter, benthic detritus, and stemflow water to mosquito nutrition, (2) that the winter deterioration of substrate quality is a direct consequence of microbial decomposition, and (3) that pre-emptive competition from pre-existing A. sierrensis greatly increases substrate deterioration.
We conclude that the progressive winter deterioration of larval resources in combination with the dry summers of western North America are the most likely environmental factors that limit species diversity in tree holes and that have selected for early recruitment (autumnal hatching) of A. sierrensis and for its univoltine life cycle from Mexico to Canada. | 8,118 |
Title:
Quitting-unmotivated and quitting-motivated cigarette smokers exhibit different patterns of cue-elicited brain activation when anticipating an opportunity to smoke.
Abstract:
The authors examined the effects of smoking expectancy on cue-reactivity among those motivated and those unmotivated to quit smoking using functional magnetic resonance imaging.
Cue-elicited activation was observed in the rostral prefrontal cortex (PFC) in smokers who expected to smoke within seconds, but not in those who expected to have to wait hours before having the chance to smoke, regardless of quitting motivation.
For quitting-unmotivated smokers expecting to smoke, rostral PFC activation was strongly positively correlated with the activation of several areas previously linked to cue-reactivity, including the medial orbitofrontal cortex (OFC) and rostral anterior cingulate cortex (ACC).
In contrast, there was a non-significant negative relationship between activation of the rostral PFC and activation of the medial OFC/rostral ACC in quitting-motivated smokers expecting to smoke.
Results extend previous work examining the effects of smoking expectancy and highlight the utility of examining interregional covariation during cue exposure.
Findings also suggest that investigators may need to pay close attention to the motivational contexts associated with their experiments when studying cue-reactivity, as these contexts can modulate not only responses to drug cues, but perhaps also the functional implications of observed activity. | 8,149 |
Title:
Inferring transcriptional gene regulation network of starch metabolism in Arabidopsis thaliana leaves using graphical Gaussian model
Abstract:
BackgroundStarch serves as a temporal storage of carbohydrates in plant leaves during day/night cycles.
To study transcriptional regulatory modules of this dynamic metabolic process, we conducted gene regulation network analysis based on small-sample inference of graphical Gaussian model (GGM).ResultsTime-series significant analysis was applied for Arabidopsis leaf transcriptome data to obtain a set of genes that are highly regulated under a diurnal cycle.
A total of 1,480 diurnally regulated genes included 21 starch metabolic enzymes, 6 clock-associated genes, and 106 transcription factors (TF).
A starch-clock-TF gene regulation network comprising 117 nodes and 266 edges was constructed by GGM from these 133 significant genes that are potentially related to the diurnal control of starch metabolism.
From this network, we found that β-amylase 3 (b-amy3: At4g17090), which participates in starch degradation in chloroplast, is the most frequently connected gene (a hub gene).
The robustness of gene-to-gene regulatory network was further analyzed by TF binding site prediction and by evaluating global co-expression of TFs and target starch metabolic enzymes.
As a result, two TFs, indeterminate domain 5 (AtIDD5: At2g02070) and constans-like (COL: At2g21320), were identified as positive regulators of starch synthase 4 (SS4: At4g18240).
The inference model of AtIDD5-dependent positive regulation of SS4 gene expression was experimentally supported by decreased SS4 mRNA accumulation in Atidd5 mutant plants during the light period of both short and long day conditions.
COL was also shown to positively control SS4 mRNA accumulation.
Furthermore, the knockout of AtIDD5 and COL led to deformation of chloroplast and its contained starch granules.
This deformity also affected the number of starch granules per chloroplast, which increased significantly in both knockout mutant lines.
ConclusionsIn this study, we utilized a systematic approach of microarray analysis to discover the transcriptional regulatory network of starch metabolism in Arabidopsis leaves.
With this inference method, the starch regulatory network of Arabidopsis was found to be strongly associated with clock genes and TFs, of which AtIDD5 and COL were evidenced to control SS4 gene expression and starch granule formation in chloroplasts. | 8,182 |
Title:
Exercise and intermittent claudication. Blood flow in the calf muscle during walking studied by the xenon-133 clearance method.
Abstract:
Nineteen patients with obliterative arteriosclerotic disease of the legs and suffering from intermittent claudication were studied before and during a 6 months' training program.
The maximal walking distance and the calf muscle blood flow during walking (xenon-133 clearance technique) was recorded at monthly intervals.
A significant correlation was established between improvement in maximal walking distance and a change on exercise toward more normal (that is, more adequate) blood flow in the calf.
In particular, it was found that calf muscle blood flow during walking was increased by physical training.
The data suggest that functional factors (for example, better coordination of the working muscles or a decrease of in-between-step intra-muscular pressure) as well as anatomic factors (increase in number or diameter of collateral vessels, or both) are involved in increasing collateral efficiency. | 8,311 |
Title:
Pregnancy with an intrauterine device in situ and preterm delivery
Abstract:
We determined the prevalence of preterm delivery in a population of women who conceived with an IUD in situ and compared the results with those in a group of women without any contraceptive method.
The study group consisted of 16 women who conceived with a copper IUD in situ.
The control group comprised 48 women matched for age, gravidity and parity.
The prevalence of preterm delivery was significantly higher in the study group than in the control group (18.7% (3/16) vs 2% (1/48)), respectively.
(P = 0.045, Fisher's exact test.) | 8,413 |
Title:
Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia
Abstract:
We recently identified a frame-shift mutation in the PAX9 gene as the underlying cause for hypodontia involving permanent molar teeth segregating in an autosomal dominant pattern in a single large family (Stockton et al. 2000).
Here we report a small nuclear family in which a father and his daughter are affected with severe hypodontia, involving agenesis of all primary and permanent molars, evidently caused by deletion of the entire PAX9 gene.
Hemizygosity at the PAX9 locus in the two affected individuals was initially discovered when an informative single nucleotide polymorphism, identified while sequencing the gene for mutations, appeared to demonstrate non-Mendelian inheritance.
Fluorescence in situ hybridization (FISH) analysis with a cosmid containing the PAX9 gene yielded a signal on only one chromosome 14 homologue and confirmed the presence of a deletion encompassing the PAX9 locus.
Analysis of microsatellite loci in the vicinity of PAX9 delineated one breakpoint of the deletion.
These data, in concert with FISH analysis with cosmids encompassing a 199 kb region, indicated that the deletion is between approximately 44 kb and 100 kb.
PAX9 is one of two genes, and the only odontogenic gene within the deletion interval, thus supporting the model of haploinsufficiency for PAX9 as the underlying basis for hypodontia. | 8,452 |
Title:
Dihydromyricetin Activates AMP-Activated Protein Kinase and P38MAPK Exerting Antitumor Potential in Osteosarcoma
Abstract:
Numerous patients with osteosarcoma either are not sensitive to chemotherapy or develop drug resistance to current chemotherapy regimens.
Therefore, it is necessary to develop several potentially useful therapeutic agents.
Dihydromyricetin is the major flavonoid component derived from Ampelopsis grossedentata , which has a long history of use in food and medicine.
The present study examined the antitumor activity both in vitro and in vivo without noticeable side effects and the underlying mechanism of action of dihydromyricetin in osteosarcoma cells.
We found that dihydromyricetin induced increased p21 expression and G 2 –M cell-cycle arrest, caused DNA damage, activated ATM–CHK2–H2AX signaling pathways, and induced apoptosis in osteosarcoma cells as well as decreasing the sphere formation capability by downregulating Sox2 expression.
Mechanistic analysis showed that the antitumor potential of dihydromyricetin may be due to the activation of AMPKα and p38 MAPK , as the activating AMPKα led to the inactivation of GSK3β in osteosarcoma cells.
Moreover, GSK3β deletion or GSK3β inhibition by LiCl treatment resulted in increased p21 expression and reduced Sox2 expression in osteosarcoma cells.
Taken together, our results strongly indicate that the antitumor potential of dihydromyricetin is correlated with P38 MAPK and the AMPKα–GSK3β–Sox2 signaling pathway.
Finally, immunohistochemical analysis indicated that some patients had a lower p-AMPK expression after chemotherapy, which supports that the combination of dihydromyricetin and chemotherapy drug will be beneficial for patients with osteosarcoma.
In conclusion, our results are the first to suggest that dihydromyricetin may be a therapeutic candidate for the treatment of osteosarcoma.
Cancer Prev Res; 7(9); 927–38.
©2014 AACR . | 8,479 |
Title:
Illicit methadone injecting during methadone maintenance treatment in a specialised out-patient clinic
Abstract:
AIM ::: The injection of non-sterile methadone designed for oral consumption is associated with serious health risks.
There is only a small number of studies on this topic, with divergent results.
The main aim of the present study was to obtain data on the frequency of methadone injecting in a state out-patient clinic specialised in substance use disorders. ::: ::: ::: METHODS ::: Eighty patients in methadone maintenance treatment were interviewed with a short questionnaire.
Mean age was 32 years, 76% were male, mean methadone dose was 55 mg. ::: ::: ::: RESULTS ::: Twenty-six patients (32%) indicated having injected methadone at least once in their life.
Only four patients (5%) reported having injected methadone within the preceding month (mean dose 56 mg).
All four had injected additional substances during this month. ::: ::: ::: CONCLUSIONS ::: Frequency rates appeared low compared with other studies despite a generous take-away policy.
The results suggest an association between methadone injecting and a more general tendency to inject substances. | 8,637 |
Title:
Halide and Alkyl Phenols Block Volume-Sensitive Chloride Channels in Human Glial Cells (U-138MG)
Abstract:
Swelling of cells in hypotonic media activates a volume-sensitive Cl channel with well-known characteristics, but its structure and its regulation are still largely undetermined.
It also has many inhibitors and most of them are also blocking other types of Cl channels.
The numerous inhibitors of Cl channels have apparently no structural relationship among them.
The purpose of this study was to try to determine the most simple molecules that could block these channels and identify some common properties among inhibitors.
From the 37 new molecules that were studied, it was found that simple halide phenols like trichloro and triiodophenols could block these channels in the micromolar range.
Also alkyl phenols, like butylphenols, are very sensitive blockers, comparable to other well-known blockers. But acidic halide phenols or nitrophenols are poor blockers.
Also neutral polyphenols are more sensitive than acidic polyphenols.
All these results indicate that the common basis for blocking these Cl channels is a phenol with hydrophobic groups, like short alkyl chains or an additional phenyl ring, attached to some of its sites, preferably sites 3-4-5.
These results identify a new family of Cl channel blockers and hopefully improve our understanding of the blocking mechanism. | 8,740 |
Title:
Genome sequence of Coxiella burnetii strain Namibia
Abstract:
We present the whole genome sequence and annotation of the Coxiella burnetii strain Namibia.
This strain was isolated from an aborting goat in 1991 in Windhoek, Namibia.
The plasmid type QpRS was confirmed in our work.
Further genomic typing placed the strain into a unique genomic group.
The genome sequence is 2,101,438 bp long and contains 1,979 protein-coding and 51 RNA genes, including one rRNA operon.
To overcome the poor yield from cell culture systems, an additional DNA enrichment with whole genome amplification (WGA) methods was applied.
We describe a bioinformatics pipeline for improved genome assembly including several filters with a special focus on WGA characteristics. | 8,774 |
Title:
Trends in blood pressure and urinary sodium and potassium excretion in Japan: reinvestigation in the 8th year after the Intersalt Study
Abstract:
Using the identical protocol of an Intersalt Study previously conducted, we undertook a new study (Intersalt-2) 8 years later.
We measured changes in various factors affecting blood pressure (BP) including urinary sodium and potassium excretion in three districts of Japan: Osaka, Tochigi, and Toyama.
Also we evaluated the trends in the relationships of those factors to BP.The Intersalt Study revealed that the average sodium excretion of all three study centres was high (particularly in Toyama) while potassium excretion was relatively low.
The sodium/potassium ratio was therefore relatively high.
The body mass index (BMI) was favourable, but the prevalence of heavy alcohol drinkers was high.
Comparing the first to the second study reveals a decrease in sodium excretion in Toyama, although that area still had the highest value of the three study centres.
The average potassium excretion increased only in Osaka.
Sodium/potassium ratio decreased in all centres.
BMI and the prevalence of heavy drinkers among the subjects of both studies were nearly the same.
The trend of the relationship of sodium to BP in Osaka changed from negative to positive.
In Toyama, it changed from positive to negative.
It is thought that this negative relationship might occur in conjunction with a reduction in salt consumption in a population.
In conclusion this study reveals that average sodium consumption in Japan remains high while potassium consumption is still low.
As a factor in the prevention of hypertension, further efforts to reduce salt consumption and increase potassium intake are still needed. | 8,805 |
Title:
Counting drugs to understand the disease: The case of measuring the diabetes epidemic
Abstract:
BackgroundDiabetes prevalence increases globally with severe consequences for afflicted individuals and societies.
Data on diabetes incidence and diabetes related mortality on a population level are, however, scarce.
As an alternative to dedicated studies it has been suggested to use pharmacoepidemiological databases that are readily available, at least in the Nordic countries.
MethodsFor all 470,000 inhabitants in Funen County, Denmark, in the period 1992–2003, data on gender, date of birth, death and migration to and from the county, and any filled prescriptions of an anti-diabetic medication was obtained from the Odense Pharmaco-Epidemiological Database.
ResultsPrevalence odds for use of an anti-diabetic medication rose annually 3.5% (95% confidence interval: 3.1%, 3.9%) for females, 4.5% (4.0%, 4.9%) for males.
Corresponding incidence rates annually rose 4.8% (3.8%, 5.8%) for females, 4.5% (3.5%, 5.4%) for males.
Mortality rates among treated annually declined 2.8% (1.4%, 4.1%) among females, 2.2% (0.9%, 3.5%) among males.
The disequilibrium in absolute numbers between incidence and mortality among treated was the main driver for the increasing prevalence, while concurrent trends in incidence and diabetes related mortality only marginally affected prevalence trends.
Trend estimates were insensitive to varying the length of the run-in period used for determining treatment status, except when using the naive and methodologically flawed run-in period of variable length.
ConclusionWhile pharmacoepidemiological databases provide a useful tool for monitoring pharmacologically treated diabetes, a dedicated diabetes database covering all prevalents and incidents is needed for a more detailed analysis of underlying causes and trends. | 9,075 |
Title:
Complex hand dexterity: a review of biomechanical methods for measuring musical performance
Abstract:
Complex hand dexterity is fundamental to our interactions with the physical, social, and cultural environment.
Dexterity can be an expression of creativity and precision in a range of activities, including musical performance.
Little is understood about complex hand dexterity or how virtuoso expertise is acquired, due to the versatility of movement combinations available to complete any given task.
This has historically limited progress of the field because of difficulties in measuring movements of the hand.
Recent developments in methods of motion capture and analysis mean it is now possible to explore the intricate movements of the hand and fingers.
These methods allow us insights into the neurophysiological mechanisms underpinning complex hand dexterity and motor learning.
They also allow investigation into the key factors that contribute to injury, recovery and functional compensation.
The application of such analytical techniques within musical performance provides a multidisciplinary framework for purposeful investigation into the process of learning and skill acquisition in instrumental performance.
These highly skilled manual and cognitive tasks present the ultimate achievement in complex hand dexterity.
This paper will review methods of assessing instrumental performance in music, focusing specifically on biomechanical measurement and the associated technical challenges faced when measuring highly dexterous activities. | 9,095 |
Title:
High-flow oxygen administration by nasal cannula for adult and perinatal patients.
Abstract:
The nasal cannula has been a commonly used patient interface to provide supplemental oxygen since its introduction in the 1940s.
Traditionally, it has been categorized as a low-flow device and capable of delivering a 0.4 F(IO(2)) with flows up to 6 L/min to adults with normal minute ventilation.
However, there is considerable performance variability among patients and design, which results in an exponential decline in delivered F(IO(2)) as breathing frequencies increase.
The nasal cannula has also been successfully adapted for use in perinatal and pediatric respiratory care; flows are reduced, in the range of 0.25-1 L/min, due to smaller minute volumes.
A decade or so ago, high-flow nasal cannula (HFNC) oxygen therapy was introduced, accompanied by heated humidification systems to prevent the associated drying of upper airway mucosa and to increase patient comfort.
Therapeutic flows for adults were in the 15-40 L/min range; F(IO(2)) could be independently adjusted with air/O(2) blending.
The HFNC has also found additional clinical application in perinatal care, as delivery systems with flows > 2 L/min could create a distending pressure similar to nasal CPAP.
There is a small but growing body of information from clinical trials that supports use of HFNC as an alternative oxygen interface for adults who present with moderate hypoxemia that persists after receiving oxygen by reservoir-bag masks or similar therapy.
Clinical observations report greater patient acceptance and comfort versus oxygen masks.
HFNC therapy has also been considered valuable in perinatal care in treating the respiratory distress syndrome or supporting patients after extubation similar to nasal CPAP.
At present, research-based evidence for the role of HFNC for its perinatal applications remains unclear.
This review will identify proposed mechanisms for therapeutic effectiveness, current delivery equipment, guidelines for rational patient application, and direction for further research. | 9,349 |
Title:
Mitochondrial disorders in children: toward development of small‐molecule treatment strategies
Abstract:
This review presents our current understanding of the pathophysiology and potential treatment strategies with respect to mitochondrial disease in children.
We focus on pathologies due to mutations in nuclear DNA-encoded structural and assembly factors of the mitochondrial oxidative phosphorylation (OXPHOS) system, with a particular emphasis on isolated mitochondrial complex I deficiency.
Following a brief introduction into mitochondrial disease and OXPHOS function, an overview is provided of the diagnostic process in children with mitochondrial disorders.
This includes the impact of whole-exome sequencing and relevance of cellular complementation studies.
Next, we briefly present how OXPHOS mutations can affect cellular parameters, primarily based on studies in patient-derived fibroblasts, and how this information can be used for the rational design of small-molecule treatment strategies.
Finally, we discuss clinical trial design and provide an overview of small molecules that are currently being developed for treatment of mitochondrial disease. | 9,380 |
Title:
Altered Urinary Kallikrein Excretion in Rats with Hypertension
Abstract:
The urinary excretion of kallikrein, an enzyme which cleaves a vasodilator kinin from kininogen substrate, was examined in three types of hypertensive rats.
Enzyme activity was measured by both esterase activity (isotopic assay) and bioassay with purified rat urinary kallikrein as a standard.
Excretion of kallikrein was found to increase with age in spontaneously hypertensive rats, but levels were lower and stable in normotensive Wistar control animals.
Rats with desoxycorticosterone-salt hypertension excreted markedly more, whereas rats with renal hypertension excreted significantly less kallikrein than did control animals.
The alterations in kallikrein excretion were unrelated to changes in urine volume and protein excretion.
The findings indicate that the kallikrein-kinin system may be involved in different forms of hypertension in the rat. | 9,391 |
Title:
MET exon 14 skipping defines a unique molecular class of non-small cell lung cancer
Abstract:
PURPOSE ::: Recurrent MET exon 14 splicing has been revealed in lung cancers and is a promising therapeutic target.
Because we have limited knowledge about the natural history of MET mutant tumors, the current study was aiming to determine the clinical and pathological characteristics in non-small cell lung cancers (NSCLC). ::: ::: ::: RESULTS ::: Twenty-three patients (1.3%) were positive for MET exon 14 skipping.
Patients with MET exon 14 skipping displayed unique characteristics: female, non-smokers, earlier pathology stage and older age.
MET exon 14 skipping indicated an early event as other drivers in lung cancer, while MET copy number gain was more likely a late event in lung cancer.
Overall survival (OS) of patients harboring MET exon 14 skipping was longer than patients with KRAS mutation.
Almost four-fifths of the lung tumors with MET exon 14 skipping had EGFR and/or HER2 gene copy number gains.
EGFR inhibitor showed moderate antitumor activity in treatment of a patient harboring MET exon 14 skipping. ::: ::: ::: PATIENTS AND METHODS ::: From October 2007 to June 2013, we screened 1770 patients with NSCLC and correlated MET status with clinical pathologic characteristics and mutations in EGFR, KRAS, BRAF, HER2, and ALK.
Quantitative Real-Time PCR was used to detect MET gene copy number gain.
Immunohistochemistry (IHC) was also performed to screen MET exon 14 skipping.
Clinicopathological characteristics and survival information were analyzed.
::: ::: ::: CONCLUSIONS ::: MET exon 14 skipping was detected in 1.3% (23/1770) of the Chinese patients with NSCLC.
MET exon 14 skipping defined a new molecular subset of NSCLC with identifiable clinical characteristics.
The therapeutic EGFR inhibitors might be an alternative treatment for patients with MET mutant NSCLC. | 9,417 |
Title:
Predictors of Genital Pain in Young Women
Abstract:
Despite the high prevalence of genital pain in healthy young adult women, limited research has addressed genital pain during intercourse using contemporary models of multidimensional sexual function.
The objectives of this study were threefold: (1) to identify differences in sexual functioning in women who experience genital pain compared to pain free women; (2) to identify predictors of sexual functioning in women with and without genital pain; and (3) to identify predictors of sexual satisfaction in women with and without genital pain.
Sexually active female undergraduates (n = 651) were administered the Female Sexual Function Index and the Derogatis Sexual Functioning Inventory.
We evaluated the sexual factors that impact the sexual function of women with any pain (including high and low pain groups) versus women with no history of pain.
Women with genital pain reported greater rates of sexual dysfunction as compared to pain-free women; however, sexual functioning in the high versus low pain groups was distinguished primarily by vaginal lubrication.
Women in the high pain group showed negative correlations between domains of sexual satisfaction and genital pain frequency and intensity that were not found in the low pain group.
For pain-free women, intercourse played a strong role in sexual satisfaction, whereas non-intercourse sexual behavior was central to sexual satisfaction in women who reported pain.
The evaluation of levels of genital pain may provide insight into the mechanisms underlying the impairment of sexual function, sexual behavior, and sexual satisfaction. | 9,538 |
Title:
Outcomes of Minimally Invasive Antireflux Operations in the Elderly: A Comparative Review
Abstract:
BACKGROUND AND OBJECTIVES ::: The objectives of this study were to assess the impact of age following laparoscopic fundoplication (LF). ::: ::: ::: METHODS ::: From March 1993 to November 1998, 193 patients underwent LF.
Patients comprised 150 young individuals (age<60; median 41) and 43 older individuals (age>60; median 68).
Follow-up included heartburn scores, dysphagia scores, and quality of life determined by the Short Form 36 Health Survey (SF36). ::: ::: ::: RESULTS ::: Older patients had more cardiac disease, psychiatric disorders, prior cancers, and upper abdominal operations (P<0.05).
DeMeester scores were similar (young 70/older 69).
Complications occurred in 13 (8.7%) of the young and 5 (11.6%) of the older patients (P=0.142).
No perioperative deaths occurred.
Length of stay was longer (P<0.000) in older patients (2.9 versus 1.6 days); resumption of oral intake (young-1.2; older-1.3 days) and return to normal activity (young-3.6; older-4.4 weeks) were similar.
Follow-up was available in 102 young (median 17 months) and 35 older (median 18 months) patients.
Heartburn and dysphagia scores were excellent in both groups.
SF36 scores were similar in both groups.
Only 6 (5.9%) of the young group and 1 (2.9%) of the older group were dissatisfied (P=0.652). ::: ::: ::: CONCLUSIONS ::: Despite differences in comorbid disease, outcomes were similar in both groups.
LF should be considered a therapeutic option in the older patient with reflux. | 9,574 |
Title:
Association of killer cell immunoglobulin–like receptor genotypes with vascular arterial events and anticardiolipin antibodies in patients with lupus
Abstract:
To determine whether killer cell immunologlobulin-like receptor (KIR) genotypes are associated with vasculitis, vascular arterial events or anticardiolipin (aCL) antibodies in patients with lupus.
A total of 304 patients followed prospectively at the University of Toronto Lupus Clinic were assessed for the occurrence of vasculitis and vascular arterial events.
Molecular HLA-C and KIR (presence or absence of KIR2DL1, 2DL2, 2DL3, 2DS1 and 2DS2) genotyping were performed.
Chi-square and logistic regression were used to analyse association between KIR genes and vascular arterial events and aCL antibodies.
In patients with vascular arterial events, there was a significant increase in KIR2DS2 (60% vs 45%, P = 0.02) and in KIR2DL2 (62% vs 47%, P = 0.01) compared with patients without events.
There was no increase in activating KIR genotypes in patients with vasculitis.
In patients with aCL antibodies, significant increases were seen in KIR2DS2 (54% vs 41%, P = 0.03) and KIR2DL2 (58% vs 41%, P = 0.003), but KIR2DL3 was decreased (87% vs 95%, P = 0.03).
Logistic regression confirmed independent association of KIR2DS2 with vascular arterial events.
We found an increase in KIR2DS2 in lupus patients with vascular arterial events, but not in patients with vasculitis. | 9,600 |
Title:
Isolated single umbilical artery--the case for routine renal screening.
Abstract:
To determine the incidence of silent renal anomalies in infants with isolated single umbilical artery (SUA), all infants with SUA and without other obvious congenital anomalies, identified over a six year period, were screened using renal ultrasonography.
Over 35,000 placentas were examined.
An isolated single umbilical artery was identified in 112 (0.32%).
Nineteen infants had abnormal renal imaging.
Eight of 112 (7.1%) had significant persisting abnormalities.
Vesicoureteric reflux was found in five infants (4.5%).
It is recommended that renal ultrasonography be performed for all infants with isolated SUA. | 9,614 |
Title:
Sex, Socioeconomic Status, Access to Cardiac Catheterization, and Outcomes for Acute Coronary Syndromes in the Context of Universal Healthcare Coverage
Abstract:
BACKGROUND ::: Sex and neighborhood socioeconomic status (nSES) may independently affect the care and outcomes of acute coronary syndrome, partly through barriers in timely access to cardiac catheterization.
We sought to determine whether sex modifies the association between nSES and the receipt of cardiac catheterization and mortality after an acute coronary syndrome in a universal healthcare system. ::: ::: ::: METHODS AND RESULTS ::: We studied 14 012 patients with acute coronary syndrome admitted to cardiology services between April 18, 2004, and December 31, 2011, in Southern Alberta, Canada.
We used multivariable logistic regression to compare the odds of cardiac catheterization within 2 and 30 days of admission and the odds of 30-day and 1-year mortality for men and women by quintile of neighborhood median household income.
Significant relationships between nSES and the receipt of cardiac catheterization and mortality after acute coronary syndrome were detected for women but not men.
When examined by nSES, each incremental decrease in neighborhood income quintile for women was associated with a 6% lower odds of receiving cardiac catheterization within 30 days (P=0.01) and a 14% higher odds of 30-day mortality (P=0.03).
For men, each decrease in neighborhood income quintile was associated with a 2% lower odds of receiving catheterization within 30 days (P=0.10) and a 5% higher odds of 30-day mortality (P=0.36). ::: ::: ::: CONCLUSIONS ::: Associations between nSES and receipt of cardiac catheterization and 30-day mortality were noted for women but not men in a universal healthcare system.
Care protocols designed to improve equity of access to care and outcomes are required, especially for low-income women. | 9,734 |
Title:
Methodological issues in developing new acute treatments for patients with bipolar illness
Abstract:
Abstract One important aim of the recent reorganization of the National Institute of Mental Health (NIMH) is to streamline the development of new treatments for patients with severe mental illnesses, such as bipolar disorder.
Researching new treatments for patients with bipolar disorder presents specific problems not readily addressed by traditional efficacy trial methodologies that aim to maximize internal validity.
This article reexamines several assumptions that have guided the design of these efficacy trials but that also create obstacles for studies of bipolar disorder and suggests potential solutions.
This article draws on literature from neurology and psychiatry and discussions at a MacArthur Foundation–sponsored Conference on Longitudinal Methodology in 1992 (David J. Kupfer, M.D., Chair), which brought together investigators to consider alternative designs for patients with severe and persistent mental illness.
In addition, we benefited from discussions at two NIMH-sponsored conferences, one held in 1989 (Prien and Potter 1990) and the other in 1994 (Prien and Rush 1996) , at which investigators and methodologists discussed issues surrounding the development and conduct of informative efficacy trials for patients with bipolar disorder.
Based on these discussions and recent literature reviews, we 1) outline common problems in the development and evaluation of effective acute treatments for bipolar disorder and 2) suggest possible solutions to these impediments.
We also discuss alternative designs by which to build a sequence of acute treatment studies from which efficacy, safety, and the comparative value of different treatments can be established. | 9,755 |
Title:
DTC genetic testing: pendulum swings and policy paradoxes
Abstract:
Caulfield T. DTC genetic testing: pendulum swings and policy paradoxes. ::: ::: ::: ::: After decades of optimistic portrayals, there has been a shift in the way that the popular press represents genomic research.
A skeptical view has become more common.
The central reason for this pendulum swing away from popular support is the harsh truth that most genetic risk information just isn't that predictive.
This reality has created a fascinating policy paradox.
If, as many in the scientific community are now saying, genetic information is not the oracle of our future health as we were once led to believe, and if access does not, for most, cause harm, why regulate the area? Why worry about shoddy direct-to-consumer (DTC) genetic testing companies?
One primary justification, and one endorsed by the recent Canadian College of Medical Geneticists (CCMG) Policy Statement on DTC Genetics Testing, is that information that is conveyed to the public about genetics via marketing and to those who access DTC tests should, at a minimum, be accurate. | 10,080 |
Title:
C2 spinal cord stimulation induces dynorphin release from rat T4 spinal cord: potential modulation of myocardial ischemia-sensitive neurons
Abstract:
During myocardial ischemia, the cranial cervical spinal cord (C1–C2) modulates the central processing of the cardiac nociceptive signal.
This study was done to determine 1) whether C2 SCS-induced release of an analgesic neuropeptide in the dorsal horn of the thoracic (T4) spinal cord; 2) if one of the sources of this analgesic peptide was cervical propriospinal neurons, and 3) if chemical inactivation of C2 neurons altered local T4 substance P (SP) release during concurrent C2 SCS and cardiac ischemia.
Ischemia was induced by intermittent occlusion of the left anterior descending coronary artery (CoAO) in urethane-anesthetized Sprague-Dawley rats.
Release of dynorphin A (1-13), (DYN) and SP was determined using antibody-coated microprobes inserted into T4.
SCS alone induced DYN release from laminae I–V in T4, and this release was maintained during CoAO.
C2 injection of the excitotoxin, ibotenic acid, prior to SCS, inhibited T4 DYN release during SCS and ischemia; it also reversed the inhibition of SP release from T4 dorsal laminae during C2 SCS and CoAO.
Injection of the κ-opioid antagonist, nor-binaltorphimine, into T4 also allowed an increased SP release during SCS and CoAO.
CoAO increased the number of Fos-positive neurons in T4 dorsal horns but not in the intermediolateral columns (IML), while SCS (either alone or during CoAO) minimized this dorsal horn response to CoAO alone, while inducing T4 IML neuronal recruitment.
These results suggest that activation of cervical propriospinal pathways induces DYN release in the thoracic spinal cord, thereby modulating nociceptive signals from the ischemic heart. | 10,136 |
Title:
Intellectual disability nursing and transcultural care
Abstract:
In today's healthcare environment, nurses are urged to use up-to-date research evidence to ensure better patient outcomes and inform nursing decisions, actions and interactions with patients.
Within the practice setting, there is an increasing challenge to provide care to patients from minority ethnic groups.
In order to deliver care to different cultural groups, nurses need to recognize and empathize with patients' belief systems, being mindful of their diverse cultural needs.
This article presents the concept of transcultural care and identifies issues within intellectual disability nursing through a focus on the components identified by Campinha-Bacote (2002; 2003) and Cortis (2003): cultural awareness, cultural skill, cultural knowledge, cultural encounter and cultural desire.
It highlights the issues which are relevant to nursing practice, cultural care and service provision for persons with intellectual disability from ethnic minorities in Ireland. | 10,211 |
Title:
High-dose etoposide, cyclophosphamide, and total body irradiation with allogeneic bone marrow transplantation for patients with acute myeloid leukemia in untreated first relapse: a study by the North American Marrow Transplant Group
Abstract:
Relapse is a major cause of treatment failure following allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML).
To reduce the risk of relapse following BMT for patients with hematologic malignancy, our group developed a novel preparative regimen which combines high-dose etoposide with cyclophosphamide and total body irradiation (VPCyTBI).
We now report the outcome of therapy with VPCyTBI followed by allogeneic BMT for 40 patients with AML in untreated first relapse.
With the exception of increased stomatitis, the toxicity of this regimen was similar to that reported by others for CyTBI.
Forty-four months after transplant the actuarial probabilities of disease-free survival (DFS), persistent or recurrent leukemia, and transplant related mortality were .29, .44, and .47 respectively.
DFS was improved (P < .01) and risk of persistent or recurrent leukemia reduced (P = .005) among patients with significant (grade > or = 2) acute GVHD.
Patients with 30% or more blasts on pre-BMT bone marrow examination were not at increased risk for persistent or recurrent leukemia.
We conclude that VPCyTBI with allogeneic BMT is effective therapy for AML in untreated first relapse and that a randomized trial comparing this regimen with CyTBI is warranted. | 10,259 |
Title:
HIF-prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques
Abstract:
The hypoxia-inducible factor (HIF) pathway is crucial in mitigating the deleterious effects of oxygen deprivation.
HIF-α is an essential component of the oxygen-sensing mechanisms and under normoxic conditions is targeted for degradation via hydroxylation by HIF–prolyl hydroxylases.
Several HIF–prolyl hydroxylase inhibitors (PHIs) induced erythropoietin (epo) expression in vitro and in mice, with peak epo expression ranging from 5.6- to 207-fold above control animals.
Furthermore, several PHIs induced fetal hemoglobin (HbF) expression in primary human erythroid cells in vitro, as determined by flow cytometry.
One PHI, FG-2216, was further tested in a nonhuman primate model without and with chronic phlebotomy.
FG-2216 was orally bioavailable and induced significant and reversible Epo induction in vivo (82- to 309-fold at 60 mg/kg).
Chronic oral dosing in male rhesus macaques was well tolerated, significantly increased erythropoiesis, and prevented anemia induced by weekly phlebotomy.
Furthermore, modest increases in HbF-containing red cells and reticulocytes were demonstrated by flow cytometry, though significant increases in HbF were not demonstrated by high-pressure liquid chromatography (HPLC).
HIF PHIs represent a novel class of molecules with broad potential clinical application for congenital and acquired anemias. | 10,261 |
Title:
Neural damage in the rat thalamus after cortical infarcts.
Abstract:
Histopathologic changes in the thalamus of 23 rats after somatosensory cortical infarction produced by middle cerebral artery occlusion were examined using the Fink-Heimer silver staining method, immunohistochemistry with antibodies against glial fibrillary acidic protein and laminin, and conventional stains.
Middle cerebral artery occlusion produced cortical infarcts in the lateral parietal region, with variable involvement of the frontoparietal parasagittal sensorimotor cortex.
Within 3 days after occlusion, massive terminal degeneration but no neuronal changes were apparent in the ipsilateral thalamus.
By 1 week after occlusion, abnormal neurons with darkly stained, shrunken nuclei and atrophic perikarya were present in the ipsilateral thalamic nuclei.
These neurons were densely argyrophilic in Fink-Heimer sections.
Rats with small lateral parietal cortical lesions had degenerating neurons limited to the medial ventroposteromedial nucleus.
Large lesions involving the parasagittal sensorimotor cortex resulted in widespread neuronal damage in the ventroposteromedial, ventroposterolateral, intralaminar, and posterior nuclear regions but nowhere else.
Immunoreactivity to laminin antibody decreased, and astrocytic proliferation was abundant in affected thalamic areas.
These findings are consistent with retrograde neuronal degeneration due to thalamocortical fiber damage in ischemic cortical regions.
Such lesions remote from the infarct may influence functional recovery in patients with stroke. | 10,383 |
Title:
Clinical outcome following coronary angioplasty in dialysis patients: a case-control study in the era of coronary stenting
Abstract:
BACKGROUND—Balloon coronary angioplasty has been reported to be ineffective in patients treated for end stage renal disease because of a high restenosis rate.
::: OBJECTIVE—To compare the clinical outcome following coronary angioplasty with provisional stenting in dialysis versus non-dialysis patients.
::: DESIGN—A case-control study. ::: PATIENTS—Of 1428 consecutive patients who underwent coronary angioplasty, 100 (7%) were being treated for end stage renal disease.
These were compared with 100 control patients matched for age, sex, coronary lesions, presence of diabetes mellitus, and rate of coronary stenting (40%). ::: MAIN OUTCOME MEASURES—In-hospital and one year clinical outcome. ::: RESULTS—The rates of procedural success (90% v 93%), in-hospital mortality (1% v 0%), stent thrombosis (0% v 0%), and Q wave myocardial infarction (0% v 1%) were similar in dialysis and non-dialysis patients.
One year clinical outcome after coronary angioplasty was similar in the two groups in terms of clinical restenosis (31% v 28%) and myocardial infarction (6% v 2%), but cardiac death was more common in dialysed patients (11% v 2%, p < 0.03). ::: CONCLUSIONS—Dialysis does not increase the risk of clinical restenosis after coronary angioplasty with provisional stenting.
Coronary angioplasty is a safe and effective therapeutic procedure in selected dialysis patients with culprit lesions accessible to stenting.
However, the one year survival is reduced in this high risk population.
::: ::: ::: Keywords: renal disease; angioplasty; stents; restenosis | 10,403 |
Title:
Limb salvage by femoral profundaplasty.
Abstract:
One hundred and seven profundaplasties have been performed for rest pain or gangrene due to advanced arterial degeneration below the inguinal ligament.
Local anaesthesia was used for 78 operations.
There were 19 early failures (2 deaths and 17 amputations) and 16 later amputations.
During 4-5 years of follow-up, 25 other patients have died.
The results for diabetic gangrene were worse than for other indications. | 10,410 |
Title:
Regulation of the immediate-early genes arc and zif268 in a mouse operant model of cocaine seeking reinstatement
Abstract:
Reinstatement of extinguished operant responding for drug is an appropriate model of relapse to drug abuse.
Due to the difficulty of implementing in mice the procedure of instrumental intravenous self-administration, mechanisms of reinstatement have so far been studied almost exclusively in rats.
A mouse model of reinstatement of cocaine seeking has recently been characterized (Soria et al. 2008).
The aim of the present study was to assess regional brain activation, as measured by induction of the immediate early genes (IEG) arc and zif268, during priming- or cue-elicited reinstatement of cocaine seeking using this new mouse model and the in situ hybridization technique.
We have demonstrated that cue-elicited reinstatement of cocaine seeking was associated with induction of the IEG in the medial prefrontal cortex (prelimbic and infralimbic) and basolateral amygdala.
Priming-induced reinstatement produced a more widespread up-regulation of those genes in forebrain regions including medial prefrontal, orbitofrontal and motor cortex, dorsal striatum and basolateral amygdala.
These patterns of IEG expression are in agreement with previous results obtained in rats and thus indicate that the new mouse model of reinstatement is functionally equivalent to rat models.
That comparability adds to the usefulness of the mouse model as a tool for addressing neurobiological mechanisms of addiction. | 10,425 |
Title:
AK: Galactosylsphingosine (psychosine)-induced expression of cytokinemediated inducible nitric oxide synthases via AP-1 and C/ EBP: implications for Krabbe disease
Abstract:
Globoid cell leukodystrophy (Krabbe disease) is characterized by the accumulation of a toxic metabolite, psychosine (galactosylsphingosine), which is a substrate for the deficient enzyme (galactoce... | 10,520 |
Title:
A black body absorber from vertically aligned single-walled carbon nanotubes
Abstract:
Abstract ::: Among all known materials, we found that a forest of vertically aligned single-walled carbon nanotubes behaves most similarly to a black body, a theoretical material that absorbs all incident light.
A requirement for an object to behave as a black body is to perfectly absorb light of all wavelengths.
This important feature has not been observed for real materials because materials intrinsically have specific absorption bands because of their structure and composition.
We found a material that can absorb light almost perfectly across a very wide spectral range (0.2–200 μm).
We attribute this black body behavior to stem from the sparseness and imperfect alignment of the vertical single-walled carbon nanotubes. | 10,591 |
Title:
Fenofibrate Improves Cerebral Blood Flow after Middle Cerebral Artery Occlusion in Mice
Abstract:
Fibrates, one group of peroxisome proliferator-activated receptor (PPAR) activators, are lipid lowering drugs.
Fibrates have been shown to attenuate brain tissue injury after focal cerebral ischemia.
In this study, we investigated the impact of fenofibrate on cerebral blood flow (CBF) in male wild type and PPARα-null mice.
Animals were treated for 7 days with fenofibrate and subjected to 2 h of filamentous middle cerebral artery occlusion and reperfusion under isoflurane anesthesia.
Cortical surface CBF was measured by laser speckle imaging.
Regional CBF (rCBF) in nonischemic animals was measured by 14C-iodoantipyrine autoradiography.
Fenofibrate did not affect rCBF and mean arterial blood pressure in nonischemic animals.
In ischemic animals, laser speckle imaging showed delayed expansions of ischemic area, which was attenuated by fenofibrate.
Fenofibrate also enhanced CBF recovery after reperfusion.
However, such effects of fenofibrate on CBF in the ischemic brain were not observed in PPARα-null mice.
These findings show that fenofibrate improves CBF in the ischemic hemisphere.
Moreover, fenofibrate requires PPARα expression for the cerebrovascular protective effects in the ischemic brain. | 10,600 |
Title:
The ubiquitin ligase LIN41/TRIM71 targets p53 to antagonize cell death and differentiation pathways during stem cell differentiation
Abstract:
Rapidity and specificity are characteristic features of proteolysis mediated by the ubiquitin-proteasome system.
Therefore, the UPS is ideally suited for the remodeling of the embryonic stem cell proteome during the transition from pluripotent to differentiated states and its inverse, the generation of inducible pluripotent stem cells.
The Trim-NHL family member LIN41 is among the first E3 ubiquitin ligases to be linked to stem cell pluripotency and reprogramming.
Initially discovered in C. elegans as a downstream target of the let-7 miRNA, LIN41 is now recognized as a critical regulator of stem cell fates as well as the timing of neurogenesis.
Despite being indispensable for embryonic development and neural tube closure in mice, the underlying mechanisms for LIN41 function in these processes are poorly understood.
To better understand the specific contributions of the E3 ligase activity for the stem cell functions of LIN41, we characterized global changes in ubiquitin or ubiquitin-like modifications using Lin41-inducible mouse embryonic stem cells.
The tumor suppressor protein p53 was among the five most strongly affected proteins in cells undergoing neural differentiation in response to LIN41 induction.
We show that LIN41 interacts with p53, controls its abundance by ubiquitination and antagonizes p53-dependent pro-apoptotic and pro-differentiation responses.
In vivo, the lack of LIN41 is associated with upregulation of Grhl3 and widespread caspase-3 activation, two downstream effectors of p53 with essential roles in neural tube closure.
As Lin41-deficient mice display neural tube closure defects, we conclude that LIN41 is critical for the regulation of p53 functions in cell fate specification and survival during early brain development. | 10,691 |
Title:
Generation Mechanism of Radical Species by Tyrosine-Tyrosinase Reaction
Abstract:
Alleviated melanin formation in the skin through inhibition of tyrosine-tyrosinase reaction is one of the major targets of cosmetics for whitening ability.
Since melanin has a pivotal role for photoprotection, there are pros and cons of inhibition of melanin formation.
This study applying electron spin resonance (ESR)-spin trapping method revealed that •H and •OH are generated through tyrosine-tyrosinase reaction.
When deuterium water was used instead of H2O, the signal of 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-H (a spin adduct of DMPO and •H) greatly decreased, whilst DMPO-OH (a spin adduct of DMPO and •OH) did not.
Thus, it is suggested that •H was derived from H2O, and •OH through oxidative catalytic process of tyrosine to dopaquinone.
Our study suggests that tyrosinase inhibitors might contribute to alleviate the oxidative damage of the skin by inhibiting •OH generation via the enzyme reaction. | 10,742 |
Title:
Diagnostic sweat testing: the Cystic Fibrosis Foundation guidelines.
Abstract:
he Cystic Fibrosis Foundation (CFF) accredits cystic fibrosis (CF) centers, located in teaching and community hospitals nationwide, which provide comprehensive diagnosis and treatment for people with CF.
The CF centers are evaluated by the CFF Center Committee according to specific criteria covering the areas of clinical care, teaching, and research.
here are specific requirements for sweat testing, and adherence to them is required for accreditation.
In 2006, the CFF Center ommittee distributed a sweat testing guidelines memorandum to the CF center directors.
Although the guidelines are based n the Clinical Laboratory Standards Institute (CLSI), formerly National Committee for Clinical Laboratory Standards, sweat esting document C34-A2 and the College of American Pathologists (CAP) Laboratory Accreditation Program Inspection hecklist items for sweat testing, they are more prescriptive for uniformity and are focused on diagnostic rather than screening weat tests.
The guidelines are applicable to patients of all ages undergoing sweat chloride testing.
Adherence to the guidelines is mandatory for CFF centers; however, the requirements are appropriate and adaptable for any acility performing diagnostic testing for CF.
Although it may be ideal for sweat testing to be centralized at CF centers, in practice his does not occur.
According to enrollment in a national proficiency testing program for sweat analysis, more than 600 laboratories erformed sweat testing in 2006.
With widespread implementation of newborn screening programs for CF, the reliance on a ell-performed and well-interpreted sweat test is critical to the success of accurately diagnosing CF.
Sweat chloride testing should be erformed on all infants with a positive newborn screen even in cases in which two CF-causing mutations have been identified.
The following represent the 2006 CFF sweat testing guidelines, along with commentary discussing the specific guidelines. | 10,767 |
Title:
Factors Associated With Substance Use in Adolescents With Eating Disorders
Abstract:
Purpose ::: To examine the prevalence and potential risk factors associated with substance use in adolescents with eating disorders (EDs). | 10,814 |
Title:
The use of routine special stains for upper gastrointestinal biopsies.
Abstract:
Helicobacter pylori and intestinal metaplasia (IM) are readily seen in hematoxylin and eosin-stained slides of gastric and/or esophageal biopsies, yet many pathology laboratories perform routine special stains on all of these biopsies.
We wished to determine if special stains are necessary for every single gastric and/or esophageal biopsy.
We prospectively studied 613 gastric and/or esophageal biopsies from 494 consecutive patients.
The slides were stained with hematoxylin and eosin, toluidine blue (TB) for H. pylori, and Alcian blue (AB) for IM.
The hematoxylin and eosin slide was classed as positive or negative for H. pylori and IM.
Then it was determined if the case needed a TB or AB stain.
A total of 436 cases (71.1%) were identified as H. pylori-negative and not needing a TB stain, and none was TB+.
A total of 126 (20.6%) of hematoxylin and eosin slides were inconclusive for H. pylori and were regarded as needing a TB stain.
Twenty of these (15.9%) were TB+.
Fifty-one biopsies (8.3%) were regarded as H. pylori+ on hematoxylin and eosin; the TB stain was also positive in 49.
IM was present in 113 (18.4%) hematoxylin and eosin biopsies.
Hematoxylin and eosin slides were IM-negative in 498 cases (81.2%).
The AB stain revealed rare goblet cells in 3 of 498 cases (0.6%).
Only one of those biopsies was esophageal, and that had one goblet cell that was missed on hematoxylin and eosin.
Only 2 (0.3%) were regarded as needing an AB stain.
We conclude that routine special stains for all gastric and/or esophageal biopsies are not required, and hematoxylin and eosin assessment combined with selective ordering of these stains will identify virtually all cases of H. pylori gastritis and intestinal metaplasia. | 10,850 |
Title:
Spatial misregistration of vascular flow during MR imaging of the CNS: cause and clinical significance.
Abstract:
Spatial misregistration of signal recovered from flowing spins within vascular structures is a common phenomenon seen in MR imaging of the CNS.
The condition is displayed as a bright line or dot offset from the true anatomic location of the lumen of the imaged vessel.
Its origin is the time delay between application of the phase- and frequency-encoding gradients used to locate spins within the plane of section.
The principal condition necessary for the production of spatial misregistration is flow oblique to the axis of the phase-encoding gradient.
Flow-related enhancement (entry slice phenomenon), even-echo rephasing, and gradient-moment nulling contribute to the production of the bright signal of spatial misregistration.
Familiarity with the typical appearance of flow-dependent spatial misregistration permits confirmation of a vessel's patency; identification of the direction of flow; estimation of the velocity of flow; and differentiation of this flow artifact from atheromas, dissection, intraluminal clot, and artifacts such as chemical shift. | 11,049 |
Title:
The B2 domain of VIVIPAROUS1 is bi-functional and regulates nuclear localization and transactivation
Abstract:
The transcriptional regulator VIVIPAROUS1 (VP1) is composed of four functional domains that control different aspects of gene expression during seed development.
The B2 domain is required for its role as a transcriptional activator, functioning at the site of transcription and/or for its transport into the nucleus.
Previous work showed that the B2 domain was required for transactivation of the Em promoter.
We demonstrate that VP1::GFP localizes to the nucleus of barley (Hordeum vulgare) aleurone cells, but when B2 is deleted, nuclear accumulation is lost.
However, the B2 domain itself is not sufficient for nuclear localization of GFP::GUS.
Using point mutagenesis on the putative NLS within B2, we show that the VP1::GFP still accumulates in the nucleus.
Utilizing a comparative approach, through the alignment of B2 domains from various VP1/ABI3 proteins, oincluding the ABI3 orthologs from Physcomitrella patens, revealed the involvement of other conserved amino acids.
Mutating VP1 at the conserved threonine on the N-terminal side of the putative NLS and at a conserved arginine-glutamine-arginine sequence on the C-terminal side prevented nuclear localization of VP1.
A single amino acid change, from alanine to threonine, within this NLS found in the Arabidopsis abi3-7 mutant prevents transcription of AtEm1 and AtEm6 in vivo.
We show that this same mutation in VP1 prevents transactivation of the Em-GUS reporter in barley aleurone but does not interfere with nuclear localization.
Our data demonstrate that the B2 domain of VP1 is bi-functional in nature regulating both nuclear localization and transactivation. | 11,057 |
Title:
Ccl2/Ccr2 signalling recruits a distinct fetal microchimeric population that rescues delayed maternal wound healing
Abstract:
Foetal microchimeric cells (FMCs) traffic into maternal circulation during pregnancy and persist for decades after delivery.
Upon maternal injury, FMCs migrate to affected sites where they participate in tissue healing.
However, the specific signals regulating the trafficking of FMCs to injury sites had to be identified.
Here we report that, in mice, a subset of FMCs implicated in tissue repair displays CD11b+ CD34+ CD31+ phenotype and highly express C-C chemokine receptor 2 (Ccr2).
The Ccr2 ligand chemokine ligand 2 (Ccl2) enhances the recruitment of FMCs to maternal wounds where these cells transdifferentiate into endothelial cells and stimulate angiogenesis through Cxcl1 secretion.
Ccl2 administration improves delayed maternal wound healing in pregnant and postpartum mice but never in virgin ones.
This role of Ccl2/Ccr2 signalling opens new strategies for tissue repair through natural stem cell therapy, a concept that can be later applied to other types of maternal diseases. | 11,154 |
Title:
What Makes Ribosome-Mediated Transcriptional Attenuation Sensitive to Amino Acid Limitation?
Abstract:
Ribosome-mediated transcriptional attenuation mechanisms are commonly used to control amino acid biosynthetic operons in bacteria.
The mRNA leader of such an operon contains an open reading frame with "regulatory" codons, cognate to the amino acid that is synthesized by the enzymes encoded by the operon.
When the amino acid is in short supply, translation of the regulatory codons is slow, which allows transcription to continue into the structural genes of the operon.
When amino acid supply is in excess, translation of regulatory codons is rapid, which leads to termination of transcription.
We use a discrete master equation approach to formulate a probabilistic model for the positioning of the RNA polymerase and the ribosome in the attenuator leader sequence.
The model describes how the current rate of amino acid supply compared to the demand in protein synthesis (signal) determines the expression of the amino acid biosynthetic operon (response).
The focus of our analysis is on the sensitivity of operon expression to a change in the amino acid supply.
We show that attenuation of transcription can be hyper-sensitive for two main reasons.
The first is that its response depends on the outcome of a race between two multi-step mechanisms with synchronized starts: transcription of the leader of the operon, and translation of its regulatory codons.
The relative change in the probability that transcription is aborted (attenuated) can therefore be much larger than the relative change in the time it takes for the ribosome to read a regulatory codon.
The second is that the general usage frequencies of codons of the type used in attenuation control are small.
A small percentage decrease in the rate of supply of the controlled amino acid can therefore lead to a much larger percentage decrease in the rate of reading a regulatory codon.
We show that high sensitivity further requires a particular choice of regulatory codon among several synonymous codons for the same amino acid.
We demonstrate the importance of a high fraction of regulatory codons in the control region.
Finally, our integrated model explains how differences in leader sequence design of the trp and his operons of Escherichia coli and Salmonella typhimurium lead to high basal expression and low sensitivity in the former case, and to large dynamic range and high sensitivity in the latter.
The model clarifies how mechanistic and systems biological aspects of the attenuation mechanism contribute to its overall sensitivity.
It also explains structural differences between the leader sequences of the trp and his operons in terms of their different functions. | 11,174 |
Title:
A method for identifying small molecule aggregators using photonic crystal biosensor microplates
Abstract:
Small molecules identified through high-throughput screens are an essential element in pharmaceutical discovery programs.
It is now recognized that a substantial fraction of small molecules exhibit aggregating behavior leading to false positive results in many screening assays, typically due to nonspecific attachment to target proteins.
Therefore, the ability to efficiently identify compounds within a screening library that aggregate can streamline the screening process by eliminating unsuitable molecules from further consideration.
In this work we show that photonic crystal (PC) optical biosensor microplate technology can be utilized to identify and quantify small molecule aggregation.
A group of aggregators and nonaggregators were tested using the PC technology, and measurements were compared with those gathered by three alternative methods: dynamic light scattering (DLS), an α-chymotrypsin colorimetric assay, and scanning electron microscopy (SEM).
The PC biosensor measurements of aggregation were confirmed by visual observation using SEM, and were in general agreement with the α-chymotrypsin assay.
As a label-free detection method, the PC biosensor aggregation assay is simple to implement and provides a quantitative direct measurement of the mass density of material adsorbed to the transducer surface, while the microplate-based sensor format enables compatibility with high-throughput automated liquid handling methods used in pharmaceutical screening. | 11,226 |
Title:
Efficacy and Safety of 2% and 4% Articaine for Lower Third Molar Surgery
Abstract:
This double-blind crossover randomized clinical trial compared the efficacy of 2 concentrations of articaine, 2% (A2) and 4% (A4), with 1:200,000 epinephrine, for lower third molar removal.
During 2 separate appointments with either A2 or A4, both similarly positioned lower third molars in 46 volunteers were extracted.
The following were evaluated: onset and duration of anesthetic action on soft tissues, intraoperative bleeding, hemodynamic parameters, postoperative analgesia, and mouth opening and wound healing during the 7th postoperative day, along with the incidence, type, and severity of adverse reactions.
Nearly identical volumes of both anesthetic solutions were used for each appointment: 3.4 ± 0.9 mL ≈ 68 mg of articaine (A2) and 3.3 ± 0.8 mL ≈ 132 mg of articaine (A4).
Statistical analysis indicated no differences in onset or duration of anesthetic action on soft tissues or duration of postoperative analgesia evoked by A2 and A4 anesthetic solutions (P > 0.05).
The surgeon’s rating of intraoperative bleeding was considered minimal throughout all surgery with both anesthetic solutions.
While transient changes in blood pressure, heart rate, and oxygen saturation were observed, these factors were clinically insignificant and were uninfluenced by articaine concentration (P > 0.05).
No systemic or local adverse reactions were observed in the preoperative and postoperative periods due to A2 or A4, but 1 case of bilateral paresthesia was observed.
There were no significant differences between preoperative and postoperative (7th day) values of mouth opening and wound healing whether volunteers received A2 or A4 (P > 0.05).
In conclusion, both A2 and A4, administered in equal volumes, were effective and safe during lower third molar surgery, and no significant differences were found between their efficacy and safety (ClinicalTrials.gov NCT02457325). | 11,248 |
Title:
Conversion to lacosamide monotherapy in the treatment of focal epilepsy: Results from a historical-controlled, multicenter, double-blind study
Abstract:
SummaryObjective ::: To evaluate the efficacy and safety of conversion to lacosamide 400 mg/day monotherapy in adults with focal epilepsy. ::: ::: Methods ::: This historical-controlled, double-blind study (NCT00520741) enrolled patients aged 16–70 years on stable doses of 1–2 antiepileptic drugs (AEDs) and experiencing 2–40 partial-onset seizures per 28 days during the 8-week prospective Baseline.
Patients were randomized to lacosamide 400 or 300 mg/day (3:1 ratio), starting at 200 mg/day and titrated over 3 weeks to randomized dose.
Patients then withdrew background AEDs over 6 weeks and entered a 10-week Monotherapy Phase.
The primary assessment was the Kaplan-Meier–predicted percentage of patients on 400 mg/day in the full analysis set (FAS) meeting ≥1 predefined seizure-related exit criterion by day 112, compared with the historical-control threshold (65.3%). ::: ::: Results ::: Four hundred twenty-five patients were enrolled and were eligible for safety analyses (400 mg/day, n = 319; 300 mg/day, n = 106).
A total of 271 (63.8%) of 425 patients completed the Lacosamide Maintenance Phase (combined AED Withdrawal and Monotherapy Phases).
Among 284 patients in the 400 mg/day group in the FAS, 82 (28.9%) met ≥1 exit criterion; the Kaplan-Meier–predicted exit percentage at day 112 for 400 mg/day (30.0%; 95% confidence interval [CI] 24.6–35.5%) was lower than the historical control.
When exit events, withdrawal due to treatment-emergent adverse events (TEAEs), and withdrawal due to lack of efficacy were summed (n = 90), the predicted exit percentage (32.3%; 95% CI 26.8–37.8%) was also lower than the historical control.
Most patients receiving 400 mg/day reported some improvement on the Clinical Global Impression of Change (75.4%) and Patient Global Impression of Change (74.3%).
Overall, the most common (>10%) TEAEs were dizziness (24.0%), headache (14.4%), nausea (13.4%), convulsion (11.5%), somnolence (10.4%), and fatigue (10.1%); most (74.1%) were mild-to-moderate in intensity.
Seventy-two patients (16.9%) discontinued due to TEAEs.
Seventeen patients (4%, all receiving 400 mg/day) experienced serious AEs. ::: ::: Significance ::: Lacosamide 400 mg/day monotherapy was effective, with a favorable safety profile in patients with focal epilepsy. ::: ::: A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. | 11,249 |
Title:
Short-term low-salinity tolerance by the longhorn sculpin,Myoxocephalus octodecimspinosus
Abstract:
The bottom-dwelling, longhorn sculpin, Myoxocephalus octodecimspinosus ,i s traditionally viewed as a stenohaline marine fish, but fishermen have described finding this sculpin in estuaries during high tide.
Little is known about the salinity tolerance of the longhorn sculpin; thus, the purposes of these experiments were to explore the effects of low environmental salinity on ion transporter expression and distribution in the longhorn sculpin gill.
Longhorn sculpin were acclimated to either 100% seawater (SW, sham), 20% SW, or 10% SW for 24 or 72hr.
Plasma osmolality, sodium, potassium, and chloride concentrations were not different between the 20 and 100% treatments; however, they were 20-25% lower with exposure to 10% SW at 24 and 72hr.
In the teleost gill, regulation of Na 1 ,K 1 -ATPase (NKA), Na 1 -K 1 -2Clcotransporter (NKCC1), and the chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR) are necessary for ion homeostasis.
We immunolocalized these proteins to the mitochondrion-rich cell of the gill and determined that acclimation to low salinity does not affect their localization.
Also, there was not a downregulation of gill NKA, NKCC1, and CFTR mRNA or protein during acclimation to low salinities.
Collectively, these results suggest that down to 20% SW longhorn sculpin are capable of completely regulating ion levels over a 72-hr period, whereas 10% SW exposure results in a significant loss of ions and no change in ion transporter density or localization in the gill.
We conclude that longhorn sculpin can tolerate low-salinity environments for days but, because they cannot regulate ion transporter density, they are unable to tolerate low salinity for longer periods or enter freshwater (FW).
The genus Myoxocephalus has three FW species, making this group an excellent model to test evolutionary and physiological mechanisms that allow teleosts to invade new low salinities successfully.
J. Exp.
Zool. 311A:45-56, 2009.
r 2008 Wiley-Liss, Inc. | 11,274 |
Title:
Gastroduodenal intussusception due to Peutz-Jeghers Syndrome in infancy
Abstract:
A case of Peutz-Jeghers Syndrome (PJS) presenting in infancy with gastric-outlet obstruction is described.
PJS may become symptomatic at any age and should be suspected when there are obstructive symptoms or gastrointestinal blood loss in a baby with a positive familiy history.
Contrast studies and endoscopy are useful in diagnosis and surveillance.
Treatment requires a combination of endoscopy and laparotomy/laparoscopy.
Because of the reported cancer risk, we recommend surveillance from the age of diagnosis. | 11,292 |
Title:
Ontogenesis of the Gut Microbiota Composition in Healthy, Full-Term, Vaginally Born and Breast-Fed Infants over the First 3 Years of Life: A Quantitative Bird’s-Eye View
Abstract:
Early-life intestinal microbiota development is crucial for host’s long-term health and is influenced by many factors including gestational age, birth and feeding modes, birth environment, ethnic/ geographical background etc.
However, ‘quantitative’ data on the actual population levels of gut bacterial communities when these influences are controlled for is relatively rare.
Herein, we demonstrate a quantitative perspective of microbiota development in natural and healthy milieus i.e. in healthy, full-term, vaginally-born and breast-fed infants (n=19) born at same clinic.
Fecal microbiota at age 1 and 7 days, 1, 3 and 6 months and 3 years is quantified using highly sensitive reverse-transcription-quantitative-PCR assays targeting bacterial rRNA molecules.
At day 1, we detect one or more bacteria in all (100%) of the babies, wherein the microbiota is composed mainly of enterobacteria (35%), Bacteroides fragilis group (23%), enterococci (18%), staphylococci (13%) and bifidobacteria (9%).
Altogether, facultative anaerobes predominate during first few weeks whereafter obligate anaerobes including bifidobacteria, B. fragilis group, Clostridium coccoides group and Clostridium leptum subgroup gradually start prevailing.
At 3 years, the composition is represented almost entirely (99%) by obligate anaerobes including C. leptum subgroup (34%), bifidobacteria (22%), B. fragilis group (21%), C. coccoides group (17%), Atopobium cluster (4%) and Prevotella (1%).
The overall obligate/facultative proportion is 32/68, 37/63, 54/46, 70/30, 64/36 and 99/1% at 1 and 7 days, 1, 3 and 6 months and 3 years, respectively.
However, interestingly, considerable individual-specific variations in the obligate/facultative ratios as well as in the proportions of Firmicutes, Bacteroides, Actinobacteria and Proteobacteria communities are seen among these babies.
This disparity even within this highly homogenous cohort manifests the magnitude of diverse patterns of gut microbiota configuration and hence underpins the importance of considering not only the gestational age, birth and feeding modes, and ethnic/ geographical background but also other potential outstanding factors when investigating the elements shaping the early microbiota development.
In summary, the data demonstrate a quantitative bird’s-eye view of the ontogenesis of early-life gut microbiota in typically natural and healthy milieus and should be informative and facilitative for future studies exploring various aspects of the human gut microbiota. | 11,312 |
Title:
Leaf-litter herpetofaunal richness, abundance, and community assembly in mono-dominant plantations and primary forest of northeastern Costa Rica
Abstract:
Given current deforestation and land-use change in species-rich tropical for- ests, a pressing need in conservation biology is to understand how converted, human- modified landscapes support biodiversity.
Here, we measured the species richness, abun- dance, and community composition of amphibians and reptiles in reference primary forest and mono-dominant plantations of three native tree species (Pentaclethra macroloba, Virola koschnyi, Vochysia guatemalensis) at La Selva Biological Station in the Caribbean lowlands of northern Costa Rica.
Because these plantation species generate markedly different forest-floor habitats, we hypothesized that tree species would support different assemblages of leaf-litter herpetofauna.
Primary forest, Virola, and Vochysia supported greater richness of frogs than Pentaclethra.
Frog densities were significantly lower in Pentaclethra and Vochysia than in nearby primary forest.
Using non-metric multidimen- sional scaling and permutational multivariate analysis of variance, we found Pentaclethra to support significantly different assemblages of frogs and lizards than primary forest reference sites, while Vochysia supported a unique assemblage of frogs.
Our results suggest that some tree species plantations can support herpetofaunal assemblages comparable to primary forest in richness, community assembly, and abundance.
While herpetofaunal community ecology varies among plantation species, our study provides a compelling example of how plantation landscapes can facilitate the restoration of native fauna on degraded landscapes. | 11,367 |
Title:
Patient adherence to allergy immunotherapy.
Abstract:
PURPOSE OF REVIEW ::: This article reviews the literature on patient adherence to two different approaches to allergen-specific immunotherapy for allergic disease.
Factors related to adherence in general, as well as the various methods used to measure adherence, will be discussed.
::: ::: ::: RECENT FINDINGS ::: Although a complex interaction of factors related to both the physician and the patient influence the adherence to a particular therapeutic regimen, effective communication between these two parties and the simplicity of the regimen are frequently noted to be of primary importance.
Variability with respect to the definition of adherence, the method of measuring adherence, and the length of the measuring period has resulted in a wide range of adherence rates to allergy immunotherapy reported in the literature.
Patients most often site inconvenience, side-effects, and poor efficacy as reasons for discontinuing allergy immunotherapy. ::: ::: ::: SUMMARY ::: Adherence to therapy not only improves individual patient outcomes, but also helps determine the best treatment modalities and reduces the burden of disease on society.
As new methods of delivering immunotherapy are being developed, such as allergy immunotherapy tablets and oral mucosal immunotherapy, the factors associated with patient adherence should be carefully considered. | 11,380 |
Title:
Feasibility of single-incision thoracoscopic surgery using a modified chest wall pulley for primary spontaneous pneumothorax: a propensity score matching analysis
Abstract:
Purpose ::: Recently, single-incision thoracoscopic surgery (SITS) has been recognized as a favorable treatment choice for primary spontaneous pneumothorax (PSP) compared with conventional three-port video-assisted thoracoscopic surgery (VATS).
However, conventional SITS bullectomy often results in collisions with surgical devices.
Therefore, we devised a method of SITS using a chest wall pulley for lung excision (PulLE) and modified PulLE (mPulLE) system, which substitutes threads to eliminate such collisions.
We compared the mPulLE system with conventional procedures using propensity score matching (PSM) to adjust for patient backgrounds. | 11,419 |
Title:
Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage alzheimer’s disease
Abstract:
Several studies show increased levels of zinc (Zn) in the Alzheimer’s disease (AD) brain.
More recently, alterations in synaptic Zn and Zn transporter proteins (ZnT) have been implicated in the accumulation of amyloid plaques in an animal model of AD.
To determine if alterations in ZnT proteins are present in AD brain, we measured levels of ZnT-1, the protein responsible for export of Zn to the extracellular space in the amygdala (AMY), hip-pocampus/parahippocampal gyrus (HPG), superior and middle temporal gyrus (SMTG), inferior parietal lobule (IPL), and cerebellum (CER) of 19 AD and 14 age-matched control subjects.
To determine if alterations of ZnT-1 occur early in the progression of AD, we analyzed protein levels in the HPG, SMTG and CER of 5 subjects with mild cognitive impairment (MCI), 5 subjects with early AD (EAD) and 4 appropriately age-matched controls.
Western blot and dot-blot analysis showed statistically significant (p <0.05) elevations of ZnT-1 in AD AMY, HPG, and IPL and significantly depleted ZnT-1 in AD SMTG compared to age-matched control subjects.
We also observed statistically significant elevations of ZnT-1 in the HPG of EAD subjects compared with controls.
In contrast to late-stage AD subjects, ZnT-1 levels were significantly decreased in HPG of subjects with MCI and were significantly elevated in the SMTG of both MCI and EAD subjects compared with age-matched controls.
Correlation analysis of ZnT-1 levels and senile plaque (SP) and neurofibrillary tangle (NFT) counts in the AMY and CA1 and subiculum of AD HPG showed a significant (p <0.05) positive correlation with SP counts and a trend towards a significant (p = 0.12) positive correlation with NFT counts in AMY.
Overall, our results show alterations in one of the key proteins responsible for maintenance of Zn homeostasis early in the progression of AD suggesting that alterations in Zn balance could be involved in the pathogenesis of neuron degeneration and amyloid deposition in AD. | 11,433 |
Title:
Pharmacokinetics of iron isomaltoside 1000 in patients with inflammatory bowel disease
Abstract:
Background ::: Iron isomaltoside 1000 is a novel injectable iron compound which offers potential advantages in the treatment of subjects with iron-deficiency anemia.
We studied the pharmacokinetics (PK) of this novel compound in subjects with mild-to-moderate inflammatory bowel disease (IBD). | 11,434 |
Title:
Adenosine-Induced Relaxation of Cultured Bovine Retinal Pericytes
Abstract:
Purpose.
To investigate the effect of adenosine on the contractile tone of cultured bovine retinal pericytes.
Methods.
Changes in the contractile tone were quantified as the changes in the summed length of wrinkles induced by pericytes on the silicone surface on which the cells were grown.
Results.
Adenosine at 10 -3 M had no effect.
In the range of 10 -8 to 10 -4 M, adenosine caused relaxation of pericytes in a concentration-dependent manner.
Complete relaxation was induced by 10 -5 M to 10 -4 M adenosine.
The concentration of adenosine that produced 50% relaxation was 3 x 10 -7 M. At all concentrations, relaxation began within 1 minute, reached the maximum within 5 to 10 minutes, and persisted for at least 30 minutes.
After a washout of 3 x 10 -7 M adenosine, the reduced contractile tone recovered to the original level in 10 minutes.
The adenosine-induced relaxation (3 x 10 -7 M) was completely abolished in the presence of 8-phenyl theophylline (10 -5 M), a nonselective adenosine receptor antagonist.
The selective A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) at 10 -6 M did not reduce the effect of adenosine (3 X 10 -7 M).
Conversely, the selective A 2 receptor antagonist CP-66,713 at 10 -8 M partially inhibited (and at 10 -7 M, completely inhibited) the relaxation induced by adenosine (3 x 10 -7 M).
The adenosine receptor antagonists-8-phenyl theophylline (10 -5 M), DPCPX (10 -6 M), and CP-66,713 (10 -7 M) by themselves had no effect on the contractile tone of pericytes.
Conclusions.
Adenosine causes relaxation of pericytes through the activation of the adenosine A 2 receptor.
Adenosine, which accumulates under ischemic conditions, may help to regulate local capillary blood flow. | 11,454 |
Title:
Rapid fluorogenic assay for differentiation of the Candida parapsilosis group from other Candida spp.
Abstract:
Abstract ::: A 30-min fluorogenic test was developed for differentiation of members of the Candida parapsilosis group from other Candida species commonly encountered in clinical material.
The fluorogenic substrate, 4-methylumbelliferyl-beta-D-glucoside, was utilized to assay beta-glucosidase activity.
A total of 50 C. parapsilosis isolates and 135 isolates of four other Candida species were tested.
Assay sensitivity and specificity were 100 and 99.3%, respectively.
The procedure was adapted for use with a spectrofluorometer. | 11,559 |
Title:
The computational neurobiology of learning and reward
Abstract:
Following the suggestion that midbrain dopaminergic neurons encode a signal, known as a ‘reward prediction error’, used by artificial intelligence algorithms for learning to choose advantageous actions, the study of the neural substrates for reward-based learning has been strongly influenced by computational theories.
In recent work, such theories have been increasingly integrated into experimental design and analysis.
Such hybrid approaches have offered detailed new insights into the function of a number of brain areas, especially the cortex and basal ganglia.
In part this is because these approaches enable the study of neural correlates of subjective factors (such as a participant's beliefs about the reward to be received for performing some action) that the computational theories purport to quantify. | 11,744 |
Title:
Limits of Brazil’s Forest Code as a means to end illegal deforestation
Abstract:
The 2012 Brazilian Forest Code governs the fate of forests and savannas on Brazil’s 394 Mha of privately owned lands.
The government claims that a new national land registry (SICAR), introduced under the revised law, could end illegal deforestation by greatly reducing the cost of monitoring, enforcement, and compliance.
This study evaluates that potential, using data from state-level land registries (CAR) in Para and Mato Grosso that were precursors of SICAR.
Using geospatial analyses and stakeholder interviews, we quantify the impact of CAR on deforestation and forest restoration, investigating how landowners adjust their behaviors over time.
Our results indicate rapid adoption of CAR, with registered properties covering a total of 57 Mha by 2013.
This suggests that the financial incentives to join CAR currently exceed the costs.
Registered properties initially showed lower deforestation rates than unregistered ones, but these differences varied by property size and diminished over time.
Moreover, only 6% of registered producers reported taking steps to restore illegally cleared areas on their properties.
Our results suggest that, from the landowner9s perspective, full compliance with the Forest Code offers few economic benefits.
Achieving zero illegal deforestation in this context would require the private sector to include full compliance as a market criterion, while state and federal governments develop SICAR as a de facto enforcement mechanism.
These results are relevant to other tropical countries and underscore the importance of developing a policy mix that creates lasting incentives for sustainable land-use practices. | 11,784 |
Title:
Predicting transcription factor activities from combined analysis of microarray and ChIP data: a partial least squares approach
Abstract:
Background ::: The study of the network between transcription factors and their targets is important for understanding the complex regulatory mechanisms in a cell.
Unfortunately, with standard microarray experiments it is not possible to measure the transcription factor activities (TFAs) directly, as their own transcription levels are subject to post-translational modifications. | 11,809 |
Title:
Exposure to Environmentally Relevant Concentrations of Genistein during Activation Does Not Affect Sperm Motility in the Fighting Fish Betta splendens
Abstract:
Sperm collected from male fighting fish Betta splendens were activated in control water, water containing the ion-channel blocker gadolinium (a putative positive control), or water containing the isoflavone phytoestrogen genistein to determine the effects of acute genistein exposure on male reproductive function.
Computer-assisted sperm analysis was used to quantify the proportion of sperm that were motile and the swimming velocity of those sperm.
The highest concentration of gadolinium (100 μ M) tested was effective at reducing sperm motility and velocity, but neither concentration of genistein tested (3.7 nM or 3.7 μ M) significantly affected these sperm parameters.
Our findings suggest that acute exposure to waterborne phytoestrogens during activation does not reduce the motility of fish sperm. | 11,847 |
Title:
Causes, Risk Factors, and Prevention of Laminitis and Related Claw Lesions
Abstract:
Introduction Laminitis is an inflammation of the laminar corium of the hoof wall.
In general, the term laminitis is used to describe a systemic disease affecting not only the hooves, but also the general condition of the animal.
Researchers believe the inflammation is primarily associated with a dysfunction of the digital vasculatory system that results in hypoxia and malnutrition of the sensitive laminar structure in the hoof wall.
The etiology of the circulatory disturbance is not fully understood and there are some possible explanations often related to nutrition, which I will discuss further.
Due to mechanical stretching of the attachment between the inner and outer laminar structures of the hoof wall, which has been affected by the inflammation (i.e. laminitis), the claw bone can rotate and or sink inside the hoof.
Depending on the severity of the laminitis, the mobility of the claw bone inside the capsule and the counter pressure on the sole from hard floors, the sole corium can be contused and secondary lesions of the sole area can develop (Ossent & Lisher 1998).
The pathological alterations inside the rigid hoof capsule cause considerable pain and, therefore, results in lameness, which is an animal welfare issue.
A United Kingdom survey (Clarkson et al. 1996) revealed a yearly lameness incidence of 55%, of which sole ulcers (40%) and white line lesions (29%) were the most prevalent lesions (Murray et al. 1996).
Such laminitis-related lesions have a greater economic effect than infectious diseases, for example, (Esslemont & Spincer 1993), due to severe influence on reproduction and consequently a higher risk for culling (Sprecher et al. 1997).
Other common lesions associated with laminitis are: hemorrhages, fissures and abscesses of the white line, sole hemorrhages and double soles, toe ulcers and toe necrosis, and under-running of the heels.
Thus, laminitis has a great economic impact on dairy operations, and all over the world dairy producers are moving towards housing cows in intensive, confined conditions.
As we understand the causes of laminitis and identify the risk factors better, it is possible to prevent and reduce the effects of the laminitis syndrome. | 11,905 |
Title:
Experiences of mental illness stigma, prejudice and discrimination: a review of measures
Abstract:
Background ::: There has been a substantial increase in research on mental illness related stigma over the past 10 years, with many measures in use.
This study aims to review current practice in the survey measurement of mental illness stigma, prejudice and discrimination experienced by people who have personal experience of mental illness.
We will identify measures used, their characteristics and psychometric properties. | 12,010 |
Title:
Effects of pCO2 and iron on the elemental composition and cell geometry of the marine diatom Pseudo-nitzschia pseudodelicatissima (Bacillariophyceae)1
Abstract:
Partial pressure of CO2 (pCO2) and iron availability in seawater show corresponding changes due to biological and anthropogenic activities.
The simultaneous change in these factors precludes an understanding of their independent effects on the ecophysiology of phytoplankton.
In addition, there is a lack of data regarding the interactive effects of these factors on phytoplankton cellular stoichiometry, which is a key driving factor for the biogeochemical cycling of oceanic nutrients.
Here, we investigated the effects of pCO2 and iron availability on the elemental composition (C, N, P, and Si) of the diatom Pseudonitzschia pseudodelicatissima (Hasle) Hasle by dilute batch cultures under 4 pCO2 (~200, ~380, ~600, and ~800 latm) and five dissolved inorganic iron (Fe′; ~5, � 1 ) | 12,112 |
Title:
Posthaemorrhagic hydrocephalus in newborn term infants.
Abstract:
Intraventricular haemorrhage may occur de novo in previously well, term newborn infants.
In a group of six neonates a high incidence of posthaemorrhagic hydrocephalus was found.
Posthaemorrhagic hydrocephalus may be more common in full term newborn infants than previously recognised. | 12,158 |
Title:
Acute bilateral cerebellar infarction in the territory of the medial branches of posterior inferior cerebellar arteries
Abstract:
BACKGROUND ::: We describe the first clinicoradiological report of acute bilateral cerebellar infarction confined to the territory of the medial branches of the posterior inferior cerebellar arteries. ::: ::: ::: CASE DESCRIPTION ::: A 65-year-old man with atrial fibrillation and hypertension had sudden onset of vertigo, followed by brief loss of consciousness.
Three days later a cranial computed tomographic scan showed acute hydrocephalus and low-density areas in the cerebellar vermis on both sides.
On transfer the patient showed mild dysarthria, dysequilibrium with retropulsion, symmetrical bilateral horizontal gaze-evoked nystagmus on lateral gaze, and marked gait ataxia without brain stem signs, followed by marked vertigo that was induced by motion.
Cranial magnetic resonance imaging revealed abnormalities consistent with fairly symmetrical bilateral cerebellar hemorrhagic infarction that was confined to the territory of the medial branches of the posterior inferior cerebellar arteries, in addition to minimal high-intensity areas in the pons on T2-weighted images.
The patient improved with conservative therapy, including intravenous administration of glycerol. ::: ::: ::: CONCLUSIONS ::: We speculate that our patient likely had initial transient occlusion of the right vertebral artery at the origin of the right posterior inferior cerebellar artery, which probably gave rise to the bilateral medial branches of posterior inferior cerebellar arteries.
This caused infarction in the territory of the medial branches on both sides without remaining brain stem signs.
Such an unusual pattern of cerebellar infarction accompanied by acute hydrocephalus posed a diagnostic challenge at the time of transfer to our care, and correct diagnosis was facilitated by cranial magnetic resonance imaging. | 12,190 |
Title:
AMINO-ACID-DEPENDENT, DIFFERENTIAL EFFECTS OF ETHANOL ON GLUCOSE PRODUCTION IN RABBIT KIDNEY-CORTEX TUBULES
Abstract:
Aims: The effect of ethanol on glucose synthesis in kidney-cortex tubules of control and diabetic rabbits has been investigated.
Methods: Both freshly isolated and grown in primary cultures, kidney-cortex tubules were incubated with alanine or aspartate plus lactate or glycerol plus octanoate in the absence and presence of 100 mmol/l ethanol.
Results: In freshly isolated renal tubules incubated in the presence of alanine plus lactate or glycerol plus octanoate, and in tubules grown in primary culture in the medium containing alanine plus lactate plus octanoate alcohol, resulted in about 30% decrease in glucose formation.
A diminished glucose production in freshly isolated tubules was accompanied by: (i) a decrease in alanine utilization, (ii) an increase in lactate or glycerol consumptions and (iii) a decline in GSH:GSSG ratio.
The ethanol action was not abolished by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase (ADH).
In view of ethanol-induced changes in gluconeogenic intermediates it is likely that in the presence of alanine plus glycerol plus octanoate ethanol causes a decline in flux through phosphoenolpyruvate carboxykinase, probably due to either an increase in intracellular content of 2-oxoglutarate, inhibitor of this key gluconeogenic enzyme and/or an enhanced flux through pyruvate kinase, as concluded from an increased lactate formation in the presence of glycerol in the incubation medium.
In renal tubules grown in primary cultures in the presence of alanine plus lactate plus octanoate a decrease in GSH:GSSG ratio was accompanied by elevated generation of reactive oxygen species (ROS).
Upon replacement of alanine by aspartate ethanol affected neither glucose production, substrate uptake, ROS accumulation nor GSH:GSSG ratio.
Conclusions: In the presence of alanine ethanol-induced decrease in glucose production and elevation of ROS might cause a limited NADPH generation resulting in a decrease in the intracellular GSH:GSSG ratio.
On the contrary, aspartate might protect against ROS generation, so intensive gluconeogenesis supports NADPH generation and in consequence high values of the intracellular GSH:GSSG ratio are maintained. | 12,206 |
Title:
Dynamic light scattering from colloidal fractal monolayers
Abstract:
We address experimentally the problem of how the structure of a surface monolayer determines the viscoelasticity of the interface.
Optical microscopy and surface quasielastic light scattering have been used to characterize aggregation of CaCO3 particles at the air-water interface.
The structures formed by cluster-cluster aggregation are two-dimensional fractals that grow to eventually form a percolating network.
This process is measured through image analysis.
On the same system we measure the dynamics of interfacial thermal fluctuations (surface ripplons), and we discuss how the relaxation process is affected by the growing clusters.
We show that the structures start damping the ripplons strongly when the two length scales are comparable.
No macroscopic surface pressure is measured and this is in contrast to lipid, surfactant, or polymer monolayers at concentrations corresponding to surface coverage.
This observation and the difficulty in fitting the ripplon spectrum with traditional models suggest that a different physical mechanism might be responsible for the observed damping of ripplons in this system. | 12,276 |
Title:
Purification, Characterization and Antitumor Activities of a New Protein from Syngnathus acus, an Officinal Marine Fish
Abstract:
Discovery and development of new antitumor agents from abundant marine fish are attracting an increasing interest.
In the present study, we extracted and purified a novel antitumor protein Syngnathusin from the whole body of Syngnathus acus L., a precious marine fish traditionally used for tumors.
Syngnathusin was comprised of 16 kinds of amino acids, mainly acidic amino acids.
Its molecular weight was 67.3 kDa and its isoelectric point was 4.57.
The N-terminal amino acid sequence of Syngnathusin was determined to be Lys-Arg-Asp-Leu-Gly-Phe-Val-Asp-Glu-Ile-Ser-Ala-His-Tyr and showed no significant homology with the known proteins.
Syngnathusin could significantly inhibit the growth of A549 and CCRF-CEM cells.
However, the obvious proliferation inhibition against human non-tumor cell lines was not observed.
Flow cytometry, morphologic assessment and comet assay revealed that Syngnathusin could induce apoptosis in A549 and CCRF-CEM cells and strongly cooperated with MTX.
Syngnathusin could inhibit the growth of S180 tumor transplanted in mice.
Syngnathusin may be developed as a novel, selective and effective antineoplastic agent. | 12,377 |
Title:
Cold Exposure and Sleep in the Rat: REM Sleep Homeostasis and Body Size
Abstract:
MANY STUDIES HAVE SHOWN THAT A SLEEP DEFICIT INDUCES A SUBSEQUENT INCREASE IN THE DURATION AND/OR IN THE INTENSITY OF SLEEP AND THAT the occurrence of sleep reduces sleep propensity.
The outcome of the regulation of such a balance between sleep and wake has been addressed as “sleep homeostasis”.1,2 ::: ::: The major hindrance in a quantitative approach to sleep homeostasis lies in the fact that sleep consists of two different states, NREM sleep (NREMS) and REM sleep (REMS), which cyclically alternate on an ultradian basis.
In particular: (1) it is not possible to carry out a selective NREMS deprivation without interfering with REMS occurrence; (2) selective REMS deprivation procedures have been shown to affect to some extent the quality of NREMS during deprivation3,4; (3) a complex interaction between NREMS and REMS rebounds has been observed following different sleep deprivation protocols5,6; and (4) NREMS and REMS regulation are influenced differently by circadian rhythmicity.7 ::: ::: In spite of this, many different “short-term” (minutes/hours) or “long-term” (hours/days) sleep deprivation studies seeking a homeostatically regulated sleep parameter have shown that NREMS is substantially regulated in terms of intensity, and REMS in terms of duration.2 However, some contradictory aspects arising from “extended” (days/weeks) sleep deprivation studies and/or from the comparison of animal and human studies still leave this topic open to discussion.2,8–11 ::: ::: As far as NREMS is concerned, the power density in the delta band (approximately, 0.5–4.5 Hz) of the electroencephalogram (EEG), not NREMS duration, is considered to be the homeostatically regulated parameter in NREMS and is commonly taken as an index of NREMS intensity.1,2,12 Such a regulation appears to be disrupted following an extended period of either sleep deprivation or sleep restriction.9,13 ::: ::: REMS appears to be precisely regulated in terms of its duration on both a short-term and long-term basis.
The short-term component is expressed as a function of the ultradian wake-sleep cycle.
Within a species, the duration of the interval between two consecutive REM episodes (REMS interval) appears to be directly related to the duration of the preceding REMS episode, but not to the duration of the subsequent REMS episode.14–17 The long-term component of REMS regulation is expressed in the total amount of REMS during the days following a total sleep or selective REM sleep deprivation.
A precise REMS conservation has been observed in both the cat and the rat, since the rebound in REMS has been found to be proportional to the total loss of REMS during the deprivation period.
11,18–22 This precise quantitative regulation of total REMS amount may not occur following an extended period of sleep deprivation or sleep restriction.9,13,23 Whereas changes in EEG power are an important component of NREMS rebound, they are considered to be of smaller relevance for REMS rebound.12,19,24 ::: ::: It is well known that exposure to low ambient temperature (Ta) deeply influences REMS occurrence in different species.25,26 In particular, REMS is depressed according to either the duration or the depth of Ta lowering,20,21,25,27 while the return to normal laboratory conditions is characterized by an intense REMS rebound that is quantitatively related to the degree of the previous REMS loss.18,20,21,28,29 However, in all the reported studies the quantitative approach to the study of REMS regulation was limited either by the incomplete recording of wake-sleep parameters during cold exposure or the insufficient duration of the recovery period.
Under the same experimental conditions, NREMS was affected to a lesser extent, no relevant rebound of NREMS being found in either cats or rats,27,28 and only a slight increase in delta power was observed in the rat during the recovery period.28 ::: ::: The rather selective effects of cold exposure on REMS make this environmental challenge a powerful physiological tool for the study of the homeostatic aspects of REMS regulation.
Because cold exposure has a limited effect on the occurrence of NREMS, it might reduce the possible impact of accumulated NREMS propensity on REMS expression during recovery.2 Moreover, cold exposure allows researchers to modulate the intensity of deprivation, leading to the possibility of inducing different degrees of deprivation without changing the duration of the exposure and, as a consequence, avoiding circadian confounds. ::: ::: On this basis, we recently carried out a study in which four groups of rats were exposed for 24 h to 4 different low Tas (10°C, 5°C, 0°C, −10°C) and then were allowed to recover at normal laboratory Ta (24°C) for 4 consecutive days.30 The results showed that the depression of REMS during cold exposure and the subsequent enhancement during the recovery period were directly related to the degree of Ta lowering.
On the contrary, smaller effects were observed on NREMS amount and delta power during cold exposure and the recovery period.
The present analysis represents the second part of the aforementioned study.
30 In particular, in the present study short-term and long-term aspects of REMS regulation were separately addressed and a quantitative analysis of the relationship between REMS loss and REMS gain were carried out.
The results of such an analysis confirm that REMS is homeostatically regulated in terms of its duration.
Furthermore, a model which relates both short and long-term REMS homeostasis in different species to either body or brain size has been proposed in the present study.
Preliminary results of this analysis have been submitted in abstract form.31 | 12,435 |
Title:
Cancer Research Participation Beliefs and Behaviors of a Southern Black Population: A Quantitative Analysis of the Role of Structural Factors in Cancer Research Participation
Abstract:
Increasing the participation of Blacks in cancer research is a vital component of a strategy to reduce racial inequities in cancer burden.
Community-based participatory research (CBPR) is especially well-suited to advancing our knowledge of factors that influence research participation to ultimately address cancer-related health inequities.
A paucity of literature focuses on the role of structural factors limiting participation in cancer research.
As part of a larger CBPR project, we used survey data from a statewide cancer needs assessment of a Black faith community to examine the influence of structural factors on attitudes toward research and the contributions of both structural and attitudinal factors on whether individuals participate in research.
Regression analyses and non-parametric statistics were conducted on data from 727 adult survey respondents.
Structural factors, such as having health insurance coverage, experiencing discrimination during health care encounters, and locale, predicted belief in the benefits, but not the risks, of research participation.
Positive attitudes toward research predicted intention to participate in cancer research.
Significant differences in structural and attitudinal factors were found between cancer research participants and non-participants; however, directionality is confounded by the cross-sectional survey design and causality cannot be determined.
This study points to complex interplay of structural and attitudinal factors on research participation as well as need for additional quantitative examinations of the various types of factors that influence research participation in Black communities. | 12,546 |
Title:
Maternal attributions for the causes and remedies of their children's abdominal pain.
Abstract:
OBJECTIVE ::: To examine mothers' attributions for the causes and remedies of their children's abdominal pain, specifically whether attributions differed according to child diagnosis, reflected a dualistic or multidimensional view of pain, and changed following medical evaluation. ::: ::: ::: METHODS ::: Mothers of children whose medical evaluation indicated peptic disease (n = 55) or unexplained pain without identifiable organic disease (n = 98) participated in telephone interviews prior to their children's medical evaluations and one year later. ::: ::: ::: RESULTS ::: About half of the mothers in each group endorsed both psychosocial and physical factors as important in the etiology of their children's abdominal pain.
Following medical evaluation, mothers in both groups tended to maintain their attributions regarding the importance of psychosocial factors.
::: ::: ::: CONCLUSIONS ::: Many mothers acknowledged the contribution of psychosocial factors to their children's abdominal pain.
They may be receptive to behavioral interventions if physicians present these remedies as an integral component of treatment. | 12,566 |
Title:
Mapping of Myxococcus xanthus Social Motility dsp Mutations to the dif Genes
Abstract:
Myxococcus xanthus dsp and dif mutants have similar phenotypes in that they are deficient in social motility and fruiting body development.
We compared the two loci by genetic mapping, complementation with a cosmid clone, DNA sequencing, and gene disruption and found that 16 of the 18 dsp alleles map to the dif genes.
Another dsp allele contains a mutation in the sglK gene.
About 36.6 kb around the dsp-dif locus was sequenced and annotated, and 50% of the genes are novel. | 12,605 |
Title:
Patient's Perception of Symptoms Related to Morning Activity in Chronic Obstructive Pulmonary Disease: The SYMBOL Study
Abstract:
Background/Aims: Patients with chronic obstructive pulmonary disease (COPD) experience more problematic respiratory symptoms and have more trouble performing daily activities in the morning.
The aim of this study was to assess the perception of COPD symptoms related to morning activities in patients with severe airflow limitation.
Methods: Data of 133 patients with severe airflow limitation were analyzed in a prospective, non-interventional study.
A clinical symptom questionnaire was completed by patients at baseline.
In patients having morning symptoms, defined by at least one or more prominent or aggravating symptom during morning activities, a morning activity questionnaire was also completed at baseline and following 2 months of COPD treatment.
Results: The most frequently reported COPD symptom was breathlessness (90.8%).
Morning symptoms were reported in 76 (57%) patients; these had more frequent and severe clinical COPD symptoms.
The most frequently reported morning activity was getting out of bed (82.9%).
The long acting muscarinic antagonist (odds ratio [OR], 6.971; 95% confidence interval [CI], 1.317 to 11.905) and chest tightness (OR, 0.075; 95% CI, 0.011 to 0.518) were identified as significantly related to absence of morning symptoms.
There was no significant correlation between the degree of forced expiratory volume in 1 second improvement and severity score differences of all items of morning activity after 2-month treatment.
Conclusions: Fifty-seven percent of COPD patients with severe airflow limitation have morning symptoms that limit their morning activities.
These patients also have more prevalent and severe COPD symptoms.
The results of this study therefore provide valuable information for the development of patient-reported outcomes in COPD. | 12,621 |
Title:
Hippocampal atrophy but not white-matter changes predicts the long-term cognitive response to cholinesterase inhibitors in Alzheimer’s disease
Abstract:
IntroductionThis study aimed to investigate the feasibility of predicting the long–term effects of cholinesterase inhibitors (ChEI) with common clinical neuroimaging parameters of Alzheimer’s disease, including medial temporal lobe atrophy (MTA) and white matter hyperintensity (WMH).MethodA cohort of 353 patients with very mild to moderate Alzheimer’s disease received cholinesterase inhibitors and were followed for a median of 46.6 months.
Baseline clinical data, including age, educational level, Clinical Dementia Rating (CDR), Taiwanese Mental State Examination (TMSE), and visual scoring for MTA and WMH were tested as possible predictive factors that influence the survival from a TMSE decline of at least 3 points.
ResultsDuring the follow-up period, 162(46 %) patients had a significant TMSE decline.
Patients with age-adjusted prominent MTA had a significantly shorter TMSE-decline free interval than those without (43.4 ± 4.5 months vs. 68.2 ± 9.5 months, log rank test p-value =0.001).
However, the severity of WMH does not significantly influence cognitive outcomes.
Cox regression analysis identified that younger age at the time of starting ChEI (p < 0.0005) and higher total MTA scores (p = 0.002) predict a more rapid TMSE decline under ChEI therapy.
ConclusionsYounger age at the time of starting ChEI and higher visual scoring of MTA may imply a more advanced Alzheimer’s pathology.
WMH load is not a prognostic indicator of treatment response to ChEI. | 12,908 |
Title:
Helicobacter pylori
Abstract:
Helicobacter pylori is a gram-negative bacterium which causes chronic gastritis and plays important roles in peptic ulcer disease, gastric carcinoma, and gastric lymphoma.
H. pylori has been found in the stomachs of humans in all parts of the world.
In developing countries, 70 to 90% of the population carries H. pylori.
In developed countries, the prevalence of infection is lower.
There appears to be no substantial reservoir of H. pylori aside from the human stomach.
Transmission can occur by iatrogenic, fecal-oral, and oral-oral routes.
H. pylori is able to colonize and persist in a unique biological niche within the gastric lumen.
All fresh isolates of H. pylori express significant urease activity, which appears essential to the survival and pathogenesis of the bacterium.
A variety of tests to diagnose H. pylori infection are now available.
Histological examination of gastric tissue, culture, rapid urease testing, DNA probes, and PCR analysis, when used to test gastric tissue, all require endoscopy.
In contrast, breath tests, serology, gastric juice PCR, and urinary excretion of [15N]ammonia are noninvasive tests that do not require endoscopy.
In this review, we highlight advances in the detection of the presence of the organism and methods of differentiating among types of H. pylori, and we provide a background for appropriate chemotherapy of the infection. | 12,958 |
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