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Chronic active hepatitis and Behçet's syndrome. In a patient with Behcet's syndrome the finding of five times the normal level of serum transaminase accompanied by weakness may be correlated to the syndrome itself. We performed needle biopsy of the liver in our patient which showed piecemeal necrosis and portal lympho-monocytic infiltration extending into the lobule. It is interesting that HLA B5 and B27 antigens were present. Simultaneous occurrence of chronic active hepatitis and Behcet's syndrome may imply the same autoimmune pathogenesis, as we suggest in this work.

A mathematical model of CO2 effect on cardiovascular regulation. The effect of changes in arterial CO2 tension on the cardiovascular system is analyzed by means of a mathematical model. The model is an extension of a previous one that already incorporated the main reflex and local mechanisms triggered by O2 changes. The new aspects covered by the model are the O2-CO2 interaction at the peripheral chemoreceptors, the effect of local CO2 changes on peripheral resistances, the direct central neural system (CNS) response to CO2, and the control of central chemoreceptors on ventilation and tidal volume. A statistical comparison between model simulation results and various experimental data has been performed. This comparison suggests that the model is able to simulate the acute cardiovascular response to changes in blood gas content in a variety of conditions (normoxic hypercapnia, hypercapnia during artificial ventilation, hypocapnic hypoxia, and hypercapnic hypoxia). The model ascribes the observed responses to the complex superimposition of many mechanisms simultaneously working (baroreflex, peripheral chemoreflex, CNS response, lung-stretch receptors, local gas tension effect), which may be differently activated depending on the specific stimulus under study. However, although some experiments can be reproduced using a single basal set of parameters, reproduction of other experiments requires a different combination of the mechanism strengths (particularly, a different strength of the local CO2 mechanism on peripheral resistances and of the CNS response to CO2). Starting from these results, some assumptions to explain the striking differences reported in the literature are presented. The model may represent a valid support for the interpretation of physiological data on acute cardiovascular regulation and may favor the synthesis of contradictory results into a single theoretical setting.

Development of early motor skills and language in children at risk for familial dyslexia. Differences in motor development and the relationship between motor and language development were studied in 88 children with familial risk for dyslexia (43 females, 45 males; at-risk group) and 88 children without familial risk for dyslexia (35 females, 53 females; control group; n=176) during the first two years of life. A structured parental questionnaire was used to assess motor development. Expressive language skills were assessed at the age of 18 months with the Reynell Developmental Language Scales and at 18 and 24 months with the MacArthur Communicative Development Inventories. At group level, the motor development of children in both the at-risk and control groups was similar. However, motor development showed a different pattern in these groups. Cluster analyses revealed three clusters in the control group: 'fast motor development', 'slow fine motor development', and 'slow gross motor development'. In the at-risk group, only two clusters were found: 'slow motor development' and 'fast motor development'. A significant difference (p=0.03) was found between the clusters in the MacArthur Communicative Development Inventories. Children with familial risk for dyslexia and slow motor development had a smaller vocabulary and produced shorter sentences than the all other children. Associations between motor and language difficulties are discussed.

Sustained virological response and baseline predictors in HIV-HCV coinfected patients retreated with pegylated interferon and ribavirin after failing a previous interferon-based therapy: systematic review and meta-analysis. Published data on retreatment with pegylated interferon and ribavirin of previously failing HIV-HCV coinfected patients are sparse and limited to observational study. We aimed to evaluate efficacy and pretreatment predictors. Systematic review and meta-analysis of observational studies. The overall and genotype-related success rate was investigated. A direct comparison was performed between genotypes 1/4 and 2/3 by evaluating the sustained virological response (SVR) rate ratio (RR). The effect of study level variables on the effect size was investigated by meta-regression. Variables that were analyzed included age, gender, advanced hepatic fibrosis, pretreatment of HCV RNA and CD4, and successful antiretroviral treatment (ART). The available evidence was from 5 open-label, cohort studies (275 patients). The overall SVR rate was 0.280 (95% CI,0.171-0.425). The SVR rate in genotype 1/4 infections was 0.174 (95% CI, 0.129-0.230), and in genotype 2/3 infections it was 0.474 (95% CI, 0.286-0.670). The pooled RR comparing the SVR of genotype 1/4 to 2/3 was 0.369 (95% CI, 0.239-0.568), with a decreased probability of response for genotype 1/4 (P < .001). HIV RNA suppression had a significant effect on SVR (P = .005). The other covariates had no effect on the overall SVR rate. The overall SVR rate was 28%, consistent with the rate reported in the retreatment of mono-infected patients with the same schedule. A substantial relative reduction in the SVR rate of about one-third, when treating genotypes 1/4, was found, with a low SVR rate of 17%. Successful HIV suppression by ART predicted a higher rate of treatment success.

Life span extension and cancer risk: myths and reality. A significant increase in the number of old people in the populations of developed countries was followed by an increase in morbidity and mortality resulting from main age-related diseases -- cardiovascular, cancer, neurodegenerative, diabetes mellitus, decrease in resistance to infections. Obviously, the development of the means of prevention of the premature aging of humans is crucial for the realization of this program. However, data available on such kind of means are rather scarce, contradictory and are often not reliable from the points of view of the adequacy of the experiments to current scientific requirements as well as the interpretation of the results and safety. Data available on the increase in life span and the adverse effects of the following geroprotectors were critically analyzed: antioxidants, chelate agents and lathyrogens, succinate, adaptogens and herbs, neurotropic drugs, inhibitors of monoamine oxidase, glucocorticoids, dehydroepiandrosterone, sex and growth hormones, melatonin, pineal peptide preparations, protein inhibitors, antidiabetic biguanides, thymic hormones and peptides, immunomodulators, enteroadsorbents, lypofuscin inhibitors, as well as calorie intake restriction and special diets. Most of the available results were insufficient and could not provide convincing evidence for the life span extension and the safety of the suggested geroprotectors. Drugs and means prolonging the life span could be subdivided into three groups: (a) geroprotectors prolonging the life span equally in all the members of the population: these postponed the beginning of the population's aging; (b) geroprotectors decreasing the mortality rate in a long-lived subpopulation, which raised their maximal life span: these slowed down the population's aging rate; (c) geroprotectors increasing the survival rate in a short-lived subpopulation without changes in the maximal life span: in this case, the aging rate increased. There was a high positive correlation between the type of geroprotector-induced aging delay and the pattern of tumour development in the same population of animals. The first type of geroprotectors did not influence the incidence of tumour but increased tumour latency. The second type of geroprotectors was effective both in the inhibition of spontaneous carcinogenesis and the increase in tumour latency. Certain drugs of the third type raised tumour incidence in the exposed populations. According to the multistage model, geroprotectors either inhibit or accelerate the passage of carcinogen-exposed cells form one stage to another. Thus, the efficacy of geroprotectors as preventive means of cancer development will decrease with respect to the age of exposure onset. Recommendations of the available drugs and means of life span increase should be carefully reconsidered under the international scientific control.

Remnant Cholesterol Elicits Arterial Wall Inflammation and a Multilevel Cellular Immune Response in Humans. Mendelian randomization studies revealed a causal role for remnant cholesterol in cardiovascular disease. Remnant particles accumulate in the arterial wall, potentially propagating local and systemic inflammation. We evaluated the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD). Arterial wall inflammation and bone marrow activity were measured using 18F-FDG PET/CT. Monocyte phenotype was assessed with flow cytometry. The correlation between remnant levels and hematopoietic activity was validated in the CGPS (Copenhagen General Population Study). We found a 1.2-fold increase of 18F-FDG uptake in the arterial wall in patients with FD (n=17, age 60±8 years, remnant cholesterol: 3.26 [2.07-5.71]) compared with controls (n=17, age 61±8 years, remnant cholesterol 0.29 [0.27-0.40]; P<0.001). Monocytes from patients with FD showed increased lipid accumulation (lipid-positive monocytes: Patients with FD 92% [86-95], controls 76% [66-81], P=0.001, with an increase in lipid droplets per monocyte), and a higher expression of surface integrins (CD11b, CD11c, and CD18). Patients with FD also exhibited monocytosis and leukocytosis, accompanied by a 1.2-fold increase of 18F-FDG uptake in bone marrow. In addition, we found a strong correlation between remnant levels and leukocyte counts in the CGPS (n=103 953, P for trend 5×10-276). In vitro experiments substantiated that remnant cholesterol accumulates in human hematopoietic stem and progenitor cells coinciding with myeloid skewing. Patients with FD have increased arterial wall and cellular inflammation. These findings imply an important inflammatory component to the atherogenicity of remnant cholesterol, contributing to the increased cardiovascular disease risk in patients with FD.

Effects of spermine and the passive avoidance learning (PAL) following cerebral ischemia in chicks: Association with neuroprotection of pyramidal cells. The aim of this study is to investigate the effects of spermine and the passive avoidance learning on hippocampus following transient cerebral ischemia in the chicks. The study is composed of the pure control (CG), sham (SG) and experimental groups (n=20). Experimental groups (ischemia group, IG and ischemia-spermine group, ISG) were exposed to ischemia for 20min whereas the SG was exposed to sham operation and CG group was not exposed to any operation. Passive avoidance learning (PAL) was applied to the half number of the subjects in each group. Both before and after 7days from the ischemia, operated animals were taken to PAL and then they were sacrificed. Total numbers of neurons in the hippocampus were stereologically estimated using Cresyl violet stained sections. We detected that number of neurons was increased following PAL and especially spermine treatment. According to our results, we suggested that spermine may reduce the deleterious effects of the ischemia by causing to increase in the neuronal number and so, it may be slightly supportive to the PAL.

Measurement of lip and skin pigmentation using reflectance spectrophotometry. Previous methods for evaluating the color of oral epithelial tissues have relied primarily on subjective indices and interpretation. In this study, a narrow-band reflectance spectrophotometer was used to measure melanin and hemoglobin pigmentation in the lips and skin of individuals who self-reported their skin type from a choice of white, olive, or black. Significant differences in melanin pigmentation were observed among skin types and at most anatomical sites evaluated between skin types. Hemoglobin levels were not significantly different among skin types at most anatomical sites, but differences were observed among anatomical sites within each skin color group. Within each skin type, melanin (except in blacks) and hemoglobin were significantly higher for both the upper and lower lips compared with most other anatomical sites. Results suggest that reflectance spectrophotometry is a useful tool for quantifying differences in melanin and hemoglobin pigmentation in oral tissues.

[Sperm count and seminal biochemistry of high altitude inhabitants and patients with chronic altitude sickness]. Semen analysis has been studied in 9 healthy adult males from sea level (150 m), age 19-32 years old and 15 healthy males from high altitude (NA), 9 from Cerro de Pasco (4,300 m) and 6 from Morococha (4,540 m), ages 19-45 years old. Five patients with chronic mountain sickness (MMC), whose ages ranged from 23 to 52 years old were also studied. The volume and motility were similar in NA and MMC, however both were below than in sea level subjects, but still in the normal range; the number of spermatozoa per 1 ml was lower at sea level than in NA and MMC, although the total number was higher at sea level due to the higher semen volume. Fructose at sea level was 356 +/- 53 mg/100 ml (mean +/- S.E.) which is similar to NA 237 +/- 45 whereas a MMC was significantly lower, 142 +/- 60. Citric acid was lower at sea level than in NA and MMC. Na, K and Cl, were similar among the three groups. The lower concentration of fructose in MMC parallels the decreased testicular function already found in these groups. However it is worthy to point out that the fertility is preserved in all the groups. The normal reproductive function in MMC is against the concept that this process occurs as a consequence of environmental disadaptation.

Technique for treatment of dens in dente. This article describes a case involving a maxillary lateral incisor with dens in dente and how it was treated with a procedure that differs from standard endodontic treatment.

Effect of aclacinomycin-doxorubicin association on differentiation and growth of human erythroleukemic K562 cells. Anthracycline antitumor drugs such as doxorubicin (DOX) and aclacinomycin (ACM) represent potent candidates for the induction of differentiation of leukemic cells. Human multipotent K562 cells were induced by DOX and ACM to differentiate towards the erythroid lineage. After 3 days of culture, DOX-induced differentiation was dose-related whereas ACM did not require total cell growth arrest to induce its optimum effect, indicating that both drugs act differently on the coupling of growth and differentiation. Simultaneous exposure to ACM and DOX and sequential exposure to ACM (30 min) first, followed immediately by DOX did not improve erythroid differentiation. However, it led to either a synergistic or a subadditive inhibition of cell growth. In contrast, DOX (30 min) first, followed by ACM, produced in a narrow range of concentrations (DOX 1000 nM/ACM 1.85 nM, 3.75 nM or 7.5 nM), a synergistic induction of differentiation. Thus, DOX 1000 nM/ACM 3. 75 nM resulted in 81% of differentiated cells compared to 63% for ACM 15 nM and 43% for DOX 30 nM when these were used alone (at their concentration inducing optimum differentiation). In conclusion, these data emphasize the importance of schedules for the combination of chemotherapeutic drugs acting as differentiation inducers.

Photoelectrochemical sensitive detection of insulin based on CdS/polydopamine co-sensitized WO3 nanorod and signal amplification of carbon nanotubes@polydopamine. An ultrasensitive photoelectrochemical sandwich immunosensor was designed for detection of insulin based on WO3/CdS/polydopamine (WO3/CdS/PDA) co-sensitized and PDA@carbon nanotubes (PDA@CNT) conjugates for signal amplification. The CdS nanoparticles were first deposited on the WO3 nanorods via sequential chemical bath deposition to form the WO3/CdS structure to enhance photocurrent. Then equipped with PDA to form the WO3/CdS/PDA photosensitive structure. The PDA was used not only to reduce the toxicity of CdS but also adsorb insulin primary antibodies (Ab1). Meanwhile, insulin secondary antibodies (Ab2) were decorated by PDA@CNT conjugates for signal amplification and further enhance photocurrent. Different photocurrent intensities were obtained by the photoelectrochemical workstation at applied bias of 0V due to the different amount of the PDA@CNT conjugates introduced by the different concentrations of insulin. A good linear relationship was obtained between the increased photocurrent and insulin concentrations range from 0.01ngmL-1 to 50ngmL-1. And a detection limit of 2.8pgmL-1 was obtained. The proposed sensor was applied to the determination of the insulin in human serum sample, and satisfactory results were obtained. The sensor presented good specificity, reproducibility and stability, thus it might find application in the clinical diagnosis of insulin or other biomarkers in the near future.

Choreoathetosis in multiple sclerosis. Extrapyramidal symptoms are extremely rare in multiple sclerosis. We examined a patient with a ten year history of multiple sclerosis, who developed choreoathetoid movements of both upper extremities. To our knowledge this is the second case report of this association.

The quality of antimicrobial discs from nine manufacturers-EUCAST evaluations in 2014 and 2017. Antimicrobial discs for susceptibility testing can be obtained from many manufacturers. We evaluated the quality of discs from nine manufacturers in 2014 and 2017. Antimicrobial discs of 16 agents from nine manufacturers were evaluated using EUCAST criteria. Discs were tested in triplicate on Müller-Hinton medium against EUCAST quality control (QC) strains. Mean values were compared with targets and ranges in the EUCAST QC tables. Three manufacturers (Becton Dickinson, Mast and Oxoid) demonstrated excellent and consistent disc quality both in 2014 and 2017. Manufacturers with discs of inadequate quality improved their results between the two periods. Overall, 92% (795/861) versus 97% (1038/1071) of zone diameter readings were within QC ranges and 58% (497/861) versus 75% (806/1071) were within the QC target ± 1 mm, for the first and second studies, respectively. One manufacturer (HiMedia) had major quality problems with 33% (26/78) of readings out of range in the first study and 17% (20/120) in the second study. Discs from some manufacturers showed unexpected variation in inhibition zone diameters (4-9 mm) for discs within the same vial. Antimicrobial discs from three of nine manufacturers exhibited excellent and reproducible quality. The discs of the other six manufacturers demonstrated various quality issues, some of which were severe. After presenting the results to manufacturers and users, all managed to improve the quality. Our study points to the need for more stringent criteria for disc manufacturing. Criteria should not only address the nominal potency of discs but also define the end result.

Does transverse apex coincide with coronal apex levels (regional or global) in adolescent idiopathic scoliosis? Cross-sectional. To identify the regional and global apexes of curves in adolescent idiopathic scoliosis and to compare the levels of those with the most rotated vertebral levels on computed tomography scans. The terminology regarding the terms and definitions had been arbitrary until being refined and standardized by the Scoliosis Research Society Working Group on Three-Dimensional Terminology of Spinal Deformity. Apical vertebra or disc is defined as the most laterally deviated vertebra or disc in a scoliosis curve, but the most rotated vertebra (or disc) has not been included in this terminology. One study suggested that the most rotated vertebral level was always located at the apex. Thirty-three structural curves of 25 consecutive patients scheduled for surgery for thoracic or thoracolumbar scoliosis were analyzed with standing anteroposterior radiographs and computed tomography scans covering the curve apexes and pelvis. Thoracic and lumbar curves were evaluated separately for all Type II curves. Vertebral rotations were normalized by the rotation of the pelvis. The most rotated vertebral (or disc) levels (transverse apex) were compared with the regional and global apex levels (vertebra or disc) (coronal apexes) of the corresponding curves separately. Regional and global apexes were at the same level in 18 (54.5%) curves, and within half a level in another 15 (45.4%), and the regional apex was one level higher in two curves (95% confidence levels: -0.82, +0.88). Comparison of the most rotated levels with regional and global apex levels revealed a higher variability, extending up to two levels for the global apex (95% confidence levels: -1.19, +1.54 levels for the global and -1.0, +1.41 levels for the regional apexes). This study demonstrated that the regional or global apex of a given curve is the most rotated level in only a minority of the curves. The most rotated level may be as far as two levels from the global apex and one level from the regional apex.

Androgen receptor mediates non-genomic activation of phosphatidylinositol 3-OH kinase in androgen-sensitive epithelial cells. Androgens are known to modulate many cellular processes such as cell growth and survival by binding to the androgen receptor (AR) and activating the transcription of target genes. Recent data suggested that AR can also mediate non-transcriptional actions outside the nucleus in addition to its ligand-inducible transcription factor function. Here, we describe a transcription-independent activation of the phosphatidylinositol 3-OH kinase (PI3-K) signaling pathway by androgens. Using non-transformed androgen-sensitive epithelial cells, we show that androgens enhance the PI3-K activity by promoting accumulation of phosphoinositide-3-P phospholipids in vitro. This activation is found in conjunction with an increased time-dependent phosphorylation of the downstream kinase AKT/protein kinase B on both Ser(473) and Thr(308) residues. Hormone-stimulated phosphorylation of AKT requires AR since incubation with the anti-androgen bicalutamide completely abolishes the androgen-stimulated AKT phosphorylation. Accordingly, we show that androgens increase AKT phosphorylation level in prostatic carcinoma PC3 cells only once they have been transfected with AR. Downstream, androgens enhance phosphorylation of transcription factor FKHR (Forkhead in rhabdomyosarcoma)-L1 and proapoptotic Bad protein and promote cell survival as they can counteract an apoptotic process. We also report that non-genomic effects of androgens are based on direct interaction between AR and the p85alpha regulatory subunit of class I(A) PI3-K. Together, these novel findings point out an important and physiologically relevant link between androgens and the PI3-K/AKT signaling pathway in governing cell survival.

[Expression of microRNA-221 and IL-17 in papillary thyroid carcinoma and correlation with clinicopathologic features]. Objective: To study the expression of microRNA-221(miR-221) and IL-17 in papillary thyroid carcinoma (PTC) and their roles in the carcinogenesis of PTC. Methods: Real-time RT-PCR, Western blot and immunohistochemistry (IHC) were used to detect the expression of miR-221 and IL-17 in 40 cases of PTC, 20 adjacent normal thyroid tissues and 20 cases of nodular goiter, and the correlation with clinicopathologic features was analyzed. Results: (1)The expression level of miR-221 was significantly higher in PTC compared with nodular goiter and adjacent normal thyroid tissue (P<0.05), but not between the latter two (P>0.05). The expression of miR-221 was related to TNM staging, capsular invasion and lymph node metastasis (P<0.05) but not to patients' age, sex, tumor size, multifocality, tumor spread and vascular invasion.(2)Real-time RT-PCR and Western blot showed that higher levels of IL-17 mRNA and IL-17 protein in PTC than nodular goiter and adjacent normal thyroid tissue (P<0.05), but not between the latter two (P>0.05). IHC assay showed positive expression of IL-17 in PTC but not in nodular goiter and adjacent normal thyroid tissue. IL-17 expression was related to TNM staging, capsular invasion and lymph node metastasis, but not to patients' age, sex, tumor size, tumor spread and vascular invasion.(3) Expression analysis revealed a significant correlation between the miR-221 and IL-17 expression (r=0.524, P=0.001). Conclusions: The expressions of miR-221 and IL-17 are significantly higher and positively correlated in PTC, suggesting that miR-221 may regulate IL-17 expression by interacting with a variety of cytokines and inflammatory cells to participate in the development of PTC. miR-221 may be a potential novel prognostic indicator and therapeutic target for PTC.

Nanoscale pumping of water by AC electric fields. Using molecular dynamics simulations we demonstrate pumping of water through a carbon nanotube by time-dependent electric fields. The fields are generated by electrodes with oscillating charges in a broad gigahertz frequency range that are attached laterally to the tube. The key ingredient is a phase shift between the electrodes to break the spatiotemporal symmetry. A microscopic theory based on a polarization-dragging mechanism accounts quantitatively for our numerical findings.

[The clinical efficacy and safety of intravenous levofloxacin in the treatment of 4888 patients with bacterial infections: a multi-center trial]. To evaluate the clinical efficiency and safety of intravenous levofloxacin in the treatment of bacterial infections at a dose of 500 mg once a day. Randomized, prospective, multicenter, open-label study. The total effective rate of levofloxacin was 90.8% (4103/4521). The effective rates of levofloxacin in the treatment of bacterial infections of respiratory tract, urinary tract, digestive tract and gynecologic infections and infections complicated with hematological disease were 90.2% (2884/3198), 92.3% (810/878), 91.9% (203/221), 94.5% (120/127), 88.7% (86/97), respectively. The bacterial eradication rate was 80.3% (677/843). The most common adverse drug reactions were gastrointestinal disorders (3.9%, 193/4888) and local irritation (1.7%, 84/4888), which were mild and disappeared after stopping administration. Intravenous levofloxacin with a dose of 500 mg once a day is effective and safe in treating bacterial infections with low adverse reactions.

Hard tissue debris removal from the mesial root canal system of mandibular molars with ultrasonically and laser-activated irrigation: a micro-computed tomography study. This study is to investigate the efficacy of different irrigant activation techniques on removal of accumulated hard tissue debris (AHTD) in mesial roots of human mandibular molars. Extracted human mandibular molars with an isthmus between the mesial root canals were selected based on micro-CT (μCT) scans. The mesial canals were instrumented to an apical diameter ISO30 using ProTaper rotary files. Teeth were randomly assigned to three irrigant activation groups (n = 10): ultrasonically activated irrigation (UAI) using a size 20 Irrisafe for 3 × 20 s, laser-activated irrigation (LAI) with an Er:YAG laser (2940 nm) and plain 300 μm fiber tip inside the canal (20 mJ, 20 Hz, 3 × 20 s), and laser-activated irrigation with identical parameters with a 400 μm photon-induced photoacoustic streaming (PIPS) tip held at the canal entrance. All teeth were scanned with μCT before and after instrumentation and after irrigant activation. After reconstruction and image processing, the canal system volume filled with hard tissue debris before and after irrigant activation was calculated. Changes in hard tissue debris volumes were compared between groups using one-way ANOVA. The percentage volume of hard tissue debris (vol%) was significantly lower after irrigant activation in all groups. Although the lowest debris values were observed in the laser groups, no significant differences in the vol% of accumulated hard tissue debris after activation were observed between groups. Accumulated hard tissue debris was reduced significantly in all activation groups. Ultrasonically and laser-activated irrigation regimens performed similarly in this respect. None of the tested methods was able to render the root canal systems free of debris.

Plasma active and inactive renin in man during infusion of angiotensin II with and without prior administration of nifedipine. Release of active renin is inhibited by angiotensin II. To determine whether plasma inactive renin is also sensitive to this hormone, the effect of stepwise infusion of angiotensin II at 5,10 and 20 ng/kg/min on active and inactive renin levels was measured in six salt-replete normal subjects. Each subject received two infusions of angiotensin II on each of 2 study days. The calcium antagonist drug nifedipine (20 mg) or placebo was administered between the angiotensin infusions on each study day. During control infusions there was a significant decline in plasma active renin but no change in inactive renin was observed. Active renin concentration was increased after nifedipine treatment and suppressed to a similar degree by angiotensin II as in control infusions, with no corresponding changes in inactive renin. These studies suggest that plasma inactive renin levels are not subject to feedback inhibition by angiotensin II, and that inactive renin is not a physiologically important precursor of active renin in man.

[Rett syndrome: double epidural catheter for the control of postoperative pain after scoliosis surgery. A literature review]. Rett syndrome is a severe and incapacitating neurological disease caused by a structural defect in the short arm of the X chromosome (Xq28). It affects females and consists of multiple and progressive neurological impairments that start from a young age, leading to lifelong disability and dependency. Scoliosis appears in more than 50% of patients and requires surgical correction in cases where the curvature is severe. Pre-anaesthetic assessment is essential in order to identify the risk factors and thus reduce the morbidity and mortality associated with the surgical procedure. We present the case of a patient affected by this syndrome and scoliosis, who was scheduled to have an instrumented thoracolumbar spine arthrodesis with general anaesthesia, which passed without incident. We evaluate the specific details of this syndrome, its potential complications, and its management from an anaesthetic point of view, emphasising the control of postoperative pain using a double epidural catheter with an infusion of local anaesthetics and fentanyl.

Cloning and expression of 51-kDa antigenic protein of Neorickettsia risticii NR-JA1. Neorickettsia (Ehrlichia) risticii is a causative agent of acute diarrheal syndrome in horses, commonly known as Potomac horse fever. Korean isolate of N. risticii NR-JA1 was cultivated in mouse macrophage cell line P388D1. A complete ORF of p51 antigenic protein gene was amplified and cloned into pQE32 and pcDNA3.1 vectors and the resultant clones were named as pQE32/Nr-51 and pcDNA3.1/Nr-51, respectively. Recombinant p51 (rp51) protein antigen was expressed in E. coli (pQE32/Nr-51) and cos-7 cell line (pcDNA3.1/Nr-51). The rp51 protein showed immunoreactivity with anti- mouse p51 antibodies. BALB/c mice were inoculated with recombinant plasmid DNA (pcDNA3.1/Nr-51). The serum samples collected from these BALB/c mice showed IgG ELISA titers of 1:128. In a Western immunoblot assay, these serum samples showed a strong reactivity to rp51 expressed in cos-7 cell line transfected with pcDNA3.1/Nr-51. The results of this preliminary indicate that N. risticii p51 protein is an immmuno-dominant antigen and may be a good target for the development of serological or a molecular diagnostic test and possibly an improved recombinant DNA based vaccine against Potomac horse fever.

Studies on carbohydrate binding to a lectin purified from Streptomyces sp. The anti-B specific lectin produced by Streptomyces sp. was shown to have two carbohydrate-binding sites with binding constants of 8.3 . 10(3) M-1 (15 degrees C) and 2.2 . 10(3) M-1 (4 degrees C) for L-rhamnose and D-galactose, respectively, calculated according to Scatchard plots. The binding of specific sugars to the lectin not only induced a peculiar ultraviolet difference spectrum showing a blue shift of tryptophan absorption, but also caused crystallization of the lectin at a concentration of 1 mg per ml or more. The solvent-perturbation studies on the lectin showed that the number of solvent-exposed tryptophan (or average extent of exposure) was two in the absence of L-rhamnose, and three in the presence of the sugar. This suggests that one tryptophan residue appears outside as the result of sugar-binding to the lectin, which is reflected by the difference spectra. Oxidation of two tryptophan residues with N-bromosuccinimide led to complete loss of carbohydrate-binding activity of the lectin, indicating that these residues are important for retaining the activity.

Isokinetic leg strength of institutionalized older adults with mental retardation with and without Down's syndrome. This study compared isokinetic leg strength of aged individuals with mental retardation (MR) with and without Down's syndrome (DS). Nine subjects with MR and DS (mean age = 61) and 16 subjects with MR but without DS (mean age = 63) performed a leg strength test on a Biodex dynamometer. Parameters measured were peak torque, peak torque percent body weight (ratio displayed as a percentage of the maximum torque production to the subject's body weight), and average power percent body weight. In addition, anthropometric measurements (height, weight, skinfolds, and body mass index) and intelligence quotient (IQ) were also analyzed and compared. The results indicate a significant increase of scores for isokinetic knee extension and flexion in the group with MR but without DS over the subjects in the group with MR and DS. As a group, the individuals with MR and DS tended to be smaller and fatter. No significant difference in IQ was observed between the 2 groups with MR. It was concluded that the strength of individuals with MR but without DS is greater than the group of subjects with MR and DS. When comparing their results to aged individuals without MR, a significant decline in muscle strength can be observed among people with MR.

DeltaFosB, but not FosB, induces delayed apoptosis independent of cell proliferation in the Rat1a embryo cell line. The fates of Rat1a cells expressing FosB and DeltaFosB as fusion proteins (ER-FosB, ER-DeltaFosB) with the ligand binding domain of human estrogen receptor were examined. The binding of estrogen to the fusion proteins resulted in their nuclear translocation and triggered cell proliferation, and thereafter delayed cell death was observed only in cells expressing ER-DeltaFosB. The proliferation of Rat1a cells, but not cell death triggered by ER-DeltaFosB, was completely abolished by butyrolactone I, an inhibitor of cycline-dependent kinases, and was partly suppressed by antisense oligonucleotides against galectin-1, whose expression is induced after estrogen administration. The cell death was accompanied by the activation of caspase-3 and -9, the fragmentation of the nuclear genome and cytochrome c release from the mitochondria, and was suppressed by zDEVD-fmk and zLEHD-fmk but not zIETD-fmk. The cell death was not suppressed by exogenous His-PTD-Bcl-x(L) at all, suggesting involvement of a Bcl-x(L)-resistant pathway for cytochrome c release.

The putative effects of green tea on body fat: an evaluation of the evidence and a review of the potential mechanisms. The increase in the prevalence of obesity in recent years has prompted research into alternative methods of modulating body weight and body fat. The last decade has reflected this with a surge in studies investigating the potential of green tea as a natural agent of weight loss, with a view to confirming and elucidating the mechanisms underlying its effect on the body. Currently, it is widely believed that the polyphenolic components present in green tea have an anti-obesogenic effect on fat homeostasis, by increasing thermogenesis or reducing fat absorption among other ways. The data published to date, however, are inconsistent, with numerous putative modes of action suggested therein. While several unimodal mechanisms have been postulated, a more plausible explanation of the observed results might involve a multimodal approach. Such a mechanism is suggested here, involving simultaneous inhibition of the enzymes catechol-O-methyltransferase, acetyl-CoA carboxylase, fatty acid synthase and impeding absorption of fat via the gut. An evaluation of the available evidence supports a role of green tea in weight loss; however the extent of the effects obtained is still subject to debate, and requires more objective quantification in future research.

Human telomerase reverse transcriptase protein expression predicts tumour aggressiveness and survival in patients with clear cell renal cell carcinoma. Human telomerase reverse transcriptase (hTERT) is an active component of telomerase and responsible for its catalytic activity, associated with cell proliferation and differentiation. For the first time, the present study was conducted to evaluate the expression and prognostic significance of hTERT in different histological subtypes of renal cell carcinoma (RCC). Expression of hTERT was examined in 176 well-defined renal tumour samples including clear cell RCCs (ccRCCs), papillary and chromophobe RCCs using immunohistochemistry on tissue microarrays. The association between hTERT expression and clinicopathological parameters as well as survival outcomes were then analysed. There was a statistically significant difference in terms of hTERT expression among various RCC subtypes. In ccRCC, increased expression of hTERT was significantly associated with advanced stage, higher grade, presence of microvascular invasion, lymph node invasion, and metastasis. Moreover, in the multivariate analysis, tumour stage and tumour size were independent predictors of the disease-specific survival (DSS). Additionally, expression of hTERT was found to be a significant predictor of worse DSS (p = 0.012) in the univariate analysis. In papillary carcinoma samples (type I and II), significant association was detected between hTERT expression and the tumour stage (p = 0.010, p = 0.050), respectively. In chromophobe RCC, no significant association was detected between expression of hTERT and clinicopathological parameters and survival data. We showed that hTERT protein expression was associated with more aggressive tumour behaviour and more advanced disease in ccRCC patients. Also, hTERT may be a novel poor prognostic indicator of DSS, if the patients are followed for more prolonged time periods.

Functional neuroimaging at different disease stages reveals distinct phases of neuroplastic changes in amyotrophic lateral sclerosis. Some previous functional magnetic resonance imaging (fMRI) studies have revealed increased activation in amyotrophic lateral sclerosis (ALS) patients but longitudinal data on such activation changes are lacking. To assess the time course of changes in fMRI patterns and their potential contribution to the understanding of ALS pathophysiology, we, therefore, investigated a total of 22 patients with ALS and matched control participants while they performed a blocked motor task. Patients were assigned to three groups according to whether they had no (MRC grade 5), mild (MRC 4), or marked (MRC 3) weakness of the examined right hand. Significant activations were seen in primary motor and premotor cortex, somatosensory cortex, supplementary motor area and subcortical areas in all groups. The size of the activated area in the contralateral sensorimotor cortex was increased to a similar degree in all three ALS groups compared to control participants irrespective of weakness on clinical examination. Whereas movement related signal change and beta weights extracted from the activated cluster were unchanged relative to controls in ALS patients with no weakness, a marked decrease of these parameters was seen in patients with weakness. Two distinct stages of neuroplastic changes could be identified in ALS (first: increase of the activated area in contralateral sensorimotor cortex; second: reduction of signal change and beta weights with increasing weakness). We interpret the increase of the activated area as a result of decreased intracortical inhibition and the reduction of movement related signal change and beta weights as a consequence of loss of upper motor neurons.

Transepithelial calcium transport in the chick chorioallantoic membrane. I. Isolation and characterization of chorionic ectoderm cells. The chicken eggshell supplies approximately 80% of the calcium found in the hatchling chick. The mobilization of eggshell calcium into the developing embryo involves the transepithelial transport of large amounts of calcium in a development-specific manner. The cells responsible for the transport of eggshell calcium into the embryonic circulation are the ectodermal cells of the chorioallantoic membrane. In this report, we present a method for the isolation and culture of chorioallantoic membrane ectodermal cells, which are amenable to direct experimental manipulation. Cell preparations are characterized with respect to the expression of an ectoderm-specific cell surface marker (transcalcin, a calcium-binding protein), and a specific enzymatic activity (elevated Ca(2+)-activated ATPase). Functional assessment of in vitro cellular calcium uptake by 45Ca2+ tracer kinetics indicates the persistence of a temperature-sensitive, rapid-influx pathway similar to that observed in vivo. The preparations of primary ectodermal cells present an in vitro system applicable to the experimental analysis of calcium metabolism and transport by the chick chorioallantoic membrane.

Reversal of thyroxine-induced hypermetabolism by puromycin. Previous studies have demonstrated that in addition to its effects on metabolic rate, thyroxine stimulates protein biosynthesis. The administration of puromycin, a drug which blocks protein synthesis and, therefore, the thyroxine effect on protein synthesis, acutely reverses the hypermetabolism induced in rats by prior administration of thyroxine and restores the oxygen consumption of the thyrotoxic rats to the euthyroid level. The results suggest that a larger fraction of the total body basal oxygen consumption in hyperthyroidism is related to the process of protein synthesis than in the euthyroid state and that the calorigenic effect of thyroxine is secondary to its effect on protein synthesis.

Selective photothermolysis and removal of cutaneous vasculopathies and tattoos by pulsed laser. The evolution of the laser as a medical device has been a process of continued improvement. Research into increasing our understanding of the optical characteristics of skin has made it possible to concentrate not on the effects of any particular laser system, but on basic biologic and physical principles of laser-tissue interaction. The lasers available in the 1960s and 1970s offered few possibilities for modification. However, modern technology allows us to manipulate the physical characteristics of lasers and design them for specific therapeutic purposes. Selective photothermolysis relies on chromophore-specific absorption of a brief pulse of light to generate and confine heat to certain targets within the skin without nonspecific thermal damage to adjacent structures. Thermally mediated target alterations can be confined from the level of large multicellular tissue structures (e.g., blood vessels) to individual microscopic pigmented structures (e.g., tattoo pigment granules). The purpose of this report is to describe the current progress being made and to summarize the present theories for achieving increasing selective removal, without scarring or other skin textural changes, of cutaneous vasculopathies and tattoo pigment by pulsed laser.

[Protective effect of perindopril on dysfunction of endothelium-dependent relaxation in diabetic rats]. To investigate the effect of Perindopril, an angiotensin converting enzyme(ACE) inhibitor, on dysfunction of ECs-dependent relaxation in diabetic rats induced by streptozotocin(STZ) at different times, acetylcholine(Ach)-induced ECs-dependent relaxation of rat aortic rings was tested, and the concentrations of plasma glucose and AngII were measured. The results showed that: 1. Four weeks later after injecting STZ, the function of ECs-dependent relaxation was not injured in diabetic control group(DC), but the concentrations of plasma glucose and AngII were increased significantly compared with normal control group(NC). The Ach-induced relaxation was declined obviously compared with NC at 8 or 16 weeks after injecting STZ. 2. treatment with Perindopril significantly protected the function of ECs-dependent relaxation, the Ach-induced relaxation was obviously increased compared with DC. The concentration of plasma glucose was not changed, but the plasma AngII was reduced compared with DC. Perindopril could protect the function of ECs-dependent relaxation in diabetic rats.

Investigation of the efficiency of the shape of chopped pulses using earthworm model. In neural electrical stimulation, limiting the charge delivered during a stimulus pulse is essential to avoid nerve tissue damage and to save power. Previous experimental and modeling studies indicated that waveforms such as non-rectangular continuous pulses or rectangular chopped pulse were able to improve stimulation efficiency. The goal of this study is to evaluate if non-rectangular chopped pulses such as quarter sine and ramp are more charge efficient than rectangular chopped pulse. We performed in vivo study on 17 lumbricus terrestris and compared the charge per stimulating phase needed to activate lateral giant fibers (LGF) and medial giant fiber (MGF) using chopped non-rectangular pulses and rectangular pulse, varying stimulation duration parameters. Results indicated that non rectangular chopped pulses activated MGF and LGF with less charge than rectangular chopped pulses. For MGF (respectively LGF), the gain of charge was up to 33.9\% (resp. 17.8\%) using chopped ramp, and up to 22.8\% (resp. 18.1\%) using chopped quarter sine.

Cyclic mechanical stretching of human tendon fibroblasts increases the production of prostaglandin E2 and levels of cyclooxygenase expression: a novel in vitro model study. Prostaglandin E(2) (PGE(2)) is a known inflammatory mediator of tendinitis, for which mechanical loading on tendons is believed to be one of the most prominent causation factors. Previous in vitro studies have shown that cyclic mechanical stretching of cells can cause changes in cell morphology and alteration of both DNA and protein syntheses. In our study, a novel system was used whereby tendon fibroblasts are cultured on microgrooved silicone surfaces and are subjected to cyclic uniaxial stretching along their long axes to mimic in vivo conditions. Using this unique model system, the cell shape and alignment can be controlled. Further, this study was designed to test the hypotheses that PGE(2) production increases in a stretching magnitude-dependent manner and that cyclooxygenase (COX) is responsible for the increased PGE(2) production in tendon fibroblasts. Human patellar tendon fibroblasts were cultured on the microgrooved silicone membranes and cyclically stretched at 4%, 8%, or 12% of nominal dish length for 24 hr. PGE(2) production was found to be increased 1.7-fold at 8% cyclic stretching and 2.2-fold at 12% cyclic stretching compared with nonstretched controls. In addition, human tendon fibroblasts had increased expression of both COX-1 and COX-2 for all three applied stretching magnitudes, with the exception of COX-1 at 4% cyclic stretching. Also, cellular PGE(2) production, after 8% cyclic stretching, was significantly decreased with the addition of indomethacin (25 microM), a COX competitive inhibitor, compared with stretched cells without indomethacin treatment. These findings suggest that the increase in PGE(2) production by the human tendon fibroblasts is stretching magnitude-dependent, and that the increase in COX expression contributes to the increased production of PGE(2) after cyclic stretching. As PGE(2) is a known inflammatory mediator of tendinitis, the contribution of COX-1 and COX-2 to PGE(2) production and their roles in tendon inflammation are clearly indicated.

[Histology of chorioamnionitis: relations to maternal and fetal infection parameters]. With regard to clinical diagnosis and prognosis, intrauterine infection continues to pose major problems for obstetricians. In recent years serum assay of CRP, an acute phase protein, has become firmly established in the obstetric management of premature rupture. We investigated the relationship between histologically confirmed chorioamnionitis and maternal and fetal inflammation parameters in 69 patients on the basis of inflammation of the membranes, placenta and cord occurring in histomorphologic stages. Our results show the C-reactive protein to be a sensitive and specific indicator of chorioamnionitis and closely correlated with both the histologic stage and the severity of the chorioamnionitis. We therefore advocate adoption of the histologic result as the "gold standard" for evaluating subclinical and clinically manifest forms of intrauterine infection.

The progression and impact of vascular calcification in peritoneal dialysis patients. Progression of coronary artery calcification (CAC) has been described in hemodialysis patients, and severe CAC has been associated with the occurrence of cardiovascular events in this population. Little information is available regarding peritoneal patients. To prospectively evaluate peritoneal dialysis patients in order to identify the variables associated with the rate of CAC progression, as well as to determine the impact that baseline CAC has on clinical outcomes over a 1-year follow-up period. Using multislice coronary tomography, calcium scores were estimated at baseline and after 12 months in 49 peritoneal dialysis patients. Patients with and without CAC progression were compared with respect to clinical characteristics and biochemical variables, including lipid profile, parameters of mineral metabolism, and markers of inflammation. Cardiovascular events, hospitalizations, and all-cause mortality were recorded. At baseline, 29 patients (59%) presented CAC and a median calcium score of 234.7 (range 10.3-2351) Agatston units. Progression of CAC was observed in 13 patients (43%) who, in comparison with those presenting no CAC progression, were older, presented higher baseline calcium scores, and had higher mean glucose levels, lower mean high density lipoprotein cholesterol levels, and more months using low calcium peritoneal solution. We also observed a trend toward more often presenting with a history of hypertension, exhibiting more hyperphosphatemic and hyperglycemic events, and having lower albumin levels. In multiple logistic regression, only baseline calcium score was independently associated with progression of CAC. A shorter cardiovascular event-free time and a trend toward lower survival rates were observed in the group with CAC. Hospitalization event-free time did not differ between the groups. Determining CAC provides important prognostic data in peritoneal dialysis patients. Baseline calcium score and disturbances in glucose, mineral, and lipid metabolism were indicative of higher risk of CAC progression in this population.

Diagnosing breast cancer: an opportunity for innovative engineering. In an ancient papyrus, dating back to 2500 BC, an Egyptian named Imhotep, thought to be the first physician and engineer in history, offers a glimpse into the earliest recorded case of breast cancer. Treatment has evolved over the years, from radical mastectomy to radiation by X-rays, and from adjuvant chemotherapy to hormonal therapy. A key challenge in fighting the 'war' on breast cancer is early diagnosis and here innovative engineers play a vital role. While full-field digital mammography has emerged in the past decade, this technique suffers from relatively high dose levels and poor sensitivity when the breasts are dense. We aimed to develop a diagnostic imaging system that exposes the patient to lower ionising radiation and improves the sensitivity and specificity for women with dense breasts. Our PantoScanner platform has been designed to implement slot scanning digital X-rays, thereby lowering the dose and increasing signal-to-noise ratio, while also accommodating automated ultrasound and digital tomosynthesis. Early results based on mammographic phantoms are encouraging while the PantoScanner is undergoing clinical testing prior to commercial release. Since breast cancer kills 500 000 people globally every year, early diagnosis by breast screening could save the lives of many women. Our fervent hope is that the PantoScanner system will significantly contribute to this effort in South Africa and around the world.

Bi4Ti3O12 nanofibers-BiOI nanosheets p-n junction: facile synthesis and enhanced visible-light photocatalytic activity. A novel p-n junction photocatalyst of Bi4Ti3O12 nanofibers-BiOI nanosheets has been fabricated through a simple and economical technique of electrospinning combined with a successive ionic layer adsorption and reaction (SILAR) process. The products are characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), UV-visible diffuse reflectance spectra (DRS), and photoluminescence (PL) spectroscopy. The as-formed Bi4Ti3O12 nanofibers are composed of inter-linked nanoparticles of 50-80 nm in size. The thickness of the as-grown BiOI nanosheets is about 10 nm and the size of the BiOI nanosheets increases with the SILAR cycles. In particular, many {001} facets of BiOI nanosheets are exposed, which is favorable to enhance the visible-light photocatalytic activity. The p-n junction photocatalyst exhibits enhanced visible-light-driven photocatalytic activity for decomposition of rhodamine B (RhB) and phenol. The enhanced photocatalytic activity can be attributed to the extended absorption in the visible light region resulting from the BiOI nanosheets and the effective separation of photogenerated carriers driven by the photo-induced potential difference generated at the Bi4Ti3O12-BiOI p-n junction interface.

Adverse reactions to food and food allergy in young children in Iceland and Sweden. To investigate the prevalence of adverse reactions to food and food allergy in Icelandic and Swedish 18-month-old children. Prospective multicentre comparative study. Primary health care centres in Sweden and Iceland. A total of 324 children in Iceland and 328 in Sweden who attended for regular 18-month check-up. Adverse reaction to food according to questionnaire, and food allergy according to skin prick tests and double blind food challenge tests. Adverse reactions to food were reported in 27% of children in Iceland and 28% in Sweden. Food allergy was confirmed in 2.0% in both countries. Allergy among other family members was reported in 45% of the Icelandic children and 62% in the Swedish (p < 0.001). Indoor smoking was reported by 30% of the Icelandic families and 3% of the Swedish. Respiratory infections were reported significantly more often in Icelandic children than Swedish. Adverse reactions to food and food allergy were similar in Icelandic and Swedish children. At the age of 18 months one can expect to confirm food allergy in approximately one out of 15 children with reported adverse reactions to food.

Dynamic and structural features of a case of compulsive neurosis as revealed in dreams. Several examples of the manifest dreams reported by a patient with a compulsive neurosis are presented. An outstanding feature of the dreams was the sudden shift of the dreamer's self-representation from the role of criminal to the role of policeman. This shift is thought to parallel the oscillation between unconscious instinctual gratification and conscious attempts at reparation which is the main dynamic feature of the compulsive neurosis in waking life. The shift of orientation of the self reflects the operation of early defense mechanisms against the sadistic impulse. It also portrays graphically an early stage in the internalization process which leads ultimately to the creation of the superego. The repetitive nature of the dreams indicated that the patient had become fixated at this particular point in the course of his psychic development. It is interesting to note that like the Rat Man this patient suffered from a chronically undescended testicle. The real defect in the sexual apparatus in both patients may have been a factor which favored regression of the libido from the genital stage to the anal-sadistic stage.

Poverty within watershed and environmentally protected areas: the case of the indigenous community in Peninsular Malaysia. "Indigenous people" have been acknowledged as among the poorest and most socio-economically and culturally marginalized all over the world. This paper explores the socio-economic status of the indigenous people and their poverty profile within watershed and environmentally protected areas in Peninsular Malaysia. The findings of the study indicate that the "indigenous community" is likely to be poor if they live in environmentally sensitive and unprotected areas as compared to families under the new resettlement scheme. Inadequate access to basic education and employment contributed significantly to their poor economic status. The findings further reveal that the indigenous community is facing difficulties in receiving access and support in terms of basic needs such as housing, education, economic livelihood, and other social infrastructure. Moreover, the regulatory structure for the management of watershed areas as well as the emphasis for commodity crops such as palm oil and natural rubber have indirectly contributed toward the poverty level of the indigenous people.

Acrosome reaction inducing activity in follicular fluid correlates with progesterone concentration but not with oocyte maturity or fertilizability. Follicular fluid is a potent mediator of sperm acrosome reaction (AR) in vitro. The aim of this study was to investigate whether individual follicular fluids vary quantitatively in their ability to stimulate an AR, and whether such variability relates to fertilizability of the corresponding egg, its maturational level and/or progesterone content. Individual follicular fluids were obtained from 24 women undergoing in-vitro fertilization and assayed for their ability to induce an AR in normal human spermatozoa. After incubation in capacitation medium for 18 h, spermatozoa were challenged with the individual follicular fluids for 30 min. AR was detected by immunofluorescence, using fluorescein-labelled Pisum sativum lectin. We found that individual follicular fluids varied markedly in their ability to induce AR. Acrosome reaction correlated linearly with progesterone concentration (Spearman's r = 0.735, P = 0.01) at constant protein level, but no correlation was found between AR and protein concentration at constant progesterone level. Progesterone concentrations were not only higher (ANOVA, P = 0.002) in fluids from mature oocytes compared to those from less mature or post-mature eggs but also in fluids from fertilized compared to unfertilized eggs (ANOVA, P = 0.015, n = 13 patients with both fertilized and unfertilized eggs). In contrast, AR-inducing ability of individual follicular fluids did not differ for fertilized and unfertilized eggs. While AR-inducing ability appeared to increase with maturational stage of the egg, this trend was not statistically significant, probably due to small sample size. Our data suggest that progesterone rather than protein is the principal mediator of acrosome reaction induced by follicular fluid in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic significance of microvessel density and vascular endothelial growth factor expression in advanced ovarian serous carcinoma. The aim of the study was to test the prognostic value of the microvessel density (MVD) within the tumor and the vascular endothelial growth factor (VEGF) expression on clinical response to chemotherapy, on brief disease-free interval, and on cause-specific survival in advanced ovarian serous carcinoma. We evaluated 83 ovarian carcinomas homogeneous for stage, type and grade histologic, surgical, and chemotherapeutic treatment. Brief disease-free interval and cause-specific survival rates (Kaplan-Meier method) were compared using the log-rank test. A multivariate analysis (Cox-proportional hazards model) was used to determine the independent effect of each variable on prognosis. Overall 60 and 120 months cause-specific survival rates were 27.7% and 2.4%, respectively. The brief disease-free interval rate was 66.2%. In univariate analysis, VEGF (P = 0.0001 and P = 0.016), MVD (P < 0.0005), and the FIGO stage IIIC even more than FIGO stage IIIA (P = 0.01 and P < 0.0005, respectively) were associated with survival and brief disease-free interval, and the residual tumor was associated with survival (P = 0.021). In multivariate analysis, the factors that were independent predictors of survival were MVD (P < 0.0005), VEGF (P = 0.027), and the FIGO stage IIIC even more than FIGO stage IIIA (P = 0.013). Moreover, MVD was an independent predictor also of brief disease relapse (P = 0.001). Both MVD and VEGF were correlated with clinical response to chemotherapy (P = 0.01 and P = 0.037). Our data suggest that MVD and VEGF may have prognostic significance in advanced ovarian serous carcinoma.

Kinetic comparisons during variations of the power clean. Comfort, P, Allen, M, and Graham-Smith, P. Kinetic comparisons during variations of the power clean. J Strength Cond Res 25(12): 3269-3273, 2011-The aim of this investigation was to determine the differences in peak power, peak vertical ground reaction forces, and rate of force development (RFD) during variations of the power clean. Elite rugby league players (n = 16; age 22 ± 1.58 years; height 182.25 ± 2.81 cm; body mass 98.65 ± 7.52 kg) performed 1 set of 3 repetitions of the power clean, hang power clean, midthigh power clean, or midthigh clean pull, using 60% of 1 repetition maximum power clean, in a randomized order, while standing on a force platform. One-way analysis of variance with Bonferroni post hoc analysis revealed a significantly (p < 0.001) greater peak power output during the midthigh power clean (3,565.7 ± 410.6 W) and the midthigh clean pull (3,686.8 ± 386.5 W) compared with both the power clean (2,591.2 ± 645.5 W) and the hang power clean (3,183.6 ± 309.1 W), along with a significantly (p < 0.001) greater peak Fz during the midthigh power clean (2,813.8 ± 200.5 N) and the midthigh clean pull (2,901.3 ± 226.1 N) compared with both the power clean (2,264.1 ± 199.6 N) and the hang power clean (2,479.3 ± 267.6 N). The midthigh power clean (15,049.8 ± 4,415.7 N·s) and the midthigh clean pull (15,623.6 ± 3,114.4 N·s) also demonstrated significantly (p < 0.001) greater instantaneous RFD when compared with both the power clean (8,657.9 ± 2,746.6 N·s) and the hang power clean (10,314.4 ± 4,238.2 N·s). From the findings of this study, when training to maximize power, Fz, and RFD, the midthigh power clean and midthigh clean pull appear to be the most advantageous variations of the power clean to perform.

Real-time 3D ultrasound guided interventional system for cardiac stem cell therapy with motion compensation. This paper describes a clinically translatable interventional guidance platform to improve the accuracy and precision of stem cell injections into a beating heart. The proposed platform overlays live position of an injection catheter onto a fusion of a pre-procedural MR roadmap with real-time 3D transesophageal echocardiography (TEE). Electromagnetic (EM) tracking is used to initialize the fusion. The fusion is intra-operatively compensated for respiratory motion using a novel algorithm that uses peri-operative full volume ultrasound images. Validation of the system on a moving heart phantom produced a landmark registration accuracy of 2.8 +/- 1.45mm. Validation on animal in vivo data produced an average registration accuracy of 2.2 +/- 1.8 mm; indicating that it is feasible to reliably and robustly fuse the MR road-map with catheter position using 3D ultrasound in a clinical setting.

Radiographic demonstration of longitudinal ulcers in patients with ulcerative colitis. During the past 10 years, 122 patients with ulcerative colitis were diagnosed by double-contrast barium enema and colonofiberscopy with endoscopic biopsy. Among them, five patients (4%) had longitudinal ulcers and eccentric deformities in the colon. Other radiologic findings included thumbprinting (two cases), sacculations (two cases), and inflammatory polyps (four cases). The possibility of the concomitance of ischemic colitis in cases of ulcerative colitis is discussed, due to their radiographic similarities.

Characterization of two bioluminescent Rhizobium meliloti strains constructed for field releases. The deliberate release of genetically engineered microorganisms requires a thorough characterization of the microbes in question. For the two bioluminescent Rhizobium meliloti strains, L1 and L33 [Selbitschka et al. (1992) Mol Ecol 1:9-19; Selbitschka et al. (1995) FEMS Microbiol Ecol 16:223-232], designated for field release, the sites of genetic modifications in the chromosomes were sequenced from amplified genomic DNA. This indicated no unexpected alterations in the nucleotide sequence. The bioluminescent phenotype was stably inherited over more than 100 generations in liquid cultures. The presence of the luciferase gene in both strains did not have secondary effects on a variety of metabolic pathways as assessed by the Biolog GN system. A specific polymerase chain reaction amplification, based on the chromosomal insertion site of the luc cassette, allowed the discrimination between the two strains and thus simplifies monitoring. The RecA-deficient strain L1 showed a strongly (more than 90%) reduced ability to nodulate alfalfa in competition with its parent strain R. meliloti 2011 and its RecA+ counterpart L33.

Direct effects of chronic beta-adrenergic receptor blockade on left ventricular and myocyte function in a model of tachycardia-induced congestive heart failure. Chronic beta-receptor blockade (beta-blockade) has been reported to improve symptoms and increase survival in patients with congestive heart failure (CHF); however, whether the mechanisms for the effects of beta-blockade in CHF are due to modulating chronotropy, inotropy, or both remains unknown. To address this issue, left ventricular function and isolated myocyte function were examined with chronic beta-blockade in a rapid pacing model of CHF, thereby eliminating potential chronotropic effects of beta-blockade. Pigs were randomly assigned to three groups of six pigs each: supraventricular tachycardia (SVT): 3 weeks of atrial pacing at 240 beats/min; SVT/beta-blockade: 3 weeks of rapid pacing and beta-blockade (25 mg atenolol twice daily on days 14-21 of pacing); control group, sham control animals. This dosage schedule for beta-blockade was chosen because catecholamines are persistently elevated by day 14 in this model of CHF. Left ventricular fractional shortening and end-diastolic dimension were measured by echocardiography in the conscious state with a resting ambient heart rate. Isolated left ventricular myocyte function was examined using high-speed videomicroscopy. Supraventricular tachycardia caused left ventricular dilation (5.4 +/- 0.1 vs 3.5 +/- 0.1 cm) and reduced fractional shortening (12 +/- 1% vs 35 +/- 1%) compared with control animals (P < .05). The SVT/beta-blockade group showed no significant effects on left ventricular size or function compared with the SVT group, but their ambient resting heart rate was reduced by 20% relative to the SVT group (P < .05). Myocyte shortening was reduced in the SVT group (2.2 +/- 0.1% vs 4.5 +/- 0.1%, P < .05) compared with the control group and increased from SVT-only values with beta-blockade (2.7 +/- 0.1%, P < .05). Similarly, myocyte shortening velocity was similarly reduced in the SVT and SVT/beta-blockade groups (31 +/- 1 and 32 +/- 1 microns/s) compared with the control group (51 +/- 1 microns/s, P < .05). With SVT/beta-blockade myocyte contraction duration was prolonged (525 +/- 5 ms) compared with SVT-only or control values (469 +/- 9 and 473 +/- 4 ms, P < .05). Thus, institution of beta-1-selective blockade during the development of SVT-induced CHF altered the temporal characteristics of the myocyte contraction process, which resulted in improved myocyte shortening. In a model of CHF due to the maintenance of a chronically elevated heart rate, institution of beta-1-selective blockade during the progression of the CHF process minimally affected left ventricular size and function. At the level of the myocyte, chronic beta-1-receptor blockade prolonged the contraction interval and thereby increased myocyte shortening. These unique results suggest that a contributory mechanism for the effects of beta-blockade in the setting of CHF is chronotropic modulation.

Associations between psychosocial factors and pain intensity, physical functioning, and psychological functioning in patients with chronic pain: a cross-cultural comparison. Current models of chronic pain recognize that psychosocial factors influence pain and the effects of pain on daily life. The role of such factors has been widely studied on English-speaking individuals with chronic pain. It is possible that the associations between such factors and adjustment may be influenced by culture. This study sought to evaluate the importance of coping responses, self-efficacy beliefs, and social support to adjust to chronic pain in a sample of Portuguese patients, and discuss the findings with respect to their similarities and differences from findings of studies on English-speaking individuals. Measures of pain intensity and interference, physical and psychological functioning, coping responses, self-efficacy, and satisfaction with social support were administered to a sample of 324 Portuguese patients with chronic musculoskeletal pain. Univariate and multivariate analyses were computed. Findings were interpreted with respect to those from similar studies using English-speaking individuals. Coping responses and perceived social support were significantly associated with pain interference and both physical and psychological functioning; self-efficacy beliefs were significantly associated with all criterion variables. All coping responses, except for task persistence, were positively associated with pain interference and negatively associated with physical and psychological functioning, with the strongest associations found for catastrophizing, praying/hoping, guarding, resting, asking for assistance, and relaxation. The findings provide support for the importance of the psychosocial factors studied in terms of adjustment to chronic pain in Portuguese patients, and also suggest the possibility of some differences in the role of these factors due to culture.

A late neurologic complication of scoliosis surgery in connection with syringomyelia. A case of scoliosis in connection with syringomyelia is described. Theories are proposed to explain the progression of the neurological symptoms after surgical correction and fusion of the deformity. Special points are emphasized that will aid in the recognition of syringomyelia in scoliosis patients. i) Abnormal neurology, in particular a dissociated disturbance of pain and temperature in the upper extremity. ii) Abnormal localization of a scoliosis curve. iii) Rapid progression of the scoliosis. iv) Bony anomalies of the upper cervical spine. v) Increased diameter of the cervical spinal canal.

Simultaneous measurement of plasma concentrations and 13C-enrichment of short-chain fatty acids, lactic acid and ketone bodies by gas chromatography coupled to mass spectrometry. A new method has been developed for the simultaneous measurement, in a reduced plasma sample, of concentration and 13C-isotopic enrichment of acetic, propionic, butyric, lactic, acetoacetic and beta-hydroxybutyric acids by gas chromatography coupled to mass spectrometry. After plasma deproteinisation, a diethylic extraction and a N-tert.-butyldimethylsilyl-N-methyltrifluoroacetamide derivatisation were performed. Both diethyl extraction and derivatisation procedures were optimised using the central composite designs methodology. The optimised method provides good linearity, intra-day and within-day repeatability. Except for beta-hydroxybutyric (49 microM) and acetoacetic acid (5 microM), detection limits were ranging between 0.2 and 0.7 microM allowing uses of this method for colonic metabolism studies.

Obesity Treatment at HealthPartners: Adaptation of Clinical Guidelines into Systems for Practice Operations. The purpose of this paper is to describe how HealthPartners health system in Minneapolis, MN, has translated a clinical guideline for obesity among adults into an efficient care delivery practice operations system. Based on a foundation provided by the physician-led Institute of Clinical Systems Improvement (ICSI)-developed Prevention and Management of Obesity for Adults Health Care Guideline, HealthPartners adapted the guideline into an electronic health record-based "Smart Set" that provides frontline physicians with the information, treatment options, and referral steps necessary to care for their patients with obesity. Additional context is provided in terms of insurance coverage and systems-based resources designed to prevent and treat obesity for adults.

Revascularization surgery for penile calciphylaxis. Calciphylaxis, a systemic disorder seen in 1%-4% of patients with end-stage renal disease, is a cause of penile ischemic gangrene. We present a case of successful revascularization surgery for penile calciphylaxis. An arterial bypass to the deep dorsal penile vein relieved the rest pain and stopped expansion of the gangrenous lesion.

Detection of CFTR mutations using PCR/ARMS in a sample of Algerian population. Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. Wrongly considered as a European disease, CF is found in Algeria; but the literature data on the clinical profile and the spectrum of CFTR gene mutations are poor. In this study we investigate twenty-four unrelated Algerian families, with at least one child with CF. DNA extracts from blood samples of patients and parents were screened for CFTR gene mutations using Elucigene CF30 Kit which is based on a PCR/ARMS technique. Only five different mutations were identified. On the 48 alleles studied, most common mutations were: c.1521_1523delCTT (F508del) 18.75%, c.579+1G>T (711+1G>T) 12.5%, c.1624G>T (G542X) 10.41%, c.3909C>G (N1303K) 4%, and c.1652G>A (G551D) 2%. The Elucigene CF30 kit highlights a portion of CFTR mutations in the Algerian population. It remains important for a first screening as it reveals the most common mutations. All this information is of interest for genetic testing and genetic counseling in Algeria and in European countries where immigration from the Maghreb is common.

An approach to managing HPV-associated anal dysplasia. Although anal cancer is rare, incidence rates are rising in the United States. Recognizing and screening high-risk patients can improve management. Vaccination may also play a role in the prevention of HPV-related anal cancer, but more research is needed.

Operative Treatment of Haglund Syndrome With Central Achilles Tendon-Splitting Approach. Haglund syndrome is characterized by chronic posterior heel pain associated with a posterosuperior calcaneal prominence. We assessed the clinical and radiologic outcomes after operative treatment of Haglund syndrome using the central tendon-splitting approach. Fifteen feet in 15 patients were investigated retrospectively after surgery. Of the 15 patients, 14 were males (93.3%) and 1 was female (6.7%). Their mean age was 33.1 ± 8.2 (range 20 to 50) years. The mean follow-up duration was 3.5 ± 1.5 years (range 24 to 90 months). The American Orthopaedic Foot and Ankle Society ankle-hindfoot Scale and Victorian Institute of Sport Assessment-Achilles scores were investigated to assess the clinical outcomes. Patient satisfaction was assessed at the latest follow-up visit. The lateral talo-first metatarsal angle, calcaneal pitch angle, Fowler-Philip angle, and parallel pitch line were measured to assess the foot shape and radiographic outcomes. Clinically, the mean American Orthopaedic Foot and Ankle Society ankle-hindfoot scale score increased from 62.1 ± 7.5 preoperatively to 92.5 ± 3.5 at the latest follow-up visit. The mean Victorian Institute of Sport Assessment-Achilles score increased from 53.2 ± 7.4 to 89.6 ± 3.4. All patients were satisfied with the operative results. Radiographically, all patients had cavus feet with an increased lateral talo-first metatarsal angle (mean +5.9° ± 5.0°) and calcaneal pitch angle (mean 26.0° ± 3.8°). The mean Fowler-Philip angle decreased from 58.9° ± 15.0° to 32.5° ± 7.2° postoperatively, and the positive parallel pitch line had changed to a negative value in all cases. Operative treatment with the central tendon-splitting approach appears to be safe and satisfactory for intractable Haglund syndrome.

Autocrine STIP1 signaling promotes tumor growth and is associated with disease outcome in hepatocellular carcinoma. Stress-induced phosphoprotein 1 (STIP1) is an adaptor protein that bridges between HSP70 and HSP90 folding and a secretory protein which regulates malignant cell growth. However, the role of STIP1 in hepatocellular carcinoma (HCC) remains unknown. Here, we found high expression of STIP1 in tumors was associated with worse overall survival (41.3 vs 62.7 months, P < 0.001) in 231 HCC patients. STIP1 was overexpressed in HCC tissues compared to adjacent non-tumor liver tissue (64.9% vs 4.0% P < 0.001), and serum STIP1 levels of HCC patients were elevated compared to healthy controls (P < 0.001). Mechanistically, STIP1 promoted HCC growth through PI3K-AKT-dependent anti-apoptotic pathway. STIP1 mediated cell growth in an autocrine fashion, which could be suppressed either by neutralizing extracellular STIP1 or by knocking down intracellular STIP1. In xenograft mouse model, knockdown of STIP1 significantly reduced tumor growth (P < 0.001). In conclusion, STIP1 is upregulated in HCC and associated with poor clinical prognosis. Blocking STIP1 activity suppresses HCC cell growth, providing the rationale for STIP1 as a potential therapeutic target in HCC.

[HGBV-C infection in patients with chronic liver disease]. Infection with HGBV-C was surveyed in 286 patients with chronic liver disease. HGBV-C RNA was detected in 19 patients (6.6%), by nested RT-PCR with 5'UTR-derived primers. There were no appreciable differences in clinical and virological features between patients with and without HGBV-C RNA in serum. HGBV-C RNA was detected in three of 83(4%) patients with HBV infection, 15(8%) of 188 patients with HCV infection, and one of 12(8%) patients without evidence of ongoing infection with HBV or HCV, suggesting that the contribution of HGBV-C to non-B non-C hepatitis would not be high. HGBV-C RNA was detected more frequently in the patients with liver cirrhosis or hepatocellular carcinoma than in those with chronic hepatitis. This could reflect a possible role of HGBV-C in aggravating liver disease in co-operation with the other hepatitis viruses.

Fermentation characteristics and angiotensin I-converting enzyme-inhibitory activity of Lactobacillus helveticus isolate H9 in cow milk, soy milk, and mare milk. Lactobacillus helveticus isolate H9 demonstrated high angiotensin I-converting enzyme (ACE)-inhibitory activity in previous research. Here, we evaluated the fermentation characteristics (pH, titratable acidity, free amino nitrogen, and viable bacterial counts), ACE-inhibitory activity, and contents of Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) peptides of stored yogurt (4°C for 28 d) fermented by L. helveticus isolate H9 (initially inoculated at 4 concentrations), from cow, mare, and soy milks. During storage, the pH and titratable acidity remained stable in yogurts produced from all milk types and all inoculation concentrations. The viable bacterial counts in all stored yogurts ranged between 10(6.72) and 10(8.59) cfu/g. The highest ACE-inhibitory activity (70.9-74.5%) was achieved at inoculation concentrations of 5×10(6) cfu/mL. The ACE-inhibitory tripeptides VPP and IPP as determined by ultra-performance liquid chromatography-tandem mass spectrometry were not produced in yogurt made from soy milk or mare milk. These evaluations indicate that L. helveticus H9 has good probiotic properties and would be a promising candidate for production of fermented food with probiotic properties.

Hid can induce, but is not required for autophagy in polyploid larval Drosophila tissues. The major cell death pathways are apoptosis and autophagy-type cell death in Drosophila. Overexpression of proapoptotic genes in developing imaginal tissues leads to the activation of caspases and apoptosis, but most of them show no effect on the polytenic cells of the fat body during the last larval stage. Surprisingly, overexpression of Hid induces caspase-independent autophagy in the fat body, as well as in most other larval tissues tested. Hid mutation results in inhibition of salivary gland cell death, but the disintegration of the larval midgut is not affected. Electron microscopy shows that autophagy is normally induced in fat body, midgut and salivary gland cells of homozygous mutant larvae, suggesting that Hid is not required for autophagy itself. Constitutive expression of the caspase inhibitor p35 produces identical phenotypes. Our results show that the large, post-mitotic larval cells do not react or activate autophagy in response to the same strong apoptotic stimuli that trigger apoptosis in small, mitotically active imaginal disc cells.

Nocodazole irreversibly reduces the capacity of rapid axoplasmic transport in vitro. Using the frog sciatic nerve as an in vitro model system, the effects of 10(-5) M nocodazole, an antimitotic drug, on rapid axoplasmic transport were quantified and tested for reversibility. After pulse-labeling the 8th dorsal root ganglia with [3H]leucine, the nerves were incubated for 4.5 to 9 hr at 25 degrees C. Transport velocities and amounts of transported material were determined from the distribution of radioactively labeled proteins. One nerve per animal served as a control. Before ganglia labeling, the nerves were preincubated for 1 or 15 hr in 10(-5) M nocodazole, respectively. In one set of experiments, the nerves were preincubated in nocodazole for 6 hr washed for 1.5 hr and further treated in Ringer's solution to test for reversibility. We found that nocodazole did not affect the maximal transport velocity under any of the conditions tested. The amounts of rapidly transported material were reduced to 60% of controls after 1 hr of pretreatment with nocodazole, and to 30% after 6 to 15 hr of pretreatment. There was no indication for a reversibility of these effects. We conclude that 10(-5) M nocodazole shows maximal effects on rapid axoplasmic transport only if given several hours before protein synthesis, and that it reduces the capacity of rapid axoplasmic transport without affecting transport velocity. These effects are not reversible during the survival time of the in vitro preparation.

Predicted highly expressed genes in Nocardia farcinica and the implication for its primary metabolism and nocardial virulence. Nocardia farcinica is a Gram positive, filamentous bacterium, and is considered an opportunistic pathogen. In this study, the highly expressed genes in N. farcinica were predicted using the codon adaptation index (CAI) as a numerical estimator of gene expressivity. Using ribosomal protein (RP) genes as references, the top approximately approximately 10% of the genes were predicted to be the predicted highly expressed (PHX) genes in N. farcinica using a CAI cutoff of greater than 0.73. Consistent with earlier analysis of Streptomyces genomes, most of the PHX genes in N. farcinica were involved in various 'house-keeping' functions important for cell growth. However, 15 genes putatively involved in nocardial virulence were predicted as PHX genes in N. farcinica, which included genes encoding four Mce proteins, cyclopropane fatty acid synthase which is involved in the modification of cell wall which may be important for nocardia virulence, polyketide synthase PKS13 for mycolic acid synthesis and a non-ribosomal peptide synthetase involved in biosynthesis of a mycobactin-related siderophore. In addition, multiple genes involved in defense against reactive oxygen species (ROS) produced by the phagocyte were predicted with high expressivity, which included alkylhydroperoxide reductase (ahpC), catalase (katG), superoxide dismutase (sodF), thioredoxin, thioredoxin reductase, glutathione peroxidase, and peptide methionine sulfoxide reductase, suggesting that combating against ROS is essential for survival of N. farcinica in host cells. The study also showed that the distribution of PHX genes in the N. farcinica circular chromosome was uneven, with more PHX genes located in the regions close to replication initiation site. The results provided the first estimates of global gene expression patterns in N. farcinica, which will be useful in guiding experimental design for further investigations.

OKT3 induces suppressor cells for mixed lymphocyte and PHA mitogenic responses in human peripheral lymphocytes. Human peripheral lymphocytes pretreated with the Orthoclone monoclonal anti-T cell antibody OKT3 for 48 h markedly suppressed the proliferative response of autologous lymphocytes in one-way MLC and the mitogenic response to PHA. The ability to induce suppression is specific to OKT3 since other monoclonal antibodies to human T cells (OKT1, OKT4 and OKT8) did not elicit similar responses, OKT3 is mitogenic but further proliferation of OKT3 pretreated lymphocytes was not required for the suppression of autologous lymphocytes since mitomycin-C treated cells were fully effective. Kinetic studies indicated that pretreatment of lymphocytes with OKT3 for 24 h was sufficient to induce marked inhibition of the mitogenic response of autologous lymphocytes to PHA whereas suppression in MLC was not observed until lymphocytes were pretreated for 48 h. These studies support the previous observations that OKT3 may be reacting with an important molecule on the T cell surface and that interaction of OKT3 with this molecule induces profound functional changes.

Screening for glycosidase activities of lactic acid bacteria as a biotechnological tool in oenology. The aim of this study was to evaluate the ability from a number of lactic acid bacteria isolated from different sources to produce glycosidase enzymes. Representative isolates (225) from clusters obtained after genotyping, using randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) analysis, of 1,464 isolates, were screened for β-D-glucosidase activity. Thirty-five of them were selected for subsequent analysis. These strains were able to hydrolyze α-D-glucopyranoside, β-D-xylopyranoside and α-L-arabinofuranoside although β-D-glucosidase activity was the predominant activity for 22 of the selected strains. Only some of them did so with α-L-rhamnopyranoside. All of these were from wine samples and were identified as belonging to the Oenococcus oeni species using Amplification and Restriction Analysis of 16S-rRNA gene (16S-ARDRA). When the influence of pH, temperature and ethanol or sugars content on β-D-glucosidase activity was assayed, a strain-dependent response was observed. The β-D-glucosidase activity occurred in both whole and sonicated cells but not in the supernatants from cultures or obtained after cell sonication. Strains 10, 17, 21, and 23 retained the most β-D-glucosidase activity when they were assayed at the conditions of temperature, pH, ethanol and sugar content used in winemaking. These results suggest that these strains could be used as a source of glycosidase enzymes for use in winemaking.

Lack of specificity of trans,trans-muconic acid as a benzene biomarker after ingestion of sorbic acid-preserved foods. The benzene metabolite, trans,trans-muconic acid (MA), has been shown to be a sensitive and specific biomarker for ambient benzene exposure levels as low as approximately 0.5 ppm. However, at lower exposure levels, the use of MA as a benzene biomarker is complicated by the fact that it is also a metabolite of the food preservative, sorbic acid. To better assess the extent of this interference, MA was measured in sequential spot urine samples over a 2-day study period from eight volunteers (four adults and two parent-children pairs) who consumed two sorbic acid-preserved foods. Large increases in MA concentration were seen after ingestion of both foods. Individual peaks ranged as high as 1673.7 ng/ml (705.3 ng/mg creatinine) in adults and 1752.1 ng/mg creatinine (1221.3 ng/ml) in children. Ratios of peak to baseline values varied from 2.5 to 60. The average peak in the seven subjects who showed an increase in MA after ingestion of the first sorbic acid-containing food was 531.1 ng/ml (693.2 ng/mg creatinine). The average in the seven participants who ingested the second food was 1102.1 ng/ml (795.3 ng/mg creatinine). Twenty-four-hour personal air benzene levels were all low (< or = 5.6 ppb). Substantial variation in MA results were seen in some males related to creatinine adjustment. These data indicate that sorbic acid-preserved foods have the potential to cause substantial interference with MA as a biomarker for both occupational and environmental benzene exposure in populations, such as in the United States, where consumption of preserved foods is common. Development of methods to minimize and/or assess sorbic acid interference will improve MA specificity in such populations.

Dispersive-scan measurement of the fast component of the third-order nonlinearity of bulk materials and waveguides. A new, simple method to measure the nonlinear refraction and absorption of bulk material and waveguides is proposed. The method relies on the evolution of the intensity and width of femtosecond-pulse spectra, owing to self-phase modulation, as a function of variable chirp and stretching introduced at the input.

Glucokinase regulates reproductive function, glucocorticoid secretion, food intake, and hypothalamic gene expression. Because appetite, hypothalamic gene expression, reproductive function, and adrenal function are highly sensitive to acute changes in plasma glucose levels, it has been hypothesized hypothalamic neurons sensitive to glucose play a role in regulating these functions. To assess this hypothesis, we examined these neuronendocrine functions in mice in which the glucokinase gene, which plays an essential role in neuroendocrine glucose sensing, has been ablated. Haploinsufficiency in heterozygous glucokinase knockout mice produced effects similar to those produced by hypoglycemia: impaired reproductive function, elevated plasma corticosterone, increased food intake, and hypothalamic gene expression similar to that observed in fasted or leptin-deficient obese mice (increased hypothalamic neuropeptide Y mRNA and reduced hypothalamic proopiomelanocortin mRNA). Plasma glucose was elevated 2-fold in glucokinase knockout mice, consistent with a maturity-onset diabetes of the young phenotype, but plasma insulin and leptin levels were normal. These data support the hypothesis that glucokinase plays a key role in the neuroendocrine regulation of metabolic economy.

Mesenchymal stromal cells uptake and release paclitaxel without reducing its anticancer activity. To improve the drug delivery efficiency on target cells, many strategies have been developed including Mesenchymal Stromal Cells (MSCs) approaches. In a previous study, we found that bone-marrow-derived MSCs (BM-MSCs) were able to incorporate and release the anti-tumor and anti-angiogenic drug, Paclitaxel (PTX). In this study, we evaluated the stability of PTX in standard cell culture conditions by analyzing the metabolites produced by MSCs after their incorporation of the drug. We are able to show that MSCs do not release either 3-OH-PTX or 6-OH-PTX metabolites (having a lower anticancer activity) but release an active PTX molecule together with the isomer 7-Epitaxol, is known to maintain the whole biological activity. This confirms that the simple procedure of MSCs priming with a drug (without any genetic cell manipulation), in our case PTX, does not modify the activity of the molecule and provides a new biological-device to carry and deliver PTX in tumor sites, by contributing to improve drug efficacy and target selectivity in cancer therapy.

Efficacy and safety of yokukansan in treatment-resistant schizophrenia: a randomized, double-blind, placebo-controlled trial (a Positive and Negative Syndrome Scale, five-factor analysis). Treating schizophrenia patients who fail to respond to antipsychotics is a major challenge, and the percentage of treatment-resistant patients is estimated to be 20-25 %. Recent studies indicate that yokukansan (YKS; D2 and 5HT1A partial agonist and 5HT2A and glutamate antagonist) to be safe and useful in treating behavioral and psychological symptoms associated with dementia and other neuropsychiatric conditions. We aimed at evaluating both the efficacy and safety of YKS in patients with treatment-resistant schizophrenia. This randomized, multicenter, double-blind, placebo-controlled study was conducted between May 2010 and August 2012. One hundred twenty antipsychotic-treated inpatients from 34 psychiatric hospitals in Japan were included. Patients were randomized to adjuvant treatment with YKS 7.5 g/day or placebo. During a 4-week follow-up, psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) with five factors [excitement/hostility (P4, P7, G8, and G14), depression/anxiety (G1, G2, G3, G4, and G6), cognition (P2, N5, N7, G5, G10, G11, G12, G13, and G15], positive (P1, P3, P5, P6, and G9), and negative (N1, N2, N3, N4, N6, G7, and G16]]. Other assessments included, Clinical Global Impression-Severity (CGI-S), Global Assessment of Functioning (GAF), and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The primary efficacy outcome was the change in PANSS five-factor scores. The secondary outcomes were changes in the scores of CGI-S. The analysis was made on a modified intention to treat basis with the help of a last observation carried forward method. YKS showed a tendency of superiority to placebo in reducing total all PANSS five-factor scores in treatment-resistant schizophrenia, but the difference was not statistically significant in total, depression/anxiety, cognition, positive, and negative factors. However, compared to the placebo group, the YKS group showed statistically significant improvements in the PANSS excitement/hostility factor scores (p<0.05). No substantial side effects were recorded. The results of the present study indicate YKS to be a potential adjunctive treatment strategy for treatment-resistant schizophrenia, particularly to improve excitement/hostility symptoms.

Preparation of a crystallizable mRNA-binding fragment of Moorella thermoacetica elongation factor SelB. SelB is a bacterial elongation factor required for the decoding of a UGA stop codon together with a specific mRNA hairpin to selenocysteine. In attempts to crystallize Moorella thermoacetica SelB, a proteolysis process occurred and crystals of a proteolytic fragment were observed. The crystals, which appeared after a year, contained a C-terminal 30 kDa fragment containing the mRNA-binding domain. This fragment was reproduced through recloning. Crystals diffracting to 2.7 A were obtained.

Condom promotion for AIDS prevention in the developing world: is it working? Two decades of experience and research provide new insights into the role of condoms for AIDS prevention in the developing world. This literature review and synthesis is based on computerized searches of the scientific literature and review of conference presentations, publications of national and international organizations, and popular media. Condoms are about 90 percent effective for preventing HIV transmission, and their use has grown rapidly in many countries. Condoms have produced substantial benefit in countries like Thailand, where both transmission and condom promotion are concentrated in the area of commercial sex. The public health benefit of condom promotion in settings with widespread heterosexual transmission, however, remains unestablished. In countries like Uganda that have curbed generalized epidemics, reducing the number of individuals' sex partners appears to have been more important than promoting the use of condoms. Other countries continue to have high rates of HIV transmission despite high reported rates of condom use among the sexually active. The impact of condoms may be limited by inconsistent use, low use among those at highest risk, and negative interactions with other strategies. Recommendations include increased condom promotion for groups at high risk, more rigorous measurement of the impact of condom promotion, and more research on how best to integrate condom promotion with other prevention strategies.

Cooperative Behavior of Fluoroquinolone Combinations against Escherichia coli and Staphylococcus aureus. The effects of different combinations of ciprofloxacin (CIP) and norfloxacin (NOR) against Escherichia coli and Staphylococcus aureus were studied using checkerboard, fractional inhibitory concentration (FIC) and time-kill analysis methods. Results obtained by the checkerboard method showed that the more effectives combinations against Escherichia coli were 0.0009 µg/mL CIP+0.0312 µg/mL NOR and 0.0037 µg/mL CIP+0.0075 µg/mL NOR with a FIC index of 0.62. For Staphylococcus aureus, the combination of 0.0625 µg/mL CIP+0.2500 µg/mL NOR showed a synergistic effect, with a FIC index of 0.50. The results of the time-kill method demonstrated either indifference or additivity of the combinations 0.0009 µg/mL CIP+0.0312 µg/mL NOR, 0.0018 µg/mL CIP+0.0312 µg/mL NOR, 0.0037 µg/mL CIP+0.0075 µg/mL NOR and 0.0037 µg/mL CIP+0.0156 µg/mL NOR at 24 h against E. coli. The combination 0.0037 µg/mL CIP+0.0312 µg/mL NOR showed synergistic activity. All the analyzed combinations evidenced bactericidal effects at 4 h. The combinations 0.0625 µg/mL CIP+0.2500 µg/mL NOR and 0.0625 µg/mL CIP+0.0625 µg/mL NOR showed indifference or additivity against S. aureus. None of them generated bactericidal effect at 4 h. Moreover, this last equimolecular combination (equivalent to 1/4 minimum inhibitory concentration (MIC) CIP+1/16 MIC NOR) generated higher reduction of nitro blue tetrazolium than drugs alone. By another way, combinations not equimolecular of CIP and NOR assayed, generated less levels of reactive oxygen species (ROS) than the components alone.

Adolescent transition to coitus and premarital childbearing in Sudan: a biosocial context. This paper examines the biosocial basis of premarital sexual and reproductive behaviour among women in Sudan. It applies Udry's biosocial perspective, which attempts to reconcile the biological and sociological models of premarital sexual and reproductive behaviour. World Fertility Survey (WFS) data were used to study premarital first motherhood. Early puberty was found to be paramount in determining childbearing in a separate biological model, but also in a biosocial model constructed to take account of social controls. This finding suggests that social controls do not influence the biological predisposition to premarital sexual behaviour. However, given the limitations of the WFS data, conclusive evidence must await a more appropriately designed study of reproductive behaviour in Sudan.

Laparoscopic surgery in polycystic ovary syndrome: reproductive and metabolic effects. Polycystic ovary syndrome (PCOS) is the most common cause of chronic anovulation. Clomiphene citrate (CC) is the first-line treatment for ovulation induction for infertile women with PCOS. In CC-resistant women, a particular surgical method, laparoscopic ovarian drilling (LOD), has been proposed in recent years as an alternative treatment. LOD produces overall spontaneous ovulation and pregnancy rates of 30 to 90% and 13 to 88%, respectively, for CC-resistant PCOS women. The mechanism of LOD is still unknown. The reduction of serum androgen level is believed to be the possible mechanism of LOD to improve spontaneous ovulation and promote fertility in women with PCOS. In addition, LOD may cause a significant reduction in serum luteinizing hormone and insulin levels. However, it should be kept in mind that postoperative adhesion is the most common adverse effect of LOD, and more punctures may be responsible for premature ovarian failure.

Pancreaticoduodenal artery aneurysm with celiac trunk occlusion. Report of a case. A case of superior mesenteric artery branch aneurysm is described. A 43-year-old female patient was hospitalized after the incidental discovery of a low echogenic mass next to the superior mesenteric artery trunk. A selective superior mesenteric arteriography confirmed aneurysms of the inferior pancreaticoduodenal artery and an aortogram demonstrated occlusion of the celiac trunk. Bypass between the abdominal aorta and the common hepatic artery and resection of aneurysms were performed. The possible etiology and operative procedure are discussed.

Semantic Cluster Unary Loss for Efficient Deep Hashing. Hashing method maps similar data to binary hashcodes with smaller hamming distance, which has received broad attention due to its low storage cost and fast retrieval speed. With the rapid development of deep learning, deep hashing methods have achieved promising results in efficient information retrieval. Most existing deep hashing methods adopt pairwise or triplet losses to deal with similarities underlying the data, but their training are difficult and less efficient because O(n2) data pairs and O(n3) triplets are involved. To address these issues, we propose a novel deep hashing algorithm with unary loss which can be trained very efficiently. First of all, we introduce a Unary Upper Bound of the traditional triplet loss, thus reducing the complexity to O(n) and bridging the classificationbased unary loss and the triplet loss. Second, we propose a novel Semantic Cluster Deep Hashing (SCDH) algorithm by introducing a modified Unary Upper Bound loss, named Semantic Cluster Unary Loss (SCUL). The resultant hashcodes form several compact clusters, which means hashcodes in the same cluster have similar semantic information. We also demonstrate that the proposed SCDH is easy to be extended to semi-supervised settings by incorporating the state-of-the-art semi-supervised learning algorithms. Experiments on large-scale datasets show that the proposed method is superior to state-of-the-art hashing algorithms.

"It depends on your pocket:" findings from a qualitative study in Uganda exploring women's and health care providers' perspectives on family planning. An unmet need for family planning among Ugandan women remains. Our research team conducted qualitative research to identify Ugandan perspectives about family planning. We facilitated interviews with Ugandan women and health care providers. Using grounded theory, our team analyzed the data to identify themes from the transcripts. The researchers identified the cross-cutting theme as the influence of money on women and health care providers. Although affordability and accessibility were recognized as determinants of ensuring family planning uptake, we found that money impacts the decision making via additional mechanisms. For women, monetary concerns associated with assuring family needs were prioritized. For health care providers, they discussed that money created barriers as well as incentives to family planning service provisions.

[Additional findings on age differences in the blood circulation in rats]. By means of microparticles labelled by radioactive strontium 85Sr (3M, USA) the authors in two experiments established cardiac output and local blood flow through bones and certain other organs and tissues of rats in two distinct age categories (35 and 90 days, 45 and 110 days). The results of both experiments showed 1) significant decrease of blood flow in skull, lumbar vertebrae, distal epiphysis, distal metaphysis and thighbone diaphysis and tibia in older rats of both sexes (proof of previous results with 86Rb), 2) constantly significant decrease of blood flow through a skin sample taken from the ventral side of the trunk and 3) nonconstant increase of blood flow through kidneys of older rats. The causes of observed changes are not known, physiological importance to be supposed particularly as regards the circulatory changes in bones, is also not clear.

[Lipoprotein lipase activity in healthy subjects and patients with metabolic disorders]. The activity of the post-heparin-lipase as well as of the cholesterol and triglyceride levels of test persons with normal weight and obese test persons of different age groups was established: 1. In normal persons (males and females) in mature age (30-45 years) a decrease of the enzyme activity takes place which is connected with an increase of the triglyceride content. Above all in older females a repeated increase of the post-heparin-lipase activity was observed, which positively correlates with the triglyceride level. While the decreases of the enzyme activity in mature age may be connected with processes of ageing, a repeated increase of the enzyme activity in older persons is perhaps induced by the increase of the triglyceride level. 2. Obese persons show higher enzyme activities in all age groups examined. Also in obese persons in mature age a decrease of the activity of post-heparin-lipase is to be established. The ageing development of the enzyme activity of the post-heparin-lipase is similar to that of normal persons, takes place, however, at a higher level. 3. The cholesterol and triglyceride levels of the obese persons examined were on an average higher than those of normal persons of the same age group. A dependence of age of these parameters was not observed in the adipose patients.

Optimization of resilience and stress distribution in porcelain veneers for the treatment of crown-fractured incisors. The present study was conducted to define, when restoring extensive loss of dentin, the configuration of the restoration that will best reproduce the biomechanical properties of the intact original tooth in terms of resilience and stress distribution. The treatment of 1/3-crown fractures and 2/3-crown fractures was investigated using different designs of facial porcelain veneers with and without underlying composite buildup. The stress distribution and tooth compliance were assessed in a numeric model reproducing a 2-dimensional buccolingual cross section of an incisor. A 50-N facial force was applied to simulate an incisal impact situation. The facial surface tangential stresses were calculated, and the maximum displacement (horizontal direction) at the most incisal node of the enamel surface was also recorded and used to calculate the tooth compliance (i.e., displacement/load or resilience) for each test condition. Tensile stresses were generated on the facial surface of the porcelain laminates with a similar pattern for all test conditions, the cervical part of the crown being the most quiescent area. Substantial differences appeared in the incisal half of the crown, the lowest stresses being observed for extensively fractured teeth restored without composite buildup (facial peaks at approximately 33 MPa). Fractured teeth restored with minimal veneers and a "dentin-like" composite buildup showed stress patterns similar to the intact tooth (facial peaks at approximately 50 MPa). The natural tooth gave the highest tooth compliance or flexibility. All restorative designs featured increased tooth stiffness. However, the original tooth compliance was almost restored when composite was used to replace the missing dentin, with the porcelain acting only as a facial and incisal enamel substitute. When restoring crown-fractured incisors, tooth compliance and stress distribution can be modulated by the combination of composite and ceramics. Optimized configurations can be reached to reproduce the original biomechanical behavior of the intact tooth. The use of ceramic alone generates low stress concentrations, but also less compliant restored teeth.

Interlayer breathing and shear modes in few-trilayer MoS2 and WSe2. Two-dimensional (2D) layered transition metal dichalcogenides (TMDs) have recently attracted tremendous interest as potential valleytronic and nanoelectronic materials, in addition to being well-known as excellent lubricants in the bulk. The interlayer van der Waals (vdW) coupling and low-frequency phonon modes and how they evolve with the number of layers are important for both the mechanical and the electrical properties of 2D TMDs. Here we uncover the ultralow frequency interlayer breathing and shear modes in few-layer MoS2 and WSe2, prototypical layered TMDs, using both Raman spectroscopy and first principles calculations. Remarkably, the frequencies of these modes can be perfectly described using a simple linear chain model with only nearest-neighbor interactions. We show that the derived in-plane (shear) and out-of-plane (breathing) force constants from experiment remain the same from two-layer 2D crystals to the bulk materials, suggesting that the nanoscale interlayer frictional characteristics of these excellent lubricants should be independent of the number of layers.

Acid induced acetylacetonato replacement in biscyclometalated iridium(III) complexes. Biscyclometalated iridium(III) complexes with an ancillary acetylacetone ligand, Ir(L)(2)(acac), (L = 2-(benzo[b]thiophen-2-yl)pyridine (btp), 1-phenylisoquinoline (piq), 2-phenylbenzothiazole (bt), 2-phenylpyridine (ppy), acac = deprotonated acetylacetone), demonstrate spectroscopic changes in their UV-Vis absorption and luminescent emission under acidic conditions. Such changes were found to be the same as those observed when certain mercury salts exist in the systems. Because some iridium(III) complexes have sulfur-containing ligands (i.e., btp and bt), a question was then raised as for whether or not the spectroscopic changes are associated with the specific affinity of Hg(2+) to the sulfur atom. Extensive studies performed in this work unambiguously proved that the observed spectroscopic changes were solely the results of the acid induced departure of acac and the follow-up coordination of solvent acetonitrile to the iridium(III) center and that the generally anticipated Hg(2+)-S affinity and its effect on the photophysical properties of iridium(III) luminophores did not play a role.

Daphnane-type diterpene esters with cytotoxic and anti-HIV-1 activities from Daphne acutiloba Rehd. Seven previously unreported daphnane-type diterpene esters named acutilobins A-G, together with 12 known ones, were isolated from EtOAc extract of Daphne acutiloba Rehd. Their structures were elucidated based on the spectroscopic data. The cytotoxic and anti-HIV-1 activities of these daphnane-type diterpene esters were evaluated through bioassays. Fourteen of these isolates exhibited definite cytotoxic activities against the five human tumor cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480. Additionally, anti-HIV-1 activities were observed in 13 daphnane-type diterpene esters, among which acutilobins A-G exhibited significant anti-HIV-1 activities with EC₅₀ below 1.5 nM and SI over 10,000. Particularly, genkwanineVIII showed the strongest activity with EC₅₀ 0.17 nM and SI 187,010.

Comparative study of tunable room-temperature laser operation in the 900-1100-nm range: LiF:F2+ and Ti3+:sapphire. We report on a comparative evaluation of efficient room-temperature solid-state lasers based on Ti:sapphire and LiF:F(2)(+) operating in the 900-1100-nm range. LiF:F(2)(+) lasers are shown to operate with substantially lower threshold, broader tuning, and higher output pulse energies. The shorter fluorescence lifetime in LiF:F(2)(+) leads to higher peak output powers and a considerable reduction in buildup-time fluctuations. The main limitations on LiF:F(2)(+) laser operation are identified as amplified spontaneous emission (ASE) and long-term thermal degradation of the color centers. ASE restricts the tuning range, slope efficiency, and bandwidth of the LiF:F(2)(+) laser for high pump intensity, but broader tuning is achieved with longer pump pulses. The beam quality of the LiF:F(2)(+) laser is comparable with that of the Ti:sapphire laser.

Hypofractionated boost with high-dose-rate brachytherapy and open magnetic resonance imaging-guided implants for locally aggressive prostate cancer: a sequential dose-escalation pilot study. To evaluate the feasibility, tolerance, and preliminary outcome of an open MRI-guided prostate partial-volume high-dose-rate brachytherapy (HDR-BT) schedule in a group of selected patients with nonmetastatic, locally aggressive prostatic tumors. After conventional fractionated three-dimensional conformal external radiotherapy to 64-64.4 Gy, 77 patients with nonmetastatic, locally aggressive (e.g., perineural invasion and/or Gleason score 8-10) prostate cancer were treated from June 2000 to August 2004, with HDR-BT using temporary open MRI-guided (192)Ir implants, to escalate the dose in the boost region. Nineteen, 21, and 37 patients were sequentially treated with 2 fractions of 6 Gy, 7 Gy, and 8 Gy each, respectively. Neoadjuvant androgen deprivation was given to 62 patients for 6-24 months. Acute and late toxicity were scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring system. All 77 patients completed treatment as planned. Only 2 patients presented with Grade > or =3 acute urinary toxicity. The 3-year probability of Grade > or =2 late urinary and low gastrointestinal toxicity-free survival was 91.4% +/- 3.4% and 94.4% +/- 2.7%, respectively. Rates of 3-year biochemical disease-free survival (bDFS) and disease-specific survival were 87.1% +/- 4.1% and 100%, respectively. Boosting a partial volume of the prostate with hypofractionated HDR-BT for aggressive prostate cancer was feasible and showed limited long-term toxicity, which compared favorably with other dose-escalation methods in the literature. Preliminary bDFS was encouraging if one considers the negatively selected population of high-risk patients in this study.

The utility of using the bispectral index-Vista for detecting cross-clamping decline in cerebral blood flow velocity. Patients undergoing carotid endarterectomy for extracranial internal carotid artery stenosis are at risk of cerebral ischemia/hypoperfusion. Criterion recommended by European and American committees to determine whether to place a shunt consisted of a decline in transcranial Doppler ultrasonography-measured middle cerebral artery blood flow velocity (MCBFV) to < 30% to 40% of intraoperative preclamp value. To assess the discriminative power of the bispectral index (BIS)-Vista monitor for detecting a 40% decline in MCBFV with cross-clamping. In 20 patients undergoing carotid endarterectomy under remifentanil/propofol anesthesia, BIS-Vista data, MCBFV, and pulsatility index from bilaterally mounted BIS-Vista and transcranial Doppler monitors were continuously recorded. Coefficient of determination revealed good correlation (r = 0.763) between ipsilateral BIS-Vista and MCBFV after cross-clamping. BIS-Vista exhibited a high discriminative power of 0.850 (95% confidence interval, 0.455-0.966) area under the receiver-operating characteristic curve in detecting an ipsilateral 40% MCBFV decline. Two-way analysis of variance (location by time) suggests that BIS-Vista exhibited a global decline; ie, both BIS-Vistas declined when 1 carotid on either side was clamped because there was no significant interhemispheric difference (P = .112) in mean BIS-Vista values over time. Although we demonstrated good correlation and high discriminative power of the BIS-Vista monitor in depicting a MCBFV decline that could serve as indicator of decline in cerebral activity, BIS-Vista cannot be considered a reliable indicator of cerebral ischemia/hypoperfusion that could replace transcranial Doppler monitoring to determine whether a shunt is to be placed.

Lipid peroxidation and decline in antioxidant status as one of the toxicity measures of diazinon in the testis. The rapid emergence of various pesticides in the market is inevitable due to the demands from agriculture industries and domestic needs to control nuisance pests and to sustain green resources worldwide. However, long-term exposure to pesticide has led to adverse effects on male fertility. Organophosphate diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphorothiote) is an often abusively used pesticide, as it is effective and economical. This study is to determine the adverse effects of low-dose diazinon exposure on the male reproductive system. In this study, 72 Sprague-Dawley rats were segregated into 1, 2, and 8 weeks of exposure groups and further sub-grouped (n = 6) to receive 0, 10, 15, and 30 mg/kg body weight diazinon treatment. Rats were gavaged orally with diazinon and sacrificed under anaesthesia the day after the last exposure. Our results showed that consistent diazinon exposure decreased glutathione and catalase, and increased lipid peroxidation which together lead to diazinon-mediated oxidative stress. Additionally, diazinon increased serum lactate dehydrogenase and decreased serum testosterone, which may have caused sperm and histopathological anomalies. In conclusion, exposure to diazinon caused changes in lipid peroxidation and sperm, and these two effects might be causally linked.

Metabolic engineering of Saccharomyces cerevisiae to improve succinic acid production based on metabolic profiling. We performed metabolic engineering on the budding yeast Saccharomyces cerevisiae for enhanced production of succinic acid. Aerobic succinic acid production in S. cerevisiae was achieved by disrupting the SDH1 and SDH2 genes, which encode the catalytic subunits of succinic acid dehydrogenase. Increased succinic acid production was achieved by eliminating the ethanol biosynthesis pathways. Metabolic profiling analysis revealed that succinic acid accumulated intracellularly following disruption of the SDH1 and SDH2 genes, which suggests that enhancing the export of intracellular succinic acid outside of cells increases succinic acid production in S. cerevisiae. The mae1 gene encoding the Schizosaccharomyces pombe malic acid transporter was introduced into S. cerevisiae, and as a result, succinic acid production was successfully improved. Metabolic profiling analysis is useful in producing chemicals for metabolic engineering of microorganisms.

Adjuvant radiation therapy improves local control after surgical resection in patients with localized adrenocortical carcinoma. Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

Local stereo matching with adaptive shape support window based cost aggregation. Cost aggregation is the most important step in a local stereo algorithm. In this work, a novel local stereo-matching algorithm with a cost-aggregation method based on adaptive shape support window (ASSW) is proposed. First, we compute the initial cost volume, which uses both absolute intensity difference and gradient similarity to measure dissimilarity. Second, we apply an ASSW-based cost-aggregation method to get the aggregated cost within the support window. There are two main parts: at first we construct a local support skeleton anchoring each pixel with four varying arm lengths decided on color similarity; as a result, the support window integral of multiple horizontal segments spanned by pixels in the neighboring vertical is established. Then we utilize extended implementation of guided filter to aggregate cost volume within the ASSW, which has better edge-preserving smoothing property than bilateral filter independent of the filtering kernel size. In this way, the number of bad pixels located in the incorrect depth regions can be effectively reduced through finding optimal support windows with an arbitrary shape and size adaptively. Finally, the initial disparity value of each pixel is selected using winner takes all optimization and post processing symmetrically, considering both the reference and the target image, is adopted. The experimental results demonstrate that the proposed algorithm achieves outstanding matching performance compared with other existing local algorithms on the Middlebury stereo benchmark, especially in depth discontinuities and piecewise smooth regions.

Antiphospholipid syndrome in SLE. The antiphospholipid syndrome, initially described in systemic lupus erythematosus (SLE), occurs in 20-35% of patients with this condition. Its clinical manifestations may precede, be concurrent with, or follow clinical features of SLE. There are no major differences between the primary antiphospholipid syndrome and the secondary form that associates with SLE. Several studies suggest that the presence of an antiphospholipid syndrome in patients with SLE conveys a worse prognosis. To prevent recurrence of thrombotic events (particularly arterial events), oral anticoagulation with an international normalized ratio (INR) close to 3 is recommended. Treatment of recurrent fetal loss is with aspirin, or with aspirin plus heparin. Controlled studies are underway to determine optimal treatment in patients with cerebral ischaemia as well as the optimal treatment in women with recurrent pregnancy loss.

Pramipexole in psychiatry: a systematic review of the literature. To assess the risks and benefits of pramipexole in psychiatric populations. A PubMed search was performed using the keywords pramipexole and ropinirole, which identified 500 articles. All clinical studies in psychiatric populations were included in the primary review (24 articles). Studies involving other populations were then reviewed to evaluate potential risks and benefits not identified in the psychiatric studies. Effect sizes were calculated from controlled studies. Rates of intolerable side effects and manic switching were estimated by pooled analysis of controlled and uncontrolled studies. Pramipexole has a large effect size (0.6-1.1) in the treatment of both bipolar and unipolar depression with a low short-term rate of manic switching in bipolar patients (1% mania, 5% hypomania). The pooled discontinuation rate for all reasons was 9%. Pramipexole is neuroprotective and exerts beneficial effects on sleep architecture. Pramipexole is associated with 3 rare but serious side effects: sleep attacks, which have only occurred in Parkinson's disease; compulsive behaviors and pathologic gambling, which have occurred in Parkinson's disease and restless legs syndrome; and psychosis, which has occurred in both psychiatric and neurologic populations. Pramipexole is an important therapeutic option for treatment-resistant bipolar and unipolar depression; further studies are warranted to evaluate its safety in psychiatric patients.

Successful surgery of the hypothalamic region: Yes, we can!

Optimization of LC method for the quantification of doxorubicin in plasma and urine samples in view of pharmacokinetic, biomedical and drug monitoring therapy studies. A simple, rapid, reliable and sensitive method based on liquid chromatography with fluorescence detection (LC-FL) for the quantification of doxorubicin (DOX) in human plasma and urine samples was developed. The assay was carried out after the solid-phase extraction procedure (SPE) with hydrophilic-lipophilic balance (HLB) cartridges, and with daunorubicin hydrochloride (DAU) used as the internal standard. Chromatographic separation was performed on a Discovery HS C18 column in isocratic elution mode, and the detection of the analytes set at excitation and emission wavelengths of 487 and 555 nm, respectively. The developed LC-FL method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification for DOX were 0.5 and 1 ng/mL in both biological fluids, respectively. Linearity was confirmed in the range of 1-1000 ng/mL and 0.001-25 μg/mL in plasma and urine samples, respectively, with a correlation coefficient greater than 0.9994. The proposed LC-FL method is selective, precise and accurate, and has been successfully applied for drug monitoring in pediatric cancer patients treated with DOX as a component of OEPA (Oncovin (Vincristine)-Etoposide-Prednisone-Adriamycin) and IOA (Ifosfamide-Oncovin-Adriamycin) chemotherapeutic schemes. Moreover, real exposure of hospital personnel to the anthracycline drugs in plasma and urine was evaluated in clinical practice.

Intervention effects on spoken-language outcomes for children with autism: a systematic review and meta-analysis. Although spoken-language deficits are not core to an autism spectrum disorder (ASD) diagnosis, many children with ASD do present with delays in this area. Previous meta-analyses have assessed the effects of intervention on reducing autism symptomatology, but have not determined if intervention improves spoken language. This analysis examines the effects of early interventions on spoken-language in children with ASD. A systematic review of 1756 studies of children with ASD who participated in early intervention resulted in the inclusion of 26 studies in the current review. These studies included 1738 participants with ASD who were, on average, 3.3 years old (SD = 0.91). This random-effects meta-analysis of spoken-language outcomes for children with ASD who received early intervention as compared with usual treatments yielded a significant overall mean effect size of g = 0.26 (CI = 0.11 to 0.42). On average, children with ASD significantly increased their use of spoken-language following experimental early interventions. Treatments delivered simultaneously by a clinician and a parent resulted in greater gains in spoken-language than treatments delivered by a clinician or parent only. No other participant or study characteristics predicted individual-study effect sizes. Early intervention improves spoken-language outcomes for children with ASD, and the largest effects are found when both parent and clinician implement the intervention. Recommendations for practice include adding systematic parent training to interventions for spoken language to potentially improve outcomes. Future research should report standard language measures as well as child (cognitive ability and socio-economic status) and intervention characteristics to improve evidence related to the effects of interventions on spoken communication in children with ASD.

Denatured state effects and the origin of nonclassical phi values in protein folding. Analysis of the phi value is one of the most powerful tools to understand the transition state for protein folding. In principle, phi values are expected to fall in the range of 0 to 1. However, a noticeable number of phi values have been observed which are either less than 0 or greater than 1. The origin of such phi values, sometimes referred to as noncanonical or nonclassical phi values, has been controversial. Here we show that mutational effects upon denatured state energetics can lead to nonclassical phi values.

Early-stage endometrioid ovarian carcinoma: population-based outcomes in British Columbia. Specific outcomes for early-stage ovarian endometrioid carcinoma (OEC) have not been well characterized. In addition, the benefit of any type of postsurgical therapy remains unclear. Our aims were to delineate (1) potential prognostic factors and (2) the impact of adjuvant treatment on survival in such patients. Women with FIGO stages I and II OEC referred to one of the centers of the British Columbia Cancer Agency from 1984 to 2008 were included in a retrospectively abstracted computerized database. Irradiation (abdominal-pelvic) in addition to chemotherapy (3 cycles of platinum combination) was to be given for stage IA/B, grade 2/3; stage IC, any grade; and stage II, any grade, except from 1989 to 1994 when irradiation was dropped from the paradigm for all patients. Univariate analysis and a multivariate analysis, using a decision tree analysis, were carried out of disease-free survival (DFS). One hundred seventy-two patients were identified. Twelve percent were grade 3; 55%, 85%, and 89% of stages IA/B, IC, and II received postoperative adjuvant treatment. Five-year DFS was 95%, 84%, and 74% for stages IA/B and IC based upon rupture alone, IC other (cytologic positivity and/or surface involvement), and II, respectively. No benefit in DFS was accrued in stage IA/B from adjuvant treatment. Decision tree analysis defined 2 poor prognostic groups: those 55 years or older with stage IC based upon positive washings or surface involvement and any patient with stage II disease; in these, an apparent DFS benefit from irradiation was seen (relative risk (RR), 1.77; 95% confidence interval (CI), 0.74-4.24). Omission of adjuvant treatment can be considered in most early-stage OECs.

Decreased calcium and magnesium urinary excretion during prostaglandin synthesis inhibition in the rat. The effect of endogenous renal prostaglandins on calcium and magnesium reabsorption was investigated. Renal tubular handling of calcium and magnesium was studied by clearance methods in anesthetized Sprague-Dawley and Brattleboro rats, either intact or thyroparathyroidectomized (ATPTX), before and during prostaglandin synthesis inhibition by meclofenamate, indomethacin, or piroxicam infusion. These three inhibitors had similar effects on calcium and magnesium excretion: A significant decrease in absolute and fractional excretions of both cations was observed in intact Sprague-Dawley rats, and in ATPTX rats of both strains, but not in intact Brattleboro rats. These results suggest an inhibitory effect of prostaglandins on vasopressin-, glucagon-, but not PTH-mediated calcium and magnesium reabsorption. This effect is likely to occur in the thick ascending limb of Henle, which is both a target site for these polypeptidic hormones, and a segment where the bulk of calcium and magnesium is reabsorbed.

[The study of candidates' genes in psychiatric diseases. I. Schizophrenia]. The study concerning the importance of genetic factors in etiopathogenesis of schizophrenia is presented below. In molecular genetics research there are two most frequently applied strategies: searching of the whole genome in order to find new genes; and molecular analysis of a candidate gene. Candidate gene analysis consist in choosing a gene which could theoretically have a connection with a given certain disease. The presented reference review includes the results of study concerning candidate genes analysis referring to biochemical hypothesis of schizophrenia. The aim of the study is to find changes at the level of nucleotide sequence in DNA, which have a connection with the disease. It was stated in many medical centres that in case of schizophrenia the polymorphism of gene's receptor D3 and gene's receptor 5HT2A can be of etiological importance. It was also proved that the clinical effect of clozapine could be connected with polymorphism of gene's receptor 5HT2A.