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Promising anitidiabetic potential of Cuscuta reflexa leaves methanol extract in alloxan-induced diabetic rats
Ronia Mostofa1,
Rayhana Begum1,
Hongbin Wang2,
Mst. Marium Begum3,
Rubaba Karim1,
Taslima Begum1,
Nur Alam Siddiquee1,
Rebeka Sultana4,
Sonia Sultana1,
A. K. Lutful Kabir5,
Sumaiya Alam1,6 &
Tasnuva Tasnim Nova3
A Correction to this article was published on 02 September 2020
This article has been updated
Cuscuta reflexa (C. reflexa) Roxb. (Convolvulaceae) has medicinal properties for the effective management of several aliments including diabetes mellitus, inflammation, and gastric ulcer.
The present investigation focuses on the antidiabetic potential of C. reflexa leaves methanol extract in alloxan-induced diabetic rats.
The antidiabetic activity of C. reflexa leaves methanol extract (CRME) was evaluated using alloxan-induced diabetes in Wistar albino rats. The duration of the study was 45 days. Diabetic model was developed by i.p. administration of alloxan monohydrate (120 mg/kg). Ingestion of CRME (100, 200, and 400 mg/kg/day) and standard (gliclazide, 10 mg/kg/day) was done via oral route from the day of diabetes induction and continued up to 45 days. The effect of CRME was investigated by evaluating the blood glucose concentrations, HbA1C, insulin, lipid profile and liver function test. Further, the protective potentials of CRME were studied by histopathology of the pancreas, liver, and kidney tissues from experimental rats.
CRME showed significant (p < 0.01 at all doses) reduction of blood glucose level (137.1 ± 5.8, 125.9 ± 6.5, and 109.5 ± 5.4 mg/dL at the doses of 100, 200, and 400 mg/kg, respectively) as compared to the diabetic control (249.7 ± 7.3 mg/dL). Moreover, CRME at the highest dose decreased HbA1C and improved insulin levels (3.96% and 11 ng/ml, respectively) when compared with diabetic control group (7.55% and 6.5 ng/ml, respectively). CRME also revealed pronounced improvement in liver function test and lipid profile test when compared to the diabetic control. Furthermore, CRME notably reversed the histopathological changes that observed in alloxan-induced diabetes.
Our research exertion clearly demonstrates that CRME can be explored as a substantial antidiabetic and organ protective agent in the management of diabetes.
Diabetes mellitus is a common disorder of carbohydrate, fat, and protein metabolism in which the circulating glucose concentration is increased and it causes complications such as retinopathy, microangiopathy, neuropathy, and nephropathy [1, 2]. This affects the metabolism of biomolecules (carbohydrate, protein, and lipid) together with injuring β-cells of pancreas and in some cases liver and kidney [3]. Diabetes is becoming one of the major causes of the global rise in morbidity and disabled people [4]. The insulin deficiency in diabetes mellitus gives rise to hyperlipidemia and fatty liver which eventually elevates the risk of heart disease and stroke [5]. Cardiovascular disease (CVD) is a major cause of death and disability among people with diabetes [6]. A good number of oral hypoglycemic agents and insulin have been used for the treatment of diabetes mellitus. However, the adverse effects of these synthetic hypoglycemic agents sometime result in disturbances of liver, kidney, hematological failure, and even coma [5, 7, 8]. Research and development of new remedies for diabetes are, therefore, in great demand. According to the demonstration of the previous studies, natural drugs have wide spread use in the practice of traditional medicine due to their curative values for various ailments [9,10,11]. However, more than 1200 plants have been described to be experimentally or ethnopharmacologically used to treat diabetes [12]. Based on the WHO recommendations, hypoglycemic agents of plant origin are important and warrant attention [13]. As a result, many conventional drugs have been derived from prototypic molecules in medicinal plants for the treatment of diabetes. At present there is a growing demand for herbal medicines worldwide and many pharmaceutical companies in Asia and Australia are conducting extensive phytochemical research on plant material to evaluate their medicinal value [14].
Cuscuta reflexa (C. reflexa) Roxb. (Cuscutaceae) is known as giant dodder in English and "swarna lota" in Bangladesh [15, 16]. This plant species is largely distributed in India, China, Bangladesh, Eastern Asia, and Afghanistan [15]. C. reflexa contains a variety of phytoconstituents for which it has a long history of ethnomedicinal use [17, 18]. The pharmacological activities of C. reflexa involve antiprotozoal, antimicrobial, antiproliferative, anticovulsant, antihypertensive, hepatoprotective, antioxidant, anti-inflammatory, and antipyretic properties [15, 19,20,21,22,23]. The extract of C. reflexa holds a promising contribution in the folk medicine of Bangladesh to control blood sugar in patients suffering from diabetes mellitus [24, 25]. According to previous reports, C. reflexa exhibited significant hypoglycemic response in oral glucose tolerance tests in animal models [24, 26]. Therefore, the present investigation was aimed to focus on antidiabetic and organ protective effects of C. reflexa methanol extract (CRME) in Wistar albino rats to support the traditional and previous scientific claim.
C. reflexa fresh leaves were collected from Banani, Dhaka during May–June 2016. The identity of the plants was authenticated by from the National Herbarium of Bangladesh, Dhaka and the voucher specimen was deposited (no. 43780).
Gliclazide (API) was obtained from Drug International Ltd. Bangladesh. Alloxan monohydrate, chemical used to induce diabetes, was purchased from Sigma Aldrich Chemicals, Germany and all other chemicals (analytical grade) were purchased from Merck (Darmstadt, Germany).
Extraction of plant material
The collected leaves of C. reflexa were washed down with tap water appropriately and then shade dried and grinded into coarse powder. About 600 g of coarse powder of C. reflexa was soaked with 1.8 L methanol for 14 days in a conical flask. This was followed by filtration and the filtrate was subjected drying using rotary evaporator at 45 °C. Later, it was air dried for few days to evaporate solvent residue. Finally, the extract of C. reflexa was weighed (35.7 g) and stored in an air tight humidity protected borosilicate glass container.
Phytochemical screening
A number of qualitative chemical tests were performed to establish the phytochemical profile of CRME by using the standard procedures [27].
Wistar albino rats of either sex weighing between 140 to 150 g have been used for the present experiment. Animals were kept in polypropylene cages where each cage contained six rats. The environment of the animal house was maintained at 12 h light/dark cycle and 25 ± 2 °C. Before perusing the experiment, one week of acclimatization of animals was done allowing free access to feed and water. During surgery all animals were euthanized via anesthesia using isoflurane (5% in 100% oxygen). The present research protocols as well as animal care were observed according to the guidelines of Guide for the Care and Use of Laboratory Animals (NIH publication No: 85–23, revised in 1985). The experimental procedures for our study have been approved by the Biomedical Research Center, University of Dhaka, Bangladesh (Ref. no. DPT/BMRC/2016–2017/467).
Induction of diabetes
Body weight and fasting blood glucose level of animals were measured before inducing diabetes. Animals with very low or high glucose levels were discarded for experimentation. Diabetes was induced by a sole dose of 120 mg/kg of alloxan monohydrate via intraperitoneal route of each animal. The induction of diabetes was confirmed by measuring fasting serum glucose level after 3 days using accu chek glucometer. Animals with blood glucose level of > 200 to < 280 mg/dL have been selected for the present study. Diabetic rats were randomly grouped and each group consisted of six rats. Treatments for 45 days in all groups were started 3 days after alloxan monohydrate injection [28]. The groups of experimental animals and treatment pattern for the present study have been represented as follows:
Groups Treatment
Group I Healthy control rats.
Group II Alloxan-induced diabetic rats.
Group III Alloxan-induced diabetic rats administered gliclazide at the dose of 10 mg/kg, p.o. once daily.
Group IV Alloxan-induced diabetic rats administered CRME at the dose of 100 mg/kg, p.o. once daily.
Group V Alloxan-induced diabetic rats administered CRME at the dose of 200 mg/kg, p.o. once daily.
Group VI Alloxan-induced diabetic rats administered CRME at the dose of 400 mg/kg, p.o. once daily.
Fasting blood glucose was measured periodically on days 9, 18, 27, 36, and 45. After 45 days of treatment, blood samples were collected from rat by cardiac puncture under anesthesia with 5% isoflurane in presence of 100% oxygen. The serum was collected by centrifugation at 5000 rpm for 5 min.
Evaluation of HbA1C level
HbA1C level in rat blood and the percentage of HbA1c in total hemoglobin were determined by using standard procedure of Nathan et al. (1984) [29]..
Evaluation of insulin level
The concentration of insulin was examined using Rat insulin enzyme-linked immunosorbent assay Kit (RayBiotech Inc. Norcross, GA, USA).
Evaluation of lipid profile
Serum was separated and the observed lipid profile includes: triglycerides, HDL, LDL, and total cholesterol by using a previously established method [30].
Evaluation of liver function
Serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and total bilirubin levels have been estimated by using standard test procedure [31].
Histological observation and evaluation
For histological examination tissues from pancreas, liver, and kidney from rats of different groups have been fixed in freshly prepared 10% neutral buffered formalin. Tissue specimens were processed for paraffin embedding tissue sections (5 μm thick), stained with Hematoxyline and Eosin prior to histopathological evaluation. All sections were examined under light microscope. Photographs of the lesions were taken with an Olympus photo microscope for observation and documentation of histopathological changes.
All experimental data obtained were presented as mean ± S.E.M, and statistical analysis was done by finding the significance among treated and control groups using One Way Analysis of Variance (ANOVA, version 3.0), followed by Dunnett's test. P < 0.05 was considered as significant value.
The phytochemical tests of CRME revealed the existence of alkaloids, flavonoids, steroids, terpinoids, cumarin, anthraquinones, saponins, and carbohydrates.
Effect of CRME extract on body weight
According to the Table 1, body weight of untreated diabetic model was significantly decreased (22.79%). However, on day 45 the weight of the CRME treated rats were increase to 2.96%, 4.85%, and 7.81% at the doses of 100, 200, and 400 mg/kg, respectively.
Table 1 Effect of CRME on body weight variation
Effect of CRME extract on blood glucose concentration
Antidiabetic activity of CRME was assessed in alloxan- induced diabetic rats. Injection of alloxan significantly increased (p < 0.01) the blood glucose concentration in all groups when compared with the healthy control group (Table 2). However, treatment with CRME and gliclazide demonstrated noteworthy downregulation of blood glucose concentration in comparison to the diabetic control group from the 18th day onwards. The continuous treatment for 45 days leads to pronounced reduction (p <0.01 at all doses) in blood glucose concentration as compared with the diabetic control group. At the end of the study, gliclazide (10 mg/kg) treated group showed 59.09% inhibition when compared with the initial blood glucose level measured on day 0 (258.4 ± 8.4 mg/dL). On the other hand, CRME at the dose of 400 mg/kg reduced blood glucose level 55.39% as compared to the initial blood glucose level measured on day 0 (245.5 ± 9.5 mg/dL) and the inhibition is comparable to the reference drug, gliclazide.
Table 2 Effect of CRME on blood glucose level
Effects of CRME on glycosylated hemoglobin and insulin levels
Figure 1a & b portrayed the variation in glycosylated hemoglobin and insulin levels, respectively. The concentration of glycosylated hemoglobin level increased significantly in diabetic control group as compared to healthy control group (p < 0.01). On the other hand, administration of CRME in diabetic rats significantly decreases the glycosylated hemoglobin level as compared to diabetic control group (p < 0.05, p < 0.01, and p < 0.01 at the doses of 100, 200, and 400 mg/kg, respectively).
Effect of C. reflexa methanol extract (CRME) on HbA1C (a) and insulin level (b). All values were expressed as mean ± S.E.M (n = 3). (*) designates statistically significant difference from the respective group (**p < 0.01) whereas (η) indicates statistically no significant difference from the relevant group (p > 0.05) using ANOVA, followed by Dunnett's multiple comparison test. a = while compared with healthy control, b = while compared with diabetic control. Group I = Healthy control, Group II = Diabetic control, Group III = Diabetic control + 10 mg/kg of gliclazide, Group IV = Diabetic control + 100 mg/kg CRME, Group V = Diabetic control + 200 mg/kg CRME, Group VI = Diabetic control + 400 mg/kg CRME
Insulin concentration in diabetic control decreased significantly compared to healthy control group (p < 0.01). However, treatment with CRME at the higher doses in diabetic rats revealed a noteworthy upregulation of insulin level in comparison with untreated diabetic group (p < 0.05 and p < 0.01 at the doses of 200 and 400 mg/kg, respectively).
Effect of CRME on lipid profiles
Table 3 showed the lipid profiles of healthy control, diabetic control, gliclazide and CRME treated groups. In diabetic rats there was a significant increase in total cholesterol, triglycerides, LDL level (p < 0.01) and significant decrease in HDL level (p < 0.01) in serum as compared with healthy control. However, administration of CRME demonstrated noteworthy reduction in total cholesterol (p < 0.01 at all doses), triglycerides (p < 0.01 at all doses), LDL-cholesterol (p < 0.01 at all doses), and significant increase in HDL-cholesterol (p < 0.01 at all doses) on day 45 in comparison with the diabetic rats. Moreover, treatment with CRME at the highest dose (400 mg/kg) revealed decreases in TC by 43.11%, TG by 46.40%, and LDL by 55.61% whereas improved HDL by 111.8% as compared to diabetic rats.
Table 3 Effect of CRME on serum lipid profile
Effect of CRME on liver function test
In diabetic model, a significant increase (p < 0.01) in the enzymatic activities of ALT, ALP, AST, and the serum bilirubin level was found as compared with the normal levels (Table 4). On the contrary, CRME revealed a significant reduction in the activities of ALT (p < 0.05, p < 0.05, and p < 0.01 at the doses of 100, 200, and 400 mg/kg, respectively), ALP (p < 0.05, p < 0.01, and p < 0.01 at the doses of 100, 200, and 400 mg/kg, respectively), AST (p < 0.01, p < 0.01, and p < 0.01 at the doses of 100, 200, and 400 mg/kg, respectively), and serum total bilirubin level (p < 0.01, p < 0.01, and p < 0.01 at the doses of 100, 200, and 400 mg/kg, respectively) in comparison to the untreated diabetic rats. Moreover, treatment with CRME at the highest dose (400 mg/kg) revealed inhibition in ALT by 38.05%, ALP by 55.13%, AST by 68.56% and bilirubin by 58.99% as compared to diabetic rats.
Table 4 Effect of CRME on Liver function test
Effect of CRME on histopathology of pancreas, liver, and kidney
Healthy control rat exhibited usual histological architecture (Fig. 2a). However, alloxan-induced cellular damage to the pancreas, areas of cell necrosis (CN), numerous fatty tissue deposition, and inflammatory cells infiltrations in diabetic control group when compared with the healthy group (Fig. 2b). On the other hand, oral administration of CRME at the doses of 100 and 200 mg/kg, conserved cell architecture and demonstrated moderate inflammatory cell infiltration, and fatty tissue deposition, which is an improvement from what occurred in the untreated alloxan-induced diabetic rats (Fig. 2d & e). Further normal architecture was maintained in gliclazide and CRME (400 mg/kg, p.o.) treated groups (Fig. 2c & f, respectively) but the group treated with gliclazide (10 mg/kg, p.o.) showed deposition of fatty tissue.
Histopathology of pancrease. Each picture is a representative for each group as follows: a = Healthy control, b = Diabetic control, c = Diabetic control + 10 mg/kg of gliclazide, d = Diabetic control + 100 mg/kg CRME, e = Diabetic control + 200 mg/kg CRME, f = Diabetic control + 400 mg/kg CRME. Each group was evaluated at 400 x magnification, scale bar: 40 μm
Figure 3a showed the histology of the liver tissue of healthy control group. However, the histology of liver tissue from the diabetic rat revealed cell necrosis, expansion, and thickening of the walls of veins, capillaries, and progression of fibrosis (Fig. 2b). However, this was not the case for those treated with CRME at the doses of 200 and 400 mg/kg, p.o. (Fig. 3e & f, respectively). In these instances, the liver tissues were compact and healthy. On the other hand, group treated with gliclazide and CRME (100 mg/kg, p.o.) illustrated moderate cellular necrosis and infiltration of inflammatory cells in the central vein (Fig. 3c & d, respectively).
Histopathology of liver. Each picture is a representative for each group as follows: a = Healthy control, b = Diabetic control, c = Diabetic control + 10 mg/kg of gliclazide, d = Diabetic control + 100 mg/kg CRME, e = Diabetic control + 200 mg/kg CRME, f = Diabetic control + 400 mg/kg CRME. Each group was evaluated at 400 x magnification, scale bar: 40 μm
Kidney histological structure was normal in the healthy control group (Fig. 4a). Alloxan-induced diabetic group showed presence of destructed glomeruli and infiltration of inflammatory cells (Fig. 4b). Groups treated with CRME showed improvements in the tissue architecture and more visible glomeruli and moderate inflammatory cells were observed (Fig. 4d & e). However, group treated with methanol extract of C. reflexa at the dose of 400 mg/kg significantly reduced the pathological destructions (Fig. 4f). On the other hand, group treated with gliclazide (10 mg/kg, p.o.) showed moderate destructed glomeruli and infiltration of inflammatory cells (Fig. 4c).
Histopathology of kidney. Each picture is a representative for each group as follows: a = Healthy control, b = Diabetic control, c = Diabetic control + 10 mg/kg of gliclazide, d = Diabetic control + 100 mg/kg CRME, e = Diabetic control + 200 mg/kg CRME, f = Diabetic control + 400 mg/kg CRME. Each group was evaluated at 400 x magnification, scale bar: 40 μm
On phytochemical screening, CRME demonstrated the presence of alkaloids, tannins, steroids, terpinoids, cumarins, anthraquinones, saponins, and flavonoids. Many previous studies have reported that certain terpenoids, steroids, flavonoids, and phenolic compounds have defensive values against hyperglycemia with respect to their antioxidant properties [32, 33]. We hypothesized that phenolic compounds, alkaloids, flavonoids, and tannins in C. reflexa can be credited to their insulinotropic effect that enables the reduction of blood glucose levels due to their antidiabetic effect. Nevertheless, extensive phytochemical analysis must be needed to evaluate the therapeutically active compounds of C. reflexa. With antidiabetic, anti-inflammatory, and antiulcer properties.
A large diversity of animal models has been developed to better understand the pathogenesis of insulin dependent diabetes and new drugs have been introduced into the market to treat the primary cause or to prevent the catastrophe of its complications [34]. Among these models, alloxan-induced diabetes model is by far the most frequently used model which has been useful for the study of multiple aspect of the disease [35,36,37]. Alloxan is a diabetogenetic, hepatotoxic, and nephrotoxic substance which by damaging the pancreatic beta cell membrane, fragmenting DNA, and reacting with enzymes, sharply decreases insulin levels and thereby increases glucose concentrations in animals [38].
The consequences of the present study pointed out that i.p. injection of alloxan destroyed beta cells in rats in which glucose level significantly increased compared to healthy control. However, blood glucose levels reduced in all experimental groups which received CRME. Moreover, the hypoglycemic effect of CRME was comparable to the standard drug, gliclazide. Gliclazide is a sulphonylurea oral hypoglycaemic agent used in the treatment of diabetes. It improves defective insulin secretion and inhibits glucogenolysis and gluconeogenesis in the liver. Through improving insulin binding to surface receptors, they also enhance the insulin sensitivity of target cells [39]. Furthermore, in vivo evidence revealed that gliclazide cause persisted hypoglycaemia in alloxan-induced diabetic rats [40].
CRME showed a dose dependent reduction of blood glucose concentration at the doses of 100, 200, and 400 mg/kg, p.o. while the standard gliclazide (10 mg/kg, p.o.) revealed a significant antidiabetic activity in alloxan-induced diabetes in continuous treatment for 45 days. However, at the end of the study, at the higher dose the normal blood sugar level was achieved by augmented hypoglycemic activity. Such activity of this extract could be due to the particular existence of phenolic, terpenoid, and flavonoid components within the plant parts.
In diabetic rats, the level of HbA1C was increased due to the persistent hyperglycemia which results in glycation of hemoglobin. The concentration of HbA1C is related to diabetic complications and it is considered as a tool for the diagnosis and prognosis of diabetes-associated complications [41, 42]. Therefore, the measurement of glycosylated hemoglobin is supposed to be a very sensitive index for glycemic control. In the present study, the diabetic untreated rats had shown higher rates of hemoglobin glycosylation in comparison with the healthy group. However, administration of CRME significantly decreased the HbA1C level as compared with diabetic group. The ability of CRME to bring about a significant decrease in HbA1C level could be indicative of its potential ability to improve glycemic status and prevent the diabetic-associated complications in diabetic rats.
Moreover, the present results also revealed that alloxan causes a significant reduction in body weight after 45 days. These results promisingly correspond to the previously reported data [43,44,45,46]. All though the food intake is more in diabetic rats than normal healthy group, diabetic rats showed enough weight loss due to catabolism of fats and proteins. Under the circumstances of lack of insulin, the proteolysis causes decrease in protein content within the muscle tissues [44]. Notable mobilization of fat within the skeletal muscle of diabetic model caused significant weight loss as observed in our present investigation. Nonetheless, treating the diabetic model with CRME (200 and 400 mg/kg/day) or gliclazide (10 mg/kg/day) demonstrated small scale reduction of body weight and this might be either as a result of increase of insulin secretion in blood or elevated food consumption.
There is a significant role of lipids that is associated with the pathogenesis of diabetes mellitus. The rise in serum cholesterol, LDL, VLDL, triglycerides, and fall in serum HDL level is one of the significant factors for developing microvascular complication which leads to atherosclerosis and other heart diseases [47, 48] Increased level of triglycerides and LDL-cholesterol was noticed in diabetic rat model [49]. Increased cholesterol level in diabetic rats could be caused by elevated intestinal fat absorption and growing biosynthesis of cholesterol. Treatment with CRME considerably lowered total cholesterol, triglycerides, and LDL levels in serum as per the range of doses applied, while at the same time the beneficial HDL level was observed to rise significantly. Thus, the results of our present investigation clearly reveal that CRME recuperated the disparity of the lipid profile in diabetes-induced rat model as per dose dependent manner.
xIn our study, the enzymatic actions of ALT, ALP, and AST as well as serum bilirubin level were upregulated in diabetic group. Evidence demonstrated that the changes in the levels of ALT, ALP, AST, and bilirubin in diabetic rats are associated with the changes in the rate of metabolic reactions catalyzed by these enzymes. The elevation of transaminases activities occur in scarcity of insulin, due to availability of amino acids, in the blood of diabetes mellitus patients [50]. Such circumstances lead to increased gluconeogenesis and ketogenesis. The recovery of AST and ALT to their normal levels was found in the groups of experimental animals treated with CRME. Serum levels of these enzymes function as biomarker of liver activity as a result of restoration of normal level of these enzymes specify normal functioning of liver. Elevated enzymatic activities of ALP have always been reported in alloxan-induced diabetic model. The enhanced activity of ALP in diabetic model is probably due to the occurrence of cell damage by altered cell membrane morphology. Serum ALP, bilirubin, and total protein levels are associated with the activities of liver cell. The rise in serum ALP level occurs due to growing rate of synthesis under inflation of biliary pressure [51].
Alloxan caused a signifcant elevation in enzyme levels such as ALT, ALP, AST, and bilirubin levels when compared to control. There was a significant restoration of these enzyme levels on the administration of CRME in a dose-dependent manner. However, there was non-significant reduction of ALP and total bilirubin concentrations in group treated with gliclazide in comparison to the diabetic control group.
The data from histopathological examination of pancreas of diabetic model exhibited islet of Langerhans with infiltration of inflammatory cell and distorted pancreas. Oral ingestion of CRME recovered the altered architecture of the pancreas to normal conformation. Moreover, the damaged structure and numerous inflammatory cells have been observed in the liver tissues of diabetic rats. These constructive changes in the hepatic cells were restored in diabetic rats treated with CRME in a dose dependent manner. Furthermore, the damaged glomeruli and numerous inflammatory cells have been noticed in the renal tissues of diabetic model. These injured tissues regained their normal conformation when treated with CRME. As per the results of microscopic examinations, the severity of pancreatic, hepatic, and renal lesions in diabetic animals extensively declined and considerably recovered by the treatment of CRME at medium to higher doses.
Monitoring medicinal plants for biological activity is believed to be one of the key subjects to demonstrate the pharmacological action of the drug. Manifestation of drug's safety and efficacy with respect to its purpose of use is necessary. For this reason a constructive and progressive order of preclinical (animal) and clinical (human) studies must be performed.
New therapeutic innovations that are dedicated to prevent DM and DM complications are of interest. Our study distinguished the antidiabetic and tissue protective potentials of methanol extract of C. reflexa. Thus, the multifactorial activity of C. reflexa would be a new alternative therapeutic agent for the treatment of DM as well as its complications. This study indicated methanol extract of C. reflexa have potential to decrease blood glucose, HBA1c, and insulin concentrations. In addition, the present treatment improved complications associated with experimental diabetes. Hence, the present study supports the traditional usefulness of this plant in the treatment of diabetes mellitus. In conclusion, the plant C. reflexa could be further investigated for antidiabetic bioactive principles.
Authors are agreed to share raw data and materials upon request.
An amendment to this paper has been published and can be accessed via the original article.
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Thapa BR, Walia A. Liver function tests and their interpretation. Indian J Pediatr. 2007;74:663–71.
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Department of Pharmacy, Primeasia University, Dhaka, Bangladesh.
It is a self-funded research contributed by all authors equally.
Department of Pharmacy, Primeasia University, Dhaka, 1213, Bangladesh
Ronia Mostofa, Rayhana Begum, Rubaba Karim, Taslima Begum, Nur Alam Siddiquee, Sonia Sultana & Sumaiya Alam
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, California Northstate University, California, USA
Hongbin Wang
Department of Pharmacy, East West University, Aftabnagar, Dhaka, 1212, Bangladesh
Mst. Marium Begum & Tasnuva Tasnim Nova
School of Molecular Medical Sciences, University of Nottingham, Nottingham, UK
Rebeka Sultana
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh
A. K. Lutful Kabir
Department of Pharmaceutical Sciences, North South University, Dhaka, 1229, Bangladesh
Sumaiya Alam
Ronia Mostofa
Rayhana Begum
Mst. Marium Begum
Rubaba Karim
Taslima Begum
Nur Alam Siddiquee
Sonia Sultana
Tasnuva Tasnim Nova
Dr. Rayhan Begum conceptualized, designed and supervised the whole research work and drafting manuscript. Ronia Mostafa, Sumiya Alam, Nur Alam Siddiquee and Sonia Sultana conducted all procedures within laboratories, Rubaba Karim, Taslima Begum, Mst. Marium Begum,and Rayhana Begum compiled data, analyzed those and wrote manuscript. Finally Hongbin Wang, Rebeka Sultana, A K Lutful Kabir and Rayhana Begum critically reviewed manuscript for final approval and instructed for submission.
Correspondence to Rayhana Begum.
The experimental procedures for our study have been approved by the Biomedical Research Center, University of Dhaka, Bangladesh (Ref. no. DPT/BMRC/2016–2017/467).
We assure that this manuscript has not been submitted and published somewhere else. All named authors have approved the final version of manuscript and agreed with the submission.
Mostofa, R., Begum, R., Wang, H. et al. Promising anitidiabetic potential of Cuscuta reflexa leaves methanol extract in alloxan-induced diabetic rats. Clin Phytosci 6, 26 (2020). https://doi.org/10.1186/s40816-020-00169-w
DOI: https://doi.org/10.1186/s40816-020-00169-w
Alloxan monohydrate


text:
Touch Of Evil (1958)
"You should lay off those candy bars... You're a mess honey".
So says brothel madam Tana (Marlene Dietrich), assessing the portly, dishevelled form of police captain Hank Quinlan (Orson Welles) in the nightmarish border country noir Touch Of Evil, based on the Whit Masterson novel Badge Of Evil (1956). The lady has a point. In his drinking days, Hank was a regular at Tana's, but tonight she hardly recognises him. Propped up against the doorway to her parlour, unshaven, perspiring in the evening heat, Henry Mancini's haunting pianola playing in a distant room, Hank is certainly in bad shape. "I wish it was your chili I was getting fat on", he wheezes, wistfully, squinting at her through glinting porcine eyes. Improbably cast as a Mexican under a raven black wig, the cheroot-smoking Dietrich was rarely more ravishing, while Orson never looked worse. The cherubic prince of Citizen Kane (1941) is long dead.
Quinlan is ostensibly visiting Tana to make inquiries about the car bomb that killed an American couple in the film's bravura opening tracking shot, the incident that has led newlywed Mexican narcotics cop Miguel "Mike" Vargas (Charlton Heston), a witness, to dog Quinlan's every step as he carries out his investigation into the attack. One suspects Hank's revived interest in Tana is only partly professional: he's always been a slippery customer, as Vargas is about to find out. Even Quinlan's long-time partner, Pete Menzies (Joseph Calleia), doesn't know the half of it. He and Hank have been solving cases for 30 years, frequently after uncovering a last minute clue that all-too-conveniently supports one of Quinlan's legendary "hunches", with Pete refusing to countenance the possibility that his friend could be systematically planting evidence to ensure they get their man, even if it isn't necessarily the right man.
In a wry cameo as a detective, Joseph Cotten warns us that we won't like Quinlan. The man himself duly arrives, oinking orders and puffing on a plump stogie, shot from below to underline both his enormous bulk and sneering air of authority. The Rabelaisian captain, a "reformed" alcoholic and unreconstructed racist, turns out to preside over this moonlit Tex-Mex nowhere town like Hades in the underworld, stabbing his walking stick into its dirt precincts and lurching passed the saloons, storefronts and oil derricks in pursuit of his own perverted conception of justice. His bloated physique speaks of the current corruption of his soul, but that limp is a reminder of his war service in 1917, a souvenir from the last time he acted in a mood of genuine public-spiritedness. Look where that got him. Early on, Hank belittles the D.A. (another Mercury Theatre veteran, Ray Collins) for arriving at the crime scene in an expensive "monkey suit", introducing us to the idea that this man does entirely as he pleases and answers to no-one, least of all his decadent superiors or anything so fundamentally absurd as the rule of law. Despite having resided in this corner of the world for decades, Hank has refused to learn Spanish and immediately treats the interloping "foreigner" Vargas with suspicion and contempt. He later slaps suspect Manolo Sanchez (Victor Millan) before framing the boy for the bombing with a shoebox full of dynamite from his own turkey ranch. Hank's failure to counter or conceal his prejudice will ultimately prove his downfall.
For the truth about Hank Quinlan is this: the Fat Man has never gotten over the murder of his wife, strangled by a "half-breed" some years before, a tragedy that has fuelled his pathological hatred of Mexicans ever since. Hank's violent murder of Uncle Joe Grandi (Akim Tamiroff) by the same method, choking him to death in a drunken frenzy while Vargas's doped wife Susan (Janet Leigh) lies oblivious nearby, is his latest attempt to turn back the clock and enact his revenge on the phantom hoodlum who did away with Mrs Quinlan. "I followed around after him... ate my heart out trying to catch him but I never did. That was the last killer that ever got out of my hands." This scene is a bad trip, but its implications are even more horrific: Quinlan has been quietly waging a private race war in honour of his late lamented love ever since, of which this is only the latest skirmish. The irony that Hank himself should be caught out by his leaving a tell-tale piece of evidence at the scene - his own cane, the discovery of which prompts Pete to finally accept the truth and aid Vargas in his entrapment ploy - is a blackly comic one indeed.
In the end, as appalling as his actions have been, the big waddling baby who dies creekside from Pete's redeeming bullet after Vargas's plan has gone awry might just deserve reappraisal as a sympathetic monster, a good man embittered and eaten up by a cancerous horror from the past that he was helpless to prevent and has been unable to avenge. He has abused his power and ruined the lives of many innocent parties, but he wasn't always this way. Evil begets evil. "A great detective", pronounces Al Schwartz (Mort Mills), looking down from the bridge at his slumped cadaver. "A lousy cop", counters Tana, before famously concluding: "He was some kind of a man... What does it matter what you say about people? Adios."
This post is part of the Great Villain Blogathon hosted by Ruth of Silver Screenings, Karen of Shadows & Satin, and Kristina of Speakeasy — see all the movie baddies at any of these three blogs
Labels: Akim Tamiroff, Charlton Heston, Dennis Weaver, Henry Mancini, Janet Leigh, Joseph Calleia, Joseph Cotten, Marlene Dietrich, Noir, Orson Welles, Ray Collins, Russell Metty, Walter Murch
Karen 21 April 2014 at 22:17
Great stuff, Joe -- you certainly have a way with words. I'm not even that crazy about Touch of Evil, and you made me want to see it again. Loved this.
Joseph S 21 April 2014 at 22:44
Thanks Karen, so glad. I absolutely love this film and can never get the Mancini theme out of my head after watching it. Some weird casting to be sure!
Clayton 22 April 2014 at 01:33
I'm generally an anti-noir guy, but I agree with Karen; you make me want to see it again, just to be slathered with all that poisonous EVIL. I'm doing this blogathon, too (my first), and it's cool to glorify the bad guys! Thanks for this one!
Silver Screenings 22 April 2014 at 03:40
I've never seen this, and I'm not sure why. However, I loved reading your review and the way it's written. I must check out "Touch of Evil" ASAP.
Thanks for participating in the blogathon with a look at Orson Welles as Quinlan. It would not be a true Villain-Fest without him!
Brilliant review! Orson Wells makes a great villain indeed. I have to watch it again now.
Leah Williams 22 April 2014 at 12:42
Great writing. I haven't seen this one in years, but want to revisit it now. What an amazing presence Orwell had as Quinlan in this film. I found myself impatient watching Leigh and Heston, waiting for him to get back on the screen. Sympathetic? Not really. But compelling, absolutely.
Thanks guys, so pleased you all enjoyed. Do check out the film again, such a treat I think. My first crack at a blogathon too Clayton - a great idea.
Leah - never thought of referring to Orson as Or-Well before but it works beautifully! But you're right: perhaps I did go a bit far here in asking for your sympathy for Ol' Hank. He's as big a bastard as they come.
Kristina Dijan 22 April 2014 at 23:43
nice work! yes Welles has such an amazing presence here that's so true, and he's so off putting, (slathered is the perfect term, ha) which of course is just right for the role and creates this kind of "can't look away from the wreck" effect. Blechh, in short. great performance, great pick by you and thanks for joining in!
Quinlan's pretty grotesque all right. The man himself blames it on "hooch and candy" but he doesn't look like he'd know what a gym was if you suggested it.
No probs Kirstina, great fun. We must do it again some time.
Grand Old Movies 23 April 2014 at 20:39
I agree with your point that the vile Quinlan is still, oddly and awkwardly, sympathetic--there's something lost in the depths of Welles' eyes when you watch him (though you might make another argument that all the characters in the film are unsympathetic, even the central couple, who seem to have picked a peculiar location for a honeymoon spot). Welles makes his look at evil complex and layered (the final irony is that the boy he framed was guilty after all); the film taking place in a border town signals that how perilous is the boundary line to crossing over to evil. You really summed up this movie so beautifully -- great post!
Thanks so much GOM, you're too kind! Welles definitely pours a lot of himself into Hank - he seems a much more rounded (no pun intended) bad guy than Orson's fugitive Nazi in The Stranger, say, whose matinee idol good looks make him somehow implausible. Quinlan carries the weight of many bitter years hanging around his midriff. You're so right to pick up on the sadness in his hangdog eyes.
Good point about the symbolic significance of the border town too - a ludicrous spot for a honeymoon indeed, I'd never thought of that! Poor old Janet Leigh, she never did have much luck in motels...
The File On Thelma Jordon (1950

redpajama_set_name: RedPajamaCommonCrawl


Apia, SAMOA — Having returned from the Conference of the Parties (COP24) in Poland this week on the convention framework on climate change, Prime Minister Tuilaepa Dr Sa'ilele Malielegaoi said the road of negotiations had some disappointments.
One of the main objectives of COP24 was to finalise the rules around the Paris Agreement: how to monitor and regulate the countries and their contributions to mitigating climate change.
Unfortunately, four nations stalled progress on completing that rulebook, with discussions over the recent report by the International Panel on Climate Change, which warned of the dangers of global warming beyond 1.5 degrees.
"The United States was willing to note the report and express appreciation to the scientists who developed it, but not to welcome it, as that would denote endorsement of the report," the U.S State Department said, underscoring that the country had not endorsed the report.
Along with the United States, Russia, Saudi Arabia and Kuwait wanted the report to be 'noted', rather than 'welcomed', despite calls by Small Island nations in particularly that the change was unacceptable.
"This is us, as the [United Nations Framework Convention on Climate Change (UNFCCC)], being in a position to welcome a report that we requested, that we invited [scientists] to prepare.
Prime Minister Tuilaepa said while their actions were disappointing, he wasn't surprised.
"That's normal for these countries, it's understandable that these countries continue to delay as much as possible because they get their money from the sale of oil and the use of coal.
"But the damage that is done now is attributable to coal and the emissions from the burning of fossil fuels," he said.
Tuilaepa emphasised the importance of encouraging large, developed nations like those that stalled the rulebook to "fall in line" with the rest of the parties.


TCU's football stadium is getting a make-over. As a self-proclaimed "facility nerd," I have been anxiously awaiting the final result. David Ubben, Big 12 Blogger for ESPN.com, ended my anxiety today when he tweeted some photos of the nearly-complete Amon G. Carter stadium at TCU.
This entry was posted in Facility, TCU by Travis Normand. Bookmark the permalink.


text:
Is the Koch Brothers' Curriculum Coming to Your Child's School?
(Photo: Doon Harder)
The Koch brothers are trying to rewrite history.
Caitlin MacNeal over at TPM is reporting that the North Carolina Department of Public Instruction has "encouraged" state high school teachers to start teaching a curriculum that was drafted by a Koch brothers-funded group.
See more news and opinion from Thom Hartmann at Truthout here.
The Koch brothers-funded conservative takeover of public education in North Carolina started back in 2011, when that state's legislature passed a law requiring public schools to offer a history course based on the United States' "Founding Principles."
That law was based on "model legislation" written by everyone's favorite corporate lobbying juggernaut, ALEC.
After North Carolina passed that law, the state hired the Bill of Rights Institute to draft the curriculum for the classes.
The Bill of Rights Institute has received numerous grants and donations from Charles Koch himself, and from a variety of Koch-funded groups and organizations.
That's why the curriculum being taught to North Carolina students is filled with the Koch brothers' libertarian beliefs and ideologies, and a whole lot of misinformation on US history.
A great deal of the curriculum focuses on the libertarian love affair with "limited government."
As MacNeal writes, "Throughout the curriculum, students are asked to tie lessons back to the concept of limited government, which the state's 2011 bill calls for."
While that may be the Koch brothers' spin on the the founders' intentions, that's simply not the truth and not historically accurate.
In his Report on Manufactures from December 5th,1791, Alexander Hamilton explained why the founders included the General Welfare clause in the Constitution.
He explained that the founders included it in the Constitution so that the government could do anything that the people thought was appropriate and beneficial.
Hamilton wrote that, "No objection ought to arise to this construction from a supposition that it would imply a power to do whatever else should appear to Congress conducive to the General Welfare."
The Constitution limits the powers of our government, but in very specific ways.
For example, the government can't take your life, liberty or property without proper cause.
But there's nothing in the Constitution that says the government can't introduce programs like Medicare, Obamacare,or Social Security, despite what the Koch brothers might try to tell our schoolchildren.
Another hunk of the Koch brothers-funded curriculum talks about "individual responsibility" – another pillar of a libertarian paradise.
According to MacNeal, this section of the curriculum asks students to, "challenge preconceived notions about what freedom means, and understand the way individual freedom is inextricably tied to personal responsibility."
But that's just Koch brothers code for "I was born rich and white, and got everything I wanted in life handed to me on a silver platter so screw you."
While the Koch brothers won't admit it, human beings are social animals. We always have been and always will be.
We have always depended on each other for help, guidance and really, survival.
The libertarian notion of the self-made man is largely a myth, and if it is possible, it takes a whole lot of luck – including the luck to be born in the right time, place, and family – that many people simply don't have.
Finally, the Koch brothers-funded curriculum focuses a lot on the libertarian talking point that our government has too much power.
According to MacNeal, "The curriculum constantly questions how much power and authority the federal government should have and subtly asserts that the federal government has gained too much power since 1789."
And a portion of the curriculum says that, "It seems that fewer people are making more decisions about the nature of our fundamental rights."
Basically, in this section of the curriculum, the Koch brothers are complaining about the rules of the game that protect We the People from the harmful effects of capitalism.
As you and I both know, industrialists have screwed us over repeatedly throughout history, but that's a little fact that the Koch brothers don't want our schoolchildren to know. Nothing in here about the Pullman Porters, for example.
Regulations are in place to protect us from being screwed over even more.
The curriculum being taught in North Carolina schools is not history.
It's not civics.
It's about whitewashing reality, and turning Gilded Age oligarchs like the Koch brothers into national heroes.
The ALEC-inspired, Koch brothers-funded North Carolina curriculum represents the Ayn Randification of our education system and our society.
It's bad enough that the Koch brothers have a stranglehold on our democracy and political system, courtesy of our Supreme Court. We don't need them in our classrooms too.


Betty is a reliably liberal, reliably hard-working, not-terribly-flashy Congressional Representative. Some profile described her as "pleasant, partisan, and liberal," which pretty well sums it up. Oh, she also has an F from the NRA, which is A-OK with me.
I just don't have all that much to say about Betty. She's solidly the sort of politician I approve of, but gives me very little to talk about.
Greg Ryan's bio says he runs a plumbing business and adds, "he is not a political elitist," which seems like it should be a swipe at Betty but is a very odd one (she's a former high school teacher).
Under Issues, Greg talks about listening to people express worries about the future ("Will hard work pay off for our children?") and says, "Greg Ryan believes that the answer to these questions will be 'yes.' But only if the government gets out of the way. Personal freedom, coupled with responsibility, has always been the recognized hallmark of the 'all-American' family." If you think that a return to the tax and regulatory structure of the Gilded Age will benefit the majority of American families, I have a beautifully decorated bridge to sell you with marble floors and pillars on the front and servants' quarters around the back.
I see no reason to vote for this guy.
Susan does not have a website. She does have a brief profile on the Legal Marijuana Now party's website. (Scroll down for a bit, you'll find her.) Her statement on her goals, in its entirety: "It has always been my goal to help the underprivileged members of society to reach a higher level of achievement and independence, for the greater good. I think the most sustainable way to do this is by removing the roadblocks to higher education, and to help people help themselves to improve their own life circumstances." So … I guess that's sort of a platform? Weirdly, she doesn't mention marijuana anywhere in her profile.
The Legal Marijuana Party itself notes on their website that they are "a progression" of the Grassroots Party, but the Grassroots Party still exists, which makes me wonder who exactly got into a fight with whom.
Anyway, I really expect more substance from my potential congressional people than she's got on offer, and she has zero chance of winning. I think the theory is that by persuading people to vote for their candidates the LMN party will show that it's not just a tiny fringe that support marijuana legalization but I don't think this is working well for them.
tl;dr vote for Betty McCollum.
This entry was posted in Minnesota Politics, St. Paul Politics, Uncategorized and tagged 4th congressional district, Election 2016, Minnesota politics by naomikritzer. Bookmark the permalink.
I found this video as well via Google. I also found her website, http://sindtforcongress.com/. It's a little late now, but dig a little deeper before pointing fingers, Namoi. You critizcize someone for not being serious enough, when it's you who either aren't serious enough or are too biased to do the job you set out to do.
Perhaps grassroots candidates with only a tiny fraction of the money, organization, and time of the two major political corporations aren't as good at getting their information to the top of the Google ranking. Maybe they use some different media than your single form of research will find. Maybe the DFL and GOP even work to keep these parties down.
P.S. Not "maybe," not "perhaps;" those were used sarcastically for emphasis.
Hey, what do you know! She's put up a website. It was either not up, or not findable with Google, in September, when I wrote this. It is still not linked from the Legal Marijuana Now CD4 Facebook page (which I read and linked to back in September) nor from the legalcannabisnow.org page (which I read and linked to back in September).
You seem to have some misconceptions about my work. This isn't a job; it's a hobby. No one pays me to do this. I am under absolutely no obligation to dig for information beyond what I can find with Google, though sometimes I do.
Google is not in a conspiracy against your candidate. Now that the web page is actually up, her web page is the sixth hit for "susan sindt." But even if it WERE, when you file for office, the forms include a line for your website address. If you include that information, it goes on the candidate list page that comes up at the MN Secretary of State's office when someone looks up their ballot! Which is where I start, and where thousands of Minnesotans start.
If you want to fight the man, you can start by using the tools that are freely made available to every single candidate.
P.S. Maybe next time you could volunteer to set up websites for LMN candidates before they all have to file. The power lies within you!


text:
On Edward Said
Edward Said died last fall, and his loss has been felt throughout the Arab world. When I was in Palestine, in both Gaza City and Ramallah, there were posters all over the place commemorating Said's life. It's hard to think of an intellectual whose death would be greeted in such a popular, populist way in the United States.
Said was a literature professor at Columbia University and known especially for his work, Orientalism, as well as for his advocacy of the Palestinian cause. In this last collection of interviews, Culture and Resistance: Conversations with Edward Said, David Barsamian, who directs Alternative Radio, asks Said questions about the Palestinian struggle in the last few years marked by the second intifada, the raised stakes after 9.11, and more.
For someone unfamiliar to Said's work, this would be a good introduction to his passion, range of concern, and insight on these non-literary matters (for more of the latter, see his recent collections of essays, Reflections on Exile).
Said reminds his listeners in the original programs and now his readers that the Israel-Palestine "conflict" is really an asymmetrical one: "The Palestinians throw stones, the Israelis have missiles, jets, helicopter gunships, tanks, and rockets. The Palestinians are resisting military occupation." [34] "This is not a battle between two states. It's a battle in which a state with a basically colonial army is attacking a colonized stateless population using all forms of collective punishment." [71-72]
Moreover, as the word terrorism has become a kind of political mantra, as if the evil of bin Laden and Hussein is all that really matters, Said critically examines the use of this term. For example, "[Terrorism] is fabricated to keep the population afraid, insecure, and to justify what the United States wishes to do globally." [89] I can testify to this as I gave a talk to some high school students who get terrified when they learn of a higher level of "alert" announced by the Bush administration. Also, we can see how eerily accurate Said was when he said a couple weeks after 9.11, that "'Terrorism' has become synonymous now with anti-Americanism, which in turn has become synonymous with being critical of the United States, which in turn has become synonymous with being unpatriotic." [111]
Another major theme of Said's work is the importance of telling the story of the Palestinians, which may sounds simple enough. But the story has been greeted by denial, by insult, by lies. The simple act of speaking about 1948 – and the dispossession of the Palestinians as a result of the founding of the state of Israel – is essential to understanding the conflict today and why refugees weren't enamored of the Geneva Accord, which basically nullifies their right of return. In the United States, especially, we have been bombarded with the Israeli Jewish narrative, tied up with narratives about the Holocaust. We have not heard the Palestinian side or story with anywhere near the same intensity and frequency. With the passing of Said, the Palestinian cause has lost one of its greatest advocates and articulators.
In this collection, Said is relentlessly critical of Israeli checkpoints, home demolitions, closures, settlements, and assassination policy. But his scorn is not for Israel alone, but also for the US and the intellectuals who support, sustain, and justify this oppression of an entire people. For all that, though, Said voices a positive, constructive and compelling alternative vision to the status quo: "I do think, however, that the settlements have to be dismantled and the populations have to face each other as not only neighbors but in fact in coexistence, in one basically homogeneous state, which we call historic Palestine, whether you call it Israel or a Palestinian state. The economies and the histories are so intertwined that I still think that in the end a binational state is the only long-term solution." [63]
Referring to the U.S. ideological system, Noam Chomsky once observed, "You're taught to be a passive, obedient follower. Unless you can break out of those habits, you're likely to be a victim of propaganda. But it's not that hard to break out." One way to begin to break such habits is to engage with the profoundly critical and humane writing of Edward Said.
Yibneh, Gaza, Palestine; November 2003
Intellectuals, Israel, Middle East, Palestine, Reviews, The War-making State
9.11, Alternative Radio, David Barsamian, Edward Said, George W. Bush, intifada, Noam Chomsky, Propaganda, Terrorism
East Timorese Testimony


Dreyfus filled out their management team with two senior marketing and sales executives to execute their distribution strategy.
Ursula C. Carty was plucked from PaineWebber to serve as the new executive vice president and director of distribution marketing, and Dreyfus raided OppenheimerFunds for Laura Mulhall, the new executive vice president and head of the independent financial planning sales division.
Carty will oversee Dreyfus' distribution marketing efforts through all sales channels and she will report to Stephen R. Burke, president of Dreyfus' marketing and advertising division.
Carty was at PaineWebber for 16 years, most recently as senior vice president of product management and development for the firm's asset management division. Before that, she was senior vice president and head of proprietary fund marketing. Carty received her bachelor's degree from Fordham University.
Mulhall is expected to drive Dreyfus' sales through the newly-formed independent financial planner sales division. She will report to Michael G. Millard, president of Dreyfus Investments.
At OppenheimerFunds, Mulhall was senior vice president and director of the financial advisor division, responsible for sales to financial planners, insurance companies, broker-dealers and small regional brokerage firms. She received her bachelor's degree in economics from Hunter College.


text:
Q: Let user change the source of a button I want to let users choose their path for the source themselves. But I can't figure it out how I do this as I'm quite new in javascript.
<iframe id="test" src="testsrc"></iframe>
<button onclick="testfunction()">Click me</button>

This is what I got in my html file. I made a new folder just for testing stuff so it's easier.
function testfunction() {
    document.getElementById('test').src = "testsrc2";
};

Thats my js file, this works but it just changes the source to testsrc2, is there are solution so that user can choose their exe as an example from a program and then it will set the path from the exe as src?

redpajama_set_name: RedPajamaStackExchange


Thank you for your interest in cooperation with FutureNet. Opening an own café branded by FutureNet is a huge deal. We are glad that you are interested in working with us.
We support all the members efforts. Opening your own FutureNet Cafe as well! Each establishment with your involvement will gain popularity and profitability.
You can count on our support, while opening the establishment and building company's image.
Now as you know we opened the first FutureNet Café' in Polend.
When we do a franchise agreement and Book of standards .Then, we will come back to you with some details regarding our cooperation.
GREAT NEWS TOWARDS THE FUTUROCOIN PROMOTION..
Sponsor 5 or more Frontline Royals and win one of 5 travel vouchers, one of 2 Rolex watches or BMW 318i!!!
But NOW some questions are answered. Existing members who upgrade to royals from other positions WILL COUNT in your favor.. PLUS for every 5 ADDITIONAL front-line royals you have.. you get an extra ticket in the raffles!! MORE CHANCES TO WIN!!
We have huge news and will share with you all on today's live MY 24 hangout 12/13/2016 11am est. if you miss it don't worry it will be the pinned post in group and also on the website as well!!!
PS. I see all the negative posts and comments about Faheem everyone we 100% positive he is not the hacker. if anything the guy helped build MY24… lets all be positive and not start rumour… think for the Future.
Question: I have a question regarding the adpacks and its deactivation. Again and again, I find in my advertising packages, the RV 30 euro and visitors under 100. Some generated only 30 visitors.
When will these adpacks deactivated?
Answer: These packs will be deactivated, if you see the 10.000 views and 100 clicks.
Question: So is the end of the pack after the clicks? And not to share from the generated? I thought I'll buy for 25 and 30 they run out!?
Answer: No. No. Each Pack falls out if the 30 euro advertising reimbursement has been achieved. Here's an example.
If the clicks are not yet achieved, it is still active until the 10.000 views and 100 clicks are achieved.
Your Pack the reached 10.000 views and 100 clicks within a week as long as it remains active until it advertising the 30 euro refund has been achieved. There's more views and clicks can guess doesn't matter, it is the minimum requirements for a pack. I hope i could help you.
If you look at something with the dashboard and click once everywhere, you can understand it a little better. Learn through doing.
Bit of a read, little click. See if all the packs inactive, active, disabled, or have expired. For Every Pack you purchase we confirm with yes the terms and conditions. Read once, or even a couple of times already and you know why you're a yes a type.
I hope i could help you with that.
Have a nice day and a successful rest of the week.
Question: What does your dashboard? Under your advertising?
Answer: What is your sponsor on 2 levels actually pays well, if you have such questions here in the group need to discuss? For a halfway decent sponsor are these questions a, b, c of adpackpro!
Keep your eyes open for the sponsor choice!
MPA is doing incredibly well. This is reflected in our Alexa ranking. From the hangouts Uday has been very clear with regards to MPA's financials. The MPA admin are being responsive and ensuring we are legally compliant in any jurisdiction. think about this logically guys. We are powering up the Alexa ranking, this correlates with doing well financially. This measure is taken so that if any government asks questions of MPA than we can stand and say we have memberships fee. This additional income stream would strengthen our business from a legal compliance stand point. Guys I can tell you that I have read all the legal docs that have been released about the 'other big company'. The addition of a membership fee really does strengthen us as a legal entity world wide. Sure we are compliant in Singapore … Although the admin are taking action to ensure we are compliant world wide.
Welcome to all those latinos who have entered the matrix in futurenet. Here we all work as a team!. If you have any questions I will be here to help you.
Hello Adpacker, here is the link for our live chat, Wednesday, 10.08. At 19 pm. Please note that it is not a meeting next week. All the questions should have use the appointment tomorrow. Until then, many greetings.


text:
Q: Google Canary - cannot uninstall I'm using google canary and somehow, the canary window is appearing all black:

When I tried unistall the google canary, nothing happens. The icon appears like if the google canary is openned:

Anyone have any ideia what is happening?
Note: I'm using windows 10 Pro version 1703 OS Build 15063.726

A: Try to launch it with compatibility mode set to Windows 7. It worked for me.
Source: https://www.ghacks.net/2017/12/12/how-to-fix-google-chrome-black-screen-issues/


text:
package javax.swing.text.html;

import javax.swing.text.*;
import java.awt.*;

/**
 * This is the view associated with the html tag NOFRAMES.
 * This view has been written to ignore the contents of the
 * NOFRAMES tag.  The contents of the tag will only be visible
 * when the JTextComponent the view is contained in is editable.
 *
 * @author  Sunita Mani
 */
class NoFramesView extends BlockView {

    /**
     * Creates a new view that represents an
     * html box.  This can be used for a number
     * of elements.  By default this view is not
     * visible.
     *
     * @param elem the element to create a view for
     * @param axis either View.X_AXIS or View.Y_AXIS
     */
    public NoFramesView(Element elem, int axis) {
        super(elem, axis);
        visible = false;
    }

    /**
     * If this view is not visible, then it returns.
     * Otherwise it invokes the superclass.
     *
     * @param g the rendering surface to use
     * @param allocation the allocated region to render into
     * @see #isVisible
     * @see text.ParagraphView#paint
     */
    public void paint(Graphics g, Shape allocation) {
        Container host = getContainer();
        if (host != null &&
            visible != ((JTextComponent)host).isEditable()) {
            visible = ((JTextComponent)host).isEditable();
        }

        if (!isVisible()) {
            return;
        }
        super.paint(g, allocation);
    }

    /**
     * Determines if the JTextComponent that the view
     * is contained in is editable. If so, then this
     * view and all its child views are visible.
     * Once this has been determined, the superclass
     * is invoked to continue processing.
     *
     * @param p the parent View.
     * @see BlockView#setParent
     */
    public void setParent(View p) {
        if (p != null) {
            Container host = p.getContainer();
            if (host != null) {
                visible = ((JTextComponent)host).isEditable();
            }
        }
        super.setParent(p);
    }

    /**
     * Returns a true/false value that represents
     * whether the view is visible or not.
     */
    public boolean isVisible() {
        return visible;
    }

    /**
     * Do nothing if the view is not visible, otherwise
     * invoke the superclass to perform layout.
     */
    protected void layout(int width, int height) {
        if (!isVisible()) {
            return;
        }
        super.layout(width, height);
    }

    /**
     * Determines the preferred span for this view.  Returns
     * 0 if the view is not visible, otherwise it calls the
     * superclass method to get the preferred span.
     * axis.
     *
     * @param axis may be either View.X_AXIS or View.Y_AXIS
     * @return   the span the view would like to be rendered into;
     *           typically the view is told to render into the span
     *           that is returned, although there is no guarantee;
     *           the parent may choose to resize or break the view
     * @see text.ParagraphView#getPreferredSpan
     */
    public float getPreferredSpan(int axis) {
        if (!visible) {
            return 0;
        }
        return super.getPreferredSpan(axis);
    }

    /**
     * Determines the minimum span for this view along an
     * axis.  Returns 0 if the view is not visible, otherwise
     * it calls the superclass method to get the minimum span.
     *
     * @param axis may be either View.X_AXIS or
     *          View.Y_AXIS
     * @return  the minimum span the view can be rendered into
     * @see text.ParagraphView#getMinimumSpan
     */
    public float getMinimumSpan(int axis) {
        if (!visible) {
            return 0;
        }
        return super.getMinimumSpan(axis);
    }

    /**
     * Determines the maximum span for this view along an
     * axis.  Returns 0 if the view is not visible, otherwise
     * it calls the superclass method ot get the maximum span.
     *
     * @param axis may be either View.X_AXIS or
     *  View.Y_AXIS
     * @return  the maximum span the view can be rendered into
     * @see text.ParagraphView#getMaximumSpan
     */
    public float getMaximumSpan(int axis) {
        if (!visible) {
            return 0;
        }
        return super.getMaximumSpan(axis);
    }

    boolean visible;
}

redpajama_set_name: RedPajamaGithub


Fishing off Herne Bay's Neptune's Arm.
This coming Saturday a small Greenpeace fishing vessel will be putting in to Ramsgate. They are coming to highlight a really important issue that I also want to draw attention to in Herne Bay and Margate too – supporting local sustainable fishing.
Greenpeace are using the boat to draw attention to their campaign for fair fishing quotas that benefit local, sustainable fishing communities, rather than huge, industrial trawlers—which the government continues to support, despite European changes to the Common Fisheries Policy (CFP).
Greenpeace argues that the government is contravening European fishing law under the CFP, which was reformed in 2013 and now requires EU Member States to adopt criteria that prioritise quota for businesses that fish in an environmentally sustainable way and most contribute to national coastal economic and social wellbeing.
Local, low impact fishermen should receive more quota because they fish more sustainably, have lower CO2 emissions and provide greater employment and job creation opportunities than the industrial scale fleet.
You can still (on a good day!) catch bass, thornback rays, red and grey mullet, dogfish, smoothounds, mackerel, flounders, conger, herring, cod, dab, gurnard, plaice, monkfish, plaice, sole and whiting of the east Kent coast.
But illegal overfishing and poor quota allocation destroy the marine environment and undermine the local fishing community. Signing Greenpeace's petition calling for the government to put local sustainable fishermen first is a good start to putting things right. To find out more drop by Ramsgate on Saturday!
Huge trawlers: Deeply destructive; often working illegally.


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text:
Gaetz associate said to be cooperating with prosecutors in investigation of the congressman
By Matt Zapotosky
April 13, 2021 at 9:36 p.m. EDT
Rep. Matt Gaetz (R-Fla.), left, and former Seminole County, Fla., tax collector Joel Greenberg. (Photos by Jabin Botsford/The Washington Post and Joe Burbank/Orlando Sentinel/AP)
A Florida politician at the center of an investigation into Rep. Matt Gaetz has provided federal law enforcement with information about the congressman's activities as he seeks a plea deal to resolve his own legal woes, offering prosecutors potentially important testimony as they build a case against a higher-profile target, according to a person familiar with the matter.
Joel Greenberg, a former tax collector for Seminole County, Fla., has since last year been outlining to prosecutors how he and Gaetz would pay women for sex using cash or gifts in potential violation of federal trafficking laws, this person said on the condition of anonymity to discuss an ongoing criminal probe.
Greenberg faces a 33-count indictment that includes a charge of sex trafficking of a child, and his attorney and a prosecutor in the case said at a court hearing last week that he was likely to plead guilty. If he decides to testify against Gaetz (R-Fla.), Greenberg could help prosecutors explain various financial transactions that have drawn attention to the congressman's conduct — though Greenberg also would be likely to face significant questions about his credibility.
Rep. Matt Gaetz (R-Fla.) first got involved in politics a decade ago. It didn't take him long to find stardom in the Republican Party. (Video: Drea Cornejo/The Washington Post, Photo: Jabin Botsford/The Washington Post)
Gaetz, whose fierce allegiance to former president Donald Trump and frequent cable news appearances won praise from fellow conservatives, has not been accused of a crime and vehemently denies wrongdoing.
Gaetz associate Joel Greenberg likely to strike plea deal with prosecutors in sex trafficking case
Greenberg's plea deal has not yet been finalized. A Justice Department spokesman declined to comment Tuesday.
Greenberg attorney Fritz Scheller has repeatedly declined to answer questions about his client's cooperation, first reported by the New York Times, though he hinted ominously after last week's court hearing that Greenberg was "uniquely situated" to provide information about the congressman.
"I'm sure Matt Gaetz is not feeling very comfortable today," Scheller said at the time.
The Justice Department has been exploring whether Greenberg procured women for Gaetz, who represents a mostly conservative district in the Florida Panhandle, and whether the two men sometimes shared sexual partners, including the 17-year-old girl at issue in Greenberg's case. Gaetz would boast to people in Florida politics that he met women through Greenberg, and he also showed them videos on his phone of naked or topless women on multiple occasions, including at parties with Greenberg, people familiar with the matter have said.
Like others, they spoke on the condition of anonymity to discuss the investigation.
Gaetz is said to have boasted of his 'access to women' provided by friend charged in sex-trafficking case
It was in the course of investigating Greenberg on other suspected crimes that federal authorities discovered evidence of possible sex trafficking by Gaetz, people familiar with the matter have said. They then launched a separate investigation into the congressman.
Gaetz has denied that as an adult he had sex with a 17-year-old, or that he paid women for sex. Harlan Hill, a representative for Gaetz, repeated that denial in a statement Tuesday and pointed to a report in Politico about an anonymous friend of Greenberg's allegedly complaining to him last year that Greenberg was trying to draw him into the matter.
"Congressman Gaetz has never paid for sex. Based on reporting from Politico, it seems Mr. Greenberg has been trying to ensnare innocent people in his troubles for quite some time," Hill said, referring to news of Greenberg's cooperation with law enforcement as a "non-story."
Even if Greenberg does agree to cooperate, he could be a problematic witness, and Gaetz could challenge his credibility.
Greenberg was initially charged with fabricating allegations and evidence against a political opponent in the race for tax collector, and prosecutors have since accused him, in addition to the alleged sex crime, of wire fraud and submitting false claims to get an Economic Injury Disaster Loan while he was out of jail on bond.
Tired of reading? Stories that explain the news through charts, maps, photography and videos.
See the evolution of lies in George Santos's campaign biography
Photos: Remembering Tyre Nichols
'This is our exchange fund': Inside Ukraine's POW detention center


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text:
Q: CalcPay method not working properly my CalcPay method is not figuring overtime properly, can anyone see any obvious problems that would cause this?
    private const double FED_TAX = 0.2;
    private const int FULL_TIME = 40;
    private const double OVER_TIME = 1.5;
    private const double STATE_TAX = 0.075;

    public double CalcPay()
    {

        double pay = hoursWorked * hourlyWage;
        double overTimeHors = hoursWorked - FULL_TIME;

        if (overTimeHours > 0)
        {
            pay = overTimeHors * (hourlyWage * OVER_TIME);
        }
        double tax1 = pay * FED_TAX;
        double tax2 = pay * STATE_TAX;
        return ((pay - tax1) - tax2);
    }

A: You need to add the overtime to the main pay, not replace it:
if (overTime > 0)
{
    pay += overTime * (hourlyWage * OVER_TIME);
     // ^ increment
}

A: The problem is that you have redefined the variable pay which means your calculation is based on the overtime rate...