Sex-specific genetic parameter estimates of body weight in Mazandaran indigenous chickens.

Body weight is an economically important trait in poultry that shows sexual dimorphism (SD). In the present study, variation in SD in Mazandaran native chickens was investigated in terms of the (Co) variance components and genetic parameters of body weight between males and females. Studied traits were body weights at hatch (BW1), 8 weeks (BW8) and 12 weeks of age (BW12). Also, for weight at sexual maturity (WSM) covariance components were only estimated in females. Cross-sex direct and maternal correlations were also estimated for studied traits except for WSM. For this purpose, a deep 21-generation pedigree and body weight data (57,576 BW1, 72,925 BW8, 62,727 BW12 and, 42,496 WSM) were used. Evaluation of SD of body weight was performed using six bivariate animal models with and without considering the genetic and permanent maternal environmental effects under the restricted maximum likelihood method in WOMBAT software. Model with direct additive genetic effects and maternal genetic effects without covariance between them was identified as the best model for BW1 and BW8. The Model including direct additive genetic effects and permanent maternal environmental effects was the best model for BW12 and WSM. Direct heritability (h2 ) estimates for BW1, BW8 and, BW12 were, respectively, 0.05 ± 0.013, 0.17 ± 0.02 and, 0.25 ± 0.03 in males and, 0.05 ± 0.012, 0.15 ± 0.01 and 0.21 ± 0.01 in females. Also, the direct heritability of WSM based on univariate analysis in females was estimated to be 0.40 ± 0.01. Maternal heritability ( h m 2 $$ {h}_m^2 $$ ) varied from 0.39 ± 0.01 (BW1) to 0.04 ± 0.009 (BW8) in males, and 0.36 ± 0.10 (BW1) to 0.04 ± 0.006 (BW8) in females. The correlation between direct genetic effects between males and females for BW1 was not significantly different from one. The direct genetic correlation between the two sexes for BW8 and BW12 was significantly different from 1 concluding that these traits are dimorphic in terms of direct genetic effects and therefore independent selection in both sexes is possible.

The Effect of Warmed Serum on Shivering and Recovery Period of Patients Under General and Spinal Anesthesia: A Randomized Clinical Trial.

PURPOSE: Postoperative hypothermia followed by shivering is a common phenomenon in patients undergoing surgery under anesthesia, and should be prevented and treated in postoperative patient care units. This study was conducted to investigate the effect of warmed serum injection on postoperative shivering and recovery period of patients operated under general and spinal anesthesia. DESIGN: In this clinical trial, patients to be operated on under general and spinal anesthesia were randomly assigned into two groups of test and control. In the test group, patients received warmed intravenous fluids and blood products. All patients were monitored to record vital signs, incidences of hypothermia and shivering, and recovery period. METHODS: The collected data were analyzed with repeated measures analysis of variance to detect significant differences between groups and significant changes within groups over time. FINDINGS: The incidence of nausea, vomiting, and shivering in the intervention and control groups was (4.7%, 42%), (2.8%, 16.8%), and (6.6%, 43%), respectively. Patients in the intervention group had higher body temperature than the control group (<0.001). Also, patients under spinal anesthesia had higher body temperature than patients under general anesthesia (<0.001). Blood pressure reduction was also significantly higher in the control group than in the intervention group. The patients who received warm intravenous serum, and especially those who had received spinal anesthesia spent less time in the recovery room (<0.001). CONCLUSIONS: The use of warmed intravenous serum increased the patients' core temperature, reduced their postoperative shivering, and shortened their recovery period. Considering the potential risks associated with hypothermia, using such methods for hypothermia prevention can be highly effective in preventing shivering and prolongation of the recovery period and other potential complications. Anesthesia specialists and technicians are therefore encouraged to use this method as a preventive measure.

Comparing Jaffe and Enzymatic Methods for Creatinine Measurement at Various Icterus Levels and Their Impacts on Liver Transplant Allocation.

The Model for End-Stage Liver Disease (MELD) scoring system is used to prioritize liver transplantations and assess disease severity. This includes the international normalized ratio (INR), creatinine, and total bilirubin. Since there are several ways to measure creatinine, MELD scores can produce inconsistent results. The objectives of this study were to define a valid cut-off for bilirubin interference in creatinine measurement and to assess the effects of various icteric levels on creatinine measurement and liver transplant allocation. A total of 400 serum samples were categorized into four groups based on their icteric indices and total bilirubin levels, including non-, mild, moderate, and severe icteric samples. Both chemical Jaffe and enzymatic techniques were used to determine the creatinine levels in all four groups, and the findings were compared. In parallel, serum samples from 83 liver transplant candidate patients were divided into three groups depending on their bilirubin levels and then similarly evaluated and interpreted. The MELD scores were then computed for each group and compared. In icteric samples, the enzymatic method produced higher results for the creatinine concentrations than the Jaffe method did, and the mean creatinine difference rose from 0.08 in nonicteric group to 1.95 in groups with severe icterus. In addition, the enzymatic approach yielded higher findings for creatinine and subsequently for MELD scores in patients who were liver transplant candidates. When the bilirubin concentration was above the 4 mg/dL threshold, there were differences between the approaches for both the creatinine and the MELD score (p values: 0.0001 and 0.027, respectively). The chemical Jaffe is a readily available and considerably cost-effective method for measuring creatinine. However, it is influenced by a variety of known and unknown interfering substances, and it should be applied cautiously when working with icteric samples. Alternate techniques such as the enzymatic method should be considered when the bilirubin level exceeds 4 mg/dL. Though this cut-off is instrument and kit-dependent, each laboratory is advised to have its cut-off for bilirubin interference.

Adolescent swimming exercise following maternal valproic acid treatment improves cognition and reduces stress-related symptoms in offspring mice: Role of sex and brain cytokines.

Valproic acid (VPA) treatment during pregnancy is a risk factor for developing autism spectrum disorder, cognitive deficits, and stress-related disorders in children. No effective therapeutic strategies are currently approved to treat or manage core symptoms of autism. Active lifestyles and physical activity are closely associated with health and quality of life during childhood and adulthood. This study aimed to evaluate whether swimming exercise during adolescence can prevent the development of cognitive dysfunction and stress-related disorders in prenatally VPA-exposed mice offspring. Pregnant mice received VPA, afterwards, offspring were subjected to swimming exercise. We assessed neurobehavioral performances and inflammatory cytokines (interleukin-(IL)6, tumor-necrosis-factor-(TNF)α, interferon-(IFN)γ, and IL-17A) in the hippocampus and prefrontal cortex of offspring. Prenatal VPA treatment increased anxiety-and anhedonia-like behavior and decreased social behavior in male and female offspring. Prenatal VPA exposure also increased behavioral despair and reduced working and recognition memory in male offspring. Although prenatal VPA increased hippocampal IL-6 and IFN-γ, and prefrontal IFN-γ and IL-17 in males, it only increased hippocampal TNF-α and IFN-γ in female offspring. Adolescent exercise made VPA-treated male and female offspring resistant to anxiety-and anhedonia-like behavior in adulthood, whereas it only made VPA-exposed male offspring resistant to behavioral despair, social and cognitive deficits in adulthood. Exercise reduced hippocampal IL-6, TNF-α, IFN-γ, and IL-17, and prefrontal IFN-γ and IL-17 in VPA-treated male offspring, whereas it reduced hippocampal TNF-α and IFN-γ in VPA-treated female offspring. This study suggests that adolescent exercise may prevent the development of stress-related symptoms, cognitive deficits, and neuroinflammation in prenatally VPA-exposed offspring mice.

Assessing the impact of COVID-19 pandemic on the performance indicators of safety management using the analytic hierarchy process (AHP) in an electricity industry.

Introduction: The importance of evaluating the performance of different management systems in industries necessitates examining the performance of the Health, Safety, and Environment (HSE) management system along with other management systems. Particularly during the COVID-19 pandemic, there is a greater need than ever to assess the impact of the COVID-19 spread on the performance of the HSE management system compared to before this pandemic. This research aims to investigate safety performance indicators (SPIs) on the performance of the HSE management system and the impact of the COVID-19 spread on these indicators. Methods: This cross-sectional, descriptive-analytical study was conducted to evaluate the influence of the COVID-19 outbreak on the safety performance to revise the industry safety index in an electricity distribution company using the multi-criteria decision-making method before and after the disease epidemic in three stages. In the first part, the safety indicators were identified according to the comprehensive safety indicators available in the industries and experts' opinions. In the second part, safety indicators were ranked, weighted, and prioritized using the Analytic Hierarchy Process (AHP). In the third part, these indicators were calculated and compared in the periods before and after the outbreak of COVID-19. Results: Two main criteria, namely the "effectiveness criterion" and the "applicability/calculation criterion", were identified for the evaluation and pairwise comparisons of performance indicators. Among these two criteria, the applicability/calculation criterion had higher priority and importance for the evaluation of indicators. Pairwise comparisons of the indicators indicated that the "accident frequency rate" and "safe T-factor" indicators (with weights of 0.238 and 0.023 respectively) had the highest and lowest priorities, respectively, for the assessment of organizational safety performance among the SPIs. Conclusion: Based on the calculations of the indicators and their analyses before and after the outbreak of COVID-19, the current status of the safety performance of the HSE unit was not significantly affected by this pandemic. However, the investigations carried out while collecting the data needed to calculate the indicators and evaluate the performance of this unit demonstrated that some indicators were not considered sufficiently in the studied electricity industry. Since conducting regular performance evaluations greatly impacts the achievement of continuous improvement, more attention should be paid to compiled indicators, which should be periodically assessed in the organization to achieve continuous improvement.

Evaluation of scale development and its regeneration potency in the desert killifish under laboratory conditions.

Scale development and its regeneration potency were evaluated in a desert killifish Aphaniops hormuzensis (family Aphaniidae) in laboratory conditions by using light and scanning electron microscopy. Scale development in A. hormuzensis took 156 days at room temperature. Four specific regions of scale formation were detected. The first scale development began 13 days post-hatching (dph) (total length [TL] = 8.5 mm) at the caudal peduncle region and is extended anteriorly 26 dph (TL = 13.6 mm) at the area below the dorsal fin. Scales began forming independently in the head region at 33 dph (TL = 21.7 mm), and in the abdominal region, began at 41 dph (TL = 25.8 mm). Additional points of scale origin were detected on the sides of the operculum or behind and below the eyes. Scale regeneration in the caudal peduncle started 6 days after removal (dar). In 16 dar, the microstructural features appeared and the growth circles, a wide and oblong focus (focus length = 0.6 ± 0.05 µm), and lepidonts were also formed. In 36 dar, the scale shape was gradually changed from circular to a polygon, and radii were distinguishable in the anterior field. The pattern of scale formation could be useful in enhancing the understanding of systematics and phylogeny, functional morphology, and habitat use. It could also be useful in helping to define the Larval/juvenile transition period.

Semi-Synthesis of New 1,2,3-Triazole Derivatives of 9-Bromonoscapine and their Anticancer Activities.

Novel 1,2,3-triazole-tethered 9-bromonoscapine derivatives were synthesized by the propargylation of N-nornoscapine followed by Huisgen's 1,3-dipolar cycloaddition of the terminal alkynes with different azides. Cytotoxicity of the products was studied by MTT assay against the MCF-7 breast cancer cell line. Most of the compounds revealed a better cytotoxicity than N-nornoscapine and 9-bromonornoscapine as the parent compounds. Among the synthesized compounds, those with a hydroxylated aliphatic side chain (5p, 5q, and 5r) showed the highest activities (IC50s: 47.2, 37.9, and 32.3 µg/mL, respectively). Molecular docking studies showed that these compounds also had the highest docking scores and effective interactions with binding sites equal to -8.074, -7.425 and -7.820 kcal/mol, respectively.

SPAAC Pulse-Chase: A Novel Click Chemistry-Based Method to Determine the Half-Life of Cellular Proteins.

Assessing the stability and degradation of proteins is central to the study of cellular biological processes. Here, we describe a novel pulse-chase method to determine the half-life of cellular proteins that overcomes the limitations of other commonly used approaches. This method takes advantage of pulse-labeling of nascent proteins in living cells with the bioorthogonal amino acid L-azidohomoalanine (AHA) that is compatible with click chemistry-based modifications. We validate this method in both mammalian and yeast cells by assessing both over-expressed and endogenous proteins using various fluorescent and chemiluminescent click chemistry-compatible probes. Importantly, while cellular stress responses are induced to a limited extent following live-cell AHA pulse-labeling, we also show that this response does not result in changes in cell viability and growth. Moreover, this method is not compromised by the cytotoxicity evident in other commonly used protein half-life measurement methods and it does not require the use of radioactive amino acids. This new method thus presents a versatile, customizable, and valuable addition to the toolbox available to cell biologists to determine the stability of cellular proteins.

Termination of Repeat Testing in Chemical Laboratories Based on Practice Guidelines: Examining the Effect of Rule-Based Repeat Testing in a Transplantation Center.

BACKGROUND: Although the automation of instruments has reduced the variability of results and errors of analysis, in some laboratories, repeating a test to confirm its accuracy is still performed for critical and noncritical results. However, the importance of repeat testing is not well established yet, and there are no clear criteria for repeating a test. MATERIALS AND METHODS: In this cross-sectional study, all repeated tests for 26 biochemical analytes (i.e., albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), bilirubin total (BT), bilirubin direct (BD), blood urea nitrogen (BUN), calcium, chloride (Cl), cholesterol total (CholT), creatine kinase (CK), creatinine (Cr), glucose, gamma-glutamyl transferase (GGT), high-density lipoprotein-cholesterol (HDL-c), iron, lactate dehydrogenase (LDH), LDL-c, lipase, magnesium (Mg), phosphorus (Ph), protein total (ProtT), total iron binding capacity (TIBC), triglyceride (TG), and uric acid) were assessed in both critical and noncritical ranges over two consecutive months (routine subjective test repeats in the first month and rule-based repeats in the second month). To determine the usefulness of test repeats, differences between the initial and verified results were compared with the allowable bias, and repeat testing was considered necessary if it exceeded the allowable bias range. All causes of repeat testing, including linearity flags, delta checks, clinically significant values, and critical values, were also documented. All data, including the cause of repeats, initial and verified results, time, and costs in the two consecutive months, were transferred to Microsoft Excel for analysis. For comparison of data between the months, Student's t-test was used. RESULTS: A total of 7714 repeat tests were performed over two consecutive months. Although a significant decline (38%) was found in repeated tests in the second month (P < 0.001), there was no significant change in the percentage of unnecessary repeats (77% in the first month and 74% in the second month). In both consecutive months, AST and ALT were the most commonly repeated tests, and delta check was the most common cause of repeat testing. Mg, ALP, AST, and lipase showed the highest rates of necessary repeats, respectively (the least stable tests), while albumin, LDL, and CholT tests showed the highest rates of unnecessary repeats, respectively (the most stable tests). The total cost and delay in turnaround time (TAT) due to repeated testing decreased by 32% and 36%, respectively. CONCLUSION: Although repeat testing has been shown to be unnecessary in most cases, having a strict policy for repeat testing appears to be more valuable than avoiding it completely. Each laboratory is advised to establish its own protocol for repeat testing based on its own practice.

Scanning electron microscopy and morphological analysis reveal size-dependent changes in the scale surface ornamentation of tooth-carp Aphaniops hormuzensis (Teleostei; Aphaniidae).

Aphanius hormuzensis is an endemic tooth-carp found in the Hormuzgan drainage in S-Iran. This study aimed to investigate the size-dependent alternations of scale surface ornamentation in this species by conducting scanning electron microscopy and morphological analysis. A total of 50 wild fish individuals were captured from Shur River, and were classified into five size classes based on the standard length; SC-I (SL = 10-20 mm), SC-II (SL = 21-30 mm), SC-III (SL = 41-50 mm), SC-IV (SL = 51-60 mm), and SC-V (SL = 61-70 mm), and their scales were removed from below the dorsal fin (key scale) and caudal peduncle regions. The results revealed a clear trend of scale structural development in A. hormuzensis. The scale of small-sized (TL < 30 mm) and large-sized fishes (TL > 30 mm) differed, respectively, in the following characters; the overall shape (often circular vs. polygonal), relative focus size (large, FL/SL = 440-610 µm vs. intermediate and small, FL/SL = 100-330 µm), types of radii (only primary vs. three types), relative radii length (short, RL/SL = 100-180 µm vs. long, RL/SL = 320-450 µm), lepidont (absent or undeveloped vs. present and developed), and the relative lepidont length (short, LL/SL = 0.83-0.90 µm vs. intermediate and long, LL/SL = 1.2-2.2 µm). These character alternations could explain certain developmental stages in this species. The size-dependent changes in the surface micro-ornamentations as shown in this study suggest that these characters should be used cautiously for taxonomic studies of the aphaniid fishes.

The Association Between Demographic Characteristics and Attempting of Pregnancy with Postpartum Depression and Anxiety Among Women Referring to Community Health Centres: A Cross Sectional Study.

BACKGROUND: Postpartum depression (PPD) and anxiety are considered as a risk factor for mother and infant health. Therefore, the present study aims to explore the association between demographic characteristics and pregnancies with PPD and anxiety. METHODS: A cross-sectional study was conducted on 400 Iranian women referring to health centres of the Zarand City four weeks to six months from the date of their childbirth, in the first half of 2018. RESULT: The results showed that employed women with pregnancies who were categorised as depression and anxiety were more likely to have low gestational age, food insecurity, several deliveries, cesarean delivery and unintended pregnancy as well as they were not satisfied with their infant's gender. Also, women with several deliveries had lower risk for PPD before and after adjustment for confounders (odds ratio [OR] = 0.92, 95% confidence interval [CI]: 0.88-0.97, P < 0.001) and had lower risk for postpartum anxiety only after adjustment for confounders (OR = 0.82, 95% CI: 0.75-0.89, P < 0.001). CONCLUSION: Eventually, demographic characteristics and attempting of pregnancy were independently associated with PPD and postpartum anxiety in women. There need to be more social and governmental support of employed women after delivery to decrease their occupational stresses to deal with PPD and anxiety in the studied population.

A Single Nucleotide Polymorphism in GAS5 lncRNA is Associated with Risk of Bladder Cancer in Iranian Population.

Down-regulation of the long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) has a pathogenic role in bladder cancer. Moreover, genomic variants of this lncRNA have been associated with risk of diverse cancers. In the present project, we genotyped two putative functional SNPs (rs2067079 and rs6790) in 122 bladder cancer patients and 150 age- and sex-matched healthy subjects. The rs2067079 was associated risk of bladder cancer in recessive inheritance model (TT vs.CC + CT: OR (95% Confidence interval (CI)) = 2.67 (1.27-5.62), adjusted P value = 0.02). The T G haplotype (rs2067079 and rs6790) increased the risk of bladder cancer in the assessed population (OR (95% CI) = 1.73 (1.18-2.56), adjusted P value = 0.02). Consequently, in the current project we introduced a novel risk locus for bladder cancer in Iranian population.

Glibenclamide mitigates cognitive impairment and hippocampal neuroinflammation in rats with type 2 diabetes and sporadic Alzheimer-like disease.

A growing body of evidence suggests that type 2 diabetes (T2D) is a risk factor for cognitive impairment and dementia. Both preclinical and clinical studies have provided evidence that brain insulin resistance is associated with cognitive decline in patients with T2D and sporadic Alzheimer disease (AD). Accordingly, antidiabetic medications have been suggested as potential drugs for the treatment of cognitive impairments in patients with sporadic AD. This study set out to determine whether glibenclamide (GBC), an antidiabetic agent, can ameliorate cognitive impairments in rats with T2D and sporadic AD. Both animal models were treated with GBC for 23 consecutive days. To assess working and spatial memory, animals were subjected to the Y-maze and Morris water-maze tests. We measured glucose and insulin levels in the blood, and inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the hippocampus of animals. Our findings indicated that T2D and sporadic AD impaired memory and elevated TNF-α and IL-6 in the hippocampus. We found increased glucose and insulin levels in the blood of T2D-induced rats but not of sporadic AD rats. In contrast, GBC treatment improved memory impairment, increased insulin, and reduced glucose and hippocampal inflammation in rats with T2D and sporadic AD. This study suggests that GBC could be considered as a potential treatment for cognitive deficits in patients with T2D and sporadic AD. Taken together, this study highlights the need for further studies in humans to test whether GBC treatment is associated with cognitive improvement in sporadic AD patients.

Serum Trace Elements in Children with End-Stage Renal Disease.

OBJECTIVES: Trace elements, which have a crucial role in metabolism and enzymatic pathways, are not routinely monitored in the blood of pediatric patients with chronic kidney disease. The present study was carried out to determine the serum levels of copper (Cu), zinc (Zn), selenium (Se), and lead (Pb) in children with ESRD who were currently receiving conservative management or were on long-term hemodialysis or continuous ambulatory peritoneal dialysis. METHODS: This study involved 200 children who met the inclusion criteria. The children were divided into 4 groups: a hemodialysis group, a peritoneal dialysis group, a group of children with ESRD treated with conservative management, and a control group. Serum levels of Zn, Cu, Se, and Pb were evaluated using an atomic absorption spectrophotometer and compared between the groups. RESULTS: There was no significant difference in the serum concentration of Cu among the 4 study groups. There was also no significant difference in the serum concentrations of Zn, Se, and Pb between healthy children and children with CKD treated with conservative management or between the hemodialysis and peritoneal dialysis groups. The levels of Zn and Se were significantly lower in the hemodialysis and peritoneal dialysis groups than in the healthy children or in children with CKD treated with conservative management. The level of Pb in the blood was significantly lower in healthy children and children with CKD treated with conservative management than in the hemodialysis or peritoneal dialysis groups. CONCLUSIONS: The levels of trace elements were substantially different between the dialysis groups and healthy children and children with CKD treated with conservative management. These results highlighted the role of osmosis during dialysis, as dialysate impurities can cause a disturbance in the levels of trace elements and the role of the kidney, even with minimum residual function, in the homeostasis of trace elements.

The frequency of clinical manifestations of hypophosphatemic rickets in patients with therapeutic strategies.

The aim of this study was to evaluate the frequency of clinical manifestations of various types of rickets in patients could be effective in therapeutic strategies. A total of eleven child patients (7 females and 4 males) were included in the present study. The patients were admitted to the hospital with hypophosphatemic rickets. In our study, the age at the time of diagnosis ranged from 1 to15 years. Mean age of first presentations at final diagnosis was determined to be 5.5 an 2 years, respectively. Five patients out of 11 patients had showed significant history of vitamin D3 resistance. Family history of similar skeletal problems was reported to be positive in six patients. Furthermore, there were seven relative marriages in parents. Mean value of Gomez index has been revealed as 64%. Mean serum phosphate level was detected as 2.9 mg/dL, that this level in males (2.2 mg/dL) was significantly less than females (3.4 mg/dL) (P=0.5). Mean serum alkaline phosphatase activity was reached 913 IU/L. Alkaline phosphatase activity in women (1075 IU/L) was significantly lower than that of men (750 IU/L), (P=0.5). Definitive treatment with oral phosphate and vitamin D3 can prevent complications of the disease and the side effects of unconventional treatments.

Inhibitory Effect of Viola odorata Extract on Tumor Growth and Metastasis in 4T1 Breast Cancer Model.

Viola odorata as a medical herb is used in liver disorders and relieving cancer pain. In the present study, the cytotoxic, antioxidant, and anti-metastatic properties of Viola odorata hydro-alcoholic extract (VOE) were investigated in 4T1 breast cancer model. After treatment of 4T1 breast cancer cells with VOE, cell viability was measured by MTT assay. The implanted mice were treated with different concentration of VOE (50, 150 and 250 mg/kg) for 21 days. Levels of lactate dehydrogenase (LDH), γ -glutamyl transferase (GGT), alkaline phosphatase (ALP), carcinoembryonic antigen (CEA) and cancer antigen 15-3(CA15-3) in serum, and also catalase (CAT) and superoxide dismutase (SOD) activities in tumor tissue were measured. Metastatic rate was investigated in liver, spleen and lung tissues. VOE decreased cell viability of 4T1 cells, significantly. VOE significantly inhibited the cell proliferation, but not vasculature in the tumors that revealed by immunohistochemical analysis for Ki-67 and CD31 expression, respectively. VOE increased the Bax/Bcl-2 ratio in VOE250-treated group compared to control group. Serum analysis showed that treatment with 250 mg/kg of VOE significantly reduced LDH (not ALP and GGT) levels compared to controls. No linear correlation was found between the values of CEA and CA15-3 with tumor size. The rate of CAT activity was increased in VOE250-treated rats whereas, CAT and SOD activities were reduced in VOE50 group. VOE250 significantly decreased the metastatic rate in liver and lung compared to the other doses of VOE. Consequently, Viola odorata has cytotoxic effects on 4T1 cells and affects antioxidant activity and metastasis in breast cancer.

ATP-sensitive potassium-channel inhibitor glibenclamide attenuates HPA axis hyperactivity, depression- and anxiety-related symptoms in a rat model of Alzheimer's disease.

Affective disorders including depression and anxiety are among the most prevalent behavioral abnormalities in patients with Alzheimer's disease (AD), which affect the quality of life and progression of the disease. Dysregulation of the hypothalamic-pituitary-adrenal-(HPA) axis has been reported in affective disorders and AD. Recent studies revealed that current antidepressant drugs are not completely effective for treating anxiety- and depression-related disorders in people with dementia. ATP-sensitive-potassium-(KATP) channels are well-known to be involved in AD pathophysiology, HPA axis function and the pathogenesis of depression and anxiety-related behaviors. Thus, targeting of KATP channel may be a potential therapeutic strategy in AD. Hence, we investigated the effects of intracerebroventricular injection of Aß25-35 alone or in combination with glibenclamide, KATP channel inhibitor on depression- and anxiety-related behaviors as well as HPA axis response to stress in rats. To do this, non-Aß25-35- and Aß25-35-treated rats were orally treated with glibenclamide, then the behavioral consequences were assessed using sucrose preference, forced swim, light-dark box and plus maze tests. Stress-induced corticosterone levels following forced swim and plus maze tests were also evaluated as indicative of abnormal HPA-axis-function. Aß25-35 induced HPA axis hyperreactivity and increased depression- and anxiety-related symptoms in rats. Our results showed that blockade of KATP channels with glibenclamide decreased depression- and anxiety-related behaviors by normalizing HPA axis activity in Aß25-35-treated rats. This study provides additional evidence that Aß administration can induce depression- and anxiety-like symptoms in rodents, and suggests that KATP channel inhibitors may be a plausible therapeutic strategy for treating affective disorders in AD patients.

Piperine restores streptozotocin-induced cognitive impairments: Insights into oxidative balance in cerebrospinal fluid and hippocampus.

Piperine has been shown to have antioxidant activity and a cognitive-enhancing effect following long-term oral administration. In a comparative study of memantine, the current investigation threw light on the cognitive benefits of piperine. Lipid peroxidation and the ferric reducing antioxidant power (FRAP) of cerebrospinal fluid (CSF) and hippocampus in streptozotocin (STZ)-induced experimental dementia of the Alzheimer's type was measured. After reaching a criterion in a memory test, STZ-induced rats received piperine [2.5, 5, and 10mg/kg, intraperitoneally (i.p.)], vehicle, and memantine (10mg/kg, i.p.) for two weeks after the first STZ administration, or two weeks before and one week after, as a preventive approach. After the behavioral studies, samples were taken for biochemical and histological assays. An appropriate concentration of piperine (2.5mg/kg), on a daily basis, effectively increased the number of correct (non-repeated) arm entries and repressed reentry to a previously visited arm, in terms of reference errors as well as memantine (10mg/kg, i.p.), irrespective of the dose administered. The cognitive-enhancing effect induced by piperine at a relevant dose was simultaneous with CSF and hippocampal malonaldehyde decrement, and the redox balance was established to some extent by maintaining the FRAP levels of CSF near to those of the control. Similarly, the neuroprotective properties of piperine are in accordance with histopathological outcomes, which have shown an increased number of live cresyl violet (CV)-positive neurons in a dentate gyrus (DG) subregion. Therefore, the effects of piperine on the redox balance of CSF and hippocampal neurons may certainly contribute to the cognitive-enhancing activity of the drug.

Role of Apoptosis in the Pathogenesis of Common Variable Immunodeficiency (CVID).

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous immune deficiency characterized by hypogammaglobulinemia. Since B cell maturation and differentiation is defective in this disorder, we evaluated apoptosis in B cells of patients with CVID compared with healthy donors (HD). METHODS: Determination of peripheral blood B-cell subsets in CVID and HDs, was performed using flow cytometry. We compared total apoptosis, early apoptosis and late apoptosis/necrosis in unstimulated and stimulated B-cells of patients with CVID and HDs. We also assessed the expression of the anti-apoptotic molecule BCL2 mRNA levels in B-cells by real-time PCR in CVID patients compared with HDs. RESULTS: Total B-cell apoptosis was increased in both unstimulated and stimulated B-cells from CVID patients compared with HDs (p=0.02 and p=0.004). Early apoptosis in stimulated B-cells (p=0.04) and late apoptosis/necrosis of B-cells in both unstimulated and stimulated B-cells (p=0.04 and p=0.03, respectively) were significantly higher in CVID patients compared with HDs. There was a significant inverse correlation between the percentages of post germinal center B-cells in the peripheral blood of CVID patients compared with percentage of apoptotic B-cells. However, anti-apoptotic BCL2 expression was not significantly reduced in B-cells from CVID patients compared with HDs (p=0.16). CONCLUSION: Increased apoptosis of B-cells may be a factor in abnormality of differentiated B-cell subsets and the impaired endogenous immunoglobulin production in CVID patients. Further studies of the expression of pro/anti-apoptotic mediators in B-cells of CVID patients may shed light on the mechanism behind this increased B-cell apoptosis, and present potential therapeutic interventions in the future.

Arbitrary Symmetric Running Gait Generation for an Underactuated Biped Model.

This paper investigates generating symmetric trajectories for an underactuated biped during the stance phase of running. We use a point mass biped (PMB) model for gait analysis that consists of a prismatic force actuator on a massless leg. The significance of this model is its ability to generate more general and versatile running gaits than the spring-loaded inverted pendulum (SLIP) model, making it more suitable as a template for real robots. The algorithm plans the necessary leg actuator force to cause the robot center of mass to undergo arbitrary trajectories in stance with any arbitrary attack angle and velocity angle. The necessary actuator forces follow from the inverse kinematics and dynamics. Then these calculated forces become the control input to the dynamic model. We compare various center-of-mass trajectories, including a circular arc and polynomials of the degrees 2, 4 and 6. The cost of transport and maximum leg force are calculated for various attack angles and velocity angles. The results show that choosing the velocity angle as small as possible is beneficial, but the angle of attack has an optimum value. We also find a new result: there exist biped running gaits with double-hump ground reaction force profiles which result in less maximum leg force than single-hump profiles.