Pelargonidin improves passive avoidance task performance in a rat amyloid beta25-35 model of Alzheimer�s disease via estrogen receptor independent pathways

Alzheimer�s disease (AD) is a disorder with multiple pathophysiological causes, destructive outcomes, and no available definitive cure. Pelargonidin (Pel), an anthocyanin derivative, is an estrogen receptor agonist with little estrogen side effects. This study was designed to assess Pel memory enhancing effects on the a rat Amyloid Beta25-35 (Aβ) intrahippocampal microinjections model of AD in the passive avoidance task performance paradigm and further evaluate the potential estrogen receptor role on the memory- evoking compound. Equally divided rats were assigned to 5 groups of sham, Aβ intrahippocampal microinjected, Pel pretreated (10 mg/kg; P.O), α estrogen antagonist intra-cerebrovascular (i.c.v.) microinjected, and β estrogen antagonist (i.c.v) microinjected animals. Intrahippocampal microinjections of Aβ were adopted to provoke AD model. Passive avoidance task test was also used to assess memory performance. Pel pretreatment prior to Aβ microinjections significantly improved step-through latency (P<0.001) in passive avoidance test. In α and β estrogen, antagonists received animals, passive avoidance task performance was not statistically changed (P=0.11 & P=0.41 respectively) compared to Pel pretreated and sham animals. Our results depicted that Pel improves Aβ induced memory dysfunction in passive avoidance test performance through estrogen receptor independently related pathways. © 2016 Tehran University of Medical Sciences. All rights reserved

Development of constitutive model for precast prestressed concrete segmental columns

The interest of using precast segmental columns in construction of concrete bridges has significantly increased in recent years. One research area of concrete bridges is the application of Precast Prestressed Concrete Segmental (PPCS) Column in any structural analysis software or FE program code. Modeling a PPCS column, which consists of various materials with interaction between them, is complicated and time-consuming. This research attempts to formulate the stiffness matrix of PPCS columns in order to form the constitutive model in linear form to evaluate the response of the columns. A two-dimensional finite element model is presented in the finite element package ANSYS. Parametric studies are conducted by finite element models to verify the constitutive models for the PPCS column with a different number of concrete segments. Comparison between the constitutive model and the FE program results indicates that the constitutive model is accurate enough to predict the deformation of the PPCS columns

In vivo E2F reporting reveals efficacious schedules of MEK1/2–CDK4/6 targeting and mTOR–s6 resistance mechanisms

Targeting cyclin-dependent kinases 4/6 (CDK4/6) represents a therapeutic option in combination with BRAF inhibitor and/or MEK inhibitor (MEKi) in melanoma; however, continuous dosing elicits toxicities in patients. Using quantitative and temporal in vivo reporting, we show that continuous MEKi with intermittent CDK4/6 inhibitor (CDK4/6i) led to more complete tumor responses versus other combination schedules. Nevertheless, some tumors acquired resistance that was associated with enhanced phosphorylation of ribosomal S6 protein. These data were supported by phospho-S6 staining of melanoma biopsies from patients treated with CDK4/6i plus targeted inhibitors. Enhanced phospho-S6 in resistant tumors provided a therapeutic window for the mTORC1/2 inhibitor AZD2014. Mechanistically, upregulation or mutation of NRAS was associated with resistance in in vivo models and patient samples, respectively, and mutant NRAS was sufficient to enhance resistance. This study utilizes an in vivo reporter model to optimize schedules and supports targeting mTORC1/2 to overcome MEKi plus CDK4/6i resistance. SIGnIFICAnCE: Mutant BRAF and NRAS melanomas acquire resistance to combined MEK and CDK4/6 inhibition via upregulation of mTOR pathway signaling. This resistance mechanism provides the preclinical basis to utilize mTORC1/2 inhibitors to improve MEKi plus CDK4/6i drug regimens

Protection of hippocampal CA1 neurons against ischemia/Reperfusion injury by exercise preconditioning via modulation of Bax/Bcl-2 ratio and prevention of Caspase-3 Activation

Introduction: Ischemia leads to loss of neurons by apoptosis in specific brain regions, especially in the hippocampus. The purpose of this study was investigating the effects of exercise preconditioning on expression of Bax, Bcl-2, and caspase-3 proteins in hippocampal CA1 neurons after induction of cerebral ischemia. Methods: Male rats weighing 260-300 g were randomly allocated into three groups (sham, exercise, and ischemia). The rats in exercise group were trained to run on atreadmill 5 days a week for 4 weeks. Ischemia was induced by the occlusion of both common carotid arteries (CCAs) for 20 min. Levels of expression of Bax, Bcl-2, and caspase-3 proteins in CA1 area of hippocampus were determined by immunohistochemical staining . Results: The number of active caspase-3-positive neurons in CA1 area were significantly increased in ischemia group, compared to sham-operated group (P<0.001), and exercise preconditioning significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group (P<0.05). Also, results indicated a significant increase in Bax/Bcl-2 ratio in ischemia group, compared to sham-operated group (P<0.001). Discussion: This study indicated that exercise has a neuroprotective effects against cerebral ischemia when used as preconditioning stimuli

The Relationship between Gestational Diabetes and Polycystic Ovary Syndrome

BACKGROUND AND OBJECTIVE: Women with polycystic ovary syndrome (PCOS) are at risk of insulin resistance and pregnancy complications. The aim of this study is to determine the relationship between gestational diabetes and polycystic ovary syndrome. METHODS: This cross-sectional study was performed on 126 pregnant women with PCOS and infertility history who became pregnant after stimulation of ovulation and referred to Imam Khomeini Hospital in Ahvaz. These patients underwent screening with 75 g OGTT (Oral Glucose Tolerance Test) during the first trimester and during 24-28 weeks of gestation. They were divided into two groups of PCOS with gestational diabetes and without gestational diabetes. Variables such as age, gestational diabetes, parity and BMI were measured and the relationship between BMI and gestational diabetes was examined. FINDINGS: The mean age of patients in the two PCOS groups with and without gestational diabetes was 26.09±2.03 and 27.07±3.03 years, respectively. Of the 126 pregnant women with PCOS, 30 (23.8%) patients were diagnosed with gestational diabetes in the first trimester of pregnancy and 11 (8.7%) patients during 24-28 weeks of gestation. Overall, 41(32.5%) patients had gestational diabetes and 85 (67.5%) patients did not have gestational diabetes. There was no significant difference in the mean BMI between the two PCOS groups with and without gestational diabetes. CONCLUSION: The results of the study showed that more than one third of women with PCOS experience gestational diabetes during pregnancy

The Evaluation of Growth, Yield and Physiological Responses of African Horned Cucumber (Cucumis metuliferus L.) to Deficit Irrigation

Introduction Water stress is the most prominent abiotic stress limiting agricultural crop growth and productivity. Deficit irrigation stress as a consequence of the progressive decrease in water availability has been a hot topic regarding food security during the last two decades. Growth and development of plants is influenced by reduction in turgor that results in decreased nutrient acquisition from dry soil. When water supply is limited, plant growth and yield is reduced and plant structure is modified by decreasing in leaf size. The effect of deficit irrigation on fruit yield and quality has been reported by numerous researchers with different results. In melon, deficit irrigation reduced marketable fruit number and yield, average fruit weight, fruit diameter and did not affect rind thickness and seed cavity, but increased total soluble solids content. Although the effects of water stress have been studied on growth and yield of different crops during the last years, recent information on the response of African horned cucumber yield and quality to deficit irrigation remains limited, particularly about the results of restricted water distributions in arid and sub-arid environments. The main goal of this study was to evaluate the effect of controlled deficit irrigation on growth, physiological parameters and yield and fruit quality of African horned cucumber.   Material and Methods Field experiment was performed based on a completely randomized block design with three irrigation regimes (60, 80 and 100 %ETc), whit three replications at Research Farm of University of Zanjan during the 2019. The African horned cucumber seeds were sown on 1th July 2020 at recommended spacing of 50 cm in row with 120 cm between rows. The irrigation system consisted of one drip line every crop row. The three irrigation levels were calculated based on actual evapotranspiration (ETc): (1) control, irrigated 100% crop water requirement, (2) deficit irrigation 80% ETc and (3) deficit irrigation 60% ETc. The Water requirement of the plant for control treatment was estimated using long-term average daily data of meteorological parameters recorded at Zanjan Meteorological Station and following relation. Before starting the differential irrigation at five-leaf stage, all treatments were supplied with similar amount of water to maximize stands and uniform crop establishment. During plant growth, the relative water content, proline content, electrolyte leakage, chlorophyll and carotenoids, P and K contents were measured. After fruit harvest, vine length of each plant, leaf dry weight and stem diameter were measured. The fruits were harvested when color changed from green to yellow. Fruit weight, fruit number per plant and fruit yield per plant was measured. Immediately after harvest, fruit firmness, total soluble solid, total phenols content, antioxidant capacity and vitamin C were determined.     Results and Discussion As the results showed water deficit stress significantly reduced plant length, chlorophyll content, and increased carotenoids content. Based on the findings, deficit irrigation caused a significant reduction in leaf relative water content. According to the results, phosphorus and potassium contents in African horned cucumber leaves decreased with deficit irrigation treatments. The highest P and K contents were found under irrigation 100 %ETc treatment. Drought stress and associated reduction in soil moisture can decrease plant nutrient uptake by reducing nutrient supply through mineralization. The proline content increased with the deficit irrigation treatments; in particular with sever deficit irrigation (60 %ETc). Mean comparisons of data showed that deficit irrigation led to a significant increase in electrolyte leakage compared to control. Water deficit stress caused significant reductions in yield. The highest fruit number per plant and yield were obtained under irrigation 100% ETc. The average fruit weigh significantly increased in response to increase water deficit stress. Deficit irrigation treatments significantly decreased vitamin C and fruit firmness. Significant differences among irrigation treatments were observed for total phenols and total soluble solid contents. The phenols and total soluble solid contents increased with the decrease of irrigation water applied. Antioxidant capacity was affected significantly by the irrigation treatments, and water deficit stress increased antioxidant capacity, which no significant difference was observed between irrigation 100 and 80 %ETc.   Conclusion Water deficit has been shown to adversely affect plant growth, fruit yield, and leaf water status of African horned cucumber, but led to increase the TSS and antioxidant capacity. According to the results, fruit yield reduced 13.9 % under irrigation 80% ETc compared to irrigation 100% ETc, However, water consumption was saved by 20% and improved fruit weight and fruit quality with increasing soluble solids and antioxidant capacity

The survival rate of hepatocellular carcinoma in asian countries: A systematic review and meta-analysis

Hepatocellular carcinoma or Liver cancer (LC) is the sixth most common cancer and the fourth cause of death worldwide in 2018. There has not been a comprehensive study on the survival rate of patients with LC in Asia yet. Therefore, the present study was conducted to evaluate the survival rate of patients with LC in Asian countries. The methodology of the present study is based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement. The researchers searched five international databases including Medline/PubMed, Scopus, Embase, Web of Knowledge and ProQuest until July 1, 2018. We also searched Google Scholar for detecting grey literature. The Newcastle-Ottawa Quality Assessment Form was used to evaluate the quality of selected papers. A total of 1425 titles were retrieved. 63 studies met the inclusion criteria. Based on the random-effect model one-year, three-year and five-year survival rate of LC were 34.8 (95 CI; 30.3-39.3), 19 (95 CI; 18.2-21.8) and 18.1 (95 CI;16.1-20.1) respectively. According to the results of our study, the LC survival rate in Asian countries is relatively lower than in Europe and North America. © 2020, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved

The protective role of carnosic acid against beta-amyloid toxicity in rats

Oxidative stress is one of the pathological mechanisms responsible for the beta- amyloid cascade associated with Alzheimer's disease (AD). Previous studies have demonstrated the role of carnosic acid (CA), an effective antioxidant, in combating oxidative stress. A progressive cognitive decline is one of the hallmarks of AD. Thus, we attempted to determine whether the administration of CA protects against memory deficit caused by beta-amyloid toxicity in rats. Beta-amyloid (1-40) was injected by stereotaxic surgery into the Ca1 region of the hippocampus of rats in the Amyloid beta (Aβ) groups. CA was delivered intraperitoneally, before and after surgery in animals in the CA groups. Passive avoidance learning and spontaneous alternation behavior were evaluated using the shuttle box and the Y-maze, respectively. The degenerating hippocampal neurons were detected by fluoro-jade b staining. We observed that beta-amyloid (1-40) can induce neurodegeneration in the Ca1 region of the hippocampus by using fluoro-jade b staining. Also, the behavioral tests revealed that CA may recover the passive avoidance learning and spontaneous alternation behavior scores in the Aβ + CA group, in comparison with the Aβ group. We found that CA may ameliorate the spatial and learning memory deficits induced by the toxicity of beta-amyloid in the rat hippocampus. © 2013 H. Rasoolijazi et al

Barriers to Physical Activity in Pregnant Women: An Explanatory Sequential Mixed-method Study (Study Protocol)

Background: Gaining insight into the obstacles holding women from engaging in physical activity during pregnancy is crucial for planning future interventions to enhance their physical activity during this period. This research aims to identify barriers to physical activity among pregnant women using an explanatory sequential mixed-methods approach. The study protocol is explained in this article. Methods: This research employs an explanatory sequential mixed-methods design. The project will be implemented in two separate phases. In the first phase, a quantitative cross-sectional study will be conducted on 358 eligible pregnant women aged 18-45 years living in Babol City, Iran. Quantitative data collection will involve using the barriers to physical activity during pregnancy scale (BPAPS) and questionnaires gathering demographic and obstetric data. The qualitative investigation will employ individual semi-structured interviews utilizing a content analysis approach. Ultimately, incorporating qualitative data will inform the interpretation of quantitative findings. Results: The results will be presented in alignment with the study objectives. Initially, the mean score of BPAPS and its subscales, along with the correlation between demographic and obstetric variables, will be reported. Subsequently, the qualitative phase will encompass the reporting of categories and the main themes. Finally, the quantitative phase findings will be interpreted, incorporating insights gained from the qualitative phase. Conclusion: Since regular physical activity during pregnancy has many benefits for maternal and fetal health, the study’s findings after its implementation can play a vital role in strategic planning to address women’s false beliefs and misconceptions regarding physical activity during pregnancy. In addition, this study will contribute to designing interventions to remove barriers to physical activity and encourag

Experiences of dementia in a foreign country: qualitative content analysis of interviews with people with dementia

Background: Dementia is a worldwide health concern of epidemic proportions. Research in the field of subjective experience of dementia suffers from a lack of diversity of their participants including immigrants. Different portraits of life with dementia could help us understand how people with dementia conceptualise their experiences of dementia and how they live. Our study aimed to explore the subjective experiences of living with dementia among Iranian immigrants in Sweden. Methods: Qualitative content analysis of interviews with fifteen people with dementia from Iranian immigrant backgrounds were conducted (8 females and 7 males). Results: Three themes and seven associated sub-themes were revealed. The themes included: Being a person with dementia means living with forgetfulness (personal sphere), living with forgetfulness in the private sphere means feeling incompetent but still loved, living with forgetfulness in the public sphere means feeling confident and secure but also isolated. Conclusions: Living with dementia for the participants meant living with forgetfulness. They experienced feeling incompetent but still loved within their families and feeling confident and secure but also isolated in the society. Educating people with dementia and their families about the course and process of dementia may help them understand the changes better and adjust their expectations. Our study can provide a basis for healthcare workers to understand the experiences of living with dementia from this specific perspective