Synergistic Effects of Capsaicin and Quercetin Improved Induced Premature Ovarian Failure in Rat

Objective: Premature ovarian failure (POF) is a heterogeneous disorder. POF is defined as hypergonadotropichypoestrogenism in women under 40 years. There is no effective treatment to cure POF patients. Antioxidants preventovarian damage by reducing the lipid peroxidation cascades affecting folliculogenesis, meiosis and ovulation. Hence;the aim of present study was to investigate the effects of Capsaicin (CAP) and Quercetin (QUR) on cyclophosphamide(CYC)-induced POF in rat model.Materials and Methods: In this experimental study, POF was induced by intraperitoneal injection of 200 mg/kg CYC onfirst day and then 8 mg/kg/day for the following 3 days. After 4 days of CYC administration, rats were randomly dividedinto five groups (n=6/group) as follows: POF, dimethyl sulfoxide (DMSO), CAP (0.5 mg/kg/day), QUR (100 mg/kg/day)and CAP+QUR. Biochemical, hormonal, gene expression, and histological evaluations were performed on blood serumand tissue samples after 14 days of treatment with the CAP and QUR.Results: CAP, QUR and CAP+QUR groups showed signs of restored ovarian function in the form of a significantincrease in serum total antioxidant capacity (TAC), estrogen, progesterone and anti-mullerian hormone (AMH) levelsversus POF and DMSO groups and a significant improvement in histological parameters and follicle numbers intreatment groups compared to POF and DMSO groups. Polymerase chain reaction (PCR) analysis demonstrated thatCAP and QUR upregulate the expression of BAX gene and decreased the expression of apoptosis inducing genes(BCL-2 and P53).Conclusion: CAP and QUR treatment of CYC-induced POF rats showed a positive effect on reducing ovarian damageby improving TAC levels, expression of apoptotic genes, levels of ovarian reserve markers, and histological parameters.Our results suggest that treatment with CAP or QUR may be a conservative treatment approach for CYC -induced POF

Prognostic value of high mobility group protein A2 (HMGA2) over-expression in cancer progression

The high mobility group A2 (HMGA2; also called HMGI-C) gene is an architectural transcription factor that belonging to the high mobility group AT-hook (HMGA) gene family. HMGA2 is aberrantly regulated in several human tumors. Over-expression of HMGA2 is correlated with a higher risk of metastasis and an unfavorable prognosis in patients with cancer. We performed a meta-analysis to determine the clinic-pathological and prognostic value of HMGA2 overexpression in different human tumors. A comprehensive literature search was performed using PubMed, Embase, Cochrane Library, Scopus, MEDLINE, Google Scholar and ISI Web of Science. Hazard ratios (HRs)/odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of the association between HMGA2 expression and overall survival (OS)/progression free survival (PFS)/disease free survival (DFS). A total of 5319 patients with 19 different types of cancer from 35 articles were evaluated. Pooled data analysis indicated that increased HMGA2 expression in cancer patients predicted a poor OS (HR = 1.70; 95% CI = 1.6–1.81; P < 0.001; fixed-effect model). In subgroup analyses, high HMGA2 expression was particularly associated with poor OS in individuals with gastrointestinal (GI) cancer (HR = 1.89, 95% CI: 1.83–1.96; fixed-effect model) and HNSCC cancer (HR-1.78, 95%CI: 1.44–2.21; fixed-effect model). Over-expression of HMGA2 was associated with vascular invasion (OR = 0.16, 95% CI = 0.05–0.49; P = 0.001) and lymphatic invasion (OR = 1.89, 95% CI = 1.06–3.38; P = 0.032). Further studies should be conducted to validate the prognostic value of HMGA2 for patients with GI cancers

The prognostic value of long noncoding RNA MEG3 expression in the survival of cancer patients: a meta-analysis

Long non-coding RNAs (lncRNAs) play an important role in carcinogenesis and cancer progression. lncRNA MEG3 is a tumor suppressor that is down-regulated in several cancers. However, its prognostic value in human malignancies remains controversial. We have therefore undertaken a meta-analysis to explore the relationship between cancer survival and the expression of long non-coding RNA MEG3. A systematic literature search identified 13 potentially eligible investigations comprising 1733 patients in nine different cancer types. In the pooled analysis, a low expression of MEG3 was associated with a low overall survival (OS) in cancer patients with a combined HR of 0.830 [hazard ratio (HR) =0.83; 95% CI: 0.70–0.98; P=0.0.03; random effect model]. However, sub-group analysis according to cancer type revealed that MEG3 expression was not associated with better OS in gastrointestinal cancer (HR = 0.58, 95% CI = 0.33 to 1.03, P = 0.06) and breast cancer patients (HR = 0.85, 95% CI: 0.12 to 5.88, P = 0.87). In conclusion, our results demonstrate that only in the pooled analysis, there was a significant relationship between MEG3 expression and cancer survival. Further investigation of other molecular biomarkers involved in tumorigenesis-related pathways is necessary

Factor Structure and Psychometric Properties of Zung SelfRating Depression Scale in Women with a Sick Child

Background: Considering the necessity of using a valid and reliable tool to assess depression in women and the lack of similar tools in Iran, the purpose of this study was to investigate the psychometric properties of the Zung Self-Rating Depression Scale (ZSDS) with an emphasis on factor analysis among Iranian women with sick children.. Methods: In the cross-sectional psychometric study, 102 eligible women were selected by multistage cluster sampling from various environments such as healthcare centers, hospitals, and public and private institutions, who completed the ZSDS. The reliability of the questionnaire was assessed using testretest and internal consistency, and its validity was tested by confirmatory factor analysis (CFA). Results: Cronbach's alpha coefficients for the total scale were equal to 0.73, and high test-retest reliability indicated the appropriate reliability of ZSDS. The CFA results indicated a poor fit of the model in determining the factors as initially expressed in ZSDS. After removing six questions with low factor loadings and freeing the covariance error between the two questions, the model was adequately fitted (CMIN/DF= 1.3, CFI= 0.92, TLI= 0.90, GFI= 0.89).Conclusions: Based on our study, the ZSDS is convenient for identifying clinically significant depressive symptoms among women with sick children. Keywords: Child, Psychometric, Zung Self-Rating Depression Scale, Wome

Anticancer activity of Pseudomonas aeruginosa derived peptide with iRGD in colon cancer therapy

Objective(s): Colon cancer is well-known as a life-threatening disease. Since the current treatment modalities for this type of cancer are powerful yet face some limitations, finding novel treatments is required to achieve better outcomes with fewer side effects. Here we investigated the therapeutic potential of Azurin-p28 alone or along with iRGD (Ac-CRGDKGPDC-amide) as a tumor-penetrating peptide and 5-fluorouracil (5-FU) for colon cancer. Materials and Methods: Inhibitory effect of p28 with or without iRGD/5-FU was studied in CT26 and HT29, as well as the xenograft animal model of cancer. The effect of p28 alone or along with iRGD/5-FU on cell migration, apoptotic activity, and cell cycle of the cell lines was assessed. Level of the BAX and BCL2 genes, tumor suppressor genes [(p53 and collagen type-Iα1 (COL1A1), collagen type-Iα2 (COL1A2)] were assessed by quantitative RT-PCR.Results: These findings show that using p28 with or without iRGD and 5-FU raised the level of p53 and BAX but decreased BCL2, compared with control and 5-FU groups in tissues of the tumor, which result in raising the apoptosis. Conclusion: It seems that p28 may be used as a new therapeutic approach in colon cancer therapy that can enhance the anti-tumor effect of 5-FU

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Bayesian Decoder Design for Investigation of Cognitive Arousal and Performance Using Physiological and Behavioral Data

Human arousal is one of the indicators of internal stress that has effects on productivity and performance. Poor stress management may lead to reduced performance. Hence, decoding the unobserved arousal and performance, and identifying the arousal-performance relationship are challenging topics of study. On the other hand, cognitive performance can be affected by several external factors such as working environment and surroundings. Decoding human cognitive performance during a cognitive task, based on the environmental variations, is an important topic of interest in the cognitive neuroengineering area. Our study has a great potential to transform workplaces and educational systems. In this study, using the state-space approach within an expectation-maximization (EM) framework, we first obtain the arousal and performance states separately. We investigate the feasibility of using the Yerkes–Dodson law from psychology to link arousal to cognitive performance. Thereafter, we develop a novel arousal decoder based on the corresponding performance. Next, in order to capture the external effects on performance, we design the performance state-space model such that it becomes adaptive to the environmental changes. We develop a time-varying state-space model by applying the autoregressive conditional heteroskedasticity (ARCH) framework to our problem. Subsequently, we present a particle filtering approach and track the human performance through a cognitive task under the EM scheme. Our findings manifest the background music effects on the obtained arousal and performance states. The arousal and performance relationship reveals the existence of Yerkes–Dodson law. The novel arousal decoder offers us a better agreement between the arousal-performance relationship and the Yerkes–Dodson law. Furthermore, our investigations indicate that applying the ARCH framework within the state-space model results in an improved performance state estimation and it outperforms the previous model in terms of capturing the environmental impacts on human performance. Our study can be implemented directly in designing non-invasive closed-loop systems, future smart workplaces, and online educational systems to regulate stress for maximizing performance and productivity