Correlation between Epstein-Barr virus infection and disease activity of systemic lupus erythematosus: A cross-sectional study

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease for whose pathogenesis viral infections are important. The Epstein-Barr virus (EBV) is the main infectious etiological agent. This study aimed to quantitative evaluation of EBV in SLE patients. Materials and Methods: In this cross-sectional study, 40 patients with SLE diagnosed based on American College of Rheumatology criteria were selected using purposive sampling. All were included in the study after obtaining informed consent for participation. Whole blood samples were taken and buffy coat preparations were isolated to determine viral load using the real-time polymerase chain reaction method and assessment with the SLE disease activity index (SLE-DAI). Results: From a total of 40 patients, 37 cases (92.5%) were women. The EBV test was positive in 67.5% and mean viral load was 5396 ± 1891.9 copy/ml. Twenty of forty patients had active and 50% inactive disease, mean EBV viral loads being 6798 and 28.25 copy/ml, respectively (P-value = 0.003). In terms of the severity of disease activity, 17.5 % of female patients had mild to moderate activity, whilst 32.5% of them had severe activity, with respective viral loads of 5,803.3 and 29.73 copy/ml (P-value = 0.003). Conclusion: The Epstein-Barr viral load in SLE patients with active disease was found to be markedly higher than in inactive cases. Thus, EBV may have an important role in the pathogenesis and activity of SLE. Keywords: Epstein-Barr virus, viral load, systemic lupus erythematosus, real-time PCR, human, infectio

Antimicrobial peptides of the vaginal innate immunity and their role in the fight against sexually transmitted diseases

Some antimicrobial peptides (AMPs) are produced in the vaginal innate immune system and play an important role in protecting this organ against pathogenic agents. Moreover, sexually transmitted diseases have become a major problem in human societies and are rapidly spreading. The emergence of antibiotic-resistant microbes (superbugs) can pose a major threat to human societies and cause rapid spread of these diseases. Finding new antimicrobial compounds to fight superbugs is therefore essential. It has been shown that AMPs have good potential to become new antibiotics. The most important AMPs in the vaginal innate immune system are defensins, secretory leucocyte protease inhibitors, calprotectin, lysozyme, lactoferrin and elafin, which play an important role in host defence against sexually transmitted infections, modulation of immune responses and anticancer activities. Some AMPs, such as LL-37, magainin 2 and nisin, show both spermicidal and antimicrobial effects in the vagina. In this summary, we will discuss vaginal AMPs and continue to address some of the challenges of using peptides to control pathogens that are effective in sexually transmitted diseases. © 2019 The Author(s

Diagnostic value of Neuron-Specific Enolase (NSE) and Cancer Antigen 15-3 (CA 15-3) in the Diagnosis of Pleural effusions

Introduction: Pleural effusion diagnosis plays an important role in determining treatment strategies. The aim of this study was to determine the diagnostic capacity of tumor markers CA 15-3 and NSE solely or in combination in differentiating the nature of pleural fluid. Methods and Materials: In this cross-sectional study we evaluated 93 patients with pleural effusions (44 malignant and 49 benign). NSE and CA 15-3 serum and pleural levels were measured simultaneously using immunoenzyme assay kits. Diagnosis was established on the basis of cytological study. Results: Sensitivity and specificity of CA 15-3 serum and pleural level measurement were 70.4%, 49.0%, and 79.5% and 49.0%, respectively. Serum NSE levels had 75.0% sensitivity and 69.4% specificity while the respective pleural figures were 75.0% and 73.5%. The combination of NSE and CA 15-3 serum and pleural levels had the highest sensitivity (93.2%), although combined serum levels had the lowest sensitivity (47.7%). With an accuracy of 74.2%, pleural levels of NSE had the highest diagnostic potential. Conclusion: Measuring NSE and CA 15-3 tumor markers is a suitable approach to distinguish the nature of pleural effusions, with NSE pleural levels demonstrating the highest diagnostic accuracy

The effect of melatonin on expression of p53 and ovarian preantral follicle development isolated from vitrified ovary

Ovarian vitrification is a strategy for conservation of fertility of young female patients, suffering from infertility, due to iatrogenic loss of ovarian function, resulting from chemotherapy and/or radiation therapy. The purpose of this study was to determine the influence of melatonin on expression of p53 and the developmental rate of preantral follicles isolated from vitrified and non-vitrified ovaries. This experimental study was carried out on 40, 14-day-old female mice (NMRI). One ovary from each mouse was used randomly for the vitrification procedure. Preantral follicles with a diameter of 120�140 μm derived from vitrified-warmed and non-vitrified ovarian tissues were cultured individually in α-MEM medium supplemented with or without melatonin. The expression of p53, diameter of follicle, survival rate, and number of antral follicles were compared using post hoc LSD, t test, and chi-square test, respectively in four groups: non-vitrified and non-melatonin (NVNM), non-vitrified and melatonin (NVM), vitrified and non-melatonin (VNM), vitrified and melatonin (VM). p53 gene was expressed in four groups and was strongly expressed in the antral follicles of VNM (p = 0.011). The addition of melatonin increased survival rate and the mean diameter of follicles in vitrified group (p = 0.001). There were no significant differences in antral formation of follicles between different groups. Adding melatonin to culture medium reduced expression of p53 apoptotic gene in vitrified group and improves in vitro maturation and survival rate in isolated follicles from vitrified ovaries. © 2017, Springer-Verlag London Ltd

The effects of vitamin D supplementation on signaling pathway of inflammation and oxidative stress in diabetic hemodialysis: A randomized, double-blind, placebo-controlled trial

Objective: This study was carried out to determine the effects of vitamin D supplementation on signaling pathway of inflammation and oxidative stress in diabetic hemodialysis (HD) patients. Methods: This randomized double-blind placebo-controlled clinical trial was conducted among 60 diabetic HD patients. Subjects were randomly allocated into two groups to intake either vitamin D supplements at a dosage of 50,000 IU (n = 30) or placebo (n = 30) every 2 weeks for 12 weeks. Gene expression of inflammatory cytokines and biomarkers of oxidative stress were assessed in peripheral blood mononuclear cells (PBMCs) of diabetic HD patients with RT-PCR method. Results: Results of RT-PCR indicated that after the 12-week intervention, compared to the placebo, vitamin D supplementation downregulated gene expression of interleukin (IL)-1β (P = 0.02), tumor necrosis factor alpha (TNF-α) (P = 0.02) and interferon gamma (IFN-γ) (P = 0.03) in PBMCs of diabetic HD patients. Additionally, vitamin D supplementation, compared to the placebo, downregulated gene expression of transforming growth factor beta (TGF-β) (P = 0.04), protein kinase C (PKC) (P = 0.001), and mitogen-activated protein kinases 1 (MAPK1) (P = 0.02) in PBMCs of diabetic HD patients. Although not significant, vitamin D supplementation let to a reduction of nuclear factor kappa B (NF-kB) (p = 0.75) expression in PBMCs isolated from diabetic patients compared to the placebo group. There was no statistically significant change following supplementation with vitamin D on gene expression of interleukin (IL)-4, IL-6, and vascular endothelial growth factor (VEGF) in PBMCs of diabetic HD patients. Conclusions: Overall, we found that vitamin D supplementation for 12 weeks among diabetic HD patients had beneficial effects on few gene expression related to inflammation and oxidative stress. © 2018 Haddad Kashani, Seyed Hosseini, Nikzad, Soleimani, Soleimani, Tamadon, Keneshlou and Asemi

Evaluation of Cisplatin efficacy on HepG2 and E. coli Cells under acidic conditions

Background: Cisplatin (Cispt) is a common anticancer drug for the treatment of several malignancies, including hepatocarcinoma. However, this drug suffers from instability in aqueous solutions. The study aimed to evaluate cisplatin efficacy on HepG2 and E. coli cells under an acidic condition. Methods: Acidic Cispt was prepared via incubation in acidic condition (pH=2) for a month duration. The chemical structure of the acidic Cispt was evaluated by using Fourier Transform Infrared Spectroscopy (FTIR) method. The cytotoxicity of the standard and acidic Cispt were then determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and minimum inhibitory concentration (MIC) assays on HepG2 and E. coli cells, respectively. Results: After preparing of acidic Cispt, its chemical structure was determined by FTIR method. In addition, cytotoxicity effects of Cispt in the standard and acidic forms were calculated 58 ± 2.9 and 65 ± 3.25 μM, respectively. MIC results also confirmed the results of MTT assay. MIC results for the standard and acidic Cispt were estimated 9.5 ± 0.47 and 9.8 ± 0.49 μM, respectively. Conclusion: Preparing Cispt in acidic condition not only did not degrade the drug, but also kept the potency of the drug approximately equal to parent drug. Regarding the instability issues of Cispt, keeping Cispt in acidic condition could be a promising approach to preserve its efficacy. © 2019, Asian Pacific Journal of Cancer Prevention

The effects of vitamin D supplementation on signaling pathway of inflammation and oxidative stress in diabetic hemodialysis: A randomized, double-blind, placebo-controlled trial

Objective: This study was carried out to determine the effects of vitamin D supplementation on signaling pathway of inflammation and oxidative stress in diabetic hemodialysis (HD) patients. Methods: This randomized double-blind placebo-controlled clinical trial was conducted among 60 diabetic HD patients. Subjects were randomly allocated into two groups to intake either vitamin D supplements at a dosage of 50,000 IU (n = 30) or placebo (n = 30) every 2 weeks for 12 weeks. Gene expression of inflammatory cytokines and biomarkers of oxidative stress were assessed in peripheral blood mononuclear cells (PBMCs) of diabetic HD patients with RT-PCR method. Results: Results of RT-PCR indicated that after the 12-week intervention, compared to the placebo, vitamin D supplementation downregulated gene expression of interleukin (IL)-1β (P = 0.02), tumor necrosis factor alpha (TNF-α) (P = 0.02) and interferon gamma (IFN-γ) (P = 0.03) in PBMCs of diabetic HD patients. Additionally, vitamin D supplementation, compared to the placebo, downregulated gene expression of transforming growth factor beta (TGF-β) (P = 0.04), protein kinase C (PKC) (P = 0.001), and mitogen-activated protein kinases 1 (MAPK1) (P = 0.02) in PBMCs of diabetic HD patients. Although not significant, vitamin D supplementation let to a reduction of nuclear factor kappa B (NF-kB) (p = 0.75) expression in PBMCs isolated from diabetic patients compared to the placebo group. There was no statistically significant change following supplementation with vitamin D on gene expression of interleukin (IL)-4, IL-6, and vascular endothelial growth factor (VEGF) in PBMCs of diabetic HD patients. Conclusions: Overall, we found that vitamin D supplementation for 12 weeks among diabetic HD patients had beneficial effects on few gene expression related to inflammation and oxidative stress. © 2018 Haddad Kashani, Seyed Hosseini, Nikzad, Soleimani, Soleimani, Tamadon, Keneshlou and Asemi

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding: Bill & Melinda Gates Foundation

Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods: The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings: Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation: Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding: Bill & Melinda Gates Foundation

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. Funding: Bill & Melinda Gates Foundation