Glutathione Peroxidase1 Gene Polymorphism (GPx1 Pro198Leu) in Association with Blighted Ovum

Objective: To evaluate salivary GPx-1 gene polymorphism in pregnant women suffering from blighted ovum. Method: In this case-control study, 34 blighted ovum patients and 34 healthy controls were studied. Genomic DNA was extracted from the saliva. The genotypes were determined by restriction fragment length polymorphism (RFLP-PCR) technique. Mad Calc (version 12.1) was used for statistical analysis. Result: The frequency of CC, CT, and TT genotypes of GPx-1 gene were 41%, 44% and 14%, respectively in blighted ovum patients and in healthy volunteers were 44%, 47%, and 8.82-9%, respectively. After statistical analysis, the study showed no significant association between this polymorphism and blighted ovum (with p = 0.63). Conclusion: These results indicated no significant association between GPx-1 (Pro198Leu) polymorphism and blighted ovum. However, further research is required to clarify the role of gene polymorphism in blighted ovum. [Indones J Obstet Gynecol 2016; 1: 15-18] Keywords: abortion, blighted ovum, glutathione peroxidase-1, GPx- 1, RFLP-PC

Human Herpesvirus-6 and Human Herpesvirus-7 Infection in Iranian Patients with Neurological Illness

Human herpes virus-6 (HHV-6) and HHV-7 have been implicated as causes of meningitis and encephalitis in children and adults. In this study the presence HHV-6 and HHV-7 DNA were tested in cerebrospinal fluid (CSF) sample taken from Iranian children, suffered from meningoencephalitis. From 2007 to 2009, 150 patients from Tehran with meningoencephalits who were referred to a pediatric ward in Rasoul Akram hospital, Tehran Iran, were enrolled in the present study. Conventional and BACTEC Ped Plus medium were used in conjunction with latex agglutination test and real time PCR for detection of HHV-6 and HHV-7 DNA in clinical specimen. All type of human herpes virus DNA was detected in 12 % (18/150) cases. HHV-6 DNA was detected in 4.7% and HHV-7 DNA was detected in 2 cases (1.4%). Human herpes virus-6 and HHV-7 DNA was detected in 6% of all studied cases. HHV-6 was slightly more frequent than HHV-7. Our findings were lower than the rate of other references but were higher than the findings of previous study in Iran. This variation might be due to differences in methods, age of study cases or epidemiologic and geographic variation

Detection of cytomegalovirus (CMV) antibodies or DNA sequences from ostensibly healthy Iranian mothers and their neonates

Cytomegalovirus (CMV) remains the most common cause of viral intrauterine infection. The objective of this research was to determine the prevalence of at-risk pregnancies for congenital cytomegalovirus transmission in a randomly selected pregnant women and their newborns. Enzyme Link Immunosorbent Assay (ELISA) and real-time polymerase chain reaction (PCR) were utilized to screen the sera of mothers (n = 100) and consecutive umbilical cord blood samples from their newborn (n = 100). Of the 100 mother's sera analyzed, 100 (100%) and 3 (3%) were positive for cytomegalovirus IgG and IgM antibodies, respectively. Of the 100 cord serum specimens analyzed, 99 (99%) and 2 (2%) were positive for cytomegalovirus IgG and IgM antibodies, respectively. Cytomegalovirus DNA was detected in 4 out of 100 (4%) cord blood samples of newborns. From four CMV DNA positive cases, Case 1 had no IgM in cord serum, but had IgM in mother's sera. Cases 2 and 4 were positive for IgM in both mother's sera and cord serum. Case 3 had no detectable CMV IgM in sera and cord serum. As many as 66 and 100% of CMV IgM-positive women in this study also had CMV IgM and CMV DNA in their delivery cord blood samples, respectively suggesting an increased risk of congenital CMV infection in those pregnancies. A paired women sera/cord blood CMV IgM-negative was found to be positive for CMV DNA. The data may also suggest the utility of PCR in place of CMV IgM as a diagnostic method for congenital CMV infection

Detection of human T-cell lymphotropic virus Type-1 among patients with malignant hematological diseases in Capital of Iran, Tehran

Human T-cell lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus linked causally to adult T-cell leukemia or lymphoma (ATL), and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The aim of this study was to detect HTLV-1 infection in patients with malignant hematological diseases and also determining the prevalence of HTLV-1 in these patient groups. Sixty patients with malignant hematological diseases were included in the study and tested by enzyme-linked immunosorbent assay (ELISA) for anti-HTLV-1, and Real time-PCR for the sequences from HTLV-1 tax gene. The mean age of patients was 33.9 ± 18.3 years. 18 of the subjects were found HTLV-1 seropositive using ELISA and the viral prevalence by Real time-PCR was 12%. HTLV-1 was found in 25% of patients with acute myelogenous leukemia (AML), 58.3% of patients with chronic myelogenous leukemia (CML), 16.7% of patients with acute lymphoblastic leukemia (ALL), and no detected in patients with lymphoma. The present study revealed that HTLV-1 is prevalent in patients with malignant hematological diseases and in our study. The major HTLV-1 associated syndromes were chronic myelogenous leukemia and acute lymphoblastic leukemia

Use of molecular modelling to probe the mechanism of the nucleoside transporter NupG.

Nucleosides play key roles in biology as precursors for salvage pathways of nucleotide synthesis. Prokaryotes import nucleosides across the cytoplasmic membrane by proton- or sodium-driven transporters belonging to the Concentrative Nucleoside Transporter (CNT) family or the Nucleoside:H(+) Symporter (NHS) family of the Major Facilitator Superfamily. The high resolution structure of a CNT from Vibrio cholerae has recently been determined, but no similar structural information is available for the NHS family. To gain a better understanding of the molecular mechanism of nucleoside transport, in the present study the structures of two conformations of the archetypical NHS transporter NupG from Escherichia coli were modelled on the inward- and outward-facing conformations of the lactose transporter LacY from E. coli, a member of the Oligosaccharide:H(+) Symporter (OHS) family. Sequence alignment of these distantly related proteins (∼ 10% sequence identity), was facilitated by comparison of the patterns of residue conservation within the NHS and OHS families. Despite the low sequence similarity, the accessibilities of endogenous and introduced cysteine residues to thiol reagents were found to be consistent with the predictions of the models, supporting their validity. For example C358, located within the predicted nucleoside binding site, was shown to be responsible for the sensitivity of NupG to inhibition by p-chloromercuribenzene sulphonate. Functional analysis of mutants in residues predicted by the models to be involved in the translocation mechanism, including Q261, E264 and N228, supported the hypothesis that they play important roles, and suggested that the transport mechanisms of NupG and LacY, while different, share common features

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

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

BackgroundDisorders 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.MethodsWe 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.FindingsGlobally, 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.InterpretationAs 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

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Structure and Function Studies of Bacterial Membrane Transport Proteins

Nucleoside transporters play key roles in the uptake of nucleosides for salvage pathways of nucleotide synthesis in many organisms. In mammals, they also influence physiological processes, such as cardiovascular activity, via regulation of extracellular adenosine concentrations, and are the route of uptake for many anticancer and antiviral drugs. Unfortunately, understanding their molecular mechanisms in humans is hampered by their low abundance in the membrane and difficulty of expression. To obviate these problems, in the present project, bacterial proteins from the Hydroxy/Aromatic Amino Acid Permease family were studied as potentially more amenable models of the human Equilibrative Nucleoside Transporter family of proteins for structure/function analysis using bioinformatic approaches including molecular modelling. Although these families show little clear sequence similarity, they share a predicted 11 transmembrane topology, with a cytoplasmic N-terminal. In parallel, attempts were made to overexpress an Hi\AAP family member for structural studies. The present project also aimed to gain an understanding of the molecular mechanisms of transport by investigating the Escherichia coli nucleoside/proton co-transporter NupG. This member of the ubiquitous Major Facilitator Superfamily of transporters provides an excellent system for structure/function studies because it can be expressed at very high levels in the. bacterium and subsequently purified in a functional form. Moreover, a molecular model of the protein, based on its distant homology to the E. coli lactose transporter, was developed in this study. To investigate structure/function relationships in NupG, residues predicted from the model to be functionally important or to be located in the vicinity of the nucleoside-binding site were mutated to cysteine or other amino acids. Analysis of the kinetic properties of the mutants, and their susceptibility to thiol reagents where appropriate, has provided considerable information on the identities of residues likely to be involved in permeant recognition and translocation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo