Assessing the reliability of serum macrophage migration inhibitory factor as a marker for diabetic nephropathy prediction in type 2 diabetes patients and the effect of ACE inhibitors on its level

Abstract Diabetic nephropathy (DN) is a prevalent chronic microvascular diabetic complication. As inflammation plays a vital role in the development and progress of DN the macrophages migration inhibitory factor (MIF), a proinflammatory multifunctional cytokine approved to play a critical function in inflammatory responses in various pathologic situations like DN. This study aimed To assess serum levels of MIF in a sample of Iraqi diabetic patients with nephropathy supporting its validity as a marker for predicting nephropathy in T2DM patients. In addition, to evaluate the nephroprotective effect of angiotensin-converting enzyme (ACE) inhibitors in terms of their influence on MIF levels. This is a case-control study involving ninety subjects that have been divided into three groups: twenty apparently healthy control group and seventy patients with type 2 diabetes mellitus divided into two equal groups according to the presence of diabetic nephropathy that has been further divided into two groups according to the use of ACE inhibitors or not. Serum MIF, urea, creatinine, RBS, HbA1c, BMI, eGFR, and urinary albumin to creatinine ratio have been measured for each subject. Serum MIF’s highest levels were observed in the diabetic nephropathy patients (24.9 ng/ml) followed by the diabetics (14. 1 ng/ml) with the lowest level observed in the control group (4.8 ng/ml). There was a significant relation between MIF levels and ACE inhibitors (p-value <0.05) with reduced MIF levels in ACE inhibitors users. The ROC curve showed that MIF has a good performance in disease prediction. These findings support the reliability of MIF as a biomarker for the prediction of diabetic nephropathy and the possible reducing effect of ACE inhibitors on MIF levels

Acquiring insights through a sequence-based approach to the critical Zika virus MTase domain

Background: ZIKV is one of the re-emerging arboviruses (viruses carried by arthropods), which is spread through the Aedes mosquito. It is an RNA virus with only one strand that is appropriate to the family Flaviviridae's  Flavivirus (genus) & has been linked to other Flaviviruses such as the West Nile virus, chikungunya virus, & dengue (DENV) virus. The envelope, precursor membrane, and capsid are three structural proteins, and seven nonstructural proteins are also encoded by the Zika virus genome.Methods: We conducted an in-silico analysis of the Zika virus' MTase domain protein for this publication. We predicted that methylation would play a significant role in the available Prosite, Pfam, and InterProScan tools to aid in locating the MTase domain. Along with alignment, amino acid composition, charged amino acids, atomic level studies, & molecular weight, we also make predictions for these variables, including theoretical Pi.Results: We also examine the MTase domain's simulated structure (alpha helix, beta sheet, turn) and its specifics, including secondary structure. We also pinpoint the locations where proteins, DNA, and RNA bind. Potential phosphorylation sites can be found on the Ser, Thr, and Tyr residues in the MTase domain.Conclusion: These outcomes imply a complicated interaction between different phosphorylation modifications that modulates the activity of the MTase domain. To fully appreciate the auxiliary and practical perspectives and to clarify the varied roles of PTM in the MTase domain will be a primary goal of future study.Keywords: I-TASSER; Secondary structure; Prosite; α-helix; Pfam; InterProScan; Binding sites; Posttranslational modification; SOPMA; Phyre2 

Septic Arthritis, Early Recognition and Responsibility of Family and Medical Physicians, Nurses and Radiology Team

When infectious arthritis is diagnosed and treated as soon as possible, it can help prevent major morbidity and mortality of the condition. When monoarticular joint pain, erythema, fever, and immobility all appear suddenly, it is reasonable to suspect that the patient is suffering from sepsis. On the other hand, constitutional signs including fever, chills, and rigors are not very sensitive to the presence of septic arthritis. The purpose of this study is to address the importance that medical treatment and early recognition play in the diagnosis and treatment of septic arthritis, as well as the significant function that family and medicine physicians, nursing, and radiological assessment play in the process. Antibiotic treatment administered early has been shown to greatly enhance the prognosis in high-income settings; but, if treatment is delayed, the patient\u27s ability to recover without complications is hindered. Symptomatic osteoarthritis and avascular necrosis of the femoral head are two examples of complications that often develop gradually over time

Annona Muricata L. extract restores renal function, oxidative stress, immunohistochemical structure, and gene expression of TNF-α, IL-β1, and CYP2E1 in the kidney of DMBA-intoxicated rats

Introduction: 7,12-dimethylbenz (a) anthracene (DMBA) is a harmful polycyclic aromatic hydrocarbon derivative known for its cytotoxic, carcinogenic, and mutagenic effects in mammals and other species. Annona muricata, L. (Graviola; GRV) is a tropical fruit tree traditionally well-documented for its various medicinal benefits. This investigation is the first report on the potential antioxidant and antinfammatory reno-protective impact of GRV against DMBA-induced nephrotoxicity in rats.Methods: Forty male albino rats were allocated into four equal groups (n = 10). The 1st group served as the control, the 2nd group (GRV) was gastro-gavaged with GRV (200 mg/kg b.wt), the 3rd group (DMBA) was treated with a single dose of DMBA (15 mg/kg body weight), and the 4th group (DMBA + GRV) was gastro-gavaged with a single dose of DMBA, followed by GRV (200 mg/kg b.wt). The GRV administration was continued for 8 weeks.Results and Discussion: Results revealed a significant improvement in renal function, represented by a decrease in urea, creatinine, and uric acid (UA) in the DMBA + GRV group. The antioxidant potential of GRV was confirmed in the DMBA + GRV group by a significant decline in malondialdehyde (MDA) and a significant increase in catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST), and reduced glutathione (GSH) compared to DMBA-intoxicated rats; however, it was not identical to the control. Additionally, the antiinflammatory role of GRV was suggested by a significant decline in mRNA expression of cytochrome P450, family 2, subfamily e, polypeptide 1 (CYP2E1), tumor necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1β) in the DMBA + GRV group. Moreover, GRV improved the histopathologic and immunohistochemical expression of TNF-α, CYP450, and IL1β in DMBA-intoxicated kidney tissue. Conclusively, GRV is a natural medicinal product that can alleviate the renal injury resulting from environmental exposure to DMBA. The reno-protective effects of GRV may involve its anti-inflammatory and/or antioxidant properties, which are based on the presence of phytochemical compounds such as acetogenins, alkaloids, and flavonoids

Immunolocalization of neurokinin 1 receptor in WHO grade 4 astrocytomas, oral squamous cell and urothelial carcinoma

Neurokinin-1 receptor (NK-1R) induces inflammatory reactions in peripheral tissues but its regulatory effects in target tissues is dependent on receptor signalling. Substance P (SP) has a high affinity for the NK-1R, to which it binds preferentially. We aimed to investigate the expression of NK-1R in World Health Organization (WHO) grade 4 astrocytomas as well as in oral squamous cell carcinoma (OSCC) and urothelial carcinoma, and its association with disease progression.The study included tissue samples from 19 brain astrocytomas, 40 OSCCs and 10 urothelial carcinomas. NK-1R expression was quantitatively assessed in the tumour cells using immunohistochemistry. The relationship between NK-1R expression in astrocytomas and recurrence-free interval has been explored.The results showed that the NK-1R was intensely expressed in patients with WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. However, cases clinically diagnosed as a low-grade cancer showed reduced NK-1R expression.NK-1R is overexpressed in all cases of WHO grade 4 astrocytoma, OSCC and urothelial carcinoma. The ubi-quitous presence of SP/NK-1R complex during tumour development and progression suggests a possible therapeutic key strategy to use NK-1R antagonist as an adjuvant therapy in the future

Health in times of uncertainty in the eastern Mediterranean region, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background: The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. Methods: GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. Findings: The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100 000 people), which increased by 17·2% since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100 000 people) in 2013, which decreased by 26·9% since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3% since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60–80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7% to 7·5% between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. Interpretation: Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts

The p.Arg435His Variation of IgG3 With High Affinity to FcRn Is Associated With Susceptibility for Pemphigus Vulgaris—Analysis of Four Different Ethnic Cohorts

IgG3 is the IgG subclass with the strongest effector functions among all four IgG subclasses and the highest degree of allelic variability among all constant immunoglobulin genes. Due to its genetic position, IgG3 is often the first isotype an antibody switches to before IgG1 or IgG4. Compared with the other IgG subclasses, it has a reduced half-life which is probably connected to a decreased affinity to the neonatal Fc receptor (FcRn). However, a few allelic variants harbor an amino acid replacement of His435 to Arg that reverts the half-life of the resulting IgG3 to the same level as the other IgG subclasses. Because of its functional impact, we hypothesized that the p.Arg435His variation could be associated with susceptibility to autoantibody-mediated diseases like pemphigus vulgaris (PV) and bullous pemphigoid (BP). Using a set of samples from German, Turkish, Egyptian, and Iranian patients and controls, we were able to demonstrate a genetic association of the p.Arg435His variation with PV risk, but not with BP risk. Our results suggest a hitherto unknown role for the function of IgG3 in the pathogenesis of PV

Burden of tracheal, bronchus, and lung cancer in North Africa and Middle East countries, 1990 to 2019: Results from the GBD study 2019

ObjectiveTo provide estimates on the regional and national burden of tracheal, bronchus, and lung (TBL) cancer and its attributable risk factors from 1990 to 2019 in the North Africa and Middle East (NAME) region.Methods and materialsThe Global Burden of Disease (GBD) 2019 data were used. Disability-adjusted life years (DALYs), death, incidence, and prevalence rates were categorized by sex and age groups in the NAME region, in 21 countries, from 1990 to 2019. Decomposition analysis was performed to calculate the proportion of responsible factors in the emergence of new cases. Data are presented as point estimates with their 95% uncertainty intervals (UIs).ResultsIn the NAME region, TBL cancer caused 15,396 and 57,114 deaths in women and men, respectively, in 2019. The age-standardized incidence rate (ASIR) increased by 0.7% (95% UI -20.6 to 24.1) and reached 16.8 per 100,000 (14.9 to 19.0) in 2019. All the age-standardized indices had a decreasing trend in men and an increasing trend in women from 1990 to 2019. Turkey (34.9 per 100,000 [27.6 to 43.5]) and Sudan (8.0 per 100,000 [5.2 to 12.5]) had the highest and lowest age-standardized prevalence rates (ASPRs) in 2019, respectively. The highest and lowest absolute slopes of change in ASPR, from 1990 to 2019, were seen in Bahrain (-50.0% (-63.6 to -31.7)) and the United Arab Emirates (-1.2% (-34.1 to 53.8)), respectively. The number of deaths attributable to risk factors was 58,816 (51,709 to 67,323) in 2019 and increased by 136.5%. Decomposition analysis showed that population growth and age structure change positively contributed to new incident cases. More than 80% of DALYs could be decreased by controlling risk factors, particularly tobacco use.ConclusionThe incidence, prevalence, and DALY rates of TBL cancer increased, and the death rate remained unchanged from 1990 to 2019. All the indices and contribution of risk factors decreased in men but increased in women. Tobacco is still the leading risk factor. Early diagnosis and tobacco cessation policies should be improved

Estimates, trends, and drivers of the global burden of type 2 diabetes attributable to PM2.5 air pollution, 1990-2019 : an analysis of data from the Global Burden of Disease Study 2019

Background Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2.5 originating from ambient and household air pollution.Methods We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2.5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure-response curve from the extracted relative risk estimates using the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2.5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2.5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals.Findings In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2.5 exposure, with an estimated 3.78 (95% uncertainty interval 2.68-4.83) deaths per 100 000 population and 167 (117-223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13.4% (9.49-17.5) of deaths and 13.6% (9.73-17.9) of DALYs due to type 2 diabetes were contributed by ambient PM2.5, and 6.50% (4.22-9.53) of deaths and 5.92% (3.81-8.64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2.5.Interpretation Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2.5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

Estimates, trends, and drivers of the global burden of type 2 diabetes attributable to PM2.5 air pollution, 1990-2019 : An analysis of data from the Global Burden of Disease Study 2019

Background Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2·5 originating from ambient and household air pollution. Methods We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2·5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure–response curve from the extracted relative risk estimates using the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2·5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2·5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals. Findings In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2·5 exposure, with an estimated 3·78 (95% uncertainty interval 2·68–4·83) deaths per 100 000 population and 167 (117–223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13·4% (9·49–17·5) of deaths and 13·6% (9·73–17·9) of DALYs due to type 2 diabetes were contributed by ambient PM2·5, and 6·50% (4·22–9·53) of deaths and 5·92% (3·81–8·64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2·5. Interpretation Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2·5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes