Isocitrate Dehydrogenase of Helicobacter pylori Potentially Induces Humoral Immune Response in Subjects with Peptic Ulcer Disease and Gastritis

Background. H. pylori causes gastritis and peptic ulcers and is a risk factor for the development of gastric carcinoma. Many of the proteins such as urease, porins, flagellins and toxins such as lipo-polysaccharides have been identified as potential virulence factors which induce proinflammatory reaction. We report immunogenic potentials of isocitrate dehydrogenase (ICD), an important house keeping protein of H. pylori. Methodology/Principal Findings. Amino acid sequences of H. pylori ICD were subjected to in silico analysis for regions with predictably high antigenic indexes. Also, computational modelling of the H. pylori ICD as juxtaposed to the E. coli ICD was carried out to determine levels of structure similarity and the availability of surface exposed motifs, if any. The icd gene was cloned, expressed and purified to a very high homogeneity. Humoral response directed against H. pylori ICD was detected through an enzyme linked immunosorbent assay (ELISA) in 82 human subjects comprising of 58 patients with H. pylori associated gastritis or ulcer disease and 24 asymptomatic healthy controls. The H. pylori ICD elicited potentially high humoral immune response and revealed high antibody titers in sera corresponding to endoscopically-confirmed gastritis and ulcer disease subjects. However, urea-breath-test negative healthy control samples and asymptomatic control samples did not reveal any detectable immune responses. The ELISA for proinflammatory cytokine IL-8 did not exhibit any significant proinflammatory activity of ICD. Conclusions/Significance. ICD of H. pylori is an immunogen which interacts with the host immune system subsequent to a possible autolytic-release and thereby significantly elicits humoral responses in individuals with invasive H. pylori infection. However, ICD could not significantly stimulate IL8 induction in a cultured macrophage cell line (THP1) and therefore, may not be a notable proinflammatory agent

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

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

SICKLE CELL DISEASE IN THE STATE OF TENNESSEE

Sickle cell disease (SCD) is an inherited blood disorder. Normal red blood cells are round. In those with SCD, the red blood cells are crescent shaped. In the Unites States (US), more than 90% of those living with SCD are Black. We conducted three epidemiological studies related to the burden of common comorbidities in individuals with SCD, the relationship between SCD and chronic kidney disease, and the effects of historical racial housing policies on births with SCD. First, we evaluated the annual incidence and demographic associations of stroke, seizures, congestive heart failure, asthma, systemic hypertension, and diabetes mellitus in individuals living with SCD. Older individuals with SCD had higher odds of stroke, seizures, congestive heart failure, systemic hypertension, and diabetes mellitus compared to those under the age of 18. Females with SCD had 1.66 (95% CI: 1.13, 2.44) times the odds of incident diabetes mellitus compared to males. Individuals living with SCD in rural Tennessee had 2.05 (95% CI: 1.14, 3.68) times the odds of incident congestive heart failure compared to urban dwellers. Next, we evaluated the incidence, demographic associations, and mortality in individuals with SCD who had chronic kidney disease (CKD). Compared to those under 18 years of age, those above 45 had 23.54 (95% CI: 7.07, 78.36) times the odds of incident CKD. In terms of mortality, individuals with SCD who had CKD, had statistically significant lower mean age of death compared to the general US population (53 years vs. 73.7 years, p-value 0.0485). The final analysis estimated the burden of births with SCD in historically redlined Zip codes along with modern-day economic implications. A higher proportion of newborns with SCD (32%) were born in historically redlined Zip codes compared to the general population (15%) of the state. There were similar findings for three (Shelby, Davidson, and Hamilton) of the four major counties. There was also a statistically significant association between births with SCD and living in a previously redlined Zip code (p-value 0.0012). In terms of modern-day economic implications, there were no significant associations between births with SCD and median household income

Characteristics of Waterpipe Smokers Who Are Willing to Quit: Population-Based Findings from Syria

Background: Many waterpipe users are willing to quit but have difficulty doing so. Little is known about the characteristics of those who are willing to quit. Methods: Using two-stage cluster sampling, we conducted a secondary analysis of a population-based household survey of 2038 adults in Aleppo, Syria. We examined the prevalence of, and reasons for, willingness to quit and compared users who were willing with those were not willing to quit based on sociodemographic, psychosocial, tobacco-related, and health-related characteristics. Results: Twelve percent of adults smoked waterpipe (n=248), of these, 56% were willing to quit, and 25% had made a quit attempt in the past year. Friends/socializing (69%) and boredom/free time (16%) were the most reported obstacles to quitting. Those who were willing to quit walked more frequently (odds ratio [OR]=1.85; 95% confidence interval [CI]=1.24-2.77), ate less fruit (OR=0.56; CI=0.42-0.73), and were more likely to experience sneezing/blocked nose (OR=2.55, CI=1.22-5.34). Compared to users who did not also smoke cigarettes, dual users who were willing to quit cigarettes were more likely to be willing to quit waterpipe (OR=2.32; CI=1.24-4.34), whereas dual users who were not willing to quit cigarettes were less likely to be willing to quit waterpipe (OR=0.24; CI=0.10-0.58). Conclusion: Many waterpipe users are willing to quit and perceive the loss of positive social functions as a major obstacle. Very few sociodemographic, tobacco-related, psychosocial, or health-related characteristics are associated with willingness to quit. However, quitting efforts may benefit from targeting dual users who are motivated to quit using all tobacco products

Sex-specific association of ambient temperature with urine biomarkers in Southwest coastal Bangladesh

Introduction: Men are vulnerable to ambient heat-related kidney disease burden; however, limited evidence exists on how vulnerable women are when exposed to high ambient heat. We evaluated the sex-specific association between ambient temperature and urine electrolytes, and 24-hour urine total protein, and volume.Methods: We pooled a longitudinal 5624 person-visits data of 1175 participants\u27 concentration and 24-hour excretion of urine electrolytes and other biomarkers (24-hour urine total protein and volume) from southwest coastal Bangladesh (Khulna, Satkhira, and Mongla districts) during November 2016 to April 2017. We then spatiotemporally linked ambient temperature data from local weather stations to participants\u27 health outcomes. For evaluating the relationships between average ambient temperature and urine electrolytes and other biomarkers, we plotted confounder-adjusted restricted cubic spline (RCS) plots using participant-level, household-level, and community-level random intercepts. We then used piece-wise linear mixed-effects models for different ambient temperature segments determined by inflection points in RCS plots and reported the maximum likelihood estimates and cluster robust standard errors. By applying interaction terms for sex and ambient temperature, we determined the overall significance using the Wald test. Bonferroni correction was used for multiple comparisons.Results: The RCS plots demonstrated nonlinear associations between ambient heat and urine biomarkers for males and females. Piecewise linear mixed-effects models suggested that sex did not modify the relationship of ambient temperature with any of the urine parameters after Bonferroni correction (P \u3c 0.004).Conclusion: Our findings suggest that women are as susceptible to the effects of high ambient temperature exposure as men

Urinary angiotensinogen is associated with albuminuria in adults with sickle cell anaemia

We explored the association of novel urinary biomarkers with albumin-creatinine ratio (ACR) in adults with sickle cell anaemia. Of 37 participants, 13 (35.2%) had persistent albuminuria (PA). Urinary levels of clusterin (p = 0.002), retinol-binding protein 4 (p = 0.008), alpha-1 microglobulin (p = 0.002) and angiotensinogen (p = 0.006) were significantly higher in participants with PA than in those without PA. Although univariate analysis showed significant associations between both alpha-1 microglobulin (p = 0.035) and angiotensinogen (p = 0.0021) with ACR, only angiotensinogen was associated with ACR in multivariable analysis (p = 0.04). Our results suggest that urinary angiotensinogen may identify sickle cell anaemia patients at risk for kidney disease

Potential Impact of Criteria Modifications on Race and Sex Disparities in Eligibility for Lung Cancer Screening

Introduction: Low-dose computed tomography (LDCT) screening reduces lung cancer mortality, but current eligibility criteria underestimate risk in women and racial minorities. We evaluated the impact of screening criteria modifications on LDCT eligibility and lung cancer detection. Methods: Using data from a Lung Nodule Program, we compared persons eligible for LDCT by the following: U.S. Preventive Services Task Force (USPSTF) 2013 criteria (55–80 y, ≥30 pack-years of smoking, and ≤15 y since cessation); USPSTF2021 criteria (50–80 y, ≥20 pack-years of smoking, and ≤15 y since cessation); quit duration expanded to less than or equal to 25 years (USPSTF2021-QD25); reducing the pack-years of smoking to more than or equal to 10 years (USPSTF2021-PY10); and both (USPSTF2021-QD25-PY10). We compare across groups using the chi-square test or analysis of variance. Results: The 17,421 individuals analyzed were of 56% female sex, 69% white, 28% black; 13% met USPSTF2013 criteria; 17% USPSTF2021; 18% USPSTF2021-QD25; 19% USPSTF2021-PY10; and 21% USPSTF2021-QD25-PY10. Additional eligible individuals by USPSTF2021 (n = 682) and USPSTF2021-QD25-PY10 (n = 1402) were 27% and 29% black, both significantly higher than USPSTF2013 (17%, p \u3c 0.0001). These additional eligible individuals were 55% (USPSTF2021) and 55% (USPSTF2021-QD25-PY10) of female sex, compared with 48% by USPSTF2013 (p \u3c 0.05). Of 1243 persons (7.1%) with lung cancer, 22% were screening eligible by USPSTF13. USPSTF2021-QD25-PY10 increased the total number of persons with lung cancer by 37%. These additional individuals with lung cancer were of 57% female sex (versus 48% with USPSTF2013, p = 0.0476) and 24% black (versus 20% with USPSTF2013, p = 0.3367). Conclusions: Expansion of LDCT screening eligibility criteria to allow longer quit duration and fewer pack-years of exposure enriches the screening-eligible population for women and black persons

Specific antibody responses to ICD protein depicted as ELISA titers.

<p>Serum Antibodies were detected by the recombinant, <i>H. pylori</i> ICD in sera samples of patients with gastroduodenal pathology such as gastritis and ulcer and were compared to clinically healthy individuals, 18 of those were detected negative by UBA. Table in the inset reveals significance or otherwise of the student's <i>t</i> test for the antibody titers obtained for various disease conditions. Two tailed <i>p</i> values were obtained through student's <i>t</i> test with a 95% power (level of significance) and a minimally significant <i>p</i> value of 0.05.</p

Results of the IL-8 ELISA performed using cultured human macrophages stimulated by the recombinant ICD of <i>H. pylori</i>.

<p>ELISA titers from unstimulated (US) macrophages were used as negative control and those from macrophages stimulated with a known proinflammatory protein JHP940 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001481#pone.0001481-Rizwan1" target="_blank">[30]</a> were used as a positive control. ICD did not induce any significant IL-8 response as compared to control; the JHP940 protein on the other hand revealed significantly high levels of IL-8 as compared to ICD (<i>p</i><0.0218).</p