Identification of Conformational B-cell Epitopes in Diphtheria Toxin at Varying Temperatures Using Molecular Dynamics Simulations.

The changes in temperature levels can potentially affect the toxins in terms of stability and immunological properties via alteration of their structures. Diphtheria Toxin (DT) is highly considered by scientists since its mechanism of action is similar to those of most bacterial toxins, such as botulinum, tetanus, and anthrax. The protection of conformational B-cell epitopes is critically important in the process of diphtheria vaccine production. This study aimed to evaluate the conformational changes of the DT structure at three different temperature levels (27˚C, 37˚C, and 47˚C) using molecular dynamic simulations. Secondary structures were analyzed in YASARA software. According to the results, significant decreases were observed in percentages of the β-sheets, turns, and the helices of the DT structure at 47˚C in comparison with those at 27˚C and 37˚C. Furthermore, the tertiary structure of the DT was compared at different temperatures using the contact map. Accordingly, the results showed that the root-mean-square deviation of the DT structure increased upon temperature rising. In addition, amino acids D68, G128, G171, C186, and K534-S535 at 27˚C and 37˚C, as well as amino acids G26, P38, S291, T267, H384, A356, and V518 at 47˚C showed higher root mean square fluctuation values. The finding demonstrated that the stability of the DT structure decreased at high temperature (47˚C). The solvent-accessible surface area diagram showed that the hydrophobicity of the DT structure increased via temperature rising, and the amino acid residues belonging to B-cell epitopes extended through increasing temperature. However, B-cell epitopes belonging to the junction region of chains A and B were only present at 37˚C. The results of this study are expected to be applicable for determining a suitable temperature level for the production process of the diphtheria vaccine.

Predictors of multimorbidity among the Kurdish population living in the Northwest of Iran.

BACKGROUND: There is limited information about the predictors of multimorbidity (MM) among ethnic minority older adults in Iran. This study aimed to examine the impact of sociodemographic and lifestyle factors on the prevalence of MM, among older Kurdish people living in the Northwest of Iran. METHODS: The current study was conducted in Bukan city located in West Azarbaijan province in the Northwest of Iran. The data for this study was based on the enrolment phase of a longitudinal study on ageing among the Kurdish population aged 50-94 yearswhich was designed according to the elderly component of the PERSIAN Cohort in Iran. Stratified random sampling was used to select people aged 50 + from eight health centres in Bukan from Oct 2017 to Dec 2018. Those who accepted the invitation and completed the baseline questionnaire were included in this study (N = 1493; Response rate 75%). A range of different factors,including sociodemographic and lifestyle factors as well as self-reported chronic conditions, was obtained by trained interviewers. MM was defined as "coexistence of two or more chronic conditions in the same person". We included a list of 36 diseases/conditions in this analysis. Descriptive analysis and logistic regression were performed to compare the prevalence of MM according to different factors. RESULTS: Over a third of the participants (36.6%) had ≥2chronic conditionsand 15.7% had≥3 chronic conditions. Hypertension, diabetes, musculoskeletal conditions, fatty liver, and heart diseases were common chronic conditions. In a fully adjusted logistic regression model, older age (ORadj = 1.92, 95% CI: 1.48-2.48), being female (ORadj = 1.49, 95%CI: 1.14-1.94), living without aspouse (ORadj = 1.81, 95%CI: 1.34-2.44), and inadequate consumption of fruit and vegetables (ORadj = 1.33, 95%CI: 1.06-1.67) were associated with the higher prevalence of MM. CONCLUSION: This study found that the prevalence of MM is relatively high among older Kurdishadults. Sociodemographic differences in the prevalence of MM might be of interest tothe health care system,and the prevalence of common chronic conditions in this study may highlight the need forlifestyle modifications in this community.

Role of glycogen synthase kinase following myocardial infarction and ischemia-reperfusion.

Glycogen synthase kinase-3 beta (GSK3ß) is principally is a glycogen synthase phosphorylating enzyme that is well known for its role in muscle metabolism. GSK3ß is a serine/threonine protein Kinase, which is responsible for several essential roles in mammalian cells. This enzyme is implicated in the pathophysiology of many conditions involved in homeostasis and cellular immigration. GSK3ß is involved in several pathways leading to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Increasing evidence has shown the potential importance of GSK3ß in ischemic heart disease and ischemia-reperfusion pathologies. Reperfusion injury may occur in tissues after prolonged ischemia following reperfusion. Reperfusion injury can be life threatening. Reperfusion injury occurs due to a change in ionic homeostasis, excess free radical production, mitochondrial damage and cell death. There are however clear, cardiac-protective signals; although the molecular pathophysiology is not clearly understood. In normal physiology, GSK3ß has a critical role in the cytoprotective pathway. However, it`s controversial role in ischemia and ischemia-reperfusion is a topic of current interest. In this review, we have opted to focus on GSK3ß interactions with mitochondria in ischemic heart disease and expand on the therapeutic interventions.

Reproduction and marriage among male survivors of cancer in childhood, adolescence and young adulthood: a national cohort study.

BACKGROUND: Increased survival after cancer in young age has made long-term follow-up studies of high external validity important. In this national cohort study, we explored the impact of cancer in young age on reproduction and marital status in male survivors. METHODS: Hazard ratios (HRs) and relative risks (RRs) of reproductive and marital outcomes were studied for male survivors of cancer in young age (<25 years) and cancer-free male comparisons, born during 1965-1985, by linking compulsory national registries in Norway. RESULTS: Male cancer survivors (n=2687) had reduced paternity (HR: 0.72, 95% confidence interval (CI): 0.68-0.76). This was most apparent in survivors of testicular cancer, brain tumours, lymphoma, leukemia and bone tumours, and when diagnosed with cancer before 15 years of age. Male cancer survivors were more likely to avail of assisted reproduction (RR: 3.32, 95% CI: 2.68-4.11). There was no increased risk of perinatal death, congenital malformations, being small for gestational age, of low birth weight or preterm birth in their first offspring. Male cancer survivors were less likely to marry (HR: 0.93, 95% CI: 0.86-1.00), in particular brain tumour survivors. CONCLUSIONS: In this national cohort study, we demonstrated reduced paternity and increased use of assisted reproduction among male cancer survivors, but no adverse outcome for their first offspring at birth.

Carotenoderma in a young woman of normal body mass index with hypothalamic amenorrhoea: a 2-year follow-up case report.

Hypothalamic amenorrhoea has been shown to be associated with hypercarotenaemia, but no causal link has been established. Many people are unaware of the health implications of carotenoderma. We report on a 36-year-old woman with normal body mass index and with a history of secondary amenorrhoea for 2 years and carotenoderma for 5 years. She had a history of practising a fixed-menu diet of predominantly leafy greens, exercised intensively and had a stressful job. Blood tests confirmed the presence of hypercarotenaemia and hypogonadotrophic hypogonadism. Carotenoderma subsided after 6 months of lifestyle modification, but she remained amenorrhoeic up to 12 months later. Since then, her condition had relapsed up to the time of 2 years of follow-up. We conclude that hypercarotenaemia/carotenoderma and hypothalamic amenorrhoea are manifestations of a constrained lifestyle rather than causally linked. The presence of carotenoderma should alert public individuals and clinicians, especially in primary care, alike for signs of potential health complications including reproductive dysfunction even without weight problems.

Increased uptake of social security benefits among long-term survivors of cancer in childhood, adolescence and young adulthood: a Norwegian population-based cohort study.

BACKGROUND: As the number of cancer survivors increases, their health and welfare have come into focus. Thus, long-term medical consequences of cancer at a young age (<25 years), obtained from social security benefit records, were studied. METHODS: Standardised incidence ratios (SIRs) of long-term medical consequences for 5-year cancer survivors, born during 1965-1985, were explored by linking population-based registries in Norway. RESULTS: Among the 5-year cancer survivors (4031 individuals), 29.7% received social security benefits. The survivors had an overall 4.4 times (95% confidence interval (95% CI): 4.1-4.6) higher risk of social security benefit uptake than the cancer-free population. Survivors of malignancies of bone and connective tissues (SIR: 10.8; 95% CI: 9.1-12.9), CNS tumours (SIR: 7.7; 95% CI: 6.9-8.6) and malignancies of the haematopoietic system (SIR: 6.1; 95% CI: 5.3-7.0) had the highest risks of social security benefits uptake. The most notified causes of social security benefit uptake were diseases of the nervous system, and injury and poisoning. CONCLUSION: The uptake of social security benefits among 5-year cancer survivors increased substantially and it may represent a solid outcome measure for the burden of the most severe late effects, especially in countries with comparable social welfare systems.