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The global obesity epidemic that was previously reported [1,2] is now to worsen with obesity to double in 73 countries around the world [3,4]. Improving the health of obese individuals by dietary restriction, anti-obese foods and increased physical activity [1] has not reduced the global obesity epidemic. Obesity is linked to nonalcoholic fatty liver disease (NAFLD) [5,6] with complications relevant to the metabolic syndrome and cardiovascular disease [7]. Appetite control has become critical to endocrinology and metabolism with the apelinergic pathway and nuclear receptor Sirtuin 1 (Sirt 1) now connected to the endocrine system [8] and critical to metabolism. The apelin-Sirt 1 interaction involves nitric oxide (NO) [9] that is now considered as the defect [10] in the interaction between the peptide apelin and calorie sensitive gene Sirt 1 involved in NO imbalances in the adipose tissue, liver and the brain.

Methylenetetrahydrofolate Reductase (MTHFR) is an important enzyme of the folate cycle, which is required to convert 5,10-methyltetrahydrofolate into 5-methyltetrahydrofolate (5-methylTHHF). 5-methyl THF is a methyl group donor for several cellular methylation processes. It also donates methyl group for the conversion of homocysteine into methionine, the higher concentration of which is toxic. MTHFR gene C677T polymorphism is clinically important polymorphism and the variant MTHFR (A222V) enzyme has reduced activity, hence increasing the requirement for folic acid. Less conversion of folate to 5-methyl-THF due to C677T polymorphism results in a higher plasma concentration of homocysteine (hyperhomocysteinemia). Individuals having C677T polymorphism are susceptible to various diseases, including reproductive problems like male infertility, polycystic ovary syndrome, Recurrent Pregnancy Loss (RPL), Preeclampsia (PE), placental abruption, and adverse pregnancy outcomes. MTHFR C677T polymorphism mimics folate deficiency, and folate is required for DNA synthesis, repair, methylation, and proper chromosome segregation, and all these processes are important for foetal growth and normal development. Methylation and demethylation processes control the gene expression of about 45% of human genes. Impaired methylation influences the expression of genes involved in the regulation of hormones, spermatogenesis, and oogenesis. In males, oxidative stress damages sperm DNA decreases sperm motility, and may impair fertilization capability. In pregnant women, hyperhomocysteinemia increases oxidative stress and inflammation within the placenta, which causes damage to placental tissue, impairs its function, and disrupts foetal development. Further, hyperhomocysteinemia (HHcy) is embryotoxic and neurotoxic and is responsible for congenital anomalies in the foetus. This review supports the idea that MTHFR C677T polymorphism is associated with an increased risk for male infertility, PCOS, RPL, PE, and congenital anomalies. This review may provide a clue toward a better understanding of the correlation between the MTHFR C677T polymorphism and its detrimental effects on human reproductive health.

The responsiveness of hypertensive subjects to different types of physical exercises and length of intervention, has been investigated in samples of our dynamic cohort study (“Move for Health” program) based on spontaneous demand for healthy lifestyle with supervised exercises and dietary counseling. After clinical selection and baseline assessments they were spontaneously assigned to exercise protocols of strength (PAc) isolated or combined with endurance (walking) exercises (PMi) daily or in alternated days(PMiA), hydrogymnastics(PHy) and tread mill high- intensity exercises(PHit), applied during 10(experiment 1) and 20(experiment 2) weeks of intervention. Baseline demographic, socioeconomic, anthropometric and physical activity and fitness characteristics were similar among protocols. Ten-week training improved VO2max. Similarly in all protocols while hand grip increased only in PAc. In average, there was a 16% reduction rate of hypertension rate from baseline with both, SBP and DBP, reduced by PHy and only SBP by the PMi. After adjustments hypertension was more reduced by PAc, PMi and PHy. In the 20-week experiment, higher SBP was similarly reduced by PAc or PMiA and DBP by PMiA, after adjustments. Hence, so far, our generated data suggest physical exercises as an effective tool for hypertension reduction, from 10 weeks to 3 year-long supervised protocols composed by surface or aquatic activities with strength or endurance exercises. PAc takes longer and short-period responsiveness can be achieved by either combined (strength-endurance) or hydrogymnastic exercises. Thus, exercise training is a time-and type-dependent tool, feasible, costless and scientific-based rheostatic-allostatic alternative for the current “sick-care” drug-dependent homeostatic approach to hypertension med care.

Although exercise has been proposed to be beneficial to type 2 diabetes, its effects on β-cell function and mass remain unclear. In the present study, the effects of long-term swimming training on the function and mass of β-cells in diabetic OLETF rats were examined. At 44 weeks of age after developing diabetes, the OLETF rats were divided into two groups: a control group and an exercise group. The exercise group had a daily swimming for 12 weeks. While not found with the control rats, in the obese OLETF rats, the exercise reduced the weight gain which was associated with improved glucose tolerance and elevated circulating insulin levels as determined by the oral glucose tolerance test and insulin ELISA. The exercise improved plasma total cholesterol and triglyceride levels, and also significantly increased the islet β-cell mass and pancreatic insulin content associated with decreased β-cell apoptosis and elevated activation of the serine/threonine kinase, Akt. The present studies suggest that exercise improves diabetes symptoms via enhancement of the β-cell mass and function through decreasing glucolipotoxicity and reducing β-cell apoptosis by activating Akt in obese OLETF rats.

Aims: Histological diagnostic criteria are used for the assessment of the degree of dysplasia and hence the risk of cancer progression for premalignant lesions. Clonal changes in the form of hyperorthokeratosis and hyperchromasia that are sharply demarcated from adjacent areas are not currently part of the criterion for dysplasia diagnosis. The objective of this study was to determine whether such clonal change should be regarded as a diagnostic feature for dysplasia. The following histological conditions were used to define such change: (1) hyperorthokeratosis; (2) hyperchromatism but no other features of dysplasia; (3) sharp margin demarcation from adjacent area by both the hyperorthokeratosis and hyperchromasia (clonal change), and (4) no prominent rete ridges, marked acanthosis or heavy inflammation. Lesions fitting these criteria were termed orthokeratotic lesions with no dysplasia. Methods: Patients from a population-based longitudinal study with more than 10 years of follow up were analyzed. Of the 214 patients with primary oral premalignant lesions, 194 had mild or moderate dysplasia (dysplasia group) and 20 fit the criteria for orthokeratotic lesions without dysplasia (orthokeratotic with no dysplasia group). The two groups were compared for their cancer risks using clinical (site and toluidine blue), histological (nuclear phenotype score), and molecular criteria (loss of heterozygosity) and by outcome (progression). Results and conclusions: The lesions from orthokeratotic with no dysplasia group showed a similar cancer risk (clinical, histological and molecular risk) and time to progression as the dysplastic lesions. We recommend that the clonal change should be included as a criterion for dysplasia diagnosis

Hypertension (HTN) is a widely prevalent disease across the globe. Recent reports from National Health and Nutrition Examination Surveys (NHANES) indicate that the prevalence of HTN is 29% in adults more than 18 years in the US [1]. This is about 72 million adults. Worldwide, about 1.3 billion people are affected by HTN [2]. This number is projected to increase several-fold in the coming years. Given the huge burden of this disease to the healthcare system and the many deleterious effects that can result from uncontrolled HTN, we need strong guidelines to manage the same. The recently published 2017 ACC/AHA guidelines [3] on hypertension management are very meticulous and include a comprehensive stepwise approach in treating hypertension. Here we present a summary of the major changes and a concise review of the new guidelines.

With the increase in incidence and prevalence of myeloid neoplasms in India, it has become a necessity to understand its molecular mechanisms, acquisition of genomic alterations, and understand its primary and secondary resistance pathways which ultimately impact the decision of therapeutics. The objective of this review is to investigate the molecular aspects of this disease type and identify the biomarkers that help with diagnosis, risk assessment, prognosis, and selecting the best line of treatment for a specific myeloid neoplasm. Advancements and innovations in molecular technologies from simplest Real-Time PCR to high throughput next-generation sequencing have played a vital role in screening the most common mutations and fusions to the novel and rare. Molecular technologies have helped to enumerate the genomic landscape of myeloid malignancies. The understanding of both- the mechanisms and the technology is a strong combination as it has helped revolutionize precision oncology and helped in giving better therapeutic choices with better clinical outcomes. The importance of cellular morphology, clinical symptoms, and molecular pathology in assessing the risk of myeloid malignancies is emphasized and summarized in the review. The review concludes that understanding molecular pathogenesis can be improved by using clinical-pathological-molecular strategies for diagnosis and therapy decision-making.

Aim: The aim of the present study is to assess the efficacy and safety of Hydroxychloroquine in comparison with Teneligliptin in type 2 diabetes patients whose blood glucose levels were inadequately controlled with metformin, Glimepiride and insulin therapy. Methods: This was a randomized, prospective, parallel-group, experimental trial done in 300 Type 2 Diabetes patients who were uncontrolled (HbA1c=7.5–10%) with metformin, Glimepiride and insulin therapy. Patients were randomly divided into two groups one received Teneligliptin 20 mg (n=152) and other received Hydroxychloroquine 400 mg (n=148) while continuing insulin therapy with other 2 OHA. Insulin doses were adjusted to maintain normal blood glucose levels. Result: The adjusted mean change from baseline to endpoint in HbA1c was −1.2±0.5% in patient group receiving Hydroxychloroquine and −0.9±0.5% in patients group receiving Teneligliptin, respectively, with a significant between-treatment difference (p<0.001). The incidence of adverse events was similar in the Hydroxychloroquine (72%) and Teneligliptin (77%) groups. However, hypoglycaemic events were less common (p<0.001) and less severe (p<0.05) in patients receiving Hydroxychloroquine than in those receiving Teneligliptin. Conclusion: Hydroxychloroquine decreases HbA1c in patients whose type 2 diabetes is poorly controlled with high doses of insulin as compare to Teneligliptin. Addition of hydroxychloroquine to insulin therapy is also associated with reduced incidence of confirmed and severe hypoglycaemia.

Atherosclerotic cardiovascular disease (ASCVD) is globally defined as coronary heart disease, cerebrovascular disease, or peripheral arterial disease presumed to be of atherosclerotic origin and it is the leading cause of morbidity and mortality for individuals with or without diabetes and is the largest contributor to the direct and indirect catastrophic costs of cardiovascular disorder. Very common conditions coexisting into the cardiovascular risk (e.g., obesity, hypertension, diabetes and dyslipidemia) are clear risk factors for ASCVD, and diabetes itself confers independent risk. Numerous studies have shown the efficacy of controlling individual cardiovascular risk factors in preventing or slowing ASCVD in people with these disorders. In other words it is not enough control one risk factor. We need to develop novel strategies to detect and control all of them at the same time. Thus, large benefits are seen when multiple cardiovascular risk factors are addressed simultaneously. Under the current paradigm of aggressive risk factor modification in patients with cardiovascular risk, there is evidence that measures of 10-year coronary heart disease (CHD) risk among U.S. adults with cardiovascular risk have improved significantly over the past decade and that ASCVD morbidity and mortality have decreased. In Mexico the Mexican Institute of Social Security is implementing new strategies of primary and secondary prevention in order to confront this pandemic. In this review, we analyze the state of the art to approach at the same time the different cardiovascular risk factors, in an integral form because of this is the real worldwide challenge of health.

The authors present the case of a 45-year-old female patient with diabetes and chronic kidney disease (CKD). She had unsatisfactory glycemic control, and showed some intellectual limitations. Her urine exam was unremarkable, and her renal ultrasound revealed single right kidney with aspects suggesting ureteropelvic junction syndrome. Her mother had also suffered from diabetes and CKD G5D presenting in the sixth to seventh decade. An hereditary cause for CKD was considered, which led the authors to investigate an autosomal dominant cause for CKD with a tubulointerstitial phenotype, taking into account the personal and family history for diabetes and also the renal imaging; a large deletion in the HNF-1β gene was identified through Multiplex Ligand Probe Assay (MLPA) analysis, explaining the phenotype. Genetic causes of CKD should be considered in the presence of positive family history for CKD, and the coexistence of diabetes with bland urine sediment should raise the possibility of a syndromic cause of the phenotype, namely involving HNF-1β gene mutations or deletions.