Diabetes mellitus epidemiology-classification, determinants, and public health impacts

Diabetes mellitus is a relatively common disease with major public health implications. Although much has been written regarding the clinical manifestations, treatment, and pathophysiology of diabetes mellitus, it remains a major problem whose rate is increasing. This article assimilates this essential information and presents diabetes from an epidemiological perspective illustrating its preventable nature and the public health necessity of confronting this emerging epidemic. Diabetes is defined conceptually and operationally. The prevalence, incidence, mortality, morbidity, cost to society, and the effectiveness of treatment and prevention are discussed. Primary preventable measures involving weight management, exercise, and glycemic control can reduce microvascular complications in diabetic patients. Macrovascular complications can be reduced by aggressive management of high blood pressure and hyperlipidemia. Early interventions can reduce specific disease complications such as end-stage renal disease, blindness, and lower extremity amputations. Future research is needed to address the implementation of effective and innovative interventions that reduce the occurrence of diabetes and its complications.     

Prevalence and Association of Physical Activity with Obesity: An Urban,Community-Based,Cross-Sectional Study

Aim:To study levels of physical activity and various measures of obesity and their association in an urban population.Results:Physical Activity (PA) levels declined with age and the decline was greater among females. The Pearson''s correlation coefficient for age against PA among males was found to be negative and weak (r = –0.104) and that among females was found to be similar (r = –0.206). The prevalence of obesity was higher among females (28.8 %) than among males (13.3 %) and the difference was statistically significant. There was a progressive increase in abdominal obesity with age in both genders. The prevalence of overweight and obesity was higher among individuals with low levels of PA as compared to those with high levels of PA.Conclusion:Sedentary behavior is prevalent in more than half of the current study sample. This was more so with increasing age, female gender and increasing obesity. PA is an important component on long-term weight control, and therefore adequate levels of activity should be prescribed to combat the obesity epidemic. Habitual moderate physical activity may be beneficial in preventing excess accumulation of fat.     

Ovariectomy exacerbates oxidative stress and cardiopathy induced by adriamycin.

Ovarian hormone depletion in ovariectomized experimental animals is a useful model with which to study the physiopathological consequences of menopause in women. It has been suggested that menopause is a risk factor for the induction of several cardiovascular disorders. In the present study we analyzed the effects of ovarian hormone depletion by ovariectomy (OVX) in a model of oxidative stress and cardiopathy induced by adriamycin (AD). To evaluate these effects, we measured parameters related to cardiac damage (creatinine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase) and oxidative stress (malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione, nitric oxide and carbonyl proteins) in cardiac tissue and erythrocytes. OVX was found to alter all markers of oxidative stress and cell damage in cardiac tissue. Similarly, the OVX-derived loss of ovarian hormones enhanced cardiac damage and oxidative stress induced by AD. Our results suggest that antioxidant status in cardiac tissue and erythrocytes is seriously compromised by OVX during the cardiomyopathy induced by AD in experimental animals. In conclusion, the absence of hormones caused by OVX or menopause may induce or accelerate pre-existing cardiovascular dysfunctions.     

Ultraviolet B radiation-induced skin cancer in mice defective in the Xpc, Trp53, and Apex (HAP1) genes: genotype-specific effects on cancer predisposition and pathology of tumors

Mutations in nucleotide excision repair (NER) genes in humans result in the UV-induced skin cancer-prone disease xeroderma pigmentosum (XP). Mouse models that mimic XP have provided an informative experimental system with which to study DNA repair, as well as the molecular pathology of UV radiation-induced skin cancer. We reported previously that mice defective in the Xpc gene (Xpc-/-) are highly predisposed to UVB radiation-induced skin cancer and that the appearance of skin cancer is more rapid in Xpc Trp53 double mutants. Extended studies now demonstrate an increased predisposition to UVB radiation-induced skin cancers in Xpc heterozygous mice compared with normal mice. We also show that Xpc Trp53 double heterozygous mutants are more predisposed to skin cancer than Trp53 single heterozygous mice. No mutations were detected in the cDNA of the remaining Xpc allele, suggesting that haploinsufficiency of the Xpc gene may be operating and is a risk factor for UVB radiation-induced skin cancer in mice. Skin tumors from Xpc-/- mice were exclusively well or moderately well-differentiated squamous cell carcinomas. In Xpc+/+ and Xpc+/- mice, many of the squamous cell carcinomas were less well differentiated. We also documented previously increased predisposition to UV radiation-induced skin cancers in Xpc-/- Apex+/- mice. Here we show the absence of mutations in the cDNA of the remaining Apex allele, a further suggestive indication of haploinsufficiency and its resulting predisposition to skin cancer. The Trp53 and Apex heterozygous conditions altered the skin tumor spectrum to more poorly differentiated forms in all Xpc genotypes.     

Regulation of onco and tumor suppressor MiRNAs by mTORC1 inhibitor PRP-1 in human chondrosarcoma

Metastatic chondrosarcoma of mesenchymal origin is the second most common bone malignancy and does not respond either to chemotherapy or radiation; therefore, the search for new therapies is relevant and urgent. This study aimed to reveal the comparative analysis of miRNAs and their targets in human JJ012 chondrosarcoma cell line between control and experimental samples, treated with mTORC1 inhibitor, cytostatic antiproliferative proline-rich polypeptide (PRP-1). Examination of tumor-specific microRNA expression profiles has revealed widespread deregulation of these molecules in diverse cancers. It was reported that microRNAs can function as novel biomarkers for disease diagnostics and therapy, as well as a novel class of oncogenes and tumor suppressor genes. mTORC 1 inhibitor PRP-1 caused significant upregulation of tumor suppressors, such as miR20a, miR125b, and miR192; and downregulation of onco miRNAs, miR509-3p, miR589, miR490-3p, miR 550 in human chondrosarcoma JJ012 cell line.     

Reconstruction of a lower eyelid defect with a V to Y island flap

Repair of full thickness defects in the lower eyelid following extirpation of malignant tumors presents a challenge to the reconstructive surgeon. There are several techniques to choose from, depending on the defect's size and location.     

The role of mutant protein level in autosomal recessive catecholamine dependent polymorphic ventricular tachycardia (CPVT2)

Humans and genetically engineered mice with recessively inherited CPVT develop arrhythmia which may arise due to malfunction or degradation of calsequestrin (CASQ2). We investigated the relation between protein level and arrhythmia severity in CASQ2^D307H/D307H (D307H), compared to CASQ2^Δ/Δ (KO) and wild type (WT) mice. CASQ2 expression and Ca²⁺ transients were recorded in cardiomyocytes from neonatal or adult mice. Arrhythmia was studied in vivo using heart rhythm telemetry at rest, exercise and after epinephrine injection. CASQ2 protein was absent in KO heart. Neonatal D307H and WT hearts expressed significantly less CASQ2 protein than the level found in the adult WT. Adult D307H expressed only 20% of CASQ2 protein found in WT. Spontaneous Ca²⁺ release was more prevalent in neonatal KO cardiomyocytes (89%) compared to 33–36% of either WT or D307H, respectively, p < 0.001. Adult cardiomyocytes from both mutant mice had more Ca²⁺ abnormalities compared to control (KO: 82%, D307H 63%, WT 12%, p < 0.01). Calcium oscillations were most common in KO cardiomyocytes. We then treated mice with bortezomib to inhibit CASQ2^D307H degradation. Bortezomib increased CASQ2 expression in D307H hearts by ∼50% (p < 0.05). Bortezomib-treated D307H mice had lower CPVT prevalence and less premature ventricular beats during peak exercise. No benefit against arrhythmia was observed in bortezomib treated KO mice. These results indicate that the mutant CASQ2^D307H protein retains some of its physiological function. Its expression decreases with age and is inversely related to arrhythmia severity. Preventing the degradation of mutant protein should be explored as a possible therapeutic strategy in appropriate CPVT2 patients.