Monogenetic forms of diabetes represent 1%-5% of all diabetes cases and are caused by mutations in a single gene. These mutations, that affect genes involved in pancreatic β-cell development, function and survival, or insulin regulation, may be dominant or recessive, inherited or de novo. Most patients with monogenic diabetes are very commonly misdiagnosed as having type 1 or type 2 diabetes. The severity of their symptoms depends on the nature of the mutation, the function of the affected gene and, in some cases, the influence of additional genetic or environmental factors that modulate severity and penetrance. In some patients, diabetes is accompanied by other syndromic features such as deafness, blindness, microcephaly, liver and intestinal defects, among others. The age of diabetes onset may also vary from neonatal until early adulthood manifestations. Since the different mutations result in diverse clinical presentations, patients usually need different treatments that range from just diet and exercise, to the requirement of exogenous insulin or other hypoglycemic drugs, e.g., sulfonylureas or glucagon-like peptide 1 analogs to control their glycemia. selleck compound As a consequence, awareness and correct diagnosis are crucial for the proper management and treatment of monogenic diabetes patients. In this chapter, we describe mutations causing different monogenic forms of diabetes associated with inadequate pancreas development or impaired β-cell function and survival, and discuss the molecular mechanisms involved in β-cell demise.Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by pancreatic islet inflammation (insulitis) and specific pancreatic β-cell destruction by an immune attack. Although the precise underlying mechanisms leading to the autoimmune assault remain poorly understood, it is well accepted that insulitis takes place in the context of a conflicting dialogue between pancreatic β-cells and the immune cells. Moreover, both host genetic background (i.e., candidate genes) and environmental factors (e.g., viral infections) contribute to this inadequate dialogue. Accumulating evidence indicates that type I interferons (IFNs), cytokines that are crucial for both innate and adaptive immune responses, act as key links between environmental and genetic risk factors in the development of T1D. This chapter summarizes some relevant pathways involved in β-cell dysfunction and death, and briefly reviews how enteroviral infections and genetic susceptibility can impact insulitis. Moreover, we present the current evidence showing that, in β-cells, type I IFN signaling pathway activation leads to several outcomes, such as long-lasting major histocompatibility complex (MHC) class I hyperexpression, endoplasmic reticulum (ER) stress, epigenetic changes, and induction of posttranscriptional as well as posttranslational modifications. MHC class I overexpression, when combined with ER stress and posttranscriptional/posttranslational modifications, might lead to sustained neoantigen presentation to immune system and β-cell apoptosis. This knowledge supports the concept that type I IFNs are implicated in the early stages of T1D pathogenesis. Finally, we highlight the promising therapeutic avenues for T1D treatment directed at type I IFN signaling pathway.Cellular senescence is a critical part of human anti-tumor defence; however, the accumulation of senescent cells with age underpins a wide range of pathologies. Senescent change in immune cells, or immunosenescence, has a wide range of physiological effects and is at least partially responsible for many diseases associated with aging. Immunosenescence underpins inflammaging, increased vulnerability to infectious disease with age, malignant change in the elderly, and auto-immunity. Understanding the effects and mechanisms of immunosenescence will improve disease outcomes and prevention in older adults, and generate new treatments for common illnesses. In this review we summarize the key changes occurring in immunosenescence across each facet of the immune system, and identify their clinical correlates. Experimental studies suggest that lipids affect bone metabolism. We aimed to elucidate whether lipid levels are associated with bone mineral density (BMD) in a cohort of postmenopausal women. A cross-sectional study of participants in the Chronic Ailment Reduction after MENopause (CARMEN) cohort. Women underwent assessment of clinical and analytical parameters, including fasting lipid levels. BMD was assessed at both lumbar spine and hip. Homogeneity in the cohort was optimized by filtering out a series of confounding variables with a known impact on bone. Association of BMD at lumbar spine and femoral neck with lipid levels. A total of 667 of the 1304 screened women were analyzed. A strong correlation was revealed between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in univariate analysis. Multivariate analysis detected a significant positive association of HDL-C with BMD at both spine (p = 0.007) and femoral neck (p = 0.013). Other independent predictors of spine BMD were years since menopause (ysm, negatively associated), and body mass index (BMI) and estradiol, both positively associated with BMD. The other independent variables in the femoral neck were ysm and glucose (negatively associated) and BMI, estradiol, and phosphate, all positively associated with BMD. Levels of HDL-C, but not TC, LDL-C or triglycerides, were positively associated with BMD at both the lumbar spine and femoral neck in a homogeneous cohort of postmenopausal women.Levels of HDL-C, but not TC, LDL-C or triglycerides, were positively associated with BMD at both the lumbar spine and femoral neck in a homogeneous cohort of postmenopausal women. The aim of the present randomized placebo-controlled single-center study was to assess the efficacy and safety of a new vaginal gel (Meclon Idra - Alfasigma) in the treatment of vulvovaginal atrophy (VVA). The gel is composed of sea buckthorn (Hippophaë rhamnoides) oil, aloe vera, 18β-glycyrrhetic acid, hyaluronic acid and glycogen. The study assessed whether the gel can reduce VVA symptoms (vaginal dryness, itching, burning sensation) and improve sexual function in postmenopausal women over 12 weeks. Postmenopausal women (n° = 60) reporting VVA symptoms were recruited and randomized in a 11 ratio to the gel or placebo. Active vaginal gel or placebo was applied for 14 days and then twice a week for 90 consecutive days. The Vaginal Health Index (VHI), including vaginal pH, was used to assess changes in objective signs, whereas the self-reported Female Sexual Function Index (FSFI) was used to investigate sexual function. Meclon Idra was effective in reducing vaginal pain, dyspareunia and vaginal pH, with the VHI showing significant improvement at day 90 (P < .