Congenital hypogonadotropic hypogonadism (CHH) is a rare and heterogeneous genetic disorder with variable penetrance caused by GnRH deficiency, leading to delayed puberty and infertility. In 50-60% of Show more
Congenital hypogonadotropic hypogonadism (CHH) is a rare and heterogeneous genetic disorder with variable penetrance caused by GnRH deficiency, leading to delayed puberty and infertility. In 50-60% of cases, CHH is associated with non-reproductive abnormalities, most commonly anosmia/hyposmia (Kallmann syndrome, KS). Over 60 genes have been implicated in CHH pathogenesis. We aimed to perform genetic screening in a cohort of 14 patients (10 males, 4 females; mean age 22 ± 7.72 years) with suspected or diagnosed HH/KS. Genetic analysis was conducted using next-generation sequencing (NGS) with a custom panel of 46 candidate genes. Variant interpretation followed ACMG standards and guidelines. Multiple tools were used to predict the structural effects of variants on tertiary protein structure, assessing their pathogenicity. Novel variants were functionally characterized by qRT-PCR on mRNA extracted from peripheral leukocytes. NGS identified nine rare variants and four novel variants in genes previously associated with normosmic isolated HH (nHH) and/or KS ( Show less
Correction of calcium and protein undernutrition using milk, yoghurt, and cheese in older adults in aged care homes is associated with reduced fractures and falls. However, these foods contain potenti Show more
Correction of calcium and protein undernutrition using milk, yoghurt, and cheese in older adults in aged care homes is associated with reduced fractures and falls. However, these foods contain potentially atherogenic fats. We aimed to determine whether this intervention that increased dairy consumption to recommended levels adversely affects serum lipid profiles. This was a sub-group analysis of a 2-year cluster-randomised trial involving 60 aged care homes in Australia. Thirty intervention homes provided additional milk, yoghurt, and cheese on menus while 30 control homes continued with their usual menus. A sample of 159 intervention and 86 controls residents (69% female, median age 87.8 years) had dietary intakes recorded using plate waste analysis and fasting serum lipids measured at baseline and 12 months. Diagnosis of cardiovascular disease and use of relevant medications were determined from medical records. Outcome measures were serum total, HDL and LDL cholesterol and ApoA-1 & B. Intervention increased daily dairy servings from 1.9 ± 1.0 to 3.5 ± 1.4 (p < 0.001) while controls continued daily intakes of ≤2 servings daily (1.7 ± 1.0 to 2.0 ± 1.0 (p = 0.028). No group differences were observed for serum total cholesterol/high-density lipoprotein-C (TC/HDL-C) ratio, Apoprotein B/Apoprotein A-1 (ApoB/ApoA-1) ratio, low-density lipoprotein-C (LDL-C), non-HDL-C, or triglycerides (TGs) at 12 months. Among older adults in aged care homes, correcting insufficiency in intakes of calcium and protein using milk, yoghurt and cheese does not alter serum lipid levels, suggesting that this is a suitable intervention for reducing the risk of falls and fractures. Australian New Zealand Clinical Trials Registry (ACTRN12613000228785) 2012; https://www.anzctr.org.au. Show less
Coronavirus disease 2019 (COVID-19) is an infection characterized by the dysregulation of systemic cytokine levels. The measurement of serum levels of inflammatory cyto-/chemokines has been suggested Show more
Coronavirus disease 2019 (COVID-19) is an infection characterized by the dysregulation of systemic cytokine levels. The measurement of serum levels of inflammatory cyto-/chemokines has been suggested as a tool in the management of COVID-19. The aim of this study is to highlight the significance of measured levels of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-10, IL-12(p70), IL-27, interferon (IFN)γ, interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in serum samples from infected and recovered subjects, possibly predictive of severity and/or duration of the disease. Serum samples from healthy (HD), positive at hospital admittance (T0), and recovered subjects (T1, 31-60, or 70-200 days post-negativization) were collected and tested through a bead-based cytometric assay and confirmed through ELISA. IL-10 levels were increased in the T0 group compared to both HD and T1. IL-27 significantly decreased in the 31-60 group. IL-1β significantly increased in the 70-200 day group. TNF-α significantly decreased in T0 compared to HD and in the 31-60 group versus HD. IP-10 significantly increased in T0 compared to HD. These results suggest that IP-10 could represent an early marker of clinical worsening, whereas IL-10 might be indicative of the possible onset of post-COVID-19 long syndrome. Show less