Hypogonadotropic hypogonadism due to compound heterozygous mutations TACR3 in siblings

The authors present a new association of two heterozygous TACR3 mutations (p.Arg230His and p.Trp275*) responsible for a clinical trait of normosmic congenital hypogonadotropic hypogonadism in a family.info:eu-repo/semantics/publishedVersio

Children with Type 1 Diabetes of Early Age at Onset - Immune and Metabolic Phenotypes

Objectives We aimed to evaluate children with type 1 diabetes (T1D) with early age at onset (EAO) for clinical, immune and metabolic features in order to identify age-related disease phenotypes. Methods Comparative study of two groups of T1D children: EAO (≤5 years) and later age at onset (LAO; >5 years), regarding the presence of other autoimmune (AI) diseases, diabetes ketoacidosis and immunologic profile at onset and metabolic data 1 year after diagnosis. Statistical analysis was performed with significance set for p < 0.05. Results The study included 137 children (EAO = 52, mean age 3.6 ± 1.5 [mean ± standard deviation (SD)] and LAO = 85, mean age 10.4 ± 2.9). EAO was more associated with concomitant AI diseases (p = 0.032). Despite no differences in disease onset, EAO presented with lower C-peptide levels (p = 0.01) and higher absolute lymphocyte number (p < 0.0001), with an inverse correlation between these two variables (p = 0.028). Additionally, the EAO group had a higher frequency of serum detection of three antibodies (Abs) (p = 0.0008), specifically insulin Abs (p = 0.0001). One year after diagnosis, EAO had higher total daily insulin (TDI) dose (p = 0.008), despite similar hemoglobin A1c (HbA1c). Conclusions Our data show an association of EAO T1D with more AI diseases, higher number of Abs, lower initial insulin reservoir and higher insulin requirements 1 year after diagnosis. In this group, immune imbalance seems more evident and disease progression faster, probably reflecting distinct "immune environment" with different ages at disease onset. Further studies in the field of immunogenetics and immune tolerance are required, to improve patient stratification and find novel targets for therapeutic intervention.info:eu-repo/semantics/publishedVersio

The Untold Story of Welfare Fraud

The experiences of women who have been charged with welfare fraud in the years following the passage of the 1996 Personal Responsibility and Work Opportunity Reconciliation Act cast a shadow over the claim that welfare reform has been an unequivocal success. This article addresses this under-explored issue by considering the face of welfare fraud in San Diego, California after the change to federal welfare law. After a brief discussion of the socio-historical context of welfare fraud prosecution and a summary of the scholarly findings related to welfare fraud post-PRWORA, the aiticle details a new poverty knowledge about welfare fraud drawn from the experiences of women. This is followed by a discussion of how this knowledge has been used to help inspire the creation of a welfare fraud diversion program that serves as an alternative to felony prosecution for first-time, low-level welfare fraud defendants in San Diego County

The Psychosocial Effects of Physical Activity on Military Veterans That Are Wounded, Injured, and/or Sick: A Narrative Synthesis Systematic Review of Quantitative Evidence

Physical activity (PA) for military veterans that are wounded, injured and/or sick (WIS) is becoming increasingly recognized as an advantageous method of increasing wellbeing. A narrative synthesis approach was used to systematically review current quanti‐ tative evidence exploring the psychological effects of PA on veterans that are WIS. Key databases were searched resulting in the inclusion of 19 studies. PA was shown to have a positive effect on post‐traumatic stress, depression, anxiety, stress, quality of life, social wellbeing, sleep quality, perceived functional impairment, participant mindfulness, and positive/negative affect; with im- provements in stress, social well-being, and positive/negative effect being greater among veterans that are WIS with lower health statuses. After comparing PA types, outdoor recreation appeared to more consistently reduce PTSD symptoms post‐intervention; whereas, yoga and horse riding were more effective in reducing anxiety and stress. Furthermore, where significant others were included in PA interventions/programs for veterans that are WIS, longer‐lasting benefits have been reported. However, in line with other reviews in this area, the methodological weaknesses of current research and non-standardized delivery of PA interven- tions limits the generalisability of the findings of this review

The anti-proliferative and anti-inflammatory response of COPD airway smooth muscle cells to hydrogen sulfide

BACKBROUND: COPD is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease caused, in part, by the aberrant function of airway smooth muscle (ASM). We have previously demonstrated that hydrogen sulfide (H2S) can inhibit ASM cell proliferation and CXCL8 release, from cells isolated from non-smokers. METHODS: We examined the effect of H2S upon ASM cells from COPD patients. ASM cells were isolated from non-smokers, smokers and patients with COPD (n = 9). Proliferation and cytokine release (IL-6 and CXCL8) of ASM was induced by FCS, and measured by bromodeoxyuridine incorporation and ELISA, respectively. RESULTS: Exposure of ASM to H2S donors inhibited FCS-induced proliferation and cytokine release, but was less effective upon COPD ASM cells compared to the non-smokers and smokers. The mRNA and protein expression of the enzymes responsible for endogenous H2S production (cystathionine-β-synthase [CBS] and 3-mercaptopyruvate sulphur transferase [MPST]) were inhibited by H2S donors. Finally, we report that exogenous H2S inhibited FCS-stimulated phosphorylation of ERK-1/2 and p38 mitogen activated protein kinases (MAPKs), in the non-smoker and smoker ASM cells, with little effect in COPD cells. CONCLUSIONS: H2S production provides a novel mechanism for the repression of ASM proliferation and cytokine release. The ability of COPD ASM cells to respond to H2S is attenuated in COPD ASM cells despite the presence of the enzymes responsible for H2S production

PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency

OBJECTIVE: Mutations of the PROP1 gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH/FSH, PRL and, less frequently, ACTH. This study was undertaken to investigate the molecular defect in a cohort of patients with CPHD. DESIGN, PATIENTS AND MEASUREMENTS: A multicentric study involving 46 cases of CPHD (17 familial cases belonging to seven kindreds and 29 sporadic cases) selected on the basis of clinical and hormonal evidence of GH deficiency, central hypothyroidism and hypogonadotrophic hypogonadism, in the absence of an identified cause of hypopituitarism. Mutations of PROP1 were investigated by DNA sequencing. Clinical, hormonal and neuroradiological data were collected at each centre. RESULTS: PROP1 mutations were identified in all familial cases: five kindreds presented a c. 301-302delAG mutation, one kindred presented a c. 358C --> T (R120C) mutation and one presented a previously unreported initiation codon mutation, c. 2T --> C. Of the 29 sporadic cases, only two (6.9%) presented PROP1 germline mutations (c. 301-302delAG, in both). Phenotypic variability was observed among patients with the same mutations, particularly the presence and age of onset of hypocortisolism, the levels of PRL and the results of pituitary imaging. One patient presented a sellar mass that persisted into adulthood. CONCLUSIONS: This is the first report of a mutation in the initiation codon of the PROP1 gene and this further expands the spectrum of known mutations responsible for CPHD. The low mutation frequency observed in sporadic cases may be due to the involvement of other unidentified acquired or genetic cause

Mismatch repair SNPs and thyroid cancer susceptibility: a potential role for the MSH6 rs1042821 (Gly39Glu) polymorphism

Abstract of the Poster presented at the 3rd ESPT Conference (European Society of Pharmacogenomics and Personalised Therapy / European Society of Pharmacogenomics and Theranostics), 7-9 October 2015, Budapest