Impact of a stress management program on weight loss, mental health and lifestyle in adults with obesity: a randomized controlled trial

Aim: To evaluate the impact of a stress management program on weight loss, depression, anxiety and stress as well as on the adoption of healthy lifestyle in adults with obesity. Methods: Adults with obesity who sought help for weight loss at a medical obesity clinic were consecutively enrolled in the study and were randomly assigned to the intervention or control group. All participants received standard instructions for a healthy lifestyle. The intervention group attended an 8-week stress management program that comprised diaphragmatic breathing, progressive muscle relaxation, guided visualization and instructions about healthy nutrition/dietary habits. Anthropometric parameters were assessed and several questionnaires were completed by all participants, at the beginning and at the end of the study. Results: A total of 45 adults (mean age±SD 45.7±10.55 years) with obesity were enrolled in the study; 22 in the intervention group and 23 in the control group. Participants in the two groups were matched for age and BMI. Participants in the intervention group achieved a significantly larger reduction in BMI compared to the control group (ΔBMI -3.1 vs. -1.74 kg/m2 respectively, P<0.001). In addition, they displayed ameliorated depression and anxiety scores and a reduction in the health locus of control based on chance

HCV genetics and genotypes dictate future antiviral strategies

At the end of the 1980s, the hepatitis C virus (HCV) was cloned and formally identified as the cause of the majority of non-A and non-B hepatitis cases. Today, around 170 million people worldwide are infected with HCV, making it five times more common than infection with the human immunodeficiency virus (HIV).  Several methods exist which mediate the spread of infection. One of the most common and efficient is sharing or re-using injecting equipment; studies have indicated that 80-90% of individuals in some populations of intravenous drug users test positive in serum HCV assays. Contracting HCV from infected blood transfusions was also a major cause of infection before screening tests were introduced in the early 1990s.  Other possible, but less common, methods of infection transmission include mother-to-child during pregnancy, sexual contact and nosocomial acquisition (for example between surgical or dialysis patients).  It appears that concurrent HIV-1 infection increases the risk of HCV transmission via the mother-to-child or sexual routes

Pathogenic and low-frequency variants in children with central precocious puberty

Background: Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were investigated in patients with CPP. Methods: Fifty-four index girls and two index boys with CPP were first tested by Sanger sequencing for the MKRN3 gene. All children found negative (n = 44) for the MKRN3 gene were further investigated by whole exome sequencing (WES). In the latter analysis, the status of variants in genes known to be related with pubertal timing was compared with an in-house Cypriot control cohort (n = 43). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes was designed. Results: Three previously described pathogenic MKRN3 variants located in the coding region of the gene were identified in 12 index girls with CPP. The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively found among the Cypriot CPP cohort, indicating a founder effect phenomenon. Seven other CPP girls harbored rare likely pathogenic upstream variants in the MKRN3. Among the 44 CPP patients submitted to WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1 variants in six girls, and two rare MAGEL2 variants in five girls. Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R gene appeared to be less frequent in the cohort of patients with CPP. Conclusion: The results of the present study confirm the importance of the MKRN3-imprinted gene in genetics of CPP and its key role in pubertal timing. Overall, the results of the present study have emphasized the importance of an approach that aligns genetics and clinical aspects, which is necessary for the management and treatment of CPP

Primary Generalized Glucocorticoid Resistance and Hypersensitivity Syndromes: A 2021 Update

Glucocorticoids are the final products of the neuroendocrine hypothalamic–pituitary—adrenal axis, and play an important role in the stress response to re-establish homeostasis when it is threatened, or perceived as threatened. These steroid hormones have pleiotropic actions through binding to their cognate receptor, the human glucocorticoid receptor, which functions as a ligand-bound transcription factor inducing or repressing the expression of a large number of target genes. To achieve homeostasis, glucocorticoid signaling should have an optimal effect on all tissues. Indeed, any inappropriate glucocorticoid effect in terms of quantity or quality has been associated with pathologic conditions, which are characterized by short-term or long-lasting detrimental effects. Two such conditions, the primary generalized glucocorticoid resistance and hypersensitivity syndromes, are discussed in this review article. Undoubtedly, the tremendous progress of structural, molecular, and cellular biology, in association with the continued progress of biotechnology, has led to a better and more in-depth understanding of these rare endocrinologic conditions, as well as more effective therapeutic management

Chrousos syndrome: from molecular pathogenesis to therapeutic management

BackgroundPrimary Generalized Glucocorticoid Resistance or Chrousos syndrome is a rare genetic condition characterized by end-organ insensitivity to glucocorticoids owing to inactivating mutations of the NR3C1 gene. Materials and methodsWe conducted a systematic review of the published, peer-reviewed medical literature using MEDLINE (1975 through November 2014) to identify original articles and reviews on this topic. The search terms included primary generalized glucocorticoid resistance’, Chrousos syndrome’, glucocorticoid receptor gene’ and glucocorticoid receptor mutations’. ResultsOnly a few cases of Chrousos syndrome have been described to date, ranging from asymptomatic to severe forms of mineralocorticoid and/or androgen excess. All reported cases have been associated with point mutations or deletions in the NR3C1 gene. The tremendous progress of molecular biology has enabled us to apply standard methods to investigate the molecular mechanisms of action of the mutant glucocorticoid receptors (GRs). We and others have identified and functionally characterized novel mutations causing Chrousos syndrome, while structural biology has enabled us to have a better understanding of how conformational changes of the receptor cause glucocorticoid resistance. In this review, we also present our results of the functional characterization of two recently described mutations, and we discuss the diagnostic approaches and therapeutic management of patients with Chrousos syndrome. ConclusionsAlthough Chrousos syndrome is a rare condition, many clinical cases remain unrecognized for a long time. We recommend determination of the 24-h urinary free cortisol excretion and sequencing of the NR3C1 gene in patients with hyperandrogenism and/or hypertension of unknown origin

Adrenal insufficiency

Adrenal insufficiency is the clinical manifestation of deficient production or action of glucocorticoids, with or without deficiency also in mineralocorticoids and adrenal androgens. It is a life-threatening disorder that can result from primary adrenal failure or secondary adrenal disease due to impairment of the hypothalamic-pituitary axis. Prompt diagnosis and management are essential. The clinical manifestations of primary adrenal insufficiency result from deficiency of all adrenocortical hormones, but they can also include signs of other concurrent autoimmune conditions. In secondary or tertiary adrenal insufficiency, the clinical picture results from glucocorticoid deficiency only, but manifestations of the primary pathological disorder can also be present. The diagnostic investigation, although well established, can be challenging, especially in patients with secondary or tertiary adrenal insufficiency. We summarise knowledge at this time on the epidemiology, causal mechanisms, pathophysiology, clinical manifestations, diagnosis, and management of this disorder