Androgens and Hypertension in Men and Women: a Unifying View.

This review was designed to revaluate the androgen role on the mechanisms of hypertension and cardiovascular risks in both men and women. Sex steroids are involved in the regulation of blood pressure, but pathophysiological mechanism is not well understood. Androgens have an important effect on metabolism, adipose and endothelial cell function, and cardiovascular risk in both men and women. A focal point in this contest is represented by the possible gender-specific regulation of different tissues and in particular of the adipose cell. Available data confirm that androgen deficiency is linked to increased prevalence of hypertension and cardiovascular diseases. Adipocyte dysfunction seems to be the main involved mechanism. Androgen replacement reduces inflammation state in man, protecting by metabolic syndrome progression. In women, androgen excess has been considered as promoting factor of cardiovascular risk. However, recent data suggest that excessive androgen production has little effect per se in inducing hypertension in young women of reproductive age. Also in postmenopausal women, data on relative androgen excess and hypertension are missing, while adrenal androgen deficiency has been associated to increased mortality. RECENT FINDINGS: Molecular mechanisms linking androgen dysregulation to hypertension are almost Unknown, but they seem to be related to increased visceral fat, promoting a chronic inflammatory state through different mechanisms. One of these may involve the recruitment and over-activation of NF-kB, a ubiquitous transcription factor also expressed in adipose cells, where it may cause the production of cytokines and other immune factors. The NF-kB signalling pathway may also influence brown adipogenesis leading to the preferential enlargement of visceral adipocytes. Chronic inflammation and adipocyte dysfunction may alter endothelial function leading to hypertension. Both in men and in women, particularly in the post-menopausal period, hypoandrogenism seems to be a major determinant of the increased prevalence of hypertension. The relationship between androgen signalling and NF-kB might explain the pathophysiological mechanism leading to the development of endothelium dysfunction and hypertension

Sex hormones in allergic conjunctivitis: altered levels of circulating androgens and estrogens in children and adolescents with vernal keratoconjunctivitis

PURPOSE: Vernal keratoconjunctivitis (VKC) is a chronic allergic disease mainly affecting boys in prepubertal age and usually recovering after puberty. To evaluate a possible role of sex hormones in VKC, serum levels of sex hormones in children and adolescents with VKC were assessed. METHODS: 12 prepubertal and 7 early pubertal boys with active VKC and 6 male patients with VKC in remission phase at late pubertal age and 48 healthy age and sex-matched subjects were included. Serum concentration of estrone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, total testosterone and free testosterone, dihydrotestosterone (DHT), cortisol, delta-4-androstenedione, follicle-stimulating hormone, luteinizing hormone, and sex-hormones binding globuline (SHBG) were evaluated. RESULTS: Serum levels of Estrone were significantly increased in all groups of patients with VKC when compared to healthy controls (P < 0.001). Prepubertal and early pubertal VKC showed a significant decrease in DHT (P = 0.007 and P = 0.028, resp.) and SHBG (P = 0.01 and P = 0.002, resp.) when compared to controls and serum levels of SHBG were increased in late pubertal VKC in remission phase (P = 0.007). CONCLUSIONS AND RELEVANCE: VKC patients have different circulating sex hormone levels in different phases of the disease and when compared to nonallergic subjects. These findings suggest a role played by sex hormones in the pathogenesis and/or activity of VKC

Can Doughnut Economics fill Amsterdam’s dietary needs? : a critical examination of the city’s new circular and climate strategy

Award date: 17 June 2022. Supervisor: Professor Diane Stone, School of Transnational GovernanceThe thesis explores Amsterdam’s engagement with Doughnut Economics as a conceptual tool with policy implications to become an ecologically safe and socially just city. The Doughnut wishes to harmonize humanity’s well-being with Earth’s planetary resources. Accordingly, this research asks: “to what extent and under what conditions can Doughnut Economics be a tool for transformative action within the city of Amsterdam?” This dissertation examines what players gather to form coalitions to advocate for the Doughnut implementation. Advocacy Coalition Framework (ACF) and systems thinking provide the theoretical frameworks, and a qualitative methodology supports the primary data collection. The interview findings suggest that there is a fruitful ACF in the city thanks to fluid and diffused actors’ alignments. From its theoretical base, the Doughnut becomes a tool with policy application through the actors’ capacity to align, create learning processes and bring policy change forward in the city

Single muscle fiber proteomics reveals unexpected mitochondrial specialization

Mammalian skeletal muscles are composed of multinucleated cells termed slow or fast fibers according to their contractile and metabolic properties. Here, we developed a high-sensitivity workflow to characterize the proteome of single fibers. Analysis of segments of the same fiber by traditional and unbiased proteomics methods yielded the same subtype assignment. We discovered novel subtype-specific features, most prominently mitochondrial specialization of fiber types in substrate utilization. The fiber type-resolved proteomes can be applied to a variety of physiological and pathological conditions and illustrate the utility of single cell type analysis for dissecting proteomic heterogeneity

A Smo/Gli multitarget hedgehog pathway inhibitor impairs tumor growth

Pharmacological Hedgehog (Hh) pathway inhibition has emerged as a valuable anticancer strategy. A number of small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector glioma-associated oncogene 1 (Gli1) has been designed and developed. In a recent study, we exploited the high versatility of the natural isoflavone scaffold for targeting the Hh signaling pathway at multiple levels showing that the simultaneous targeting of Smo and Gli1 provided synergistic Hh pathway inhibition stronger than single administration. This approach seems to effectively overcome the drug resistance, particularly at the level of Smo. Here, we combined the pharmacophores targeting Smo and Gli1 into a single and individual isoflavone, compound 22, which inhibits the Hh pathway at both upstream and downstream level. We demonstrate that this multitarget agent suppresses medulloblastoma growth in vitro and in vivo through antagonism of Smo and Gli1, which is a novel mechanism of action in Hh inhibition

MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2 activity

The myogenic regulatory factor MRF4 is highly expressed in adult skeletal muscle but its function is unknown. Here we show that Mrf4 knockdown in adult muscle induces hypertrophy and prevents denervation-induced atrophy. This effect is accompanied by increased protein synthesis and widespread activation of muscle-specific genes, many of which are targets of MEF2 transcription factors. MEF2-dependent genes represent the top-ranking gene set enriched after Mrf4 RNAi and a MEF2 reporter is inhibited by co-transfected MRF4 and activated by Mrf4 RNAi. The Mrf4 RNAi-dependent increase in fibre size is prevented by dominant negative MEF2, while constitutively active MEF2 is able to induce myofibre hypertrophy. The nuclear localization of the MEF2 corepressor HDAC4 is impaired by Mrf4 knockdown, suggesting that MRF4 acts by stabilizing a repressor complex that controls MEF2 activity. These findings open new perspectives in the search for therapeutic targets to prevent muscle wasting, in particular sarcopenia and cachexia

PSYCHIATRIC COMORBIDITY IN BARIATRIC SURGERY: A RETROSPECTIVE STUDY IN A GENERAL HOSPITAL

Background: Candidates for bariatric surgery undergo a multidisciplinary evaluation in the pre-operative phase, including a psychiatric visit aimed at the screening for psychiatric comorbidities, including feeding and eating disorders (FEDs), which are shortcomings to the intervention or predictors of worse prognosis. The presence of FEDs, such as Binge Eating Disorder (BED) and Bulimia Nervosa (BN), is associated with higher rates of other psychiatric disorders. Furthermore, there is evidence of the association between obesity and Depressive Disorders, as well as B and C Cluster Personality Disorders. The aim of this study was to evaluate the presence of psychiatric comorbidities among a population of candidates for bariatric surgery. Subjects and methods: Subjects were recruited at the outpatient service of the Section of Psychiatry, Clinical Psychology and Rehabilitation of the General Hospital/University of Perugia after being referred by surgeons. Psychiatric comorbidities were investigated by means of the Structured Clinical Interview for DSM-5 Disorders. Subjects underwent specific assessment with scales for the evaluation of FEDs, namely Binge Eating Scale, Obesity Questionnaire, Bulimia Test-Revised and Body Shape Questionnaire. Results: The sample consisted of 101 subjects: 43 (42.6%) were diagnosed with at least one psychiatric disorder, including FEDs. In particular, 30 subjects (29.7%) presented at least one FED, among which the most frequent were FED not otherwise specified (24.1%) and BED (6.8%). Moreover, 26 subjects (25.7%) were diagnosed with at least one psychiatric disorder other than FEDs, such as Personality Disorders (17.1%), with a higher prevalence of B and C Cluster Disorders. Depressive Disorders were detected in 5% of the sample. Conclusions: Subjects undergoing bariatric surgery often display psychiatric comorbidities, more frequently one or more FEDs. The systematic screening of these conditions should be implemented in the clinical practice in order to provide early intervention strategies and adequate monitoring

Estressores e crença de autoeficácia em universitários negros

The scientific literature highlights that higher levels of self-efficacy are associated with more satisfactory academic performance. Among the variables that can affect this phenomenon, it is highlighted that the racial prejudice suffered by black students can be a stressor capable of impacting the belief in self-efficacy in the university context. The aim of this study was to characterize the perception of stressors and the self-efficacy belief of self-declared black and brown university students. This is a descriptive, predictive, comparative and correlational survey. 60 university students with an average age of 23.1 years participated, being 45 women and 15 men, self-declared black. Through an online data collection, instruments were used to characterize academic performance, self-efficacy assessment in academic situations and stress symptoms. The sample faced greater stress with regard to academic demands compared to other contexts. The belief in self-efficacy had a significant impact on the perception of stressors in most contexts. Another stressor refers to relationships with family and colleagues. It is suggested the development of institutional policies that allow students to develop their potential, especially their belief in self-efficacy, seeking to alleviate the perception of stressors. Such policies must dialogue directly with the needs brought up by black students.La literatura científica destaca que los niveles más altos de autoeficacia están asociados con un rendimiento académico más satisfactorio. Entre las variables que pueden afectar este fenómeno, se destaca que el prejuicio racial sufrido por los estudiantes negros puede ser un factor estresante capaz de afectar la creencia en la autoeficacia en el contexto universitario. El objetivo de este estudio fue caracterizar la percepción de estresores y la creencia de autoeficacia de los estudiantes universitarios negros y marrones autodeclarados. Esta es una encuesta descriptiva, predictiva, comparativa y correlacional. Participaron 60 estudiantes universitarios con una edad promedio de 23.1 años, siendo 45 mujeres y 15 hombres, autodeclarados negros. A través de una recopilación de datos en línea, se utilizaron instrumentos para caracterizar el rendimiento académico, la evaluación de la autoeficacia en situaciones académicas y los síntomas de estrés. La muestra enfrentó un mayor estrés con respecto a las demandas académicas en comparación con otros contextos. La creencia en la autoeficacia tuvo un impacto significativo en la percepción de estresores en la mayoría de los contextos. Otro factor estresante se refiere a las relaciones con familiares y colegas. Se sugiere el desarrollo de políticas institucionales que permitan a los estudiantes desarrollar su potencial, especialmente su creencia en la autoeficacia, buscando aliviar la percepción de estresores. Dichas políticas deben dialogar directamente con las necesidades planteadas por los estudiantes negros.A literatura científica destaca que maiores níveis de autoeficácia estão associados a um desempenho acadêmico mais satisfatório. Entre as variáveis que podem afetar esse fenômeno, destaca-se que o preconceito racial sofrido por estudantes negros pode constituir-se como um fator estressor capaz de impactar na crença de autoeficácia no contexto universitário. O objetivo deste estudo foi caracterizar a percepção de estressores e a crença de autoeficácia de estudantes universitários autodeclarados negros e pardos. Trata-se de estudo survey descritivo, preditivo, comparativo e correlacional. Participaram 60 estudantes universitários com idade média de 23,1 anos, sendo 45 mulheres e 15 homens, autodeclarados pardos/negros. Por meio de uma coleta de dados online, foram empregados instrumentos para caracterização de rendimento acadêmico, de avaliação de autoeficácia em situações acadêmicas e de sintomas de estresse. A amostra enfrentou maior estresse no tocante às demandas acadêmicas em comparação com outros contextos. A crença de autoeficácia teve impacto significativo na percepção de estressores na maioria dos contextos. Outro estressor refere-se às relações com família e colegas. Diante disso, sugere-se o desenvolvimento de políticas institucionais que permitam ao aluno desenvolver suas potencialidades, especialmente sua crença de autoeficácia, buscando amenizar a percepção de estressores. Tais políticas devem dialogar diretamente com as possíveis necessidades trazidas pelos estudantes negros