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

Numb Isoforms Deregulation in Medulloblastoma and Role of p66 Isoform in Cancer and Neural Stem Cells

Numb is an intracellular protein with multiple functions. The two prevalent isoforms, Numb p66 and Numb p72, are regulators of differentiation and proliferation in neuronal development. Additionally, Numb functions as cell fate determinant of stem cells and cancer stem cells and its abnormal expression has been described in several types of cancer. Involvement of deregulated Numb expression has been described in the malignant childhood brain tumor medulloblastoma, while Numb isoforms in these tumors and in cancer stem-like cells derived from them, have not been studied to date. Here we show that medulloblastoma stem-like cells and cerebellar neuronal stem cells (NSCs) express Numb p66 where its expression tampers stemness features. Furthermore, medulloblastoma samples evaluated in this study express decreased levels of Numb p66 while overexpressed Numb p72 compared with normal tissues. Our results uncover different roles for the two major Numb isoforms examined in medulloblastoma and a critical role for Numb p66 in regulating stem-like cells and NSCs maintenance

H+ implanted channel waveguides in buried epitaxial crystalline YAG:Nd, Tm layers and infrared-to-blue upconversion characterization

Nd, Tm:YAG codoped single crystal waveguides were studied in order to discover if the presence of Nd3+ ions favors blue luminescence at 486 nm. Innovative implantation techniques were applied to locally change Delta n and form varied H+ implanted channel structures in Nd, Tm: YAG buried epitaxial waveguiding layers. The guided blue luminescence due to the Tm3+ (1)G(4)-> H-3(6) transition was studied under infrared excitation at 785 nm (Tm3+ absorption) and 808 nm (Nd3+ absorption) for the epitaxial planar waveguides of different Tm3+ and Nd3+ concentrations for all the implanted channel waveguide structures

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

The construction of a Quality of Life Wellbeing Index for cancer patients in follow-up: the ONCORELIEF project

ONCORELIEF aims to improve post-treatment health status, wellbeing, and follow-up care of cancer patients in a patient-centric way: independent of the specific treatment and pathway points, but specific to each patient’s experience and needs, incorporating the patient’s illness experience and the psychosocial context

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