Integral inequalities for closed linear Weingarten submanifolds in the product spaces.

An integral inequality for closed linear Weingarten 𝑚-submanifolds with parallel normalized mean curvature vector field (pnmc lw-submanifolds) in the product spaces 𝑀𝑛(𝑐) × â„, 𝑛 > 𝑚 ≥ 4, where 𝑀𝑛(𝑐) is a space form of constant sectional curvature 𝑐 ∈ {-1, 1}, is proved. As an application is shown that the sharpness in this inequality is attained in the totally umbilical hypersurfaces, and in a certain family of standard product of the form 𝕊1(√1 - 𝑟2) × ð•Šð‘š-1(𝑟) with 0 < 𝑟 < 1 when 𝑐 = 1. In the case where 𝑐 = -1, is obtained an integral inequality whose sharpness is attained only in the totally umbilical hypersurfaces. When 𝑚 = 2 and 𝑚 = 3, an integral inequality is also obtained with equality happening in the totally umbilical hypersurfaces.

Nischarin Is Not the Functional I1 Imidazoline Receptor Involved in Blood Pressure Regulation.

ABSTRACT: Imidazoline receptor antisera selected/Nischarin was proposed several years ago as the functional entity for the I1 medullary receptors (I1Rs) targeted, together with α2-adrenoceptors, by the centrally acting antihypertensive drugs, such as clonidine. The objective of this study was to test this assumption using a pyrroline analog of clonidine, LNP599, which, unlike clonidine and related compounds, displays high selectivity toward I1Rs. Cardiovascular effects of LNP599 (3 mg/kg intravenous) were evaluated in anesthetized, artificially ventilated nischarin mutant rats expressing a truncated form of nischarin lacking the putative imidazoline binding site. LNP599 induced a rapid and pronounced fall in arterial blood pressure in wild-type animals (-42.7% ± 11.0% after 15 minutes), associated with a ≈30% heart rate reduction. Similar effects were obtained in homozygous and heterozygous nischarin mutant rats. The observation that the hypotensive response to I1R activation is not affected by the absence of the putative imidazoline binding site on nischarin strongly suggests that nischarin cannot be regarded as the functional I1R. Carbohydrate regulation was improved in nischarin mutant rats, further supporting the conclusion that nischarin and I1R are 2 distinct molecular entities.

Chronic REM sleep restriction in young rats increases energy expenditure with no change in food intake.

NEW FINDINGS: What is the central question of this study? What are the effects of different periods of REM sleep restriction (7, 14 and 21 days) on metabolic parameters in young rats? What is the main finding and its importance? Animals submitted to each period of REM sleep deprivation showed a negative energy balance, with reduced body weight gain, body energy gain and gross food efficiency, less body fat content, and increased energy expenditure. There was no increase in food intake after any of the REM sleep restriction periods. In young rats, negative energy balance is not compensated by increased dietary intake as observed in adult rats. ABSTRACT: Reduced sleep is associated with metabolic alterations, not only in adults, but also in children and adolescents. Several studies have shown that sleep restricted (SR) adult rats exhibit metabolic changes, followed by increased food intake, but few have evaluated these functions in young animals. The aim of the present study was to establish the metabolic parameters of young rats subjected to different periods of REM sleep restriction and to propose a correction factor for the correct measurement of food intake. Young male Wistar rats were distributed in control and SR groups for 7, 14 or 21 days. Sleep restriction was performed by the single platform method for 18 h. Regardless of the length of sleep restriction, all SR rats had a negative energy balance, evidenced by reduction in body weight gain, body energy gain and gross food efficiency, accompanied by increased energy expenditure. In addition, sleep restriction reduced body fat content throughout the entire period. Discounting food spillage, there was no increase in food intake by SR rats. In conclusion, the present study revealed metabolic changes in SR young rats after different lengths of REM sleep restriction and that weight loss and increased energy expenditure were not compensated by increased dietary intake as occurs in adult rats, indicating that young rats use other mechanisms to cope with the negative energy balance caused by sleep restriction. In addition, we propose a correction factor for food intake, to prevent overestimation of this parameter, due to food spillage in the water containers.

Serotonin contribution to cardiac valve degeneration: new insights for novel therapies?

Heart valve disease (HVD) is a complex entity made by different pathological processes that ultimately lead to the abnormal structure and disorganization of extracellular matrix proteins resulting to dysfunction of the leaflets. At its final evolutionary step, treatments are limited to the percutaneous or surgical valve replacement, whatever the original cause of the degeneration. Understanding early molecular mechanisms that regulate valve interstitial cells remodeling and disease progression is challenging and could pave the way for future drugs aiming to prevent and/or reverse the process. Some valve degenerative processes such as the carcinoid heart disease, drug-induced valvulopathy and degenerative mitral valve disease in small-breed dogs are clearly linked to serotonin. The carcinoid heart is typically characterized by a right-sided valve dysfunction, observed in patients with carcinoid tumors developed from serotonin-producing gut enterochromaffin cells. Fenfluramine or ergot derivatives were linked to mitral and aortic valve dysfunction and share in common the pharmacological property of being 5-HT2B receptor agonists. Finally, some small-breed dogs, such as the Cavalier King Charles Spaniel are highly prone to degenerative mitral valve disease with a prevalence of 40% at 4 years-old, 70% at 7 years-old and 100% in 10-year-old animals. This degeneration has been linked to high serum serotonin, 5-HT2B receptor overexpression and SERT downregulation. Through the comprehension of serotonergic mechanisms involved into these specific situations, new therapeutic approaches could be extended to HVD in general. More recently, a serotonin dependent/ receptor independent mechanism has been suggested in congenital mitral valve prolapse through the filamin-A serotonylation. This review summarizes clinical and molecular mechanisms linking the serotonergic system and heart valve disease, opening the way for future pharmacological research in the field.

Chronic bacterial infection activates autoreactive B cells and induces isotype switching and autoantigen-driven mutations.

The links between infections and the development of B-cell-mediated autoimmune diseases are still unclear. In particular, it has been suggested that infection-induced stimulation of innate immune sensors can engage low affinity autoreactive B lymphocytes to mature and produce mutated IgG pathogenic autoantibodies. To test this hypothesis, we established a new knock-in mouse model in which autoreactive B cells could be committed to an affinity maturation process. We show that a chronic bacterial infection allows the activation of such B cells and the production of nonmutated IgM autoantibodies. Moreover, in the constitutive presence of their soluble antigen, some autoreactive clones are able to acquire a germinal center phenotype, to induce Aicda gene expression and to introduce somatic mutations in the IgG heavy chain variable region on amino acids forming direct contacts with the autoantigen. Paradoxically, only lower affinity variants are detected, which strongly suggests that higher affinity autoantibodies secreting B cells are counterselected. For the first time, we demonstrate in vivo that a noncross-reactive infectious agent can activate and induce autoreactive B cells to isotype switching and autoantigen-driven mutations, but on a nonautoimmune background, tolerance mechanisms prevent the formation of consequently dangerous autoimmunity.

Restriction of rapid eye movement sleep during adolescence increases energy gain and metabolic efficiency in young adult rats.

NEW FINDINGS: What is the central question of this study? Sleep curtailment in infancy and adolescence may lead to long-term risk for obesity, but the mechanisms involved have not yet been determined. This study examined the immediate and long-term metabolic effects produced by sleep restriction in young rats. What is the main finding and its importance? Prolonged sleep restriction reduced weight gain (body fat stores) in young animals. After prolonged recovery, sleep-restricted rats tended to save more energy and to store more fat, possibly owing to increased gross food efficiency. This could be the first step to understand this association. Sleep curtailment is associated with obesity and metabolic changes in adults and children. The aim of the present study was to evaluate the immediate and long-term metabolic alterations produced by sleep restriction in pubertal male rats. Male Wistar rats (28 days old) were allocated to a control (CTL) group or a sleep-restricted (SR) group. This was accomplished by the single platform technique for 18 h per day for 21 days. These groups were subdivided into the following four time points for assessment: sleep restriction and 1, 2 and 4 months of recovery. Body weight and food intake were monitored throughout the experiment. At the end of each time period, blood was collected for metabolic profiling, and the carcasses were processed for measurement of body composition and energy balance. During the period of sleep restriction, SR animals consumed less food in the home cages. This group also displayed lower body weight, body fat, triglycerides and glucose levels than CTL rats. At the end of the first month of recovery, despite eating as much as CTL rats, SR animals showed greater energy and body weight gain, increased gross food efficiency and decreased energy expenditure. At the end of the second and fourth months of recovery, the groups were no longer different, except for energy gain and gross food efficiency, which remained higher in SR animals. In conclusion, sleep restriction affected weight gain of young animals, owing to reduction of fat stores. Two months were sufficient to recover this deficit and to reveal that SR rats tended to save more energy and to store more fat.

Flavoured and nicotine-containing e-liquids impair homeostatic properties of an alveolar-capillary cell model.

Most people consider that electronic cigarettes are safer than tobacco and are marketed as quit-smoking products. The e-liquid, which usually contains propylene glycol (PG) and vegetable glycerin (VG) in different ratios, nicotine and a wide variety of flavours, is heated by a coil and the aerosol droplets are primarily delivered to the alveolar area where nicotine and other molecules cross the alveolar-capillary barrier (ACB). However, e-cigarettes effects on the ACB are not yet established. In our study, a well-characterised in vitro model of the ACB was exposed to PG and VG and to five flavoured e-liquids with and without nicotine. The vehicles, due to their hypertonic properties, modulated the ACB integrity by modifying occludin expression. Below a 10% concentration, the vehicles did not trigger oxidative stress or cell death. Different results were observed between flavoured e-liquids: while red fruits and mint-eucalyptus disrupted ACB integrity, triggered oxidative stress and cell death, blond tobacco had no worse effect compared to the vehicles. However, the addition of nicotine in the latter e-liquid increased oxidative stress and cell death compared to the vehicles. Finally, mint-eucalyptus e-liquid increased some inflammation markers. Our results revealed that e-liquids alter ACB homeostasis, depending on flavour and nicotine presence.

Blood-Brain Barrier Permeability: Is 5-Hydroxytryptamine Receptor Type 4 a Game Changer?

Serotonin affects many functions in the body, both in the central nervous system (CNS) and the periphery. However, its effect on the blood-brain barrier (BBB) in separating these two worlds has been scarcely investigated. The aim of this work was to characterize the serotonin receptor 5-HT4 in the hCMEC/D3 cell line, in the rat and the human BBB. We also examined the effect of prucalopride, a 5-HT4 receptor agonist, on the permeability of the hCMEC/D3 in an in vitro model of BBB. We then confirmed our observations by in vivo experiments. In this work, we show that the 5-HT4 receptor is expressed by hCMEC/D3 cells and in the capillaries of rat and human brains. Prucalopride increases the BBB permeability by downregulating the expression of the tight junction protein, occludin. This effect is prevented by GR113808, a 5-HT4 receptor antagonist, and is mediated by the Src/ERK1/2 signaling pathway. The canonical G-protein-dependent pathway does not appear to be involved in this phenomenon. Finally, the administration of prucalopride increases the diffusion of Evans blue in the rat brain parenchyma, which is synonymous with BBB permeabilization. All these data indicate that the 5-HT4 receptor contributes to the regulation of BBB permeability.

Klotho genetic variants mediate the association between obstructive sleep apnea and short telomere length.

The core features of obstructive sleep apnea (OSA) can potentially contribute to the acceleration of telomere shortening mechanisms. Other factor associated with telomeres is Klotho gene as it can negatively regulates telomerase activity. Noteworthy, KLOTHO protein level has recently been associated with OSA. In this sense, it was plausible to hypothesize that OSA would be associated with short telomere length and those with OSA plus risk single nucleotide polymorphisms (SNPs) in Klotho gene would present even shorter telomere length. As part of the EPISONO cohort, 1042 individuals answered questionnaires, underwent polysomnography and had blood collected for DNA extraction. OSA was defined according to AHI≥ 15 events/hour. Leukocyte telomere length (LTL) was measured through real-time polymerase chain reaction (qPCR) and Klotho SNPs were genotyped by array. Mediation analyses considered the presence of SNPs in Klotho gene and how this interaction can affect OSA and its consequence in telomere length. All the analyses were corrected for multiple comparisons. LTL was significantly shorter in OSA compared to controls in a severity-dependent manner (B = 0.055; CI = 0.007-0.102; p = 0.02). Among the 43 Klotho SNPs analyzed, we observed that 4 SNPs (rs525014, rs7982726, rs685417 and rs9563124) significantly mediated the association between OSA and short LTL. Klotho gene opens a new venue in OSA research since it can contribute in the increase of knowledge of the mechanisms involved in the consequences of short telomeres in individuals with OSA.

Characterization of the spontaneous degenerative mitral valve disease in FVB mice.

BACKGROUND: The development of new non-surgical treatments dedicated to mitral valve degeneration is limited by the absence of relevant spontaneous and rapidly progressing animal experimental models. ANIMALS: We characterized the spontaneous mitral valve degeneration in two inbred FVB mouse strains compared to C57BL/6J and investigated a contribution of the serotonergic system. METHODS: Males and females FVB/NJ and FVB/NRj were compared to the putative C57BL/6J control at 12, 16, 20 and 24 weeks of age. Body weight, systolic blood pressure, heart rate, urinary 5-hydroxyindoleacetic acid (5-HIAA), whole blood and plasma serotonin, tail bleeding time, blood cell count, plasma TGF-ß1 and plasma natriuretic peptide concentrations were measured. Myocardium and mitral valves were characterized by histology. mRNA mitral expression of 5-HT2A and 5-HT2B receptors was measured in the anterior leaflet. Cardiac anatomy and function were assessed by echocardiography. RESULTS: Compared to C57BL/6J, FVB mice strains did not significantly differ regarding body weight increase, arterial blood pressure and heart rate. A progressive augmentation of plasma pro-ANP was observed in FVB mice. Nevertheless, no cardiac hypertrophy or left-ventricular fibrosis were observed. Accordingly, plasma TGF-ß1 was not different among the three strains. Conversely, FVB mice demonstrated a high prevalence of fibromyxoid highly cellularized and enriched in glycosaminoglycans lesions, inducing major mitral leaflets thickening without increase in length. The increased thickness was correlated with urinary 5-HIAA and blood platelet count. Whole blood serotonin concentration was similar in the two strains but, in FVB, a reduction of plasma serotonin was observed together with an increase of the bleeding time. Finally, echocardiography identified left atrial and left ventricular remodeling associated with thickening of both mitral leaflets and mitral insufficient in 30% of FVB mice but no systolic protrusion of mitral leaflets towards the atrium. CONCLUSION: The FVB mouse strain is highly prone to spontaneous mitral myxomatous degeneration. A contribution of the peripheral serotonergic system is suggested.

10Boron Is Mobile in Cowpea Plants.

Cowpea [Vigna unguiculata (L.) Walp] is cultivated in tropical and subtropical regions worldwide, but its production is usually limited by boron (B) deficiency, which can be mitigated by applying B via foliar spraying. In plants with nutrient mobility, the residual effect of foliar fertilization increases, which might improve its efficiency. An experiment was carried out to evaluate the concentration and mobility of the B isotopic tracer (10B) in different organs of cowpea plants, after the application of this micronutrient in the growing media and also to leaves. Treatments were designed based on B fertilization as follows: without B in the growth media, with 10B applied via foliar spraying (10B-L), with B in the growth media (substrate) and 10B via foliar spraying (10B-L + B-S), and with 10B in the growth media (substrate) without foliar spraying (10B-S), and a control without fertilization. A redistribution of 10B was observed in new leaves when the element was supplied via foliar spraying, resulting in greater leaf area, dry mass and dry matter production of aerial parts, and also the whole plant. 10Boron was redistributed when applied via foliar spraying in cowpea plants, regardless of the plant's nutritional status, which in turn might increase internal B cycling.

Effect of food restriction on energy expenditure of monosodium glutamate-induced obese rats.

The neonatal administration of monosodium glutamate (MSG) to rodents leads to obesity in the adult animal, characterized by increased fat storages. Chronic food restriction is known to induce reduction in body energy expenditure, as an adaptive mechanism to save energy. Our purpose was to examine whether obesity can alter the mechanism of energy conservation in food-restricted animals. Newborn female Wistar rats were injected either MSG (obese) or saline (control). At the age of 90 days, the animals were fed daily ad libitum (control and MSG) or restricted (50%) (control-restricted and MSG-restricted). After 30 days the animals were sacrificed and the energy balance was determined by calorimetric analysis. Some parameters of energy balance and body composition were affected by MSG treatment as well as food restriction. The percent reduction of the energy expenditure and fat content in MSG-restricted animals was lower than control-restricted animals, when compared with their respective ad libitum groups. These results indicate that all food-restricted animals were able to develop the mechanism of energy conservation, regardless of the obesity, but it was less efficient in MSG-obese animals.

Stigma perceived by overweight women.

OBJECTIVE: to understand the experience of discrimination perceived by overweight women. METHODS: a qualitative research conducted at an outpatient clinic in Salvador, Bahia, where eleven women were interviewed. The interviews were transcribed and submitted to thematic content analysis. RESULTS: the analysis of the statements expressed three categories: Suffering discrimination in different social contexts: denounced disrespect, hostility, veiled and/or explicit exclusion, prejudice, injustice and insults lived in public transport, at work, in the family environment, in social events and commercial establishments; Experiencing negative feelings about discrimination: revealed inferiority, sadness, shame, fear, anger, frustration, low esteem and discouragement faced by women; Reacting to discrimination: expressed isolation of marital intimacy and social encounters, removal from work, concealment of body and feelings and even illness of women. FINAL CONSIDERATIONS: the discrimination experienced in various settings has caused suffering, embarrassment, negative feelings, shame, isolation and loss in women's lives.

Remission in Crohn's disease is accompanied by alterations in the gut microbiota and mucins production.

Previous studies have demonstrated that patients with Crohn's disease (CD) in remission do not exhibit an improvement in gut microbiota composition, which might trigger relapses. The present study investigated the dysbiosis and mucins production in CD patients during remission. We performed an analytical cross-sectional single center study, which recruited 18 CD patients and 18 healthy controls (CG) residing in the same home, meaning that all of the participants experienced the same environmental factors, with similar hygiene status, diet, pollution and other common lifestyle characteristics that may influence the composition of the gut microbiota. When compared to healthy controls, the CD patients exhibited lower microbial α-diversity (p = 0.047), a greater abundance of the Proteobacteria phylum (p = 0.037) and a reduction in the Deltaproteobacteria class (p = 0.0006). There was also a reduction in the Akkermansia (p = 0.002) and Oscillospira (p = 0.024) genera and in the proportion of the yeast Saccharomyces cerevisiae (p = 0.01). Additionally, CD patients in remission presented increased neutral (p = 0.001) and acid mucin (p = 0.002) concentrations. The reductions in the proportions of Oscollospira and Akkermansia genera, sulfate-reducing bacteria and Saccharomyces cerevisiae, observed in the CD group, may account for the increased mucins production observed in these patients.

Effect of angiotensin converting enzyme inhibitor enalapril on body weight and composition in young rats.

Obesity is considered a worldwide public health problem showing an increased prevalence in developing countries, with urgent need for new and more efficient drugs and therapies. Enalapril, an angiotensin-I converting enzyme inhibitor (ACEi), is classically used in anti-hypertensive therapies, however, earlier publications have shown that this drug could also have significant impact on body weight in rats as well as in humans, besides reducing blood pressure. The effect of this drug in the white adipose tissue has been neglected for long time, even considering that most components of the renin-angiotensin and kallikrein-kinin system are expressed in this tissue. Furthermore, the adipose tissue is considered today as one of the most important sites for endocrine/inflammatory regulation of appetite and energy output and AngII has been linked to the metabolism in this tissue. Therefore, we analyzed the influence of chronic enalapril treatment in normotensive rats at earlier ages, evaluating body weight, energy homeostasis, lipid profile and serum levels of the hormones leptin and insulin, in the presence of a standard or a palatable hyperlipidic diet regimen for one month. Our results show that enalapril treatment is able to reduce body fat on both diets, without alteration in serum lipid profile. Furthermore, animals receiving enalapril showed reduction in food intake, leptin level and energy intake. In summary, these findings show for the first time that the ACEi enalapril reduces body fat in young normotensive rats and highlights a novel target to treat obesity and associated diseases.

Cutaneous leishmaniasis imported from Colombia to Northcentral Venezuela: implications for travel advice.

BACKGROUND: Imported leishmaniasis could be defined as any case acquired outside of a defined area in which the diagnosis of leishmaniasis is made. This definition has been used for the diagnosis of disease in a patient who arrives from an endemic area and displays symptoms or seeks medical attention in a nonendemic zone. However, this phenomenon can also occur between two endemic zones. METHODS: We evaluated the epidemiologic features of imported cases of cutaneous leishmaniasis imported from Colombia into Northcentral Venezuela from 2001 to 2006. A total of 29 patients with the clinical diagnosis of cutaneous leishmaniasis arriving from Colombia were evaluated at our referral center. Different diagnostic methods were used to confirm the diagnosis (the Montenegro skin test; an indirect immunofluorescence test and smear of cutaneous lesion). Clinical and epidemiological features of cutaneous leishmaniasis among these patients were evaluated. RESULTS: We identified that most identified patients were male with a mean age of 35 years (age range was 7-64); all cases were from northern departments of Colombia. These patients presented a mean clinical evolution of 3 months. Most patients presented with one cutaneous lesion (17%), which were located mostly in extremities (20%). Of the 29 patients, in 16 (55%) cutaneous leishmaniasis was confirmed by different diagnostic techniques. In 2 patients the diagnosis was made by smear. In the rest, 14 (100%) patients were positive by the Montenegro skin test and 11 (79%) were positive by the indirect immunofluorescence test (79% were positive simultaneously by both tests). DISCUSSION: The identification of imported cutaneous leishmaniasis in our setting becomes important, given the differences in the epidemiology of the disease and the clinical severity of leishmaniasis between both zones (ecological characteristics, circulating Leishmania spp., and population characteristics) and the risk of the mucocutaneous forms of the disease.

Anjos da Guarda: ferramenta para o ensino médico / Anjos Da Guarda (Guardian Angels): Medical Teaching Tool

Resumo A verdadeira medicina combina conhecimento biotecnocientífico ao cuidado. No entanto, as escolas médicas têm dado maior ênfase ao conhecimento científico em detrimento da relação médico-paciente. Objetivos: Este relato tem como objetivo descrever a experiência de imersão vivida por quatro estudantes de medicina do sexto período nos meses de fevereiro e março de 2020. Método: Tal imersão deu-se em um projeto de ensino denominado Anjos da Guarda, o qual é usado como ferramenta de educação médica no Hospital Universitário Gaffrée e Guinle da Universidade Federal do Estado do Rio de Janeiro (HUGG-UNIRIO). Resultados: O Projeto Anjos da Guarda desenvolve o profissionalismo médico, a empatia e os fundamentos da medicina centrados na pessoa do paciente como parte do processo de cuidado, sem menosprezar a importância do conhecimento biotecnocientífico e do raciocínio clínico. Conclusão: A experiência possibilitou ganhos em aprendizado para os estudantes, além de contribuir com o sistema de saúde e de beneficiar os pacientes envolvidos.

Abstract Conventional medicine combines biotechnoscientific knowledge with care. However, medical schools have placed greater emphasis on scientific knowledge to the detriment of the doctor-patient relationship. Objectives: This report aims to describe the immersion experience lived by four sixth-term medical students during the months of February and March 2020. Method: Such immersion took place in a teaching project named Anjos da Guarda, which is used as a medical education tool at the Gaffrée e Guinle University Hospital of the Federal University of the State of Rio de Janeiro (HUGG-UNIRIO). Results: The Anjos da Guarda Project develops medical professionalism, empathy and the fundamentals of medicine centered on the patient as part of the care process, without underestimating the importance of biotechnoscientific knowledge and clinical reasoning. Conclusion: The experience enabled gains in learning for students, in addition to contributing to the health system and benefiting the patients involved.

The role of 5-HT2B receptors in mitral valvulopathy: bone marrow mobilization of endothelial progenitors.

BACKGROUND AND PURPOSE: Valvular heart disease (VHD) is highly prevalent in industrialized countries. Chronic use of anorexigens, amphetamine or ergot derivatives targeting the 5-HT system is associated with VHD. Here, we investigated the contribution of 5-HT receptors in a model of valve degeneration induced by nordexfenfluramine, the main metabolite of the anorexigens, dexfenfluramine and benfluorex. EXPERIMENTAL APPROACH: Nordexfenfluramine was infused chronically (28 days) in mice ((WT and transgenic Htr2B -/- , Htr2A -/- , and Htr2B/2A -/- ) to induce mitral valve lesions. Bone marrow transplantation was also carried out. Haemodynamics were measured with echocardiography; tissues and cells were analysed by histology, immunocytochemistry, flow cytometry and RT -qPCR. Samples of human prolapsed mitral valves were also analysed. KEY RESULTS: Chronic treatment of mice with nordexfenfluramine activated 5-HT2B receptors and increased valve thickness and cell density in a thick extracellular matrix, mimicking early steps of mitral valve remodelling. Lesions were prevented by 5-HT2A or 5-HT2B receptor antagonists and in transgenic Htr2B -/- or Htr2A/2B -/- mice. Surprisingly, valve lesions were mainly formed by numerous non-proliferative CD34+ endothelial progenitors. These progenitors originated from bone marrow (BM) as revealed by BM transplantation. The initial steps of mitral valve remodelling involved mobilization of BM-derived CD34+ CD31+ cells by 5-HT2B receptor stimulation. Analysis of human prolapsed mitral valves showing spontaneous degenerative lesions, demonstrated the presence of non-proliferating CD34+ /CD309+ /NOS3+ endothelial progenitors expressing 5-HT2B receptors. CONCLUSIONS AND IMPLICATIONS: BM-derived endothelial progenitor cells make a crucial contribution to the remodelling of mitral valve tissue. Our data describe a new and important mechanism underlying human VHD.

O fazer dos estágios curriculares na formação em psicologia: uma experiência coletiva / The making of curricular internships in psychology training: a collective experience

O presente trabalho apresenta a concepção e o fazer dos estágios básicos e específicos do curso de Psicologia da Escola Bahiana de Medicina e Saúde Pública (EBMSP), instituição vocacionada para a saúde. Em seguida, descreve o funcionamento das referidas práticas, apresentando o contexto na qual elas estão inseridas e o processo de gestão do processo. Os estágios ocupam um lugar diferenciado na organização curricular do curso de Psicologia da EBMSP, pois oferecem aos discentes possibilidades de articulação entre teoria e prática de maneira crítica e reflexiva, conforme orientação das Diretrizes Curriculares Nacionais para os Cursos de Graduação de Psicologia. Os componentes fazem parte do eixo pré-profissionalizante e possibilitam a experiência em espaços e processos diversos de trabalho, nas duas ênfases do curso, Saúde e Trabalho. As atividades acontecem ao longo do quarto e quinto ano e são mediadas por vários participantes: corpo discente, corpo docente, coordenação e supervisor de campo. É a organização acadêmica e pedagógica dos estágios que permite a oferta de experiências práticas diferenciadas para o desenvolvimento de competências relacionadas ao fazer do Psicólogo. Observa-se que ao longo dos 20 anos do curso de Psicologia da EBMSP, os estágios estão em aprimoramento contínuo com foco na construção da identidade profissional do discente. Evidenciase, a partir da avaliação dos discentes, docentes e dos supervisores de campo que o egresso do curso de Psicologia da EBMSP, apresenta uma formação generalista, com competências práticas adquiridas para atuarem nos campos da saúde e trabalho com elevado nível técnico, integrados de forma crítica à sociedade, à realidade e ao mundo de trabalho.

This work presents the conception and implementation of basic and specific internships in the Psychology course at the Bahiana School of Medicine and Public Health (EBMSP), an institution dedicated to health. Then, it describes the functioning of these practices, presenting the context in which they are inserted and the process management process. The internships occupy a different place in the curricular organization of the Psychology course at EBMSP, as they offer students possibilities of articulation between theory and practice in a critical and reflective way, as guided by the National Curricular Guidelines for Psychology Undergraduate Courses. The components are part of the pre-professional axis and enable the experience in different work spaces and processes, in the two emphases of the course, Health and Work. The activities take place over the fourth and fifth year and are mediated by several participants: student body, faculty, coordination and field supervisor. It is the academic and pedagogical organization of the internships that allows the offering of different practical experiences for the development of skills related to the Psychologist's work. It is observed that throughout the 20 years of the Psychology course at EBMSP, the internships are in continuous improvement with a focus on building the student's professional identity. It is evident from the evaluation of students, teachers and field supervisors that the graduate of the Psychology course at EBMSP, presents a generalist training, with practical skills acquired to work in the fields of health and work with high technical level, integrated critically to society, reality and the world of work.

Stigma perceived by overweight women / Estigma percibido por mujeres con sobrepeso / Estigma percebido por mulheres com excesso de peso

ABSTRACT Objective: to understand the experience of discrimination perceived by overweight women. Methods: a qualitative research conducted at an outpatient clinic in Salvador, Bahia, where eleven women were interviewed. The interviews were transcribed and submitted to thematic content analysis. Results: the analysis of the statements expressed three categories: Suffering discrimination in different social contexts: denounced disrespect, hostility, veiled and/or explicit exclusion, prejudice, injustice and insults lived in public transport, at work, in the family environment, in social events and commercial establishments; Experiencing negative feelings about discrimination: revealed inferiority, sadness, shame, fear, anger, frustration, low esteem and discouragement faced by women; Reacting to discrimination: expressed isolation of marital intimacy and social encounters, removal from work, concealment of body and feelings and even illness of women. Final considerations: the discrimination experienced in various settings has caused suffering, embarrassment, negative feelings, shame, isolation and loss in women's lives.

RESUMEN Objetivo: comprender la experiencia de discriminación percibida por las mujeres con sobrepeso. Métodos: investigación cualitativa realizada en una clínica ambulatoria en Salvador, Bahia, donde se entrevistó a once mujeres. Las entrevistas fueron transcritas y sometidas a Análisis de Contenido Temático. Resultados: el análisis de las declaraciones expresó tres categorías: Sufriendo discriminación en diferentes contextos sociales: denunciando falta de respeto, hostilidad, exclusión velada y/o explícita, prejuicios, injusticias e insultos experimentados en el transporte público, en el trabajo, en el entorno familiar, en eventos sociales y establecimientos comerciales; Experimentar sentimientos negativos sobre la discriminación: inferioridad revelada, tristeza, vergüenza, miedo, ira, frustración, baja estima y desánimo que enfrentan las mujeres; Reacción a la discriminación: aislamiento expresado de la intimidad conyugal y encuentros sociales, retiro del trabajo, ocultación del cuerpo y los sentimientos e incluso enfermedades de las mujeres. Consideraciones finales: la discriminación experimentada en diversos entornos ha causado sufrimiento, vergüenza, sentimientos negativos, vergüenza, aislamiento y pérdida en la vida de las mujeres.

RESUMO Objetivo: compreender a vivência da discriminação percebida por mulheres com excesso de peso. Métodos: pesquisa qualitativa desenvolvida em ambulatório, em Salvador, Bahia, onde onze mulheres foram entrevistadas. As entrevistas foram transcritas e submetidas à Análise de Conteúdo Temática. Resultados: a análise dos depoimentos expressou três categorias: Sofrendo discriminação em diferentes contextos sociais: denunciou desrespeito, hostilidade, exclusão velada e/ou explícita, preconceito, injustiça e insultos vividos em transportes coletivos, no trabalho, no ambiente familiar, em eventos sociais e estabelecimentos comerciais; Experienciando sentimentos negativos face à discriminação: revelou inferioridade, tristeza, vergonha, medo, raiva, frustração, baixa da estima e desânimo enfrentados pelas mulheres; Reagindo à discriminação: expressou o isolamento da intimidade conjugal e de encontros sociais, o afastamento do trabalho, a ocultação do corpo e de sentimentos e até mesmo adoecimento de mulheres. Considerações finais: a discriminação vivida em diversos cenários causou sofrimento, constrangimento, sentimentos negativos, vergonha, isolamento e perdas na vida das mulheres.