Static evaluation of scapular positioning in healthy individuals

OBJECTIVE: Evaluate the static positioning of the scapula on the rib cage in healthy subjects by means of clinical and radiographic evaluation to assess inter-examiner reliability of clinical examination and verify the reliability of this evaluation method compared to the radiographic examination. METHODS: We selected 30 adult individuals of both sexes with no diagnosis of shoulder pathology. The static clinical examination, following the protocol suggested by Burkhart et al, was performed repeatedly by two independent examiners, followed by the radiographic examination, which was later examined by the first evaluator. RESULTS: 73.3% of the subjects showed positioning of the scapula considered normal. The inter-examiner reliability and that of the clinical examination in relation to radiography were considered low and very low, respectively. CONCLUSION: The reproducibility of the evaluation performed by Burkhart was considered satisfactory to good, while the inter-examiner reproducibility of the clinical examination and the static reproducibility of the clinical examination with radiography were considered poor to satisfactory. Level of Evidence III, Study of Nonconsecutive Patientes.OBJETIVOS: Avaliar o posicionamento estático da escápula no gradil costal em indivíduos saudáveis, por meio da avaliação clínica e radiográfica, avaliar a confiabilidade interavaliador do exame clínico e verificar a confiabilidade do método de avaliação em comparação ao exame radiográfico. MÉTODOS: Foram selecionados 30 indivíduos adultos de ambos os sexos sem diagnóstico de doenças nos ombros. O exame clínico estático, seguindo o protocolo sugerido por Burkhart e cols., foi realizado repetidamente por 2 examinadores independentes; a seguir, foi realizado o exame radiográfico, que posteriormente foi examinado pelo primeiro avaliador. RESULTADOS: 73,3% dos indivíduos apresentaram o posicionamento da escápula considerado dentro da normalidade. A confiabilidade interavaliador e a confiabilidade do exame clínico em relação à radiografia foram considerados baixa e muito baixa respectivamente. CONCLUSÃO: A reprodutibilidade da avaliação realizada por Burkhart foi considerada de satisfatória a boa, enquanto que a reprodutibilidade inter-avaliador do exame clínico estático e a reprodutibilidade do exame clínico com a radiografia foram consideradas de pobres a satisfatórias. Nível de Evidência III, Estudo de Pacientes não Consecutivos.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Ortopedia e TraumatologiaUNIFESP, EPM, Depto. de Ortopedia e TraumatologiaSciEL

Improvement of health-related quality of life and psychological well-being after HCV eradication with direct-acting antiviral agents. Real life setting data of an Italian cohort valued by Hepatitis Quality of Life Questionnaire (HQLQv2)

HCV (Hepatitis C Virus) decreases Health-Related Quality of Life with detriments to physical, mental and social health domains. Interferon and Ribavirin treatment is associated with depression and anxiety that further impairs HRQoL (Health- Related Quality of Life). IFN-free (interferon-free) regimes (Direct Acting Antivirals, DAAs) are safe and highly effective drugs, with improvement also of HRQoL and related Psychological Well-Being. Our aim is to describe how the latest generation IFN-free treatment can change quality of life and related Psychological Well-Being in Italian Chronic Hepatitis C/Cirrhosis affected patients. SF-36v2 (Short Form Health Survey is a 36-item, patient-reported survey of patient health) – HQLQv2 (Hepatitis Quality of Life Questionnaire) was administered at two time points: baseline (n=72) and 12 weeks after the end of therapy [n=72, SVR=72 - Sustained Virologic Response (SVR)]. Patients with chronic HCV undergoing DAAs treatment from two Italian centers were enrolled. The overall average of the answers is configured for most of the domains that make up the questionnaire, with scores above 50. The quality of life of this sample is very close to the average of the US population, with a minimum average score of 45.9 for the Role Emotional scale and an average maximum score of 56.4 for the Vitality scale. Both are significant results from statistical analysis. It seems that DAAs treatment therapy does not affect but improves the general quality and psychological state of adult patients with Chronic HCV infection

Off to a good start: environmental imprinting in the childbirth period

Our organism and the expression of our genetic inheritance are conditioned by the environment. This is demonstrated by experimental models on animals, but more and more evidence shows similarities also in humans. Evidence now supports that neonatal and maternal health also depends on the interactions between the environment and the DNA itself. Even though the DNA sequence remains the same over the years, some genetic traits of human beings can be affected by the silencing or activation of some nucleotide sequences, for example by DNA methylation. Today, epigenetics is much more important than we used to think in 1942 when Waddington used the word “epigenetics” for the first time. The environment can modify DNA sequence methylation, affecting protein production and the phenotype. Examples of how epigenetics affects childbirth phenomenon are given and mechanisms are discussed. Four biological mechanisms of epigenetics are presented: genomic imprinting and silencing of the paternal set of chromosomes, the unpredictable “on/off” expression patterns of wild type genes, paramutations, and alternative states of protein folding. Some genes are triggered by stress, maternal nutrition, drugs (namely oxytocin, fentanyl), childbirth modalities, labor, environmental behavior, microorganism colonization. Imprinting theory is a good scientific basis, to explain the permanence of some biological effects at a considerable time after birth. Imprinting is an important mechanism of DNA expression, and different types of imprinting are described. The consequences of antibiotic use in the childbirth period are discussed, along with the importance of awareness in the use of antibiotics for maternal prophylaxis. Prenatal antibiotics and cesarean sections do affect neonatal microbiome considerably and, therefore, may be the causes of inflammatory intestinal disorders, asthma, obesity, diabetes. Mode of delivery, labor, breastfeeding, and skin-to-skin practice are strictly related to future neonatal health, and the effects are shown here. One of the most important factors to explain the diseases mentioned above is probably the lack of “bacterial contamination” through the birth canal. However, this mechanism cannot be the only one to act, and, in fact, here we also discuss other mechanisms that contribute to the development of future pathologies. Last but not least, the culture and education of the operators, as well as maternal and providers’ attendance behavior during childbirth,  can change the relative outcomes of children’s long-term health

Novel synthesis of platinum complexes and their intracellular delivery to tumor cells by means of magnetic nanoparticles

Platinum-based drugs are popular in clinics as chemotherapeutic agents to treat solid tumors

DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport.

The small intestine is a dynamic and complex organ that is characterized by constant epithelium turnover and crosstalk among various cell types and the microbiota. Lymphatic capillaries of the small intestine, called lacteals, play key roles in dietary fat absorption and the gut immune response; however, little is known about the molecular regulation of lacteal function. Here, we performed a high-resolution analysis of the small intestinal stroma and determined that lacteals reside in a permanent regenerative, proliferative state that is distinct from embryonic lymphangiogenesis or quiescent lymphatic vessels observed in other tissues. We further demonstrated that this continuous regeneration process is mediated by Notch signaling and that the expression of the Notch ligand delta-like 4 (DLL4) in lacteals requires activation of VEGFR3 and VEGFR2. Moreover, genetic inactivation of Dll4 in lymphatic endothelial cells led to lacteal regression and impaired dietary fat uptake. We propose that such a slow lymphatic regeneration mode is necessary to match a unique need of intestinal lymphatic vessels for both continuous maintenance, due to the constant exposure to dietary fat and mechanical strain, and efficient uptake of fat and immune cells. Our work reveals how lymphatic vessel responses are shaped by tissue specialization and uncover a role for continuous DLL4 signaling in the function of adult lymphatic vasculature

Práticas psi na desconstrução da homofobia e dos gêneros

Introdução: o projeto de extensão e estágio Clínica da Diversidade Sexual desenvolvido junto ao Departamento de Psicologia Clínica (UNESP de Assis) propõe-se a conhecer teórica e praticamente as questões relacionadas à produção da discriminação em relação às sexualidades não-heterossexuais, bem como a construção do masculino e do feminino. Objetivos: Temos como objetivo problematizar as práticas de opressão de gênero que se exercem sobre homens e mulheres heteros, homos e/ou bissexuais, que vem aliado às conquistas dos direitos das mulheres, de lésbicas, gays, bissexuais, travestis e transexuais (LGBT). Estas atividades têm o intuito de desconstruir alguns estereótipos e instigar a reflexão das normatividades de gênero previamente estabelecidos e institucionalizados discursivamente. Métodos: Trabalhamos com atendimentos clínicos individuais com base na psicanálise (lacaniana), intervenções no campus da universidade, tais como entrega de insumos de prevenção às DST/HIV-Aids e plantões junto ao Centro de Referência em Direitos Humanos no Oeste Paulista (CR) instaurado na ONG Núcleo de Estudos e Pesquisas sobre as Sexualidades (NEPS), no qual prestamos serviços de acolhimento e empoderamento à população LGBT. Junto a essas atividades realizamos, semanalmente (desde abril do corrente), exibição de filmes temáticos LGBT, seguidos de debates. Esta intervenção se dá às terças-feiras com temática lésbica (“Teta com Teta”) e às quintas-feiras com temática gay, travestis e transgêneros (“GTT”). Do mesmo modo, atendemos pessoas que se queixam de disfunções sexuais na Clínica Psicológica da Universidade (CPPA). Resultados: Atendemos 8 pessoas em psicoterapia psicanalítica e realizamos diversos acolhimentos junto ao CR. Constatamos que a presença do psicólogo se faz necessária na medida em que encontramos muito sofrimento decorrente da homofobia seja esta externa e/ou internalizada. Como nossa clínica não se reduz ao atendimento de pessoas LGBT, nos casos de pacientes heterossexuais que a nós chegaram com queixas de disfunções sexuais, encontramos cada qual se posicionando frente às pressões sociais das normatividades de gênero

Práticas psi na desconstrução da homofobia e dos gêneros

Introdução: o projeto de extensão e estágio Clínica da Diversidade Sexual desenvolvido junto ao Departamento de Psicologia Clínica (UNESP de Assis) propõe-se a conhecer teórica e praticamente as questões relacionadas à produção da discriminação em relação às sexualidades não-heterossexuais, bem como a construção do masculino e do feminino. Objetivos: Temos como objetivo problematizar as práticas de opressão de gênero que se exercem sobre homens e mulheres heteros, homos e/ou bissexuais, que vem aliado às conquistas dos direitos das mulheres, de lésbicas, gays, bissexuais, travestis e transexuais (LGBT). Estas atividades têm o intuito de desconstruir alguns estereótipos e instigar a reflexão das normatividades de gênero previamente estabelecidos e institucionalizados discursivamente. Métodos: Trabalhamos com atendimentos clínicos individuais com base na psicanálise (lacaniana), intervenções no campus da universidade, tais como entrega de insumos de prevenção às DST/HIV-Aids e plantões junto ao Centro de Referência em Direitos Humanos no Oeste Paulista (CR) instaurado na ONG Núcleo de Estudos e Pesquisas sobre as Sexualidades (NEPS), no qual prestamos serviços de acolhimento e empoderamento à população LGBT. Junto a essas atividades realizamos, semanalmente (desde abril do corrente), exibição de filmes temáticos LGBT, seguidos de debates. Esta intervenção se dá às terças-feiras com temática lésbica (“Teta com Teta”) e às quintas-feiras com temática gay, travestis e transgêneros (“GTT”). Do mesmo modo, atendemos pessoas que se queixam de disfunções sexuais na Clínica Psicológica da Universidade (CPPA). Resultados: Atendemos 8 pessoas em psicoterapia psicanalítica e realizamos diversos acolhimentos junto ao CR. Constatamos que a presença do psicólogo se faz necessária na medida em que encontramos muito sofrimento decorrente da homofobia seja esta externa e/ou internalizada. Como nossa clínica não se reduz ao atendimento de pessoas LGBT, nos casos de pacientes heterossexuais que a nós chegaram com queixas de disfunções sexuais, encontramos cada qual se posicionando frente às pressões sociais das normatividades de gênero

DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport

The small intestine is a dynamic and complex organ that is characterized by constant epithelium turnover and crosstalk among various cell types and the microbiota. Lymphatic capillaries of the small intestine, called lacteals, play key roles in dietary fat absorption and the gut immune response; however, little is known about the molecular regulation of lacteal function. Here, we performed a high-resolution analysis of the small intestinal stroma and determined that lacteals reside in a permanent regenerative, proliferative state that is distinct from embryonic lymphangiogenesis or quiescent lymphatic vessels observed in other tissues. We further demonstrated that this continuous regeneration process is mediated by Notch signaling and that the expression of the Notch ligand delta-like 4 (DLL4) in lacteals requires activation of VEGFR3 and VEGFR2. Moreover, genetic inactivation of Dll4 in lymphatic endothelial cells led to lacteal regression and impaired dietary fat uptake. We propose that such a slow lymphatic regeneration mode is necessary to match a unique need of intestinal lymphatic vessels for both continuous maintenance, due to the constant exposure to dietary fat and mechanical strain, and efficient uptake of fat and immune cells. Our work reveals how lymphatic vessel responses are shaped by tissue specialization and uncover a role for continuous DLL4 signaling in the function of adult lymphatic vasculature

Optimized low-dose combinatorial drug treatment boosts selectivity and efficacy of colorectal carcinoma treatment.

The current standard of care for colorectal cancer (CRC) is a combination of chemotherapeutics, often supplemented with targeted biological drugs. An urgent need exists for improved drug efficacy and minimized side effects, especially at late-stage disease. We employed the phenotypically driven therapeutically guided multidrug optimization (TGMO) technology to identify optimized drug combinations (ODCs) in CRC. We identified low-dose synergistic and selective ODCs for a panel of six human CRC cell lines also active in heterotypic 3D co-culture models. Transcriptome sequencing and phosphoproteome analyses showed that the mechanisms of action of these ODCs converged toward MAP kinase signaling and cell cycle inhibition. Two cell-specific ODCs were translated to in vivo mouse models. The ODCs reduced tumor growth by ~80%, outperforming standard chemotherapy (FOLFOX). No toxicity was observed for the ODCs, while significant side effects were induced in the group treated with FOLFOX therapy. Identified ODCs demonstrated significantly enhanced bioavailability of the individual components. Finally, ODCs were also active in primary cells from CRC patient tumor tissues. Taken together, we show that the TGMO technology efficiently identifies selective and potent low-dose drug combinations, optimized regardless of tumor mutation status, outperforming conventional chemotherapy

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

It has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response, can severely compromise hematopoietic stem cell (HSC) regeneration. Here we show that the NAD(+)-boosting agent nicotinamide riboside (NR) reduces mitochondrial activity within HSCs through increased mitochondrial clearance, leading to increased asymmetric HSC divisions. NR dietary supplementation results in a significantly enlarged pool of progenitors, without concurrent HSC exhaustion, improves survival by 80%, and accelerates blood recovery after murine lethal irradiation and limiting-HSC transplantation. In immune-deficient mice, NR increased the production of human leucocytes from hCD34+ progenitors. Our work demonstrates for the first time a positive effect of NAD(+)-boosting strategies on the most primitive blood stem cells, establishing a link between HSC mitochondrial stress, mitophagy, and stem-cell fate decision, and unveiling the potential of NR to improve recovery of patients suffering from hematological failure including post chemo- and radiotherapy.Peer reviewe