TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice

The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication

Genetic variation in the E6 and E7 genes of human papillomavirus type 16 in northeastern Argentina

The province of Misiones is considered a region with a high mortality rate due to cervical cancer (CC). To gain insight into this problem, we explored the association between genetic variation in the E6 and E7 oncogenes of HPV16 and the risk of CC. We studied 160 women with cytological diagnoses of negative for intraepithelial lesion or malignity, low-grade squamous intraepithelial lesion, and high-grade squamous intraepithelial lesion/CC and a positive test for HPV16 infection. The genetic characterization of E6 and E7 genes was undertaken through PCR amplification and direct Sanger sequencing. Phylogenetic classification was conducted using Bayesian methods. To estimate the odds ratio (OR) for an association between genetic variants in the E6 and E7 genes and the risk of CC, we used ordinal logistic regression adjusted by age. The final data set comprised 112 samples. Diagnostic single-nucleotide polymorphisms (SNPs) and phylogenetic trees confirmed the presence of Lineage A (95.5%) and D (4.5%) in the samples. For the E6 gene, we identified eleven different sequences, with the most common ones being Lineage A E6 350G (58.9%) and E6 350T (37.5%). The E6 350G was associated with progression to HSIL/CC, with an OR of 19.41 (4.95–76.10). The E7 gene was more conserved than E6, probably due to the functional constraints of this small protein. Our results confirmed the association of the E6 350G SNP with a higher risk of developing CC. These data will contribute to understanding the biological bases of CC incidence in this region.Fil: Totaro, María Elina. Universidad Nacional de Misiones; ArgentinaFil: Gili, Juan Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Liotta, Domingo Javier. Universidad Nacional de Misiones; Argentina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; ArgentinaFil: Schurr, Theodore. University of Pennsylvania; Estados UnidosFil: Picconi, María Alejandra. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Badano, Ines. Universidad Nacional de Misiones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentin

Statin therapy blunts inflammatory activation and improves prognosis and left ventricular performance assessed by Tissue Doppler Imaging in subjects with chronic ischemic heart failure: results from the Daunia Heart Failure Registry

BACKGROUND: A limited number of studies have used Tissue Doppler Imaging (TDI) to evaluate the effect of statin therapy on left ventricular dysfunction in patients with chronic heart failure. In this work, we aimed to determine whether statin administration influenced prognosis, inflammatory activation and myocardial performance evaluated by Tissue Doppler Imaging in subjects enrolled in the Daunia Heart Failure Registry, a local registry of patients with chronic heart failure. METHODS: This study retrospectively analyzed 353 consecutive outpatients with chronic heart failure (mean follow-up 384 days), based on whether statin therapy was used. In all patients, several Tissue Doppler Imaging parameters were measured; circulating levels of interleukin (IL)-6, IL-10 and C-reactive protein were also assayed. RESULTS: Statin administration in 128 subjects with ischemic heart disease was associated with a lower incidence of adverse events (rehospitalization for HF 15% vs. 46%, p<0.001; ventricular arrhythmias 5% vs. 21%, p<0.01; cardiac death 1% vs. 8%, p<0.05), lower circulating levels of IL-6 (p<0.05) and IL-10 (p<0.01), lower rates of chronic heart failure (p<0.001) and better Tissue Doppler Imaging performance (E/E' ratio 12.82 + 5.42 vs. 19.85 + 9.14, p<0.001; ET: 260.62+ 44.16 vs. 227.11 +37.58 ms, p<0.05; TP: 176.79 + 49.93 vs. 136.7 + 37.78 ms, p<0.05 and St: 352.35 + 43.17 vs. 310.67 + 66.46 + 37.78 ms, p<0.05). CONCLUSIONS: Chronic ischemic heart failure outpatients undergoing statin treatment had fewer readmissions for adverse events, blunted inflammatory activation and improved left ventricular performance assessed by Tissue Doppler Imaging

Sildenafil improves clinical and functional status of an elderly postmenopausal female with ‘out of proportion’ PH associated with left heart disease

We report a case of an elderly woman with heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF-PH), refractory to conventional therapy for left heart failure and successfully treated by sildenafil

Avaliação da efetividade de intervenções de promoção da atividade física no Sistema Único de Saúde

OBJECTIVE To assess the effect of interventions on the levels of physical activity of healthy adults, users of the Brazilian Unified Health System and attended by the Family Health Strategy. METHODS Non-randomized experimental study with 157 adults allocated in three groups: 1) physical exercise classes (n = 54), 2) health education (n = 54), 3) control (n = 49). The study lasted for18 months, with 12 months of interventions and six months of follow-up after intervention. Assessments took place at the beginning, in the 12 months, and in the 18 months of study. Physical activity has been assessed by questionnaires and accelerometry. For the analyses, we have used the intention-to-treat principle and generalized estimating equations. RESULTS After 12 months, both intervention groups have increased the minutes of weekly leisure time physical activity and annual scores of physical exercise, leisure and transport-related physical activity. The exercise class group has obtained the highest average annual physical exercises score when compared to the other groups (p < 0.001). In the follow-up period, the exercise class group reduced its annual score (average: -0.3; 95%CI -0.5–-0.1), while the health education group increased this score (average: 0.2; 95%CI 0.1–0.4). There have been no differences in the levels of physical activity measured by accelerometry. CONCLUSIONS The interventions have been effective in increasing the practice of physical activity. However, we have observed that the health education intervention was more effective for maintaining the practice of physical activity in the period after intervention. We recommend the use of both interventions to promote physical activity in the Brazilian Unified Health System, according to the local reality of professionals, facilities, and team objectives.OBJETIVO Avaliar o efeito de intervenções nos níveis de atividade física de adultos saudáveis, usuários do Sistema Único de Saúde e atendidos pela Estratégia de Saúde da Família. MÉTODOS Estudo experimental, não randomizado, com 157 adultos alocados em três grupos: 1) classes de exercícios físicos (n = 54); 2) educação em saúde (n = 54); 3) controle (n = 49). O estudo teve duração de 18 meses, sendo 12 meses de intervenções e seis meses de acompanhamento pós-intervenção. As avaliações ocorreram no início, nos 12 e nos 18 meses de estudo. A atividade física foi avaliada por questionários e por acelerometria. Para as análises, utilizaram-se o princípio de intenção de tratar e equações de estimativas generalizadas. RESULTADOS Após 12 meses, ambos os grupos de intervenção aumentaram os minutos semanais de atividade física no lazer e os escores anuais de exercícios físicos, de lazer e de deslocamento. O grupo das classes de exercícios físicos obteve maior média de escore anual de exercícios físicos em comparação com os outros grupos (p < 0,001). No período pós-intervenção, o grupo de classes de exercícios físicos reduziu o escore anual de exercícios físicos (média: -0,3; IC95% -0,5–-0,1), enquanto o grupo de educação em saúde aumentou este escore (média: 0,2; IC95% 0,1–0,4). Não houve diferenças nos níveis de atividade física mensurados por acelerometria. CONCLUSÕES As intervenções foram efetivas para aumentar a prática de atividade física. No entanto, observou-se que a intervenção de educação em saúde foi mais efetiva para a manutenção da prática de atividade física no período pós-intervenção. Recomenda-se a utilização de ambas as intervenções para a promoção da atividade física no Sistema Único de Saúde, de acordo com as realidades locais de profissionais, instalações e objetivos das equipes

Asbestos in drinking water and hazards to human health: a narrative synthesis

The term asbestos refers to six unique fibrous minerals mostly used in the production of asbestos cement sheets and pipes. According to the World Health Organization and the International Agency for Research on Cancer (IARC), there exists at least "sufficient evidence" that all types of asbestos may cause cancer in humans (mesothelioma, lung cancer, laryngeal tumor and ovarian cancer). The only asbestos limit in drinking water is 7 million fiber/liter. This study is a narrative synthesis about the possible hazards to human health related to the presence of asbestos in drinking water. The various scientific studies and epidemiological reports examined highlight that there is an ongoing debate on the possible carcinogenic risk associated with asbestos exposure through ingestion. Nevertheless, considering the latency with which diseases caused by asbestos may emerge, control measures should be adopted

Assessment of the effectiveness of physical activity interventions in the Brazilian Unified Health System.

OBJECTIVE: To assess the effect of interventions on the levels of physical activity of healthy adults, users of the Brazilian Unified Health System and attended by the Family Health Strategy. METHODS: Non-randomized experimental study with 157 adults allocated in three groups: 1) physical exercise classes (n = 54), 2) health education (n = 54), 3) control (n = 49). The study lasted for18 months, with 12 months of interventions and six months of follow-up after intervention. Assessments took place at the beginning, in the 12 months, and in the 18 months of study. Physical activity has been assessed by questionnaires and accelerometry. For the analyses, we have used the intention-to-treat principle and generalized estimating equations. RESULTS: After 12 months, both intervention groups have increased the minutes of weekly leisure time physical activity and annual scores of physical exercise, leisure and transport-related physical activity. The exercise class group has obtained the highest average annual physical exercises score when compared to the other groups (p < 0.001). In the follow-up period, the exercise class group reduced its annual score (average: -0.3; 95%CI -0.5--0.1), while the health education group increased this score (average: 0.2; 95%CI 0.1-0.4). There have been no differences in the levels of physical activity measured by accelerometry. CONCLUSIONS: The interventions have been effective in increasing the practice of physical activity. However, we have observed that the health education intervention was more effective for maintaining the practice of physical activity in the period after intervention. We recommend the use of both interventions to promote physical activity in the Brazilian Unified Health System, according to the local reality of professionals, facilities, and team objectives. OBJETIVO: Avaliar o efeito de intervenções nos níveis de atividade física de adultos saudáveis, usuários do Sistema Único de Saúde e atendidos pela Estratégia de Saúde da Família. MÉTODOS: Estudo experimental, não randomizado, com 157 adultos alocados em três grupos: 1) classes de exercícios físicos (n = 54); 2) educação em saúde (n = 54); 3) controle (n = 49). O estudo teve duração de 18 meses, sendo 12 meses de intervenções e seis meses de acompanhamento pós-intervenção. As avaliações ocorreram no início, nos 12 e nos 18 meses de estudo. A atividade física foi avaliada por questionários e por acelerometria. Para as análises, utilizaram-se o princípio de intenção de tratar e equações de estimativas generalizadas. RESULTADOS: Após 12 meses, ambos os grupos de intervenção aumentaram os minutos semanais de atividade física no lazer e os escores anuais de exercícios físicos, de lazer e de deslocamento. O grupo das classes de exercícios físicos obteve maior média de escore anual de exercícios físicos em comparação com os outros grupos (p < 0,001). No período pós-intervenção, o grupo de classes de exercícios físicos reduziu o escore anual de exercícios físicos (média: -0,3; IC95% -0,5--0,1), enquanto o grupo de educação em saúde aumentou este escore (média: 0,2; IC95% 0,1-0,4). Não houve diferenças nos níveis de atividade física mensurados por acelerometria. CONCLUSÕES: As intervenções foram efetivas para aumentar a prática de atividade física. No entanto, observou-se que a intervenção de educação em saúde foi mais efetiva para a manutenção da prática de atividade física no período pós-intervenção. Recomenda-se a utilização de ambas as intervenções para a promoção da atividade física no Sistema Único de Saúde, de acordo com as realidades locais de profissionais, instalações e objetivos das equipes

Reprogramming normal cells into tumour precursors requires ECM stiffness and oncogene-mediated changes of cell mechanical properties

Defining the interplay between the genetic events and microenvironmental contexts necessary to initiate tumorigenesis in normal cells is a central endeavour in cancer biology. We found that receptor tyrosine kinase (RTK)–Ras oncogenes reprogram normal, freshly explanted primary mouse and human cells into tumour precursors, in a process requiring increased force transmission between oncogene-expressing cells and their surrounding extracellular matrix. Microenvironments approximating the normal softness of healthy tissues, or blunting cellular mechanotransduction, prevent oncogene-mediated cell reprogramming and tumour emergence. However, RTK–Ras oncogenes empower a disproportional cellular response to the mechanical properties of the cell’s environment, such that when cells experience even subtle supra-physiological extracellular-matrix rigidity they are converted into tumour-initiating cells. These regulations rely on YAP/TAZ mechanotransduction, and YAP/TAZ target genes account for a large fraction of the transcriptional responses downstream of oncogenic signalling. This work lays the groundwork for exploiting oncogenic mechanosignalling as a vulnerability at the onset of tumorigenesis, including tumour prevention strategies