17 research outputs found

    Dual Functions of ASCIZ in the DNA Base Damage Response and Pulmonary Organogenesis

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    Zn2+-finger proteins comprise one of the largest protein superfamilies with diverse biological functions. The ATM substrate Chk2-interacting Zn2+-finger protein (ASCIZ; also known as ATMIN and ZNF822) was originally linked to functions in the DNA base damage response and has also been proposed to be an essential cofactor of the ATM kinase. Here we show that absence of ASCIZ leads to p53-independent late-embryonic lethality in mice. Asciz-deficient primary fibroblasts exhibit increased sensitivity to DNA base damaging agents MMS and H2O2, but Asciz deletion or knock-down does not affect ATM levels and activation in mouse, chicken, or human cells. Unexpectedly, Asciz-deficient embryos also exhibit severe respiratory tract defects with complete pulmonary agenesis and severe tracheal atresia. Nkx2.1-expressing respiratory precursors are still specified in the absence of ASCIZ, but fail to segregate properly within the ventral foregut, and as a consequence lung buds never form and separation of the trachea from the oesophagus stalls early. Comparison of phenotypes suggests that ASCIZ functions between Wnt2-2b/ß-catenin and FGF10/FGF-receptor 2b signaling pathways in the mesodermal/endodermal crosstalk regulating early respiratory development. We also find that ASCIZ can activate expression of reporter genes via its SQ/TQ-cluster domain in vitro, suggesting that it may exert its developmental functions as a transcription factor. Altogether, the data indicate that, in addition to its role in the DNA base damage response, ASCIZ has separate developmental functions as an essential regulator of respiratory organogenesis

    Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

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    PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

    Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

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    PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

    Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan

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    Abstract: The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes

    Cultura e utilização das plantas medicinais e aromáticas

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    Este livro divide-se em três capítulos: “A qualidade das plantas medicinais e aromáticas”, “Constituintes activos das plantas medicinais e aromáticas e suas principais acções farmacológicas” e “Fitotecnia das plantas medicinais e aromáticas”. Para além dos capítulos genéricos estão presentes as monografias de 60 taxa, que incluem as mais diversas informações desde características botânicas e ecológicas a aspectos relativos à sua cultura. De forma a auxiliar a leitura foram incluídos dois glossários: um de nomes botânicos e outro de termos médicos. Segundo os autores, “todos os anos a indústria farmacêutica e a de cosmética necessitam de maiores quantidades de plantas medicinais e aromáticas mas com apropriados padrões de qualidade. Este facto tem vindo a proporcionar novas possibilidades à agricultura, existindo em Portugal, como em muitos outros países, uma marcada apetência dos agricultores para a cultura deste tipo de plantas, pois oferecem uma possibilidade de maior rendimento económico em relação à cultura tradicional de plantas

    Prevalence of anemia and its relationship with neurological status in patients undergoing surgery for degenerative cervical myelopathy and radiculopathy: A retrospective study of 2 spine centers

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    Both degenerative cervical myelopathy (DCM) and anemia are common among older patients, however insufficient data exists evaluating their co-occurrence and the influence of anemia on baseline neurological status. To address this, we examined a retrospective multicenter series of patients treated for DCM or radiculopathy. Myelopathy was graded using the Nurick scale. Established criteria for diagnosing abnormalities were used to identify blood abnormalities, including macrocytic and microcytic anemia. Multivariable regression was used to determine the impact of hematological anomalies on Nurick grades. In our analysis, we included 725 patients (age of 57.1 ± 11.7), of whom 398 presented with myelopathy and 327 presented with radiculopathy alone. Twenty six percent of all patients were anemic at baseline and the mean preoperative Nurick grade across all patients was 2.09 ± 1.29; mean Nurick grade amongst those with DCM was 2.98 ± 1.12. Compared to those with myelopathy, patients with radiculopathy were significantly younger (53.8 ± 11.0 vs 59.8 ± 11.6, p < 0.001) and less likely to be anemic (16.8% vs 33.7%, p < 0.0001). Nurick grading was significantly higher in myelopathy patients with anemia (3.13 ± 1.19 vs 2.91 ± 1.07, p = 0.05) and macrocytic anemia (4.00 ± 1.41 vs 2.97 ± 1.11, p = 0.04). Multivariate regression demonstrated that anemia (p < 0.001), age (p < 0.0001), and posterior surgical approach (p < 0.0001) were related to worse preoperative Nurick grade. In sum, these data suggest that anemia and degenerative cervical spine pathologies commonly co-occur. Anemia, and macrocytic anemia specifically, is associated with poorer neurological status in myelopathic patients. These data suggest anemia may influence baseline neurological status and impact surgical recovery in patients treated for DCM or radiculopathy

    Atención de salud de los adolescentes en Brasil: scoping review

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    The study seeks to map the characteristics and trends of scientific production regarding adolescent health care in Brazil. This is a scoping review conducted in 2018 using the BVS, Cochrane, SciELO, Ebsco and Web of Science databases. Original articles with the following populations were included: adolescents, health professionals and/or managers. A total of 72 studies published from 2006 to 2017 were reviewed. The analysis identified seven categories: sexual and reproductive health, risk factors and behaviors, health care and promotion actions, violence, oral health, HIV and mental health. The paper concludes that the conception of adolescence as a phase of human development and as an at-risk population. There are knowledge gap on topics such as lethal violence, social determinants of health and mental and digital health.O estudo objetivou mapear as características e tendências da pro-dução científica sobre a atenção à saúde de adolescentes no Brasil. Scoping review desenvolvida em 2018, nas bases BVS, Cochrane, SciELO, Ebsco e Web of Science. Foram incluídos artigos originais com os participantes: adolescentes, profissionais de saúde e/ou ges-tores/gestoras. Foram revisados 72 estudos publicados entre 2006 e 2017. A análise apontou sete categorias: saúde sexual e reprodutiva, fatores e comportamentos de risco, ações de atenção e promoção da saúde, violências, saúde bucal, HIV e saúde mental. Conclui-se que persiste a visão da adolescência como fase do desenvolvimento humano e como população de risco. Há lacuna em temas como vio-lência letal, determinantes sociais da saúde e saúde mental e digital.El estudio busca mapear las características y tendencias de la producción científica sobre el cuidado de la salud de los adolescentes en Brasil, Scoping review, realizado en 2018, basado en BVS, Cochrane, SciELO, Ebsco y Web of Science. Se incluyeron artículos originales con los siguientes participantes: adolescentes, profesionales de la salud y/o gerentes. Se revisaron 72 estudios publicados de 2006 a 2017. El análisis identificó siete categorías: salud sexual y reproductiva, factores y comportamientos de riesgo, acciones de atención y promoción, violencia, salud oral, VIH y salud mental. Concluye que persiste la concepción de la adolescencia como fase del desarrollo humano y como población en riesgo. Hay una brecha sobre temas como la violencia letal, los determinantes sociales de la salud, así como la salud mental y digital

    Atenção à saúde de adolescentes no Brasil: scoping review

    No full text
    El estudio busca mapear las características y tendencias de la producción científica sobre el cuidado de la salud de los adolescentes en Brasil, Scoping review, realizado en 2018, basado en BVS, Cochrane, SciELO, Ebsco y Web of Science. Se incluyeron artículos originales con los siguientes participantes: adolescentes, profesionales de la salud y/o gerentes. Se revisaron 72 estudios publicados de 2006 a 2017. El análisis identificó siete categorías: salud sexual y reproductiva, factores y comportamientos de riesgo, acciones de atención y promoción, violencia, salud oral, VIH y salud mental. Concluye que persiste la concepción de la adolescencia como fase del desarrollo humano y como población en riesgo. Hay una brecha sobre temas como la violencia letal, los determinantes sociales de la salud, así como la salud mental y digital
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