27 research outputs found

    Targeting SNARE proteins and the trafficking of sodium channels in inflammatory pain

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    Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

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    Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

    Mortality of emergency abdominal surgery in high-, middle- and low-income countries

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    Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI). Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression. Results: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1â‹…6 per cent at 24 h (high 1â‹…1 per cent, middle 1â‹…9 per cent, low 3â‹…4 per cent; P < 0â‹…001), increasing to 5â‹…4 per cent by 30 days (high 4â‹…5 per cent, middle 6â‹…0 per cent, low 8â‹…6 per cent; P < 0â‹…001). Of the 578 patients who died, 404 (69â‹…9 per cent) did so between 24 h and 30 days following surgery (high 74â‹…2 per cent, middle 68â‹…8 per cent, low 60â‹…5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2â‹…78, 95 per cent c.i. 1â‹…84 to 4â‹…20) and low-income (OR 2â‹…97, 1â‹…84 to 4â‹…81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days. Conclusion: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role. Registration number: NCT02179112 (http://www.clinicaltrials.gov)

    Effects of type of light on mouse circadian behaviour and stress levels

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    Light is the principal synchronizing environmental factor for the biological clock. Light quantity (intensity), and light quality (type of light source) can have different effects. The aim of this study was to determine the effects of the type of light experienced from the time of birth on mouse growth, circadian behaviour and stress levels. We raised pigmented and albino mice under 24 h light–dark cycles of either fluorescent or white light-emitting diode (LED) light source during the suckling stage, and the animals were then exposed to various light environments after weaning and their growth rate, locomotor activity and plasma corticosterone concentration were measured. We found that the type of light the animals were exposed to did not affect the animals’ growth rates or stress levels. However, we observed significant effects on the expression of the locomotor activity rhythm under low contrast light–dark cycles in pigmented mice, and under constant light in both albino and pigmented mice. These results highlight the importance of environmental light quality (light source) on circadian behavioural rhythms, and the need for close monitoring of light environments in animal facilities. </jats:p

    Ecoturismo no município de Brotas-SP: suas contribuições econômicas e sociais

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    Este trabalho teve como objetivo geral contribuir no entendimento do setor de ecoturismo no município de Brotas-SP. Como objetivo específico, calculou o valor econômico, e apresentou as contribuições econômicas e social deste setor no município. Utilizou-se como metodologia um estudo de caso em que foi aplicado um questionário formulado para os turistas e gestores, além do cálculo do Valor Econômico Total (VET) do município. Descobriu-se que os principais setores turísticos do município estão ligados as atividades de arvorismo, off-road, rafiting, trilha, tirolesa, visitação, hospedagem, eventos, dentre outros serviços. Observou-se que 40% dos turistas que responderam o questionário são do Estado de São Paulo; 37,15% tem ensino superior completo; gastam diariamente entre R300eR 300 e R 400 reais; a maior parte tem uma renda familiar entre 4 e 6 salários mínimos; a população é jovem entre 20 e 40 anos; 31,40% apreciaram mais a parte de locação de imóveis; o VET ficou em R$ 150 reais, este foi o valor gerado pelo município para cada indivíduo como benefício e satisfação pessoal. Conclui-se que o Ecoturismo em Brotas-SP é um setor gerador de empregos e renda de forma sustentável

    Insulin protects pancreatic acinar cells from palmitoleic acid-induced cellular injury.

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    Acute pancreatitis is a serious and sometimes fatal inflammatory disease where the pancreas digests itself. The non-oxidative ethanol metabolites palmitoleic acid (POA) and POA-ethylester (POAEE) are reported to induce pancreatitis caused by impaired mitochondrial metabolism, cytosolic Ca(2+) ([Ca(2+)](i)) overload and necrosis of pancreatic acinar cells. Metabolism and [Ca(2+)](i) are linked critically by the ATP-driven plasma membrane Ca(2+)-ATPase (PMCA) important for maintaining low resting [Ca(2+)](i). The aim of the current study was to test the protective effects of insulin on cellular injury induced by the pancreatitis-inducing agents, ethanol, POA, and POAEE. Rat pancreatic acinar cells were isolated by collagenase digestion and [Ca(2+)](i) was measured by fura-2 imaging. An in situ [Ca(2+)](i) clearance assay was used to assess PMCA activity. Magnesium green (MgGreen) and a luciferase-based ATP kit were used to assess cellular ATP depletion. Ethanol (100 mm) and POAEE (100 μm) induced a small but irreversible Ca(2+) overload response but had no significant effect on PMCA activity. POA (50–100 μm) induced a robust Ca(2+) overload, ATP depletion, inhibited PMCA activity, and consequently induced necrosis. Insulin pretreatment (100 nm for 30 min) prevented the POA-induced Ca(2+) overload, ATP depletion, inhibition of the PMCA, and necrosis. Moreover, the insulin-mediated protection of the POA-induced Ca(2+) overload was partially prevented by the phosphoinositide-3-kinase (PI3K) inhibitor, LY294002. These data provide the first evidence that insulin directly protects pancreatic acinar cell injury induced by bona fide pancreatitis-inducing agents, such as POA. This may have important therapeutic implications for the treatment of pancreatitis

    Morphological and morphometric analysis of the adrenal cortex of androgenized female rats

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    Aim: We evaluated the thickness of the adrenal cortex zones of female rats androgenized to mimic polycystic ovary syndrome. Methods: Forty-four female virgin Wistar-Hannover rats were divided into two groups: controls ( n = 17) and animals which received testosterone propionate on the 2nd day of life ( n = 27). At 90 days of life, after confirmation of persistent estrus, the animals were sacrificed, and the adrenal cortex zones were evaluated. Student's t test and Levene's test were used in the statistical analysis ( p < 0.05 considered significant). Results: the adrenal glands of the androgenized rats were more voluminous and had a more intensely vascularized zona reticularis than the control animals. the mean thicknesses of zona glomerulosa and zona reticularis in the androgenized rats were 58.4 and 730.7 mu m, respectively, significantly thicker than the values in the control group ( 45.0 and 328.3 mu m, respectively). Conclusion: Zona reticularis and zona glomerulosa of the androgenized female rats were significantly thicker than those of the control animals. Copyright (c) 2007 S. Karger AG, Basel.Univ São Paulo, Dept Stat, São Paulo, BrazilUniv Estadual Campinas, Sch Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol, São Paulo, BrazilUniv Fed Piaui, Dept Gynecol, Teresina, BrazilUniversidade Federal de São Paulo, Dept Morphol, São Paulo, BrazilWeb of Scienc

    Tools for analysis and conditional deletion of subsets of sensory neurons

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    Background: somatosensation depends on primary sensory neurons of the trigeminal and dorsal root ganglia (DRG). Transcriptional profiling of mouse DRG sensory neurons has defined at least 18 distinct neuronal cell types. Using an advillin promoter, we have generated a transgenic mouse line that only expresses diphtheria toxin A (DTA) in sensory neurons in the presence of Cre recombinase. This has allowed us to ablate specific neuronal subsets within the DRG using a range of established and novel Cre lines that encompass all sets of sensory neurons. Methods: a floxed-tdTomato-stop-DTA bacterial artificial chromosome (BAC) transgenic reporter line (AdvDTA) under the control of the mouse advillin DRG promoter was generated. The line was first validated using a Nav1.8Cre and then crossed to CGRPCreER (Calca), ThCreERT2, Tmem45bCre, Tmem233Cre, Ntng1Cre and TrkBCreER (Ntrk2) lines. Pain behavioural assays included Hargreaves’, hot plate, Randall-Selitto, cold plantar, partial sciatic nerve ligation and formalin tests.Results: motor activity, as assessed by the rotarod test, was normal for all lines tested. Noxious mechanosensation was significantly reduced when either Nav1.8 positive neurons or Tmem45b positive neurons were ablated whilst acute heat pain was unaffected. In contrast, noxious mechanosensation was normal following ablation of CGRP-positive neurons but acute heat pain thresholds were significantly elevated and a reduction in nocifensive responses was observed in the second phase of the formalin test. Ablation of TrkB-positive neurons led to significant deficits in mechanical hypersensitivity in the partial sciatic nerve ligation neuropathic pain model.Conclusions: ablation of specific DRG neuronal subsets using the AdvDTA line will be a useful resource for further functional characterization of somatosensory processing, neuro-immune interactions and chronic pain disorders.<br/
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