199 research outputs found
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PPARĪ±-independent effects of nitrate supplementation on skeletal muscle metabolism in hypoxia
Hypoxia is a feature of many disease states where convective
oxygen delivery is impaired, and is known to suppress oxidative
metabolism. Acclimation to hypoxia thus requires metabolic remodelling,
however hypoxia tolerance may be aided by dietary nitrate
supplementation. Nitrate improves tissue oxygenation and has been shown
to modulate skeletal muscle tissue metabolism via transcriptional
changes, including through the activation of peroxisome proliferator-
activated receptor alpha (PPARĪ±), a master regulator of fat metabolism.
Here we investigated whether nitrate supplementation protects skeletal
muscle mitochondrial function in hypoxia and whether PPARĪ± is required
for this effect. Wild-type and PPARĪ± knockout (PPARĪ±-/-) mice were
supplemented with sodium nitrate via the drinking water or sodium
chloride as control, and exposed to environmental hypoxia (10% O2) or
normoxia for 4 weeks. Hypoxia suppressed mitochondrial respiratory
function in mouse soleus, an effect partially alleviated through nitrate
supplementation, but occurring independently of PPARĪ±. Specifically,
hypoxia resulted in 26% lower mass specific fatty acid-supported LEAK
respiration and 23% lower pyruvate-supported oxidative phosphorylation
capacity. Hypoxia also resulted in 24% lower citrate synthase activity in
mouse soleus, possibly indicating a loss of mitochondrial content. These
changes were not seen, however, in hypoxic mice when supplemented with
dietary nitrate, indicating a nitrate dependent preservation of
mitochondrial function. Moreover, this was observed in both wild-type and
PPARĪ±-/- mice. Our results support the notion that nitrate
supplementation can aid hypoxia tolerance and indicate that nitrate can
exert effects independently of PPARĪ±.This work was supported by Kingās College London, the Biotechnology and Biological Sciences Research Councils [grant number: BB/F016581/1] and the Research Councils UK [grant number:
EP/E500552/1]
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Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration-probing the role of PPARĪ±.
Dietary inorganic nitrate prevents aspects of cardiac mitochondrial dysfunction induced by hypoxia, although the mechanism is not completely understood. In both heart and skeletal muscle, nitrate increases fatty acid oxidation capacity, and in the latter case, this involves up-regulation of peroxisome proliferator-activated receptor (PPAR)Ī± expression. Here, we investigated whether dietary nitrate modifies mitochondrial function in the hypoxic heart in a PPARĪ±-dependent manner. Wild-type (WT) mice and mice without PPARĪ± (Ppara-/-) were given water containing 0.7 mM NaCl (control) or 0.7 mM NaNO3 for 35 d. After 7 d, mice were exposed to normoxia or hypoxia (10% O2) for the remainder of the study. Mitochondrial respiratory function and metabolism were assessed in saponin-permeabilized cardiac muscle fibers. Environmental hypoxia suppressed mass-specific mitochondrial respiration and additionally lowered the proportion of respiration supported by fatty acid oxidation by 18% (P < 0.001). This switch away from fatty acid oxidation was reversed by nitrate treatment in hypoxic WT but not Ppara-/- mice, indicating a PPARĪ±-dependent effect. Hypoxia increased hexokinase activity by 33% in all mice, whereas lactate dehydrogenase activity increased by 71% in hypoxic WT but not Ppara-/- mice. Our findings indicate that PPARĪ± plays a key role in mediating cardiac metabolic remodeling in response to both hypoxia and dietary nitrate supplementation.-Horscroft, J. A., O'Brien, K. A., Clark, A. D., Lindsay, R. T., Steel, A. S., Procter, N. E. K., Devaux, J., Frenneaux, M., Harridge, S. D. R., Murray, A. J. Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration-probing the role of PPARĪ±
The role of the Quality and Outcomes Framework in the care of long-term conditions: a systematic review
Background: Improving care for people with long-term conditions is central to NHS policy. It has been suggested that the Quality and Outcomes Framework (QOF), a pay-for-performance scheme in primary care that rewards practices for delivering effective interventions in the management of longterm conditions, does not encourage high quality care for this group of patients. Aim: To examine the evidence that the QOF has improved quality of care of patients with long-term conditions. Design Systematic review Method We used electronic databases to search for peer-reviewed empirical quantitative research on the QOF published since the schemeās introduction in 2004. We searched for studies examining the effect of QOF on a broad range of processes and outcomes of care, including coordination and integration of care, holistic and personalised care, self-care, patient experience, physiological and biochemical outcomes, health service utilisation, and mortality. We carried out a narrative synthesis because the studies were heterogeneous. Results: The QOF was associated with a modest slowing of the increase in emergency admission rates, a modest slowing of the increase in consultation rates in severe mental illness, and modest improvements in certain aspects of the care of diabetes. The nature of the evidence means that we cannot be sure that any of these associations is causal. No clear effect on mortality has been demonstrated. We found no evidence to suggest that QOF influences, positively or negatively, integration or coordination of care, holistic or personalised care, self-care, or patientsā experience, quality of life or satisfaction. Conclusion: The NHS should consider more broadly what constitutes high quality primary care for people with long-term conditions, and consider other ways of motivating primary care to deliver it
Evaluation of a new model of care for people with complications of diabetic retinopathy : The EMERALD Study
Objectives
The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent and life-long follow-up, have markedly increased hospital demands. Resulting delays in the evaluation/treatment of patients are leading to sight loss. Strategies to increase capacity of medical retina clinics are urgently needed. EMERALD tested diagnostic accuracy, acceptability and costs of a new health care pathway for people with previously treated DME/PDR.
Design
Prospective, multicentric, case-referent, cross-sectional, diagnostic accuracy study, undertaken in 13 hospitals in the United Kingdom.
Participants
Adults with type 1 or 2 diabetes and previously successfully treated DME/PDR who, at the time of enrolment, had active or inactive disease.
Methods
A new health care pathway entailing multimodal imaging (spectral domain optical coherence tomography [SD-OCT] for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-wide-field fundus images [UWF] for PDR) interpreted by trained non-medical staff (ophthalmic graders) to detect re-activation of disease was compared with the current standard care (ophthalmologists face-to-face examination).
Main outcome measures
Primary outcome: sensitivity of the new pathway. Secondary outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, with inadequate images/indeterminate findings.
Results
The new pathway had sensitivity of 97% (95% confidence interval [CI] 92-99%) and specificity of 31% (95% CI 23-40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS (85%, 95% CI 77-91%; 48%; 95% CI 41-56%, respectively) or UWF (83%, 95% CI 75-89%; 54%; 95% CI 46-61%, respectively) were comparable. For detection of high risk PDR sensitivity and specificity were higher when using UWF images (87%, 95% CI 78-93%; 49% 95% CI 42-56%, respectively for UWF, versus 80%, 95% CI 69-88%; 40% CI 34-47%, respectively, for 7-field ETDRS). Participants preferred ophthalmologistās assessments; in their absence, wished immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard care, the new pathway could save Ā£1,390/100 DME visits and between Ā£461-Ā£1,189/100 PDR visits.
Conclusion
The new ophthalmic grader pathway has acceptable sensitivity and would release resources. Usersā suggestions should guide implementatio
Stress ocupacional e alteraĆ§Ć£o do Estatuto da Carreira Docente portuguĆŖs
Este estudo foi realizado com 1162 professores, tendo como objetivo analisar a experiĆŖncia de stress e a sĆndrome de āburnoutā, antes a apĆ³s a alteraĆ§Ć£o do Estatuto da Carreira Docente em Portugal. Assim, foram efetuadas duas avaliaƧƵes em momentos temporais distintos, assumindo-se um plano transversal de recolha de dados (2004/2005, n=689 e 2008/2009, n=473). O protocolo de avaliaĆ§Ć£o incluiu medidas de fontes de stress (QuestionĆ”rio de Stress nos Professores, Gomes, Silva, Mourisco, Mota, & Montenegro, 2006) e de āburnoutā (InventĆ”rio de āBurnoutā de Maslach ā VersĆ£o para Professores, Maslach, Jackson, & Leiter, 1996; Maslach, Jackson, & Schwab, 1996, AdaptaĆ§Ć£o de Gomes et al., 2006). Os resultados indicaram que a experiĆŖncia de stress e de āburnoutā aumentou entre as duas avaliaƧƵes, verificando-se em 2008/2009 aumentos em Ć”reas relacionadas com as pressƵes de tempo/excesso de trabalho e com o trabalho burocrĆ”tico/administrativo e, inversamente, diminuiƧƵes em Ć”reas relacionadas com as diferentes capacidades e motivaƧƵes dos alunos. Quanto Ć prediĆ§Ć£o da sĆndrome de āburnoutā, nĆ£o se verificaram alteraƧƵes substanciais nas variĆ”veis preditoras nos dois momentos. Em sĆntese, os resultados indicaram aumentos nas exigĆŖncias profissionais dos professores, mas nĆ£o se pode afirmar que tal se deva Ć s alteraƧƵes do Estatuto da Carreira Docente uma vez que nĆ£o observĆ”mos alteraƧƵes no stress associado Ć carreira docente.(undefined
Perspectives in visual imaging for marine biology and ecology: from acquisition to understanding
Durden J, Schoening T, Althaus F, et al. Perspectives in Visual Imaging for Marine Biology and Ecology: From Acquisition to Understanding. In: Hughes RN, Hughes DJ, Smith IP, Dale AC, eds. Oceanography and Marine Biology: An Annual Review. 54. Boca Raton: CRC Press; 2016: 1-72
Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
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 (74Ā·0%) had emergency surgery and 280 (24Ā·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26Ā·1%) patients. 30-day mortality was 23Ā·8% (268 of 1128). Pulmonary complications occurred in 577 (51Ā·2%) of 1128 patients; 30-day mortality in these patients was 38Ā·0% (219 of 577), accounting for 81Ā·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1Ā·75 [95% CI 1Ā·28ā2Ā·40], p\textless0Ā·0001), age 70 years or older versus younger than 70 years (2Ā·30 [1Ā·65ā3Ā·22], p\textless0Ā·0001), American Society of Anesthesiologists grades 3ā5 versus grades 1ā2 (2Ā·35 [1Ā·57ā3Ā·53], p\textless0Ā·0001), malignant versus benign or obstetric diagnosis (1Ā·55 [1Ā·01ā2Ā·39], p=0Ā·046), emergency versus elective surgery (1Ā·67 [1Ā·06ā2Ā·63], p=0Ā·026), and major versus minor surgery (1Ā·52 [1Ā·01ā2Ā·31], p=0Ā·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
Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study
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-19āfree 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-19āfree 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-19āfree surgical pathways. Patients who underwent surgery within COVID-19āfree 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-19āfree 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 scoreāmatched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19āfree surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19āfree surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks
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