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Olanzapine is a second-generation antipsychotic that disrupts metabolism and is associated with an increased risk of type 2 diabetes. The hypothalamus is a key region in the control of whole-body metabolic homeostasis. The objective of the current study was to determine how acute peripheral olanzapine administration affects transcription and serine/threonine kinase activity in the hypothalamus. Hypothalamus samples from rats were collected following the pancreatic euglycemic clamp, thereby allowing us to study endpoints under steady state conditions for plasma glucose and insulin. Olanzapine stimulated pathways associated with inflammation, but diminished pathways associated with the capacity to combat endoplasmic reticulum stress and G protein-coupled receptor activity. These pathways represent potential targets to reduce the incidence of type 2 diabetes in patients taking antipsychotics.
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Antipsicóticos , Diabetes Mellitus Tipo 2 , Humanos , Ratos , Animais , Olanzapina/farmacologia , Olanzapina/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Benzodiazepinas/farmacologia , Benzodiazepinas/metabolismo , Antipsicóticos/farmacologia , Antipsicóticos/metabolismo , Hipotálamo/metabolismo , Perfilação da Expressão GênicaRESUMO
Antipsychotic (AP)-naive first-episode psychosis (FEP) patients display early dysglycemia, including insulin resistance and prediabetes. Metabolic dysregulation may therefore be intrinsic to psychosis spectrum disorders (PSDs), independent of the metabolic effects of APs. However, the potential biological pathways that overlap between PSDs and dysglycemic states remain to be identified. Using meta-analytic approaches of transcriptomic datasets, we investigated whether AP-naive FEP patients share overlapping gene expression signatures with non-psychiatrically ill early dysglycemia individuals. We meta-analyzed peripheral transcriptomic datasets of AP-naive FEP patients and non-psychiatrically ill early dysglycemia subjects to identify common gene expression signatures. Common signatures underwent pathway enrichment analysis and were then used to identify potential new pharmacological compounds via Integrative Library of Integrated Network-Based Cellular Signatures (iLINCS). Our search results yielded 5 AP-naive FEP studies and 4 early dysglycemia studies which met inclusion criteria. We discovered that AP-naive FEP and non-psychiatrically ill subjects exhibiting early dysglycemia shared 221 common signatures, which were enriched for pathways related to endoplasmic reticulum stress and abnormal brain energetics. Nine FDA-approved drugs were identified as potential drug treatments, of which the antidiabetic metformin, the first-line treatment for type 2 diabetes, has evidence to attenuate metabolic dysfunction in PSDs. Taken together, our findings support shared gene expression changes and biological pathways associating PSDs with dysglycemic disorders. These data suggest that the pathobiology of PSDs overlaps and potentially contributes to dysglycemia. Finally, we find that metformin may be a potential treatment for early metabolic dysfunction intrinsic to PSDs.
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Antipsicóticos , Diabetes Mellitus Tipo 2 , Metformina , Transtornos Psicóticos , Humanos , Transcriptoma , Antipsicóticos/farmacologia , Antipsicóticos/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/genética , Glucose , Metformina/farmacologia , Metformina/uso terapêuticoRESUMO
BACKGROUND: Despite recent systematic reviews suggesting their benefit for postoperative nausea, vomiting, or both (PONV) prevention, benzodiazepines have not been incorporated into guidelines for PONV prophylaxis because of concerns about possible adverse effects. We conducted an updated meta-analysis to inform future practice guidelines. METHODS: We included randomised controlled trials (RCTs) of all languages comparing benzodiazepines with non-benzodiazepine comparators in adults undergoing inpatient surgery. Our outcomes were postoperative nausea, vomiting, or both. We assessed risk of bias for RCTs using the Cochrane Risk of Bias tool. We pooled data using a random-effects model and assessed the quality of evidence for each outcome using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: We screened 31 413 abstracts and 950 full texts. We included 119 RCTs; 104 were included in quantitative synthesis. Based on moderate certainty evidence, we found that perioperative benzodiazepine administration reduced the incidence of PONV (52 studies, n=5086, relative risk [RR]: 0.77, 95% confidence interval [CI] 0.66-0.89; number needed to treat [NNT] 16; moderate certainty), postoperative nausea (55 studies, n=5916, RR: 0.72, 95% CI 0.62-0.83; NNT 21; moderate certainty), and postoperative vomiting (52 studies, n=5909, RR: 0.74, 95% CI 0.60-0.91; NNT 55; moderate certainty). CONCLUSIONS: Moderate quality evidence shows that perioperative benzodiazepine administration decreases the incidence of PONV. The results of this systematic review and meta-analysis will inform future clinical practice guidelines. SYSTEMATIC REVIEW PROTOCOL: The protocol for this systematic review was pre-registered with PROSPERO International Prospective Register of Systematic Reviews (CRD42022361088) and published in BMJ Open (PMID 31831540).
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Antieméticos , Benzodiazepinas , Náusea e Vômito Pós-Operatórios , Ensaios Clínicos Controlados Aleatórios como Assunto , Náusea e Vômito Pós-Operatórios/prevenção & controle , Humanos , Benzodiazepinas/administração & dosagem , Benzodiazepinas/uso terapêutico , Antieméticos/administração & dosagem , Antieméticos/uso terapêutico , Assistência Perioperatória/métodosRESUMO
Antipsychotic drug (AP)-naïve first-episode psychosis (FEP) patients display premorbid cognitive dysfunctions and dysglycemia. Brain insulin resistance may link metabolic and cognitive disorders in humans. This suggests that central insulin dysregulation represents a component of the pathophysiology of psychosis spectrum disorders (PSDs). Nonetheless, the links between central insulin dysregulation, dysglycemia, and cognitive deficits in PSDs are poorly understood. We investigated whether AP-naïve FEP patients share overlapping brain gene expression signatures with central insulin perturbation (CIP) in rodent models. We systematically compiled and meta-analyzed peripheral transcriptomic datasets of AP-naïve FEP patients along with hypothalamic and hippocampal datasets of CIP rodent models to identify common transcriptomic signatures. The common signatures were used for pathway analysis and to identify potential drug treatments with discordant (reverse) signatures. AP-naïve FEP and CIP (hypothalamus and hippocampus) shared 111 and 346 common signatures respectively, which were associated with pathways related to inflammation, endoplasmic reticulum stress, and neuroplasticity. Twenty-two potential drug treatments were identified, including antidiabetic agents. The pathobiology of PSDs may include central insulin dysregulation, which contribute to dysglycemia and cognitive dysfunction independently of AP treatment. The identified treatments may be tested in early psychosis patients to determine if dysglycemia and cognitive deficits can be mitigated.
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Antipsicóticos , Resistência à Insulina , Transtornos Psicóticos , Humanos , Antipsicóticos/uso terapêutico , Insulina , Transcriptoma , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/genética , Transtornos Psicóticos/complicaçõesRESUMO
Antipsychotics (APs) are the cornerstone of treatment for schizophrenia (SCZ) spectrum disorders. Previous research suggests that there may be a positive association between AP-induced weight gain and/or dyslipidemia and improvement in psychiatric symptoms, often referred to as a "metabolic threshold". To determine whether a similar relationship exists for glucose parameters, we conducted a systematic search in six databases from inception to June 2022 for all longitudinal studies that directly examined the relationship between changes in glucose-related outcomes and changes in psychopathology among patients with SCZ treated with APs. We identified 10 relevant studies and one additional study that considered cognition. In most cases, we found that increased levels of fasting glucose and insulin following treatment were associated with clinical improvement. These findings contribute to existing literature that could suggest a common mechanism between AP action and metabolic side effects and support a need for additional work aimed at exploring the validity of a glucose-psychopathology relation in SCZ.
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Factor V Leiden is the commonest hereditary prothrombotic allele, affecting 1% to 5% of the world's population. The objective of this study was to characterize the perioperative and postoperative outcomes of patients with Factor V Leiden compared to patients without a diagnosis of hereditary thrombophilia. This was a focused systematic review of studies including adult (>18 years) patients with Factor V Leiden (heterozygous or homozygous) undergoing noncardiac surgery. Included studies were either randomized controlled trials or observational. The primary clinical outcomes of interest were thromboembolic events occurring from the perioperative period up to 1 year postoperatively, defined as deep venous thrombosis, pulmonary embolism, or other clinically significant thrombosis occurring during or after a surgical procedure. Secondary outcomes included cerebrovascular events, cardiac events, death, transplant-related outcomes, and surgery-specific morbidity. Pediatric and obstetrical patients were excluded, as were case reports and case series. Databases searched included MEDLINE and EMBASE from inception until August 2021. Study bias was assessed through the CLARITY (Collaboration of McMaster University researchers) Risk of Bias tools, and heterogeneity through analysis of study design and end points, as well as the I 2 statistic with its confidence interval and the Q statistic. A total of 5275 potentially relevant studies were identified, with 115 having full text assessed for eligibility and 32 included in the systematic review. On the whole, the literature suggests that patients with Factor V Leiden have an increased risk of perioperative and postoperative thromboembolic events compared to patients without the diagnosis. Increased risk was also seen in relation to surgery-specific morbidity and transplant-related outcomes, particularly arterial thrombotic events. The literature did not support an increased risk for mortality, cerebrovascular, or cardiac complications. Limitations of the data include predisposition toward bias due in many study designs and small sample sizes across the majority of published studies. Variable outcome definitions and durations of patient follow-up across different surgical procedures resulted in high study heterogeneity precluding the effective use of meta-analysis. Factor V Leiden status may confer additional risk for surgery-related adverse outcomes. Large, adequately powered studies are required to accurately estimate the degree of this risk by zygosity.
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Cardiopatias , Trombofilia , Humanos , Adulto , Criança , Fator V/genéticaRESUMO
BACKGROUND: Older patients with preoperative cognitive impairment are at risk for increased postoperative complications after noncardiac surgery. This systematic review and meta-analysis aimed to determine the association between preoperative cognitive impairment and dementia and postoperative outcomes in older surgical patients after cardiac surgery. METHODS: Eight electronic databases were searched from inception to January 4, 2022. Inclusion criteria were cardiac surgery patients ≥60 years of age; preoperative cognitive impairment; ≥1 postoperative complication reported; comparator group with no preoperative cognitive impairment; and written in English. Using a random-effects model, we calculated effect sizes as odds ratio (OR) and standardized mean differences (SMDs). Risk of random error was assessed by applying trial sequential analysis. RESULTS: Sixteen studies (62,179 patients) were included. Preoperative cognitive impairment was associated with increased risk of delirium in older patients after cardiac surgery (70.0% vs 20.5%; OR, 8.35; 95% confidence interval [CI], 4.25-16.38; I 2 , 0%; P < .00001). Cognitive impairment was associated with increased hospital length of stay (LOS; SMD, 0.36; 95% CI, 0.20-0.51; I 2 , 22%; P < .00001) and intensive care unit (ICU) LOS (SMD, 0.39; 95% CI, 0.09-0.68; I 2 , 70%; P = .01). No significant association was seen for 30-day mortality (1.7% vs 1.1%; OR, 2.58; 95% CI, 0.64-10.44; I 2 , 55%; P = .18). CONCLUSIONS: In older patients undergoing cardiac surgery, cognitive impairment was associated with an 8-fold increased risk of delirium, a 5% increase in absolute risk of major postoperative bleeding, and an increase in hospital and ICU LOS by approximately 0.4 days. Further research on the feasibility of implementing routine neurocognitive testing is warranted.
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Procedimentos Cirúrgicos Cardíacos , Disfunção Cognitiva , Delírio , Humanos , Idoso , Delírio/etiologia , Delírio/complicações , Disfunção Cognitiva/complicações , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Unidades de Terapia IntensivaRESUMO
Schizophrenia is a debilitating psychiatric disorder that is treated with antipsychotics. However, despite their efficacy, antipsychotics increase the risk of metabolic disorders in a population that suffers from premature cardiovascular death. Published reports to date strongly suggest that antipsychotic-induced alterations in lipid metabolism are part of the causal relationship between antipsychotic treatment and both metabolic and cardiovascular disease. Notably, some of the adverse effects of antipsychotics on lipid metabolism are independent of antipsychotic-induced weight gain. Moreover, some antipsychotics also have beneficial effects on certain aspects of lipid metabolism. In this review, we summarize the current knowledge regarding how antipsychotics modulate lipid turnover at the whole-body, tissue, and cellular levels. We also highlight gaps in the literature, especially with respect to the intracellular mechanisms through which antipsychotics affect lipid metabolism.
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Antipsicóticos , Doenças Metabólicas , Esquizofrenia , Humanos , Antipsicóticos/efeitos adversos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Esquizofrenia/metabolismo , Aumento de Peso , LipídeosRESUMO
Hypothalamic detection of elevated circulating glucose triggers suppression of endogenous glucose production (EGP) to maintain glucose homeostasis. Antipsychotics alleviate symptoms associated with schizophrenia but also increase the risk for impaired glucose metabolism. In the current study, we examined whether two acutely administered antipsychotics from different drug classes, haloperidol (first generation antipsychotic) and olanzapine (second generation antipsychotic), affect the ability of intracerebroventricular (ICV) glucose infusion approximating postprandial levels to suppress EGP. The experimental protocol consisted of a pancreatic euglycemic clamp, followed by kinomic and RNA-seq analyses of hypothalamic samples to determine changes in serine/threonine kinase activity and gene expression, respectively. Both antipsychotics inhibited ICV glucose-mediated increases in glucose infusion rate during the clamp, a measure of whole-body glucose metabolism. Similarly, olanzapine and haloperidol blocked central glucose-induced suppression of EGP. ICV glucose stimulated the vascular endothelial growth factor (VEGF) pathway, phosphatidylinositol 3-kinase (PI3K) pathway, and kinases capable of activating KATP channels in the hypothalamus. These effects were inhibited by both antipsychotics. In conclusion, olanzapine and haloperidol impair central glucose sensing. Although results of hypothalamic analyses in our study do not prove causality, they are novel and provide the basis for a multitude of future studies.
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Antipsicóticos , Antipsicóticos/farmacologia , Glucose/metabolismo , Fosfatidilinositol 3-Quinases , Fator A de Crescimento do Endotélio Vascular , Olanzapina/farmacologia , Olanzapina/metabolismo , Benzodiazepinas/farmacologiaRESUMO
OBJECTIVE: Individuals with intellectual and/or developmental disability (IDD) are often prescribed antipsychotics (APs). However, despite their known propensity to cause metabolic adverse effects, including weight gain, diabetes, and increased risk of cardiovascular events, there is currently a limited body of literature describing the metabolic consequences of AP use in this population. METHODS: We searched MEDLINE, EMBASE, PsychINFO, CENTRAL, and CINAHL databases to identify all randomized trials that reported on the metabolic effects of APs in individuals with IDD. Random effects meta-analyses were used to examine weight gain as both a continuous and dichotomous outcome. RESULTS: Eighteen randomized trials met our inclusion criteria with a total of 1376 patients across a variety of IDDs. AP use was associated with significantly greater weight gain compared with placebo (Continuous: mean difference = 1.10 kg, [0.79, 1.40], p < 0.00001, I2 = 54%; Dichotomous: odds ratio = 3.94, [2.15, 7.23], p < 0.00001, I2 = 0). Sub-group analysis revealed no significant effect of AP type. Data regarding the effects of APs on other metabolic outcomes were limited. CONCLUSION: This review (PROSPERO # CRD42021255558) demonstrates that AP use is associated with significant weight gain among patients with IDD. Concerningly, most reported studies were in children and adolescents, which sets up an already vulnerable population for adverse medical sequalae at an early age. There was also a lack of long-term studies in adults with IDD. Further studies are required to better understand how AP use affects metabolic parameters in this group of individuals.
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Antipsicóticos , Adolescente , Antipsicóticos/efeitos adversos , Criança , Deficiências do Desenvolvimento/induzido quimicamente , Humanos , Aumento de PesoRESUMO
OBJECTIVE: Online recovery communities offer support for people with eating disorders who may not otherwise seek professional help. Instagram is a popular platform that is widely used for eating disorder recovery, but little is known about the population that uses it or its potential benefits. METHOD: A mixed-methods study surveyed 163 users of the Instagram recovery community to identify their descriptive characteristics, their reasons for using the community, and what they perceived to be helpful or unhelpful about the platform. RESULTS: The community included users who were diverse in gender, ethnicity and eating disorder presentation and severity, with cases of potential anorexia nervosa, bulimia nervosa and binge eating disorder identified. Reasons for engaging in the community included to see representations of diverse individuals and as an alternative to professional treatment. Results indicate that the community may provide benefits for recovery such as social support and validation, but that its lack of moderation and potential for harmful content can also prevent recovery. CONCLUSIONS: These findings highlight the need for better recognition of diverse eating disorder presentations and improved accessibility to professional treatment in the wider community. Moderated use of the platform should be considered in order to minimize risks and increase benefits.
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Anorexia Nervosa , Transtorno da Compulsão Alimentar , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Mídias Sociais , Anorexia Nervosa/terapia , Transtorno da Compulsão Alimentar/epidemiologia , Bulimia Nervosa/epidemiologia , Bulimia Nervosa/terapia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , HumanosRESUMO
Schizophrenia (SCZ) is a severe mental disorder with high morbidity and lifetime disability rates. Patients with SCZ have a higher risk of developing metabolic comorbidities such as obesity and diabetes mellitus, leading to increased mortality. Antipsychotics (APs), which are the mainstay in the treatment of SCZ, increase the risk of these metabolic perturbations. Despite extensive research, the mechanism underlying SCZ pathophysiology and associated metabolic comorbidities remains unclear. In recent years, gut microbiota (GMB) has been regarded as a 'chamber of secrets', particularly in the context of severe mental illnesses such as SCZ, depression, and bipolar disorder. In this scoping review, we aimed to investigate the underlying role of GMB in the pathophysiology of SCZ and metabolic alterations associated with APs. Furthermore, we also explored the therapeutic benefits of prebiotic and probiotic formulations in managing SCZ and AP-induced metabolic alterations. A systematic literature search yielded 46 studies from both preclinical and clinical settings that met inclusion criteria for qualitative synthesis. Preliminary evidence from preclinical and clinical studies indicates that GMB composition changes are associated with SCZ pathogenesis and AP-induced metabolic perturbations. Fecal microbiota transplantation from SCZ patients to mice has been shown to induce SCZ-like behavioral phenotypes, further supporting the plausible role of GMB in SCZ pathogenesis. This scoping review recapitulates the preclinical and clinical evidence suggesting the role of GMB in SCZ symptomatology and metabolic adverse effects associated with APs. Moreover, this scoping review also discusses the therapeutic potentials of prebiotic/probiotic formulations in improving SCZ symptoms and attenuating metabolic alterations related to APs.
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STUDY OBJECTIVE: To determine the effect of cognitive impairment (CI) and dementia on adverse outcomes in older surgical patients. DESIGN: A systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs). Various databases were searched from their inception dates to March 8, 2021. SETTING: Preoperative assessment. PATIENTS: Older patients (≥ 60 years) undergoing non-cardiac surgery. MEASUREMENTS: Outcomes included postoperative delirium, mortality, discharge to assisted care, 30-day readmissions, postoperative complications, and length of hospital stay. Effect sizes were calculated as Odds Ratio (OR) and Mean Difference (MD) based on random effect model analysis. The quality of included studies was assessed using the Cochrane Risk Bias Tool for RCTs and Newcastle-Ottawa Scale for observational cohort studies. RESULTS: Fifty-three studies (196,491 patients) were included. Preoperative CI was associated with a significant risk of delirium in older patients after non-cardiac surgery (25.1% vs. 10.3%; OR: 3.84; 95%CI: 2.35, 6.26; I2: 76%; p < 0.00001). Cognitive impairment (26.2% vs. 13.2%; OR: 2.28; 95%CI: 1.39, 3.74; I2: 73%; p = 0.001) and dementia (41.6% vs. 25.5%; OR: 1.96; 95%CI: 1.34, 2.88; I2: 99%; p = 0.0006) significantly increased risk for 1-year mortality. In patients with CI, there was an increased risk of discharge to assisted care (44.7% vs. 38.3%; OR 1.74; 95%CI: 1.05, 2.89, p = 0.03), 30-day readmissions (14.3% vs. 10.8%; OR: 1.36; 95%CI: 1.00, 1.84, p = 0.05), and postoperative complications (40.7% vs. 18.8%; OR: 1.85; 95%CI: 1.37, 2.49; p < 0.0001). CONCLUSIONS: Preoperative CI in older surgical patients significantly increases risk of delirium, 1-year mortality, discharge to assisted care, 30-day readmission, and postoperative complications. Dementia increases the risk of 1-year mortality. Cognitive screening in the preoperative assessment for older surgical patients may be helpful for risk stratification so that appropriate management can be implemented to mitigate adverse postoperative outcomes.
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Disfunção Cognitiva , Delírio , Demência , Idoso , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Delírio/epidemiologia , Delírio/etiologia , Delírio/prevenção & controle , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controleRESUMO
BACKGROUND: We conducted a systematic review and meta-analysis to assess effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) as adjuncts for postoperative pain management. METHODS: We searched seven databases and two trial registers from inception to February 2021 for RCTs that compared SSRIs or SNRIs with placebo or an active control for postoperative pain management. RESULTS: We included 24 RCTs with 2197 surgical patients (21 trials for SNRIs and three trials for SSRIs). Moderate-quality evidence found that, compared with placebo, SSRIs/SNRIs (majority SNRIs) significantly reduced postoperative pain within 6 h {weighted mean difference (WMD) -0.73 cm on a 10 cm VAS (95% confidence interval [CI]: -1.04 to -0.42)}, 12 h (-0.68 cm [-1.28 to -0.07]), 24 h (-0.68 cm [-1.16 to -0.20]), 48 h (-0.73 cm [-1.22 to -0.23]), 10 days to 1 month (-0.71 cm [-1.11 to -0.31]), 3 months (-0.64 cm [-1.05 to -0.22]), and 6 months (-0.95 cm [-1.64 to -0.25]), and opioid consumption within 24 h (WMD -12 mg [95% CI: -16 to -8]) and 48 h (-10 mg [-15 to -5]), and improved patient satisfaction (WMD 0.49 point on a 1-4 Likert scale [95% CI: 0.09 to 0.89]) without significant increase in adverse events. Selective serotonin reuptake inhibitors tended to be less effective despite non-significant subgroup effects. CONCLUSIONS: Serotonin-norepinephrine reuptake inhibitors as an adjunct to standard perioperative care probably provide small reduction in both acute and chronic postoperative pain and opioid consumption, and small improvement in patient satisfaction without increases in adverse events. The effects of SSRIs are inconclusive because of very limited evidence.
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Dor Pós-Operatória/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Analgésicos Opioides/administração & dosagem , Humanos , Satisfação do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversosRESUMO
Many bacteria use the second messenger cyclic diguanylate (c-di-GMP) to control motility, biofilm production and virulence. Here, we identify a thermosensory diguanylate cyclase (TdcA) that modulates temperature-dependent motility, biofilm development and virulence in the opportunistic pathogen Pseudomonas aeruginosa. TdcA synthesizes c-di-GMP with catalytic rates that increase more than a hundred-fold over a ten-degree Celsius change. Analyses using protein chimeras indicate that heat-sensing is mediated by a thermosensitive Per-Arnt-SIM (PAS) domain. TdcA homologs are widespread in sequence databases, and a distantly related, heterologously expressed homolog from the Betaproteobacteria order Gallionellales also displayed thermosensitive diguanylate cyclase activity. We propose, therefore, that thermotransduction is a conserved function of c-di-GMP signaling networks, and that thermosensitive catalysis of a second messenger constitutes a mechanism for thermal sensing in bacteria.
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Proteínas de Bactérias/metabolismo , GMP Cíclico/análogos & derivados , Proteínas de Escherichia coli/metabolismo , Fósforo-Oxigênio Liases/metabolismo , Pseudomonas aeruginosa/metabolismo , Sistemas do Segundo Mensageiro/fisiologia , Transdução de Sinais/fisiologia , Algoritmos , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Cromatografia Líquida , GMP Cíclico/metabolismo , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Espectrometria de Massas , Fósforo-Oxigênio Liases/genética , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiologia , TemperaturaRESUMO
Crohn's disease is a disorder characterized by transmural inflammation which can potentially affect any part of the gastrointestinal tract from the mouth to the perianal area. Cohn's disease is a systemic disease characterized by a relapsing remitting course, with variable intestinal and extra-intestinal complications. Abdominal and pelvic abscesses are not an uncommon complication of Crohn's disease occurring in 10-30 percent of all patients. We present the case of a 21-year-old male with Crohn's disease presenting with a massive abdominal abscess, whose diagnosis was delayed given lack of typical symptoms. Shortly after initiating therapy with Prednisone and Adalimumab he presented with worsening abdominal distention. Cross sectional imaging of the abdomen with IV contrast (Figure 1) demonstrated a 34cm x 23 cm x 11 cm rim-enhancing fluid collections in the abdomen and pelvis consistent with a large intra-abdominal abscess. He underwent an exploratory laparotomy, abdominal washout, and wound vacuum placement. Five liters of purulent fluid were aspirated and cultures grew citrobacter, veillonella and candida glabrata. A bowel perforation was suspected as the etiology for abscess formation; however magnetic resonance heterography (Figure2) was unremarkable. He was treated with appropriate antibiotics, antifungal agents, and was started on Aprisa. His course was complicated with recurrence of intra-abdominal abscesses and a colocutaneous fistula for which he underwent an open sigmoidectomy with a diverting loop colostomy. After condirmation of healing with repeat imaging, he was an uneventful postoperative course. He followed as an outpatient and continues to do well on Infliximab. Most abscesses are picked up in their early stages given characteristic symptoms; however in presence of immunosuppressive therapy the host immune system can be suppressed leading to delayed diagnosis. The presence of a massive intra-abdominal purulent fluid collection of this size has not been described on our review of the literature. Furthermore, despite the abscess taking up most of the abdominal cavity, the fairly limited symptom burden highlights the importance of having high degree of clinical suspicion for infectious compications in Crohn's disease patients even when classical symptoms are not present.
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Abscesso Abdominal/etiologia , Abscesso Abdominal/terapia , Doença de Crohn/complicações , Imunomodulação , Abscesso Abdominal/tratamento farmacológico , Abscesso Abdominal/cirurgia , Antibacterianos/uso terapêutico , Terapia Combinada , Fármacos Gastrointestinais/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Laparotomia/métodos , Masculino , Sucção , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The medial longitudinal arch of the foot is important because it helps protect the foot from injury. Researchers have developed many measures to quantify the characteristics of the arch, and there is ongoing debate about the suitability of these different metrics. This article compares the various measures related to the foot arch, including a new metric, the midfoot dorsal angle, and then investigates the differences in the dimensional measures among various foot types. METHODS: The right feet of 48 healthy individuals (24 men and 24 women) were measured, and various metrics, including the arch height index, the navicular height to arch length ratio, the arch index, the footprint index, the subjective ranking, the modified arch index, the malleolar valgus index, and the midfoot dorsal angle, were determined. RESULTS: Correlation analyses showed that the arch index obtained from the inked footprint has a moderate to high correlation (Pearson correlation coefficients >0.50) with all measured foot-type metrics except for the malleolar valgus index. There were no differences in participant age, stature, weight, body mass index, foot length, foot width, and midfoot height among high, normal, and low foot arches. However, the high-arched group had significantly shorter arch lengths but larger navicular heights and higher midfoot dorsal angles compared with the low-arched group. There were differences in force distributions and peak pressures as well. The rearfoot had more loading and greater peak pressure whereas the midfoot had less load in the high-arched group compared with the low-arched group. CONCLUSIONS: The midfoot dorsal angle may be an appropriate metric for characterizing the foot arch because it is quick and easy to measure, without the tedious procedures associated with area calculations and dimension measurements.
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Antropometria/métodos , Pé/anatomia & histologia , Adulto , Feminino , Humanos , MasculinoRESUMO
A shoe wearer's comfort is related to the shape of the footbed of a shoe. Even though the footbed shape is important in footwear design, there exists no methodology to evaluate the existing guidelines used in last making. Thirty-two females participated in an experiment where heel seat length, heel seat inclination and heel height were investigated using the profile assessment device. The dependent variables were plantar pressure and perceived feeling of each participant. The results show that perceived feel is best for wedge angles of 4 degrees and 5 degrees at a heel height of 25 mm, 10 degrees and 11 degrees at a heel height of 50 mm and 16 degrees and 18 degrees at a heel height of 75 mm. A regression model was derived and this explained approximately 80% of the variation of perceived feeling with the contact area, peak plantar pressure and percentage of force acting on the forefoot region. Both heel wedge angle and heel seat length play an important role in the perceived feel of high-heeled shoes. This study, in relation to the load-bearing heel part of a shoe, highlights the importance of good footbed design. The findings can be used to design footwear with enhanced comfort.
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Ergonomia , Pé , Aparelhos Ortopédicos , Postura , Sapatos , Adulto , Análise de Variância , Antropometria , Fenômenos Biomecânicos , Desenho de Equipamento , Feminino , Humanos , Análise de Regressão , Estatística como Assunto , Propriedades de Superfície , Inquéritos e QuestionáriosRESUMO
Orthotics and other types of shoe inserts are primarily designed to reduce injury and improve comfort. The interaction between the plantar surface of the foot and the load-bearing surface contributes to foot and surface deformations and hence to perceived comfort, discomfort or pain. The plantar shapes of 16 participants' feet were captured when standing on three support surfaces that had different cushioning properties in the mid-foot region. Foot shape deformations were quantified using 3D laser scans. A questionnaire was used to evaluate the participant's perceptions of perceived shape and perceived feeling. The results showed that the structure in the mid-foot could change shape, independent of the rear-foot and forefoot regions. Participants were capable of identifying the shape changes with distinct preferences towards certain shapes. The cushioning properties of the mid-foot materials also have a direct influence on perceived feelings. This research has strong implications for the design and material selection of orthotics, insoles and footwear.
Assuntos
Pé/anatomia & histologia , Aparelhos Ortopédicos/efeitos adversos , Percepção do Tato , Adulto , Estudos de Coortes , Humanos , Masculino , Suporte de Carga , Adulto JovemRESUMO
The application of foot anthropometry to design good-fitting footwear has been difficult due to the lack of generalised models. This study seeks to model foot dimensions so that the characteristic shapes of feet, especially in the midfoot region, can be understood. Fifty Hong Kong Chinese adults (26 males and 24 females) participated in this study. Their foot lengths, foot widths, ball girths and foot heights were measured and then evaluated using mathematical models. The results showed that there were no significant allometry (p > 0.05) effects of foot length on ball girth and foot width. Foot height showed no direct relationship with foot length. However, a normalisation with respect to foot length and foot height resulted in a significant relationship for both males and females with R(2) greater than 0.97. Due to the lack of a direct relationship between foot height and foot length, the current practice of grading shoes with a constant increase in height or proportionate scaling in response to foot length is less than ideal. The results when validated with other populations can be a significant way forward in the design of footwear that has an improved fit in the height dimension.