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1.
Artigo em Inglês | MEDLINE | ID: mdl-35532889

RESUMO

CONTEXT: Effects of testosterone on integrated muscle protein metabolism and muscle mass during energy deficit are undetermined. OBJECTIVE: The objective was to determine the effects of testosterone on mixed-muscle protein synthesis (MPS), proteome-wide fractional synthesis rates (FSR), and skeletal muscle mass during energy deficit. DESIGN: This was a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov, NCT02734238). SETTING: The study was conducted at Pennington Biomedical Research Center. PARTICIPANTS: Fifty healthy men. INTERVENTION: The study consisted of 14 days of weight maintenance, followed by a 28-day 55% energy deficit with 200 mg testosterone enanthate (TEST, n=24) or placebo (PLA, n=26) weekly, and up to 42 days of ad libitum recovery feeding. MAIN OUTCOME MEASURES: Mixed-MPS and proteome-wide FSR before (Pre), during (Mid) and after (Post) the energy deficit were determined using heavy water (days 1-42) and muscle biopsies. Muscle mass was determined using the D3-Creatine dilution method. RESULTS: Mixed-MPS was lower than Pre at Mid and Post (P<0.0005), with no difference between TEST and PLA. The proportion of individual proteins with numerically higher FSR in TEST than PLA was significant by two-tailed binomial test at Post (52/67; P<0.05), but not Mid (32/67; P>0.05). Muscle mass was unchanged during energy deficit, but was greater in TEST than PLA during recovery (P<0.05). CONCLUSIONS: The high proportion of individual proteins with greater FSR in TEST than PLA at Post suggests exogenous testosterone exerted a delayed but broad stimulatory effect on synthesis rates across the muscle proteome during energy deficit, resulting in muscle mass accretion during subsequent recovery.

2.
Am Surg ; : 31348221078958, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35437020

RESUMO

BACKGROUND: Use of endovascular intervention (EI) for blunt cerebrovascular injury (BCVI) is without consensus guidelines. Rates of EI use and radiographic characteristics of BCVI undergoing EI nationally are unknown. METHODS: A post-hoc analysis of a prospective, observational study at 16 U.S. trauma centers from 2018 to 2020 was conducted. Internal carotid artery (ICA) BCVI was included. The primary outcome was EI use. Multivariable logistic regression was performed for predictors of EI use. RESULTS: From 332 ICA BCVI included, 21 (6.3%) underwent EI. 0/145 (0%) grade 1, 8/101 (7.9%) grade 2, 12/51 (23.5%) grade 3, and 1/20 (5.0%) grade 4 ICA BCVI underwent EI. Stroke occurred in 6/21 (28.6%) ICA BCVI undergoing EI and in 33/311 (10.6%) not undergoing EI (P = .03), with all strokes with EI use occurring prior to or at the same time as EI. Percentage of luminal stenosis (37.75 vs 20.29%, P = .01) and median pseudoaneurysm size (9.00 mm vs 3.00 mm, P = .01) were greater in ICA BCVI undergoing EI. On logistic regression, only pseudoaneurysm size was associated with EI (odds ratio 1.205, 95% CI 1.035-1.404, P = .02). Of the 8 grade 2 ICA BCVI undergoing EI, 3/8 were grade 2 and 5/8 were grade 3 prior to EI. Of the 12 grade 3 ICA BCVI undergoing EI, 11/12 were grade 3 and 1/12 was a grade 2 ICA BCVI prior to EI. DISCUSSION: Pseudoaneurysm size is associated with use of EI for ICA BCVI. Stroke is more common in ICA BCVI with EI but did not occur after EI use.

3.
Elife ; 112022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-35144728

RESUMO

The vertebrate stress response comprises a suite of behavioural and physiological traits that must be functionally integrated to ensure organisms cope adaptively with acute stressors. Natural selection should favour functional integration, leading to a prediction of genetic integration of these traits. Despite the implications of such genetic integration for our understanding of human and animal health, as well as evolutionary responses to natural and anthropogenic stressors, formal quantitative genetic tests of this prediction are lacking. Here, we demonstrate that acute stress response components in Trinidadian guppies are both heritable and integrated on the major axis of genetic covariation. This integration could either facilitate or constrain evolutionary responses to selection, depending upon the alignment of selection with this axis. Such integration also suggests artificial selection on the genetically correlated behavioural responses to stress could offer a viable non-invasive route to the improvement of health and welfare in captive animal populations.


Assuntos
Comportamento Animal , Poecilia/genética , Poecilia/fisiologia , Estresse Psicológico/genética , Animais , Feminino , Água Doce/análise , Hidrocortisona/análise , Masculino
4.
J Trauma Acute Care Surg ; 92(2): 347-354, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34739003

RESUMO

BACKGROUND: Stroke risk factors after blunt cerebrovascular injury (BCVI) are ill-defined. We hypothesized that factors associated with stroke for BCVI would include medical therapy (i.e., Aspirin), radiographic features, and protocolization of care. METHODS: An Eastern Association for the Surgery of Trauma-sponsored, 16-center, prospective, observational trial was undertaken. Stroke risk factors were analyzed individually for vertebral artery (VA) and internal carotid artery (ICA) BCVI. Blunt cerebrovascular injuries were graded on the standard 1 to 5 scale. Data were from the initial hospitalization only. RESULTS: Seven hundred seventy-seven BCVIs were included. Stroke rate was 8.9% for all BCVIs, with an 11.7% rate of stroke for ICA BCVI and a 6.7% rate for VA BCVI. Use of a management protocol (p = 0.01), management by the trauma service (p = 0.04), antiplatelet therapy over the hospital stay (p < 0.001), and Aspirin therapy specifically over the hospital stay (p < 0.001) were more common in ICA BCVI without stroke compared with those with stroke. Antiplatelet therapy over the hospital stay (p < 0.001) and Aspirin therapy over the hospital stay (p < 0.001) were more common in VA BCVI without stroke than with stroke. Percentage luminal stenosis was higher in both ICA BCVI (p = 0.002) and VA BCVI (p < 0.001) with stroke. Decrease in percentage luminal stenosis (p < 0.001), resolution of intraluminal thrombus (p = 0.003), and new intraluminal thrombus (p = 0.001) were more common in ICA BCVI with stroke than without, while resolution of intraluminal thrombus (p = 0.03) and new intraluminal thrombus (p = 0.01) were more common in VA BCVI with stroke than without. CONCLUSION: Protocol-driven management by the trauma service, antiplatelet therapy (specifically Aspirin), and lower percentage luminal stenosis were associated with lower stroke rates, while resolution and development of intraluminal thrombus were associated with higher stroke rates. Further research will be needed to incorporate these risk factors into lesion specific BCVI management. LEVEL OF EVIDENCE: Prognostic and Epidemiologic, Level IV.


Assuntos
Lesões das Artérias Carótidas/complicações , Traumatismo Cerebrovascular/complicações , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Artéria Vertebral/lesões , Ferimentos não Penetrantes/complicações , Adulto , Anticoagulantes/uso terapêutico , Lesões das Artérias Carótidas/diagnóstico por imagem , Traumatismo Cerebrovascular/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Estados Unidos , Artéria Vertebral/diagnóstico por imagem , Ferimentos não Penetrantes/diagnóstico por imagem
5.
J Trauma Acute Care Surg ; 92(2): 305-312, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34813581

RESUMO

BACKGROUND: The American Society for Gastrointestinal Endoscopy and Society of American Gastrointestinal and Endoscopic Surgeons provide guidelines for managing suspected common bile duct (CBD) stones. We sought to evaluate adherence to the guidelines among patients with choledocholithiasis and/or acute biliary pancreatitis (ABP) and to evaluate the ability of these guidelines to predict choledocholithiasis. METHODS: We prospectively identified patients undergoing same-admission cholecystectomy for choledocholithiasis and/or ABP from 2016 to 2019 at 12 United States medical centers. Predictors of suspected CBD stones were very strong (CBD stone on ultrasound; bilirubin >4 mg/dL), strong (CBD > 6 mm; bilirubin ≥1.8 to ≤4 mg/dL), or moderate (abnormal liver function tests other than bilirubin; age >55 years; ABP). Patients were grouped by probability of CBD stones: high (any very strong or both strong predictors), low (no predictors), or intermediate (any other predictor combination). The management of each probability group was compared with the recommended management in the guidelines. RESULTS: The cohort was comprised of 844 patients. High-probability patients had 64.3% (n = 238/370) deviation from guidelines, intermediate-probability patients had 29% (n = 132/455) deviation, and low-probability patients had 78.9% (n = 15/19) deviation. Acute biliary pancreatitis increased the odds of deviation for the high- (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.06-2.8; p = 0.03) and intermediate-probability groups (OR, 1.6; 95% CI, 1.07-2.42; p = 0.02). Age older than 55 years (OR, 2.19; 95% CI, 1.4-3.43; p < 0.001) also increased the odds of deviation for the intermediate group. A CBD greater than 6 mm predicted choledocholithiasis in the high (adjusted OR (aOR), 2.16; 95% CI, 1.17-3.97; p = 0.01) and intermediate group (aOR, 2.78; 95% CI, 1.59-4.86; p < 0.001). Any very strong predictor (aOR, 2.43; 95% CI, 1.76-3.37; p < 0.0001) and both strong predictors predicted choledocholithiasis (aOR, 2; 95% CI, 1.35-2.96; p < 0.001). CONCLUSION: Almost 45% of patients with suspected CBD stones were managed discordantly from the American Society for Gastrointestinal Endoscopy and Society of American Gastrointestinal and Endoscopic Surgeons guidelines. We believe these guidelines warrant revision to better reflect the ability of the clinical variables at predicting choledocholithiasis. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.


Assuntos
Coledocolitíase/diagnóstico , Coledocolitíase/terapia , Fidelidade a Diretrizes , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/terapia , Valor Preditivo dos Testes , Estudos Prospectivos , Estados Unidos
6.
Biol Lett ; 17(10): 20210409, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34665991

RESUMO

As telomere length (TL) often predicts survival and lifespan, there is considerable interest in the origins of inter-individual variation in TL. Cross-generational effects of parental age on offspring TL are thought to be a key source of variation, but the rarity of longitudinal studies that examine the telomeres of successive offspring born throughout the lives of parents leaves such effects poorly understood. Here, we exploit TL measures of successive offspring produced throughout the long breeding tenures of parents in wild white-browed sparrow weaver (Plocepasser mahali) societies, to isolate the effects of within-parent changes in age on offspring TLs. Our analyses reveal the first evidence to date of a positive within-parent effect of advancing age on offspring TL: as individual parents age, they produce offspring with longer telomeres (a modest effect that persists into offspring adulthood). We consider the potential for pre- and post-natal mechanisms to explain our findings. As telomere attrition predicts offspring survival to adulthood in this species, this positive parental age effect could impact parent and offspring fitness if it arose via differential telomere attrition during offspring development. Our findings support the view that cross-generational effects of parental age can be a source of inter-individual variation in TL.


Assuntos
Pardais , Telômero , Animais , Animais Selvagens , Longevidade , Telômero/genética , Encurtamento do Telômero
7.
Front Physiol ; 12: 709804, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34588992

RESUMO

Individuals sojourning at high altitude (≥2,500m) often develop acute mountain sickness (AMS). However, substantial unexplained inter-individual variability in AMS severity exists. Untargeted metabolomics assays are increasingly used to identify novel biomarkers of susceptibility to illness, and to elucidate biological pathways linking environmental exposures to health outcomes. This study used untargeted nuclear magnetic resonance (NMR)-based metabolomics to identify urine metabolites associated with AMS severity during high altitude sojourn. Following a 21-day stay at sea level (SL; 55m), 17 healthy males were transported to high altitude (HA; 4,300m) for a 22-day sojourn. AMS symptoms measured twice daily during the first 5days at HA were used to dichotomize participants according to AMS severity: moderate/severe AMS (AMS; n=11) or no/mild AMS (NoAMS; n=6). Urine samples collected on SL day 12 and HA days 1 and 18 were analyzed using proton NMR tools and the data were subjected to multivariate analyses. The SL urinary metabolite profiles were significantly different (p≤0.05) between AMS vs. NoAMS individuals prior to high altitude exposure. Differentially expressed metabolites included elevated levels of creatine and acetylcarnitine, and decreased levels of hypoxanthine and taurine in the AMS vs. NoAMS group. In addition, the levels of two amino acid derivatives (4-hydroxyphenylpyruvate and N-methylhistidine) and two unidentified metabolites (doublet peaks at 3.33ppm and a singlet at 8.20ppm) were significantly different between groups at SL. By HA day 18, the differences in urinary metabolites between AMS and NoAMS participants had largely resolved. Pathway analysis of these differentially expressed metabolites indicated that they directly or indirectly play a role in energy metabolism. These observations suggest that alterations in energy metabolism before high altitude exposure may contribute to AMS susceptibility at altitude. If validated in larger cohorts, these markers could inform development of a non-invasive assay to screen individuals for AMS susceptibility prior to high altitude sojourn.

8.
Sci Adv ; 7(39): eabe8980, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34550732

RESUMO

Altruism is globally associated with unpredictable environments, but we do not understand why. New theory has highlighted that unpredictable environments could favor the evolution of altruism if altruistic acts reduce environmentally induced variance in the reproductive success of relatives ("altruistic bet-hedging"). Here, we show that altruism does indeed reduce environmentally induced reproductive variance in a wild cooperative bird. Our decade-long field study reveals that altruistic helping actually has no overall effect on the mean reproductive success of relatives but instead reduces their reproductive variance. This remarkable pattern arises because helpers improve reproductive performance in dry conditions but reduce it in wet conditions. Helpers thereby specifically reduce rainfall-induced reproductive variance, the very mechanism required for altruistic bet-hedging to explain the enigmatic global association between avian altruism and unpredictable rainfall.

9.
Am J Clin Nutr ; 114(4): 1546-1559, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34375387

RESUMO

BACKGROUND: Lifestyle interventions are the first-line treatment for obesity, but participant weight loss is typically low. OBJECTIVES: We evaluated the efficacy of an alternative lifestyle intervention [Healthy Weight for Living (HWL)] compared with a modified Diabetes Prevention Program (m-DPP). HWL was based on a revised health behavior change model emphasizing hunger management and the development of healthy food preferences. m-DPP was a standard Diabetes Prevention Program implemented with counselor time matched to HWL. Participants were adult dependents of military personnel and had overweight or obesity. METHODS: Participants were randomly assigned to HWL (n = 121) or m-DPP (n = 117), delivered primarily by group videoconference with additional midweek emails. The primary outcome was 12-mo weight change. Secondary outcomes included 6-mo changes in cardiometabolic risk factors and diet. Intention-to-treat (ITT) and complete case (CC) analyses were performed using linear mixed models. RESULTS: Retention did not differ between groups (72% and 66% for HWL and m-DPP at 12 mo, respectively; P = 0.30). Mean ± SE adjusted 12-mo weight loss in the ITT cohort was 7.46 ± 0.85 kg for HWL and 7.32 ± 0.87 kg for m-DPP (P = 0.91); in the CC cohort, it was 7.83 ± 0.82 kg for HWL and 6.86 ± 0.88 kg for m-DPP (P = 0.43). Thirty-eight percent of HWL and 30% of m-DPP completers achieved ≥10% weight loss (P = 0.32). Improvements in systolic blood pressure, LDL cholesterol, triglycerides, fasting glucose, general health, sleep, and mood were similar across groups; improvements in diastolic blood pressure were greater in m-DPP. Adjusted group mean reductions in energy intake were not significantly different between groups, but HWL participants were more adherent to their dietary prescription for lower glycemic index and high fiber and protein (P = 0.05 to <0.001 for ITT). CONCLUSIONS: HWL and m-DPP showed equivalent and clinically impactful mean weight loss with cardiometabolic benefits. These results identify an alternative approach for behavioral treatment of overweight and obesity.This trial was registered at clinicaltrials.gov as NCT02348853.


Assuntos
Diabetes Mellitus/prevenção & controle , Dieta Redutora , Estilo de Vida , Perda de Peso , Adulto , Glicemia , Família , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Militares , Obesidade/terapia , Comportamento de Redução do Risco
10.
Am J Physiol Regul Integr Comp Physiol ; 321(1): R1-R11, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33949213

RESUMO

Hypoxia-induced insulin resistance appears to suppress exogenous glucose oxidation during metabolically matched aerobic exercise during acute (<8 h) high-altitude (HA) exposure. However, a better understanding of this metabolic dysregulation is needed to identify interventions to mitigate these effects. The objective of this study was to determine if differences in metabolomic profiles during exercise at sea level (SL) and HA are reflective of hypoxia-induced insulin resistance. Native lowlanders (n = 8 males) consumed 145 g (1.8 g/min) of glucose while performing 80-min of metabolically matched treadmill exercise at SL (757 mmHg) and HA (460 mmHg) after 5-h exposure. Exogenous glucose oxidation and glucose turnover were determined using indirect calorimetry and dual tracer technique ([13C]glucose and [6,6-2H2]glucose). Metabolite profiles were analyzed in serum as change (Δ), calculated by subtracting postprandial/exercised state SL (ΔSL) and HA (ΔHA) from fasted, rested conditions at SL. Compared with SL, exogenous glucose oxidation, glucose rate of disappearance, and glucose metabolic clearance rate (MCR) were lower (P < 0.05) during exercise at HA. One hundred and eighteen metabolites differed between ΔSL and ΔHA (P < 0.05, Q < 0.10). Differences in metabolites indicated increased glycolysis, tricarboxylic acid cycle, amino acid catabolism, oxidative stress, and fatty acid storage, and decreased fatty acid mobilization for ΔHA. Branched-chain amino acids and oxidative stress metabolites, Δ3-methyl-2-oxobutyrate (r = -0.738) and Δγ-glutamylalanine (r = -0.810), were inversely associated (P < 0.05) with Δexogenous glucose oxidation. Δ3-Hydroxyisobutyrate (r = -0.762) and Δ2-hydroxybutyrate/2-hydroxyisobutyrate (r = -0.738) were inversely associated (P < 0.05) with glucose MCR. Coupling global metabolomics and glucose kinetic data suggest that the underlying cause for diminished exogenous glucose oxidative capacity during aerobic exercise is acute hypoxia-mediated peripheral insulin resistance.


Assuntos
Exercício Físico , Glucose/metabolismo , Hipóxia , Resistência à Insulina , Metabolômica , Adulto , Estudos Cross-Over , Glucose/administração & dosagem , Glicogênio/metabolismo , Humanos , Masculino , Oxirredução , Adulto Jovem
11.
J Trauma Acute Care Surg ; 91(5): 841-848, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33901052

RESUMO

BACKGROUND: Damage-control resuscitation (DCR) improves survival in severely bleeding patients. However, deviating from balanced transfusion ratios during a resuscitation may limit this benefit. We hypothesized that maintaining a balanced resuscitation during DCR is independently associated with improved survival. METHODS: This was a secondary analysis of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Patients receiving >3 U of packed red blood cells (PRBCs) during any 1-hour period over the first 6 hours and surviving beyond 30 minutes were included. Linear regression assessed the effect of percent time in a high-ratio range on 24-hour survival. We identified an optimal ratio and percent of time above the target ratio threshold by Youden's index. We compared patients with a 6-hour ratio above the target and above the percent time threshold (on-target) with all others (off-target). Kaplan-Meier analysis assessed the combined effect of blood product ratio and percent time over the target ratio on 24-hour and 30-day survival. Multivariable logistic regression identified factors independently associated with 24-hour and 30-day survival. RESULTS: Of 1,245 PROMMTT patients, 524 met the inclusion criteria. Optimal targets were plasma/PRBC and platelet/PRBC of 0.75 (3:4) and ≥40% time spent over this threshold. For plasma/PRBC, on-target (n = 213) versus off-target (n = 311) patients were younger (median, 31 years; interquartile range, [22-50] vs. 40 [25-54]; p = 0.002) with similar injury burdens and presenting physiology. Similar patterns were observed for platelet/PRBC on-target (n = 116) and off-target (n = 408) patients. After adjusting for differences, on-target plasma/PRBC patients had significantly improved 24-hour (odds ratio, 2.25; 95% confidence interval, 1.20-4.23) and 30-day (odds ratio, 1.97; 95% confidence interval, 1.14-3.41) survival, while on-target platelet/PRBC patients did not. CONCLUSION: Maintaining a high ratio of plasma/PRBC during DCR is independently associated with improved survival. Performance improvement efforts and prospective studies should capture time spent in a high-ratio range. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level II; Therapeutic, level IV.


Assuntos
Transfusão de Sangue/estatística & dados numéricos , Hemorragia/terapia , Ressuscitação/estatística & dados numéricos , Ferimentos não Penetrantes/terapia , Adulto , Transfusão de Sangue/métodos , Transfusão de Sangue/normas , Feminino , Hemorragia/etiologia , Hemorragia/mortalidade , Mortalidade Hospitalar , Humanos , Escala de Gravidade do Ferimento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Ressuscitação/métodos , Ressuscitação/normas , Estudos Retrospectivos , Resultado do Tratamento , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/mortalidade , Adulto Jovem
12.
Mol Ecol ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657651

RESUMO

In many vertebrate societies dominant individuals breed at substantially higher rates than subordinates, but whether this hastens ageing remains poorly understood. While frequent reproduction may trade off against somatic maintenance, the extraordinary fecundity and longevity of some social insect queens highlight that breeders need not always suffer more rapid somatic deterioration than their nonbreeding subordinates. Here, we used extensive longitudinal assessments of telomere dynamics to investigate the impact of dominance status on within-individual age-related changes in somatic integrity in a wild social bird, the white-browed sparrow-weaver (Plocepasser mahali). Dominant birds, who monopolise reproduction, had neither shorter telomeres nor faster telomere attrition rates over the long-term (1-5 years) than their subordinates. However, over shorter (half-year) time intervals dominants with shorter telomeres showed lower rates of telomere attrition (and evidence suggestive of telomere lengthening), while the same was not true among subordinates. Dominants may therefore invest more heavily in telomere length regulation (and/or somatic maintenance more broadly); a strategy that could mitigate the long-term costs of reproductive effort, leaving their long-term telomere dynamics comparable to those of subordinates. Consistent with the expectation that reproduction entails short-term costs to somatic integrity, telomere attrition rates were most severe for all birds during the breeding seasons of wetter years (rainfall is the key driver of reproductive activity in this arid-zone species). Our findings suggest that, even in vertebrate societies in which dominants monopolise reproduction, dominants may experience long-term somatic integrity trajectories indistinguishable from those of their nonreproductive subordinates.

13.
J Surg Res ; 257: 118-127, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32823009

RESUMO

BACKGROUND: As the population ages, the incidence of traumatic falls has been increasing. We hypothesize that a machine learning algorithm can more accurately predict mortality after a fall compared with a standard logistic regression (LR) model based on immediately available admission data. Secondary objectives were to predict who would be discharged home and determine which variables had the largest effect on prediction. METHODS: All patients who were admitted for fall between 2012 and 2017 at our level 1 trauma center were reviewed. Fourteen variables describing patient demographics, injury characteristics, and physiology were collected at the time of admission and were used for prediction modeling. Algorithms assessed included LR, decision tree classifier (DTC), and random forest classifier (RFC). Area under the receiver operating characteristic curve (AUC) values were calculated for each algorithm for mortality and discharge to home. RESULTS: About 4725 patients met inclusion criteria. The mean age was 61 ± 20.5 y, Injury Severity Score 8 ± 7, length of stay 5.8 ± 7.6 d, intensive care unit length of stay 1.8± 5.2 d, and ventilator days 0.7 ± 4.2 d. The mortality rate was 3% and three times greater for elderly (aged 65 y and older) patients (5.0% versus 1.6%, P < 0.001). The AUC for predicting mortality for LR, DTC, and RFC was 0.78, 0.64, and 0.86, respectively. The AUC for predicting discharge to home for LR, DTC, and RFC was 0.72, 0.61, and 0.74, respectively. The top five variables that contribute to the prediction of mortality in descending order of importance are the Glasgow Coma Score (GCS) motor, GCS verbal, respiratory rate, GCS eye, and temperature. CONCLUSIONS: RFC can accurately predict mortality and discharge home after a fall. This predictive model can be implemented at the time of patient arrival and may help identify candidates for targeted intervention as well as improve prognostication and resource utilization.


Assuntos
Acidentes por Quedas/mortalidade , Acidentes por Quedas/estatística & dados numéricos , Aprendizado de Máquina , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Árvores de Decisões , Feminino , Escala de Coma de Glasgow , Humanos , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Curva ROC , Estudos Retrospectivos , Centros de Traumatologia
14.
Am Surg ; 87(7): 1140-1144, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33342278

RESUMO

BACKGROUND: Prompt drainage of traumatic hemothorax is recommended to prevent empyema and trapped lung. Some patients do not present the day of their trauma, leading to their delayed treatment. Delayed drainage could be challenging as clotted blood may not evacuate through a standard chest tube. We hypothesized that such delays would increase the need for surgery or secondary interventions. METHODS: Our trauma registry was reviewed for patients with a hemothorax admitted to our level 1 trauma center from 1/1/00 to 4/30/19. Patients were included in the delayed group if they received a drainage procedure >24 hours after injury. These patients were matched 1:1 by chest abbreviated injury score to patients who received drainage <24 hours from injury. RESULTS: A total of 19 patients with 22 hemothoraces received delayed drainage. All but 3 patients had a chest tube placed as initial treatment. Four patients received surgery, including 3 who initially had chest tubes placed. Longer time to drainage increased the odds of requiring intrathoracic thrombolytics or surgery. In comparison, 2 patients who received prompt drainage received thrombolytics (P = .11) and none required surgery (P = .02). Patients needed surgery when initial drainage was on or after post-injury day 5, but pigtail catheter drainage was effective 26 days after injury. DISCUSSION: Longer times from injury to intervention are associated with increased likelihood of needing surgery for hemothorax evacuation, but outcomes were not uniform. A larger, multicenter study will be necessary to provide better characterization of treatment outcomes for these patients.


Assuntos
Drenagem , Hemotórax/cirurgia , Tempo para o Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrinolíticos/uso terapêutico , Hemotórax/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo , Centros de Traumatologia , Resultado do Tratamento , Adulto Jovem
15.
Front Med (Lausanne) ; 7: 580796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363183

RESUMO

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly transfers from human to human via respiratory and gastrointestinal routes. The S-glycoprotein in the virus is the key factor for the entry of SARS-CoV-2 into the cell, which contains two functional domains: S1 is an angiotensin-converting enzyme 2 (ACE2) receptor binding domain, and S2 is necessary for fusion of the coronavirus and cell membranes. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, mRNA level expression of Furin enzyme and ACE2 receptor had been reported in airway epithelia, cardiac tissue, and enteric canals. However, the expression patterns of ACE2 and Furin in different cell types of oral tissues are still unclear. Methods: In order to investigate the potential infective channel of the new coronavirus via the oropharyngeal cavity, we analyze the expression of ACE2 and Furin in human oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemistry was performed in mucosal tissue from different oral anatomical sites to confirm the expression of ACE2 and Furin at the protein level. Results: The bioinformatics results indicated the differential expression of ACE2 and Furin on epithelial cells from different oral anatomical sites. Immunohistochemistry results revealed that both the ACE2-positive and Furin-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, further confirming the bioinformatics results. Conclusions: Based on these findings, we speculated that SARS-CoV-2 could invade oral mucosal cells through two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by Furin protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2 that could facilitate COVID-19 infection via respiratory and fecal-oral routes.

17.
Am J Physiol Endocrinol Metab ; 319(4): E678-E688, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32776828

RESUMO

Testosterone supplementation during energy deficit promotes whole body lean mass accretion, but the mechanisms underlying that effect remain unclear. To elucidate those mechanisms, skeletal muscle molecular adaptations were assessed from muscle biopsies collected before, 1 h, and 6 h after exercise and a mixed meal (40 g protein, 1 h postexercise) following 14 days of weight maintenance (WM) and 28 days of an exercise- and diet-induced 55% energy deficit (ED) in 50 physically active nonobese men treated with 200 mg testosterone enanthate/wk (TEST) or placebo (PLA) during the ED. Participants (n = 10/group) exhibiting substantial increases in leg lean mass and total testosterone (TEST) were compared with those exhibiting decreases in both of these measures (PLA). Resting androgen receptor (AR) protein content was higher and fibroblast growth factor-inducible 14 (Fn14), IL-6 receptor (IL-6R), and muscle ring-finger protein-1 gene expression was lower in TEST vs. PLA during ED relative to WM (P < 0.05). Changes in inflammatory, myogenic, and proteolytic gene expression did not differ between groups after exercise and recovery feeding. Mechanistic target of rapamycin signaling (i.e., translational efficiency) was also similar between groups at rest and after exercise and the mixed meal. Muscle total RNA content (i.e., translational capacity) increased more during ED in TEST than PLA (P < 0.05). These findings indicate that attenuated proteolysis at rest, possibly downstream of AR, Fn14, and IL-6R signaling, and increased translational capacity, not efficiency, may drive lean mass accretion with testosterone administration during energy deficit.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Modificação Traducional de Proteínas/efeitos dos fármacos , Receptores Androgênicos/biossíntese , Testosterona/farmacologia , Adolescente , Adulto , Composição Corporal , Dieta , Exercício Físico , Hormônios/sangue , Humanos , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Receptores de Interleucina-6/metabolismo , Receptor de TWEAK/metabolismo , Regulação para Cima , Adulto Jovem
18.
Am Surg ; 86(7): 766-772, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32723186

RESUMO

BACKGROUND: Trauma centers with low observed:expected (O:E) mortality ratios are considered high performers; however, it is unknown whether improvements in this ratio are due to a small number of unexpected survivors with high mortality risk (big saves) or a larger number of unexpected survivors with moderate mortality risk (marginal gains). We hypothesized that the highest-performing centers achieve that status via larger numbers of unexpected survivors with moderate mortality risk. METHODS: We calculated O:E ratios for trauma centers in Pennsylvania for 2016 using a risk-adjusted mortality model. We identified high and low performers as centers whose 95% CIs did not cross 1. We visualized differences between these centers by plotting patient-level observed and expected mortality; we then examined differences in a subset of patients with a predicted mortality of ≥10% using the chi-squared test. RESULTS: One high performer and 1 low performer were identified. The high performer managed a population with more blunt injuries (97.2% vs 93.6%, P < .001) and a higher median Injury Severity Score (14 vs 11, P < .001). There was no difference in survival between these centers in patients with an expected mortality of <10% (98.0% vs 96.7%, P = .11) or ≥70% (23.5% vs 10.8%, P = .22), but there was a difference in the subset with an expected mortality of ≥10% (77.5% vs 43.1%, P < .001). CONCLUSIONS: Though patients with very low predicted mortality do equally well in high-performing and low-performing centers, the fact that performance seems determined by outcomes of patients with moderate predicted mortality favors a "marginal gains" theory.


Assuntos
Centros de Traumatologia/estatística & dados numéricos , Ferimentos e Lesões/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Pennsylvania , Estudos Retrospectivos , Análise de Sobrevida
19.
Artigo em Inglês | MEDLINE | ID: mdl-32431766

RESUMO

Creation of an inclusive environment requires a culture of equity, justice, value and respect for diverse backgrounds, and opportunities for students to engage with communities while addressing issues in science and society. These tasks are particularly challenging for institutions lacking a diverse population. Here, we demonstrate evidence of a successful model for creating an inclusive environment in an interinstitutional course between a large, public, historically black institution and a small, private, primarily white institution. Because many individuals from underrepresented minority groups tend to value communal goals of working together and helping their communities, we incorporated two high-impact practices of community-engaged learning and course-based undergraduate research experiences (CUREs) focused on health disparities research in neighboring communities. Although the research projects varied each semester, they were linked by their impact on and engagement with the community. Students practiced cultural competency skills in both small group projects within the class and engagement activities in the community. We measured the efficacy of CURE components (novel authentic research, scientific process skills, iteration, collaboration, and broader impact) through a combination of direct and indirect assessments, quantitative and qualitative analysis. More than simply scientific skills, students from both institutions developed lasting interest in working with diverse populations as well as respecting and valuing different backgrounds. This inclusive environment, combined with increased interest in research, suggests that this course could potentially serve as a model for interinstitutional collaborations in creating inclusive environments that support the future success of diverse students, eventually changing the STEM research culture.

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