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1.
Curr Pharm Teach Learn ; 13(7): 885-894, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34074523

RESUMO

BACKGROUND: There are a variety of designs and implementation strategies reported for interprofessional education (IPE); however, most of these descriptions lack robust evaluations of interprofessional (IP) outcomes. INTERPROFESSIONAL EDUCATION ACTIVITY: An IPE Workshop Series was implemented for preclinical and prelicensure students in eight health professions, consisting of four sessions: health professionals' roles and responsibilities (1A); introduction to patient safety (1B); IP diabetes management (2A); and IP pain management in the opioid epidemic (2B). For Workshops 2A and 2B, student perceptions of IPE were measured using the validated Students Perceptions of Interprofessional Clinical Education Revised Version 2 and IP team care plans were assessed with a rubric. Five hundred twenty-seven students attended all four workshops and completed all surveys. Student perceptions of IPE and collaboration were significantly increased after completing the IPE Workshop Series. Most teams met or exceeded expectations on the diabetes team care plans for collaboration, addressing patient concerns, and gaps in care; however, most teams needed improvement on addressing additional workup and management. The pain management team care plans were below expectations for most teams. DISCUSSION: Student perceptions of IP collaboration increased and were maintained longitudinally indicating a positive impact on this IPE outcome; however, performance on team care plans did not meet faculty expectations suggesting areas for improvement in the design and evaluation for this outcome. IMPLICATIONS: These findings reinforce the importance of evaluation to ensure IPE curricula are achieving IP outcomes, notably, utilizing validated instruments and incorporating faculty assessments that are appropriately leveled for learners.

2.
J Trauma Acute Care Surg ; 91(1): 164-170, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34108420

RESUMO

BACKGROUND: Police transport (PT) of penetrating trauma patients decreases the time between injury and trauma center arrival. Our study objective was to characterize trends in the rate of PT and its impact on mortality. We hypothesized that PT is increasing and that these patients are more injured. METHODS: We conducted a single-center, retrospective cohort study of adult (≥18 years) patients presenting with gunshot wounds (GSWs) to a level 1 center from 2012 to 2018. Patients transported by police or ambulance (emergency medical service [EMS]) were included. The association between mode of transport (PT vs. EMS) and mortality was evaluated using χ2, t tests, Mann-Whitney U tests, and logistic regression. RESULTS: Of 2,007 patients, there were 1,357 PT patients and 650 EMS patients. Overall in-hospital mortality was 23.7%. The rate of GSW patients arriving by PT increased from 48.9% to 78.5% over the study period (p < 0.001). Compared with EMS patients, PT patients were sicker on presentation with lower initial systolic blood pressure (98 vs. 110, p < 0.001), higher Injury Severity Score (median [interquartile range], 10 [2-75] vs. 9 [1-17]; p < 0.001) and more bullet wounds (3.5 vs. 2.9, p < 0.001). Police-transported patients more frequently underwent resuscitative thoracotomy (19.2% vs. 10.0%, p < 0.001) and immediate surgical exploration (31.3% vs. 22.6%, p < 0.001). There was no difference in adjusted in-hospital mortality between transport groups. Of patients surviving to discharge, PT patients had higher Injury Severity Score (9.6 vs. 8.3, p = 0.004) and lower systolic blood pressure on arrival (126 vs. 130, p = 0.013) than EMS patients. CONCLUSION: Police transport of GSW patients is increasing at our urban level 1 center. Compared with EMS patients, PT patients are more severely injured but have similar in-hospital mortality. Further study is necessary to understand the impact of PT on outcomes in specific subsets in penetrating trauma patients. LEVEL OF EVIDENCE: Epidemiological, level III.

3.
Sci Total Environ ; 777: 146020, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-33677289

RESUMO

Microplastics (MPs) are regarded as one of the major atmospheric contaminants that have gained wide attention across the globe in the current dispensation. Airborne MPs have been collected in atmospheric fallouts, in indoor and outdoor air as well as along roadways and indoor dust. The most dominating constituent shapes and forms of identified airborne MPs are fibers and synthetic textiles, respectively. With the breathing mechanism as a spontaneous practice for survival, the inhalation of airborne MPs is an inevitable deal. The level of toxicity of MPs to organisms stems from its physiochemical speciation. The smaller size and almost weightless nature make it possible to suspend in the atmosphere and be inhaled and create potential health problems. Nonetheless, the data available concerning the presence of airborne MPs and its environmental and human health impacts is limited. In this review, we extensively discuss the rigorous and suitable methodologies adopted for the analysis of airborne MPs in previous studies. The characteristics and sources of airborne MPs, the potential health impacts on humans, and some mitigating measures have also been discussed thoroughly.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33780602

RESUMO

Background: Comorbid disease is a risk factor for severe COVID-19 infection, however, initial rates of chronic obstructive pulmonary disease (COPD) in case series were low and severity of COVID-19 in COPD patients was variable. Methods: We performed a retrospective study of patients admitted with COVID-19 and evaluated outcomes in those with and without COPD and/or emphysema. Patients were identified as having COPD if they had a diagnosis in the medical record and a history of airflow-obstruction on spirometry, or a history of tobacco use and prescribed long-acting bronchodilator(s). Computed tomography scans were evaluated by radiologists. Propensity matching was performed for age, body-mass index (BMI), and serologic data correlated with severity of COVID-19 disease (D-dimer, C-reactive protein, ferritin, fibrinogen, absolute lymphocyte count, lymphocyte percentage, and lactate dehydrogenase). Results: Of 577 patients admitted with COVID-19, 103 had a diagnosis of COPD and/or emphysema. The COPD/emphysema cohort was older (67 vs 58, p<0.0001) than the other cohort and had a lower BMI. Among unmatched cohorts those with COPD/emphysema had higher rates of intensive care unit (ICU) admission (35% vs 24.9%, p=0.036) and maximal respiratory support requirements, with more frequent invasive mechanical ventilation (21.4% vs 11.8%), but no significant difference in mortality. After propensity-matching there was no difference in ICU admission, maximal respiratory support requirements, or mortality. Univariate and multivariate regression analyses yielded similar results. Discussion: Our propensity-matched retrospective cohort study suggests that patients hospitalized with COVID-19 that have COPD and/or emphysema may not have worse outcomes than those without these comorbid conditions.

5.
BMJ Open Respir Res ; 8(1)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33762361

RESUMO

INTRODUCTION: Acute pulmonary embolism (PE) remains a common cause for morbidity and mortality in patients over 65 years. Given the increased risk of bleeding in the elderly population with the use of systemic thrombolysis, catheter-directed therapy (CDT) is being increasingly used for the treatment of submassive PE. Nevertheless, the safety of CDT in the elderly population is not well studied. We, therefore, aimed to evaluate the safety of CDT in our elderly patients. METHODS: We conducted a retrospective observational study of consecutive patients aged >65 years with a diagnosis of PE from our Pulmonary Embolism Response Team database. We compared the treatment outcomes of CDT versus anticoagulation (AC) in elderly. Propensity score matching was used to construct two matched cohorts for final outcomes analysis. RESULTS: Of 346 patients with acute PE, 138 were >65 years, and of these, 18 were treated with CDT. Unmatched comparison between CDT and AC cohorts demonstrated similar in-hospital mortality (11.1% vs 5.6%, p=0.37) and length of stay (LOS) (3.81 vs 5.02 days, p=0.5395), respectively. The results from the propensity-matched cohort mirrored results of the unmatched cohort with no significant difference between CDT and AC in-hospital mortality (11.8% vs 5.9%, p=0.545) or median LOS (3.76 vs 4.21 days, p=0.77), respectively. CONCLUSION: In this observational study using propensity score-matched analysis, we found that patients >65 years who were treated with CDT for management of acute PE had similar mortality and LOS compared with those treated with AC. Further studies are required to confirm these findings.

6.
J Thromb Haemost ; 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33638931

RESUMO

BACKGROUND: Statins are widely used to lower lipids and reduce cardiovascular events. In vitro studies and small studies in patients with hyperlipidemias show statins inhibit tissue factor (TF) and blood coagulation mechanisms. We assessed the effects of simvastatin on TF and coagulation biomarkers in patients entered in STATCOPE, a multicenter, randomized, placebo-controlled trial of simvastatin (40 mg daily) versus placebo on exacerbation rates in patients with chronic obstructive pulmonary disease (COPD). METHODS: In 227 patients (114 simvastatin, 113 placebo; mean [± standard error of the mean] age 62 ± 0.53 years, 44.5% women) we measured (baseline, and 6 and 12 months): whole blood membrane TF-procoagulant activity (TF-PCA) and plasma factors VIIa, VII, VIII, fibrinogen, TF antigen, tissue factor pathway inhibitor (TFPI), thrombin-antithrombin complexes (TAT), and D-dimer. We excluded patients with diabetes, cardiovascular disease, and those taking or requiring a statin. RESULTS: In the statin group, there was a small increase in TF-PCA (from 25.18 ± 1.08 to 30.36 ± 1.10 U/ml; p = .03) over 12 months; factors VIIa and VIII, fibrinogen, TAT, and D-dimer did not change. Plasma TFPI (from 52.4 ± 1.75 to 44.7 ± 1.78 ng/ml; p < .0001) and FVIIC (1.23 ± 0.04 to 1.15 ± 0.03 U/ml; p = .03) decreased and correlated with total cholesterol levels. No changes in biomarkers were observed with placebo. CONCLUSIONS: In contrast to previous studies on statins, in COPD patients without diabetes, cardiovascular disease, or requiring a statin treatment, simvastatin (40 mg per day) did not decrease TF or factors VIIa and VIII, fibrinogen, TAT, or D-dimer. The decreases in TFPI and factor VII reflect the decrease in serum lipids.

7.
Crit Care Med ; 49(5): 760-769, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33590996

RESUMO

OBJECTIVE: Management of patients experiencing massive pulmonary embolism-related cardiac arrest is controversial. Venoarterial extracorporeal membranous oxygenation has emerged as a potential therapeutic option for these patients. We performed a systematic review assessing survival and predictors of mortality in patients with massive PE-related cardiac arrest with venoarterial extracorporeal membranous oxygenation use. DATA SOURCES: A literature search was started on February 16, 2020, and completed on March 16, 2020, using PubMed, Embase, Cochrane Central, Cinahl, and Web of Science. STUDY SELECTION: We included all available literature that reported survival to discharge in patients managed with venoarterial extracorporeal membranous oxygenation for massive PE-related cardiac arrest. DATA EXTRACTION: We extracted patient characteristics, treatment details, and outcomes. DATA SYNTHESIS: About 301 patients were included in our systemic review from 77 selected articles (total screened, n = 1,115). About 183 out of 301 patients (61%) survived to discharge. Patients (n = 51) who received systemic thrombolysis prior to cannulation had similar survival compared with patients who did not (67% vs 61%, respectively; p = 0.48). There was no significant difference in risk of death if PE was the primary reason for admission or not (odds ratio, 1.62; p = 0.35) and if extracorporeal membranous oxygenation cannulation occurred in the emergency department versus other hospital locations (odds ratio, 2.52; p = 0.16). About 53 of 60 patients (88%) were neurologically intact at discharge or follow-up. Multivariate analysis demonstrated three-fold increase in the risk of death for patients greater than 65 years old (adjusted odds ratio, 3.08; p = 0.03) and six-fold increase if cannulation occurred during cardiopulmonary resuscitation (adjusted odds ratio, 5.67; p = 0.03). CONCLUSIONS: Venoarterial extracorporeal membranous oxygenation has an emerging role in the management of massive PE-related cardiac arrest with 61% survival. Systemic thrombolysis preceding venoarterial extracorporeal membranous oxygenation did not confer a statistically significant increase in risk of death, yet age greater than 65 and cannulation during cardiopulmonary resuscitation were associated with a three- and six-fold risks of death, respectively.

8.
Arterioscler Thromb Vasc Biol ; 41(2): 839-853, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33380174

RESUMO

OBJECTIVE: Electronic cigarette (e-cig) use has recently been implicated in promoting atherosclerosis. In this study, we aimed to investigate the mechanism of e-cig exposure accelerated atherosclerotic lesion development. Approach and Results: Eight-week-old ApoE-/- mice fed normal laboratory diet were exposed to e-cig vapor (ECV) for 2 hours/day, 5 days/week for 16 weeks. We found that ECV exposure significantly induced atherosclerotic lesions as examined by Oil Red O staining and greatly upregulated TLR9 (toll-like receptor 9) expression in classical monocytes and in the atherosclerotic plaques, which the latter was corroborated by enhanced TLR9 expression in human femoral artery atherosclerotic plaques from e-cig smokers. Intriguingly, we found a significant increase of oxidative mitochondria DNA lesion in the plasma of ECV-exposed mice. Administration of TLR9 antagonist before ECV exposure not only alleviated atherosclerosis and the upregulation of TLR9 in plaques but also attenuated the increase of plasma levels of inflammatory cytokines, reduced the plaque accumulation of lipid and macrophages, and decreased the frequency of blood CCR2+ (C-C chemokine receptor type 2) classical monocytes. Surprisingly, we found that cytoplasmic mitochondrial DNA isolated from ECV extract-treated macrophages can enhance TLR9 activation in reporter cells and the induction of inflammatory cytokine could be suppressed by TLR9 inhibitor in macrophages. CONCLUSIONS: E-cig increases level of damaged mitochondrial DNA in circulating blood and induces the expression of TLR9, which elevate the expression of proinflammatory cytokines in monocyte/macrophage and consequently lead to atherosclerosis. Our results raise the possibility that intervention of TLR9 activation is a potential pharmacological target of ECV-related inflammation and cardiovascular diseases.


Assuntos
Aorta/metabolismo , Aterosclerose/etiologia , Dano ao DNA , DNA Mitocondrial/metabolismo , Vapor do Cigarro Eletrônico/efeitos adversos , Inflamação/etiologia , Macrófagos/metabolismo , Mitocôndrias/metabolismo , Receptor Toll-Like 9/metabolismo , Animais , Aorta/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , DNA Mitocondrial/genética , Modelos Animais de Doenças , Feminino , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Mitocôndrias/genética , Mitocôndrias/patologia , Células RAW 264.7 , Transdução de Sinais , Fumantes , Vaping
9.
Surg Obes Relat Dis ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33257274

RESUMO

BACKGROUND: The rate of robotic-assisted metabolic and bariatric surgery (MBS) is increasing. While discord remains about racial disparity in primary MBS, there are no data on robotic MBS outcomes in racial cohorts. OBJECTIVES: To determine whether outcomes following robotic-assisted Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are mediated by race or ethnicity. SETTING: University Hospital, United States. METHODS: Robotic RYGB and SG cases were identified from the 2015-2017 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) databases using Current Procedure Terminology codes 43644, 43645, and 43775. Selected cases were stratified by race and ethnicity. Case-control matched and logistic regression analyses were performed. RESULTS: Matched analyses compared outcomes in 2666 RYGB cases of Black versus White patients and 1794 RYGB cases of Hispanic versus White patients. Black RYGB patients had longer operative lengths (OLs; P = .0008) and postoperative lengths of stay (P = .001), and a higher rate of pulmonary embolism (P = .05). Hispanic (versus White) RYGB patients had longer lengths of stay (P = .007). All other outcomes were similar between RYGB racial and ethnic cohorts. Matched analyses also compared outcomes of 8328 SG cases in Black versus White patients and 4852 SG cases in Hispanic versus White patients. Black patients had longer OLs (P = .004), had longer lengths of stay (P < .0001), had higher overall morbidity (P = .02), had higher bariatric-related morbidity (P = .02), had higher rates of readmission (P = .009), and were more likely to have an operative drain present at 30 days (P = .001). All other outcome measures were similar between racial/ethnic SG cohorts. CONCLUSION: Robotic-assisted SG is associated with higher overall and bariatric-related morbidity, but not mortality. However, robotic-assisted RYGB and SG remain safe, with lower rates of mortality and morbidity.

10.
Fertil Res Pract ; 6(1): 22, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33292597

RESUMO

BACKGROUND: To evaluate fertility knowledge among current Obstetrics and Gynecology (OB-GYN) residents using a recently published validated instrument, the Fertility and Infertility Treatment Knowledge Score (FIT-KS). METHODS: OB-GYN residents in the United States were recruited through an email to all residency coordinators nationwide. They were asked to voluntarily respond to a short questionnaire including demographic information and the FIT-KS instrument, through an online survey platform. Of approximately 5000 OB-GYN residents in the country, 177 responded. RESULTS: The sample was 91% female, with 69% between the ages of 26 and 30. Participants evenly represented all 4 years of training. Mean FIT-KS score was 21.2 (73% correct; range 17-26). No statistically significant differences were noted across the level of training. Several knowledge gaps were noted. Residents could define the common assisted reproductive technologies; however overestimated their success rates per cycle. CONCLUSIONS: Substantial gaps exist in fertility knowledge among OB-GYN residents, with understanding of male fertility and success rates of Assisted Reproductive Technologies (ART) being particularly limited. Knowledge of fertility does not change throughout residency training, demonstrating consistent gaps in fertility knowledge. Knowledge during post graduate year (PGY)-1 year is consistent with mean scores found in prior research in Internal Medicine residents (65%), as well as a cohort of female medical students and obstetrics and gynecology residents and fellows (64.9%) (Fertil Steril 108:711-7, 2017; Fertil Steril 110:e239, 2018).

11.
PLoS One ; 15(12): e0244725, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382797

RESUMO

The pathogenesis of human immunodeficiency virus associated neurological disorders is still not well understood, yet is known to result in neurological declines despite combination anti-retroviral therapy. HIV-1 transgenic (Tg26) mice contain integrated non-infectious HIV-1 proviral DNA. We sought to assess the integrity of neurocognitive function and sensory systems in HIV-1 Tg26 mice using a longitudinal design, in both sexes, to examine both age- and sex-related disease progression. General neurological reflexive testing showed only acclimation to repeated testing by all groups. Yet, at 2.5 months of age, female Tg26 +/- mice showed hyposensitivity to noxious hot temperatures, compared to wild types (both sexes) and male Tg26 +/- mice, that worsened by 10 months of age. Female Tg26 +/- mice had short-term spatial memory losses in novel object location memory testing at 2.5 and 7 months, compared to female wild types; changes not observed in male counterparts. Female Tg26 +/- mice showed mild learning deficits and short- and long-term spatial memory deficits in olfactory and visually cued Barnes Maze testing at 3 months of age, yet greater learning and memory deficits by 8 months. In contrast, male Tg26 +/- mice displayed no learning deficits and fewer spatial memory deficits (mainly heading errors in nontarget holes). Thus, greater sex-specific temperature hyposensitivity and spatial memory declines were observed in female HIV Tg26 +/- mice, than in male Tg26 +/- mice, or their wild type littermates, that increased with aging. Additionally, tibial bones were examined using ex vivo micro-CT after tissue collection at 11 months. Sex-dependent increases in bone volume and trabecular number were seen in males, matching their greater weights at this age. These results indicate that HIV-1 Tg26 mice is a promising model in which to study neuropathic mechanisms underlying peripheral pathology as well as cognitive deficits seen with HIV.


Assuntos
Temperatura Corporal/fisiologia , HIV-1/genética , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/genética , Memória Espacial/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Fatores Sexuais
12.
J Int Assoc Provid AIDS Care ; 19: 2325958220981265, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33327851

RESUMO

Patient acceptance of long-acting injectable antiretroviral (LAI-ARV) HIV-1 regimens will determine uptake. Although previous literature reports high satisfaction, these data stem from clinical trials subject to selection bias. This cross-sectional survey from the HIV practices of an urban academic medical center assessed perceptions and preferences using Likert scales toward overall acceptability, proposed frequencies, injection-site reaction durations, and distribution venue. 59% of surveys were completed resulting 202 respondents. 60% were male, 72% black, and the median age was 49 (IQR 36-58). 93% reported a once daily tablet frequency, 69% reported single tablet regimens, and 59% reported missing zero doses in the prior 30 days. Patients self-categorized as likely (57%) or unlikely (43%) to accept LAI-ARV. Both decreasing frequencies between injections and durations of injection-site reactions resulted higher acceptability scores. 57% of respondents preferred receiving an injectable from their clinician's office over other potential options. These data demonstrate positive LAI-ARV acceptance potential.

13.
BMC Med Res Methodol ; 20(1): 281, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33238884

RESUMO

BACKGROUND: There is little consensus on how to sample hospitalizations and analyze multiple variables to model readmission risk. The purpose of this study was to compare readmission rates and the accuracy of predictive models based on different sampling and multivariable modeling approaches. METHODS: We conducted a retrospective cohort study of 17,284 adult diabetes patients with 44,203 discharges from an urban academic medical center between 1/1/2004 and 12/31/2012. Models for all-cause 30-day readmission were developed by four strategies: logistic regression using the first discharge per patient (LR-first), logistic regression using all discharges (LR-all), generalized estimating equations (GEE) using all discharges, and cluster-weighted (CWGEE) using all discharges. Multiple sets of models were developed and internally validated across a range of sample sizes. RESULTS: The readmission rate was 10.2% among first discharges and 20.3% among all discharges, revealing that sampling only first discharges underestimates a population's readmission rate. Number of discharges was highly correlated with number of readmissions (r = 0.87, P < 0.001). Accounting for clustering with GEE and CWGEE yielded more conservative estimates of model performance than LR-all. LR-first produced falsely optimistic Brier scores. Model performance was unstable below samples of 6000-8000 discharges and stable in larger samples. GEE and CWGEE performed better in larger samples than in smaller samples. CONCLUSIONS: Hospital readmission risk models should be based on all discharges as opposed to just the first discharge per patient and utilize methods that account for clustered data.

14.
Neurobiol Dis ; 148: 105181, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33189883

RESUMO

INTRODUCTION: Alterations of white matter integrity and subsequent white matter structural deficits are consistent findings in Fetal Alcohol Syndrome (FAS), but knowledge regarding the molecular mechanisms underlying these abnormalities is incomplete. Experimental rodent models of FAS have shown dysregulation of cytokine expression leading to apoptosis of oligodendrocyte precursor cells (OPCs) and altered oligodendrocyte (OL) differentiation, but whether this is representative of human FAS pathogenesis has not been determined. METHODS: Fetal brain tissue (12.2-21.4 weeks gestation) from subjects undergoing elective termination of pregnancy was collected according to an IRB-approved protocol. Ethanol (EtOH) exposure status was classified based on a detailed face-to-face questionnaire adapted from the National Institute on Alcohol Abuse and Alcoholism Prenatal Alcohol and Sudden Infant Death Syndrome and Stillbirth (PASS) study. Twenty EtOH-exposed fetuses were compared with 20 gestational age matched controls. Cytokine and OPC marker mRNA expression was quantified by Real-Time Polymerase chain reaction (qRT-PCR). Patterns of protein expression of OPC markers and active Capase-3 were studied by Fluorescence Activated Cell Sorting (FACS). RESULTS: EtOH exposure was associated with reduced markers of cell viability, OPC differentiation, and OL maturation, while early OL differentiation markers were unchanged or increased. Expression of mRNAs for proteins specific to more mature forms of OL lineage (platelet-derived growth factor α (PDGFRα) and myelin basic protein (MBP) was lower in the EtOH group than in controls. Expression of the multifunctional growth and differentiation-promoting growth factor IGF-1, which is essential for normal development, also was reduced. Reductions were not observed for markers of early stages of OL differentiation, including Nuclear transcription factor NK-2 homeobox locus 2 (Nkx2.2). Expression of mRNAs for the proinflammatory cytokine, tumor necrosis factor-α (TNFα), and several proinflammatory chemokines was higher in the EtOH group compared to controls, including: Growth regulated protein alpha/chemokine (C-X-C motif) ligand 1 (GRO-α/CXCL1), Interleukin 8/chemokine (C-X-C motif) ligand 8 (IL8/CXCL8), Chemokine (C-X-C motif) ligand 6/Granulocyte chemotactic protein 2 (CXCL16/GCP2), epithelial-derived neutrophil-activating protein 78/chemokine (C-X-C motif) ligand 5 (ENA-78/CXCL5), monocyte chemoattractant protein-1 (MCP-1). EtOH exposure also was associated with an increase in the proportion of cells expressing markers of early stage OPCs, such as A2B5 and NG2. Finally, apoptosis (measured by caspase-3 activation) was increased substantially in the EtOH group compared to controls. CONCLUSION: Prenatal EtOH exposure is associated with excessive OL apoptosis and/or delayed OL maturation in human fetal brain. This is accompanied by markedly dysregulated expression of several chemokines and cytokines, in a pattern predictive of increased OL cytotoxicity and reduced OL differentiation. These findings are consistent with findings in animal models of FAS.

15.
Sci Rep ; 10(1): 20133, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208859

RESUMO

COPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD. We hypothesized that the primary determinant of GCH in ever smokers with or without airflow obstruction is active smoking. Goblet Cell Density (GCD) was measured in 71 current or former smokers [32 subjects without COPD and 39 COPD subjects]. Endobronchial mucosal biopsies were stained with Periodic Acid Schiff-Alcian Blue, and GCD was measured as number of goblet cells/mm basement membrane. GCD was divided into tertiles based on log10 transformed values. Log10GCD was greater in current smokers compared to former smokers. Those with classically defined CB or SGRQ defined CB had a greater log10 GCD compared to those without CB. Current smoking was independently associated with tertile 3 (high log10GCD) whereas CB was not in multivariable regression when adjusting for lung function and demographics. These results suggest that GCH is induced by active smoke exposure and does not necessarily correlate with the clinical symptoms of CB.

16.
Surg Obes Relat Dis ; 16(12): 1929-1937, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33036945

RESUMO

BACKGROUND: Robotic-assisted metabolic and bariatric surgery (MBS) is being performed with increased frequency in the United States, including for revisional MBS. However, little is known about perioperative outcomes between racial and ethnic cohorts after revisional robotic-assisted MBS. OBJECTIVE: The goal of our study was to determine if there are racial differences in outcomes after robotic-assisted revisional MBS. SETTING: University Hospital, United States. METHODS: Using the 2015-2017 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database, we identified patients undergoing revisional MBS by a robotic-assisted approach. Univariate analyses were performed of unmatched and matched racial and ethnic cohorts, comparing black versus white patients and Hispanic versus white patients. RESULTS: Of 2027 robotic-assisted revisional MBS cases in the database, 1922 were included in our analysis, including 67%, 22.6%, and 10.4% white, black, and Hispanic patients, respectively. At baseline, there were some differences in patient characteristics between racial and ethnic cohorts. After propensity matching, outcomes between black and white patients were similar, except for higher rates of superficial surgical site infection among white patients (P = .05) and higher rates of organ space surgical site infection in black patients (P = .05). Outcomes were also similar between matched white and Hispanic patients, except for a higher bleeding in white patients (2% versus 0%, P = .04). There were no mortality or morbidity differences between racial and ethnic cohorts. CONCLUSION: Morbidity and mortality after robotic-assisted revisional MBS do not seem to be mediated by race or ethnicity.

18.
Aging (Albany NY) ; 12(18): 17786-17799, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32960787

RESUMO

Rapamycin delays multiple age-related conditions and extends lifespan in organisms ranging from yeast to mice. However, the mechanisms by which rapamycin influences longevity are incompletely understood. The objective of this study was to investigate the effect of rapamycin on NAD+/NADH redox balance. We report that the NAD+/NADH ratio of C2C12 myoblasts or differentiated myotubes significantly decreases over time in culture, and that rapamycin prevents this effect. Despite lowering the NADH available to support ATP generation, rapamycin increases ATP availability, consistent with lowering energetic demand. Although rapamycin did not change the NAD+/NADH ratio or steady-state ATP concentration in the livers, kidneys, or muscles of young mice, optical redox imaging revealed that rapamycin caused a substantial decline in the NADH content and an increase in the optical redox ratio (a surrogate of NAD+/NADH redox ratio) in muscles from aged mice. Collectively, these data suggest that rapamycin favors a more oxidized NAD+/NADH ratio in aged muscle, which may influence metabolism and the activity of NAD+-dependent enzymes. This study provides new insight into the mechanisms by which rapamycin might influence the aging process to improve health and longevity among the aging population.

20.
Chest ; 158(3): 1290-1291, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32892873
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