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Importance: Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. Distributed white matter (WM) impairments in individuals with heroin use disorder (iHUD) have been associated with increased drug craving, a reliable predictor of treatment outcomes. However, little is known about the extent of whole-brain structural connectivity changes with inpatient treatment and abstinence in iHUD. Objective: To assess WM microstructure and associations with drug craving changes with inpatient treatment in iHUD (effects of time/re-scan compared to controls; CTL). Design: Longitudinal cohort study (12/2020-09/2022) where iHUD and CTL underwent baseline magnetic resonance imaging (MRI#1) and follow-up (MRI#2) scans, (mean interval of 13.9 weeks in all participants combined). Setting: The iHUD and CTL were recruited from urban inpatient treatment facilities and surrounding communities, respectively. Participants: Thirty-four iHUD (42.1yo; 7 women), 25 age-/sex-matched CTL (40.5yo; 9 women). Intervention: Between scans, inpatient iHUD continued their medically-assisted treatment and related clinical interventions. CTL participants were scanned at similar time intervals. Main Outcomes and Measures: Changes in white matter diffusion metrics [fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivities (RD)] in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance). Results: Main findings showed HUD-specific WM microstructure changes encompassing mostly frontal major callosal, projection, and association tracts, characterized by increased FA (.949<1-p<.986) and decreased MD (.949<1-p<.997) and RD (.949<1-p<.999). The increased FA (r=-0.72, p<.00001) and decreased MD (r=0.69, p<.00001) and RD (r=0.67, p<.0001) in the genu and body of the corpus callosum and the left anterior corona radiata in iHUD were correlated with a reduction in baseline craving (.949<1-p<.999). No other WM correlations with outcome variables reached significance. Conclusions and Relevance: Our findings suggest whole-brain normalization of structural connectivity with inpatient medically-assisted treatment in iHUD encompassing recovery in frontal WM pathways implicated in emotional regulation and top-down executive control. The association with decreases in baseline craving further supports the relevance of these WM markers to a major symptom in drug addiction, with implications for monitoring clinical outcomes.
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Surgical repair of the diaphragm is essential for survival in congenital diaphragmatic hernia (CDH). There are many considerations surrounding the operation - why the operation matters, optimal timing of repair and its relation to extracorporeal life support (ECLS) use, minimally invasive versus open approaches, and strategies for reconstruction. Surgery is both affected by, and affects, the physiology of these infants and is an important factor in determining long-term outcomes. Here we discuss the evidence and provide insight surrounding this complex decision making, technical pearls, and outcomes in repair of CDH.
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Hernias Diafragmáticas Congénitas , Herniorrafia , Hernias Diafragmáticas Congénitas/cirugía , Humanos , Herniorrafia/métodos , Oxigenación por Membrana Extracorpórea/métodos , Recién NacidoRESUMEN
Electron imaging of biological samples stained with heavy metals has enabled visualization of subcellular structures critical in chemical-, structural-, and neuro-biology. In particular, osmium tetroxide OsO4 has been widely adopted for selective lipid imaging. Despite the ubiquity of its use, the osmium speciation in lipid membranes and the process for contrast generation in electron microscopy (EM) have continued to be open questions, limiting efforts to improve staining protocols and therefore high-resolution nanoscale imaging of biological samples. Following our recent success using photoemission electron microscopy (PEEM) to image mouse brain tissues with synaptic resolution, we have used PEEM to determine the nanoscale electronic structure of Os-stained biological samples. Os(IV), in the form of OsO2, generates nanoaggregates in lipid membranes, leading to a strong spatial variation in the electronic structure and electron density of states. OsO2 has a metallic electronic structure that drastically increases the electron density of states near the Fermi level. Depositing metallic OsO2 in lipid membranes allows for strongly enhanced EM signals and conductivity of biological materials. The identification of the chemical species and understanding of the membrane contrast mechanism of Os-stained biological specimens provides a new opportunity for the development of staining protocols for high-resolution, high-contrast EM imaging.
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BACKGROUND: Emergency department (ED) crowding is a global burden. Interventions to reduce ED utilization have been widely discussed in the literature, but previous reviews have mainly focused on specific interventions or patient groups within the EDs. The purpose of this scoping review was to identify, summarize, and categorize the various types of non-ED-based interventions designed to reduce unnecessary visits to EDs. METHODS: This scoping review followed the JBI Manual for Evidence Synthesis and the PRISMA-SCR checklist. A comprehensive structured literature search was performed in the databases MEDLINE and Embase from 2008 to March 2024. The inclusion criteria covered studies reporting on interventions outside the ED that aimed to reduce ED visits. Two reviewers independently screened the records and categorized the included articles by intervention type, location, and population. RESULTS: Among the 15,324 screened records, we included 210 studies, comprising 183 intervention studies and 27 systematic reviews. In the primary studies, care coordination/case management or other care programs were the most commonly examined out of 15 different intervention categories. The majority of interventions took place in clinics or medical centers, in patients' homes, followed by hospitals and primary care settings - and targeted patients with specific medical conditions. CONCLUSION: A large number of studies have been published investigating interventions to mitigate the influx of patients to EDs. Many of these targeted patients with specific medical conditions, frequent users and high-risk patients. Further research is needed to address other high prevalent groups in the ED - including older adults and mental health patients (who are ill but may not need the ED). There is also room for further research on new interventions to reduce ED utilization in low-acuity patients and in the general patient population.
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Aglomeración , Servicio de Urgencia en Hospital , Humanos , Servicio de Urgencia en Hospital/estadística & datos numéricosRESUMEN
Existing barriers to care were exacerbated by the development and implementation of necessary public health restrictions during the COVID-19 pandemic. Children with complex care needs and their families represent a small portion of the paediatric population, and yet they require disproportionately high access to services. Little is known about the impact of COVID-19 public health measures on this population. This study will generate evidence to uncover the wider impact of COVID-19 measures on the lives of children with complex care needs and their families in relation to policy and service changes. This multi-site sequential mixed methods study will take place across the Canadian Maritime provinces and use an integrated knowledge translation approach. There are two phases to this study: 1) map COVID-19 public health restrictions and service changes impacting children with complex care needs by conducting an environmental scan of public health restrictions and service changes between March 2020 and March 2022 and interviewing key informants involved in the development or implementation of restrictions and service changes, and 2) explore how children with complex care needs and their families experienced public health restrictions and service changes to understand how their health and well-being were impacted.
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COVID-19 , Humanos , COVID-19/epidemiología , Niño , Canadá/epidemiología , Familia , SARS-CoV-2/aislamiento & purificación , Pandemias , Accesibilidad a los Servicios de Salud , Adolescente , Preescolar , Masculino , Femenino , Salud PúblicaRESUMEN
BACKGROUND: Skilled nursing facilities (SNFs) are an ideal setting to implement the Age-Friendly Health System (AFHS) approach, an initiative by the Institute for Healthcare Improvement (IHI) centered on the 4Ms: what matters, mobility, mentation, and medication. AFHS implementation has not been well studied in SNFs. METHODS: A 112-bed VA SNF implemented a facility-wide AFHS initiative including the following: (1) participating in a national IHI Age-Friendly Action Community; (2) establishing an AFHS workgroup centered on the 4Ms; (3) identifying meaningful clinical tools and frameworks for capturing each M; and (4) developing sustainment methods. Clinical (life-sustaining treatment, falls, disruptive behaviors, and medication deprescribing) and quality outcomes (rehospitalization, emergency department utilization, and discharge to the community) in addition to patient satisfaction were compared pre- and post-AFHS implementation (bed days of care [BDOC] 17413) to post-implementation (BDOC 20880). RESULTS: Clinical outcomes demonstrated improvements in the 4Ms, including: (1) what matters: 14% increase in life-sustaining treatment documentation (82%-96%; p < 0.01); (2) mobility: reduction in fall rate by 34% (8.15 falls/1000 BDOC to 5.41; p < 0.01); (3) mentation: decrease in disruptive behavior reporting system (DBRS) by 62% (5.11 DBRS/1000 BDOC to 1.96; p = 0.04); (4) medications: 53% increase in average potentially inappropriate medications (PIMs) deprescribing (0.38-0.80 interventions/patient; p < 0.01). Quality outcomes improved including rehospitalization (25.6%-17.9%) and emergency department utilization (5.3%-2.8%) within 30 days of admission. Patient satisfaction scores improved from a mean of 77.2 (n = 31, scale 1-100) to 81.3 (n = 42). CONCLUSIONS: Implementation of the AFHS initiative in a SNF was associated with improved clinical and quality outcomes and patient satisfaction. We describe here a sustainable, interprofessional approach to implementing the AFHS in a SNF.
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BACKGROUND: Statins lower circulating low-density lipoprotein cholesterol (LDLC) levels and reduce cardiovascular disease risk. Though highly efficacious in general, there is considerable inter-individual variation in statin efficacy that remains largely unexplained. METHODS: To identify novel genes that may modulate statin-induced LDLC lowering, we used RNA-sequencing data from 426 control- and 2 µM simvastatin-treated lymphoblastoid cell lines (LCLs) derived from European and African American ancestry participants of the Cholesterol and Pharmacogenetics (CAP) 40 mg/day 6-week simvastatin clinical trial (ClinicalTrials.gov Identifier: NCT00451828). We correlated statin-induced changes in LCL gene expression with plasma LDLC statin response in the corresponding CAP participants. For the most correlated gene identified (ZNF335), we followed up in vivo by comparing plasma cholesterol levels, lipoprotein profiles, and lipid statin response between wild-type mice and carriers of a hypomorphic (partial loss of function) missense mutation in Zfp335 (the mouse homolog of ZNF335). RESULTS: The statin-induced expression changes of 147 human LCL genes were significantly correlated to the plasma LDLC statin responses of the corresponding CAP participants in vivo (FDR = 5%). The two genes with the strongest correlations were zinc finger protein 335 (ZNF335 aka NIF-1, rho = 0.237, FDR-adj p = 0.0085) and CCR4-NOT transcription complex subunit 3 (CNOT3, rho = 0.233, FDR-adj p = 0.0085). Chow-fed mice carrying a hypomorphic missense (R1092W; aka bloto) mutation in Zfp335 had significantly lower non-HDL cholesterol levels than wild-type C57BL/6J mice in a sex combined model (p = 0.04). Furthermore, male (but not female) mice carrying the Zfp335R1092W allele had significantly lower total and HDL cholesterol levels than wild-type mice. In a separate experiment, wild-type mice fed a control diet for 4 weeks and a matched simvastatin diet for an additional 4 weeks had significant statin-induced reductions in non-HDLC (-43 ± 18% and -23 ± 19% for males and females, respectively). Wild-type male (but not female) mice experienced significant reductions in plasma LDL particle concentrations, while male mice carrying Zfp335R1092W allele(s) exhibited a significantly blunted LDL statin response. CONCLUSIONS: Our in vitro and in vivo studies identified ZNF335 as a novel modulator of plasma cholesterol levels and statin response, suggesting that variation in ZNF335 activity could contribute to inter-individual differences in statin clinical efficacy.
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LDL-Colesterol , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Simvastatina , Animales , Humanos , Ratones , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Simvastatina/farmacología , LDL-Colesterol/sangre , Línea Celular , Masculino , Femenino , Perfilación de la Expresión Génica , Transcriptoma , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Unión al ADN/genética , Colesterol/sangre , Mutación MissenseRESUMEN
BACKGROUND: Textbook outcome (TBO) has been proposed as a composite measure of quality in esophagogastric surgery, and achieving a TBO has been associated with improved overall survival (OS). The Dutch Upper Gastrointestinal Cancer Audit group determined their TBO rate for gastrectomy to be 32.1%, using 10 parameters. Our study aimed to assess the TBO rate in patients who had a gastrectomy for cancer in an Australian Upper GI unit, allowing for comparisons with international specialist centers. METHODS: Retrospective analysis of a prospectively maintained database of patients who had a gastrectomy for cancer performed by the surgeons in a single Australian center between 2013 and 2018. Postoperative complications were analyzed using Clavien-Dindo (CD) ≥2 and CD ≥3 definitions. Baseline factors and their association with TBO were analyzed using multivariable logistical regression. The association between TBO and survival rates was determined by Cox proportional hazards regression analysis. RESULTS: In 136 patients, 84 (62%) achieved a TBO when complications were graded as CD ≥2. Greatest negative impact on TBO was the complication rate, lymph node yield, and length of stay. Patients more likely to achieve a TBO were younger, with an increased body mass index and absence of underlying respiratory disease. A nonsignificant trend toward improved OS was seen when TBO was achieved. CONCLUSION: Our TBO rate compares favorably with published data from high-volume centers. Assessment of a unit's TBO may provide a stronger evaluation of quality when assessing where complex surgery should be performed within Australia.
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Antiferroelectric (AFE) materials are excellent candidates for sensors, capacitors, and data storage due to their electrical switchability and high-energy storage capacity. However, imaging the nanoscale landscape of AFE domains is notoriously inaccessible, which has hindered development and intentional tuning of AFE materials. Here, we demonstrate that polarization-dependent photoemission electron microscopy can resolve the arrangement and orientation of in-plane AFE domains on the nanoscale, despite the absence of a net lattice polarization. Through direct determination of electronic transition orientations and analysis of domain boundary constraints, we establish that antiferroelectricity in ß'-In2Se3 is a robust property from the scale of tens of nanometers to tens of micrometers. Ultimately, the method for imaging AFE domain organization presented here opens the door to investigations of the influence of domain formation and orientation on charge transport and dynamics.
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In Sub-Saharan Africa, efficacy trials of brief interventions to reduce unhealthy drinking among persons living with HIV (PLWH) have yielded mixed results. A better understanding of the perceptions of drinking, especially by PLWH, and how drinking is talked about at HIV treatment clinics in this setting, may guide more optimal designs for future trials. We conducted a qualitative study at an HIV treatment clinic in South Western Uganda to better understand perceptions of drinking, how drinking is talked about, and perceptions of interventions, especially a protocolled screening and brief intervention (SBI) for unhealthy drinking among PLWH. We conducted in-depth interviews with 17 PLWH who engaged in unhealthy drinking and 6 health workers, and one focus group discussion with 3 community advisory-board members. We performed manual preliminary data analysis and computer-assisted detailed thematic analysis to identify emergent themes. Four themes emerged: perceptions of alcohol use in the general population; perceptions of alcohol use in PLWH; interaction between PLWH and health workers about alcohol use; perceptions of interventions for unhealthy drinking including SBI. Unhealthy drinking was seen as a problem in the general population and among those with HIV, where it was negatively perceived. Communication about drinking was done by counselors, but doctors participated in screening for unhealthy alcohol use. Messages about drinking covered reduction and abstinence. Participants expressed positive attitudes towards SBI and preference for person-delivered SBI over technological alternatives. A protocolled SBI for unhealthy alcohol use among PLWH would be well-received but successful implementation may depend on mode of delivery.
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Consumo de Bebidas Alcohólicas , Grupos Focales , Infecciones por VIH , Investigación Cualitativa , Humanos , Uganda/epidemiología , Masculino , Femenino , Infecciones por VIH/psicología , Adulto , Consumo de Bebidas Alcohólicas/psicología , Consumo de Bebidas Alcohólicas/epidemiología , Persona de Mediana Edad , Entrevistas como Asunto , Conocimientos, Actitudes y Práctica en Salud , PercepciónRESUMEN
There are two species of free-roaming feral equids in North America: horses (Equus caballus) and donkeys or "burros" (E. asinus). Both species were introduced as domestic animals to North America in the early 1500s and currently inhabit rangelands across the western United States, Canada, and all continents except Antarctica. Despite their global distribution, little is known about their fine scale spatial ecology. Contemporary research tools to assess space use include global positioning system (GPS) tracking collars, but older models were problematic due to stiff collar belting causing poor fit. We tested modern designs of GPS collars on n = 105 horses and n = 60 burros for 4 years in five populations (3 horse, 2 burro) across the western United States, to assess whether collars posed welfare risks to horses or burros. We found no difference in survival of collared versus uncollared mares and jennies, and no difference in survival of their foals. In 4036 of 4307 observations for horses (93.7%) and 2115 of 2258 observations for burros (93.6%), collars were observed symmetrical, maintaining proper fit on the neck. Fur effects from collars (sweaty neck, indented fur, broken fur) were seen in 3% of horse observations and 25% of burro observations. Superficial effects (chafes and marks on skin surface) were seen in 2% of horse observations and 11% of burro observations; no severe effects from collars were seen. Body condition was not affected by collars; mean body condition of collared horses was 4.70 ± 0.54 (mean ± s.d) and 4.71 ± 0.65 for collared burros. Behavior results indicated minimal effects; collared horses stood slightly more than uncollared, and collared burros stood and foraged more in one population, but not in the other. For 6.3% of observations of horses and 6.4% of observations of burros, we found an effect of time wearing a collar on the cumulative sum of fur effects which increased over time (burros: rs = 0.87, P = <0.0001; horses: rs = 0.31, P = 0.002). Burros also showed an increase over time in the number of superficial effects, but horses did not. Collars occasionally moved into the wrong position, shifting forward over the ears; we observed this on 19 horses and 1 burro. Of those, most collars went over the ears in summer (n = 12). All collars were equipped with a remote release mechanism as well as a timed-release mechanism for redundancy, thus removed when observed in wrong position to avoid rubbing or discomfort. Our finding of no consequential physical effects in 98% of horse observations, and 89% of burro observations suggests the consequences of collars on free-roaming equid welfare and survival is biologically insignificant, although collars should be monitored regularly and continue to be equipped with a remote release mechanism to remove a collar if needed. With frequent welfare-driven, visual monitoring, collaring of free-roaming equids can be a safe and useful tool to increase our understanding of their spatial ecology, demography, habitat use, behavior, and interactions with other wildlife.
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Equidae , Sistemas de Información Geográfica , Telemetría , Animales , Equidae/fisiología , Caballos , Femenino , MasculinoRESUMEN
BACKGROUND: Emergency department (ED) crowding is a common healthcare issue with multiple causes. One important knowledge area is understanding where patients arrived from and what care they received prior to ED admission. This information could be used to inform strategies to provide care for low acuity patients outside of the hospital and reduce unnecessary ED admissions. The aim of this scoping review was to provide a comprehensive overview of global published research examining the acute care trajectory of all ED patients. METHODS: The scoping review was performed according to the JBI Manual for Evidence Synthesis and the PRISMA-SCR checklist. A comprehensive literature search was performed to identify studies describing where patients arrived from and/or whose pathway of care was before an ED visit. The search was conducted in MEDLINE, Embase, and the Cochrane Library from inception through December 5th, 2022. Two reviewers independently screened the records. RESULTS: Out of the 6,465 records screened, 14 studies from Australia, Canada, Haiti, Norway, Sweden, Switzerland, Belgium, Indonesia, and the UK met the inclusion criteria. Four studies reported on where patients physically arrived from, ten reported how patients were transported, six reported who referred them, and six reported whether medical care or advice was sought prior to visiting an ED. CONCLUSION: This scoping review revealed a lack of studies describing patients' pathways to the ED. However, studies from some countries indicate that a relatively large proportion of patients first seek care or guidance from a primary care physician (PCP) before visiting an ED. However, further research and published data are needed. To improve the situation, we recommend the development and implementation of a template for the uniform reporting of factors outside the ED, including where the patient journey began, which healthcare facilities they visited, who referred them to the ED, and how they arrived.
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Background: Unplanned readmission to intensive care units (UR-ICU) in trauma is associated with increased hospital length of stay and significant morbidity and mortality. We identify independent predictors of UR-ICU and construct a nomogram to estimate readmission probability. Materials and Methods: We performed an IRB-approved retrospective case-control study at a Level I trauma center between January 2019 and December 2021. Patients with UR-ICU (n = 175) were matched with patients who were not readmitted (NR-ICU) (n = 175). Univariate and multivariable binary linear regressionanalyses were performed (SPSS Version 28, IBM Corp), and a nomogram was created (Stata 18.0, StataCorp LLC). Results: Demographics, comorbidities, and injury- and hospital course-related factors were examined as potential prognostic indicators of UR-ICU. The mortality rate of UR-ICU was 22.29% vs 6.29% for NR-ICU (P < .001). Binary linear regression identified seven independent predictors that contributed to UR-ICU: shock (P < .001) or intracranial surgery (P = .015) during ICU admission, low hematocrit (P = .001) or sedation administration in the 24 hours before ICU discharge (P < .001), active infection treatment (P = .192) or leukocytosis on ICU discharge (P = .01), and chronic obstructive pulmonary disease (COPD) (P = .002). A nomogram was generated to estimate the probability of UR-ICU and guide decisions on ICU discharge appropriateness. Discussion: In trauma, UR-ICU is often accompanied by poor outcomes and death. Shock, intracranial surgery, anemia, sedative administration, ongoing infection treatment, leukocytosis, and COPD are significant risk factors for UR-ICU. A predictive nomogram may help better assess readiness for ICU discharge.
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Unidades de Cuidados Intensivos , Nomogramas , Readmisión del Paciente , Heridas y Lesiones , Humanos , Readmisión del Paciente/estadística & datos numéricos , Masculino , Femenino , Estudios Retrospectivos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Persona de Mediana Edad , Adulto , Estudios de Casos y Controles , Heridas y Lesiones/terapia , Heridas y Lesiones/mortalidad , Factores de Riesgo , Tiempo de Internación/estadística & datos numéricos , Centros Traumatológicos , Anciano , PronósticoRESUMEN
Chest tube thoracostomy (CTT) is essential for lung expansion, but protocol discrepancies exist across trauma centers. This prospective study compared CTT protocols between an urban (center 1) and rural (center 2) level 1 trauma center in East Tennessee from June to August 2023. 66 trauma patients required CTT (51 from center 1 and 15 from center 2). Diagnostic practices and post-pull chest X-rays (CXR) differed significantly. Center 1 favored CXR for diagnosis (P = 0.012), while center 2 relied more on clinical presentation (P = 0.012). Post-pull CXR was less common at center 2 (P = 0.012). Center 2 had lower Glasgow Coma Scale scores (P = 0.028), shorter tube duration (P = 0.044), and more needle thoracostomy use (P = 0.393). These findings underscore the need for regional protocols considering pre-arrival factors, hospital practices, and injury patterns. Protocol adjustments aim to improve adherence and patient outcomes, with ongoing data collection exploring factors influencing protocol evolution.
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Tubos Torácicos , Toracostomía , Centros Traumatológicos , Humanos , Tennessee , Estudios Prospectivos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Traumatismos Torácicos/cirugía , Hospitales UrbanosRESUMEN
OBJECTIVE: Advanced-stage laryngeal squamous cell carcinoma is treated with primary surgery or chemoradiation. We aim to determine if there are differences in postoperative functional oral intake in primary (PL) versus salvage laryngectomees (SL). STUDY DESIGN: Retrospective cohort study. SETTING: Patients who underwent laryngectomy between 2011 and 2021. METHODS: We examined demographic, diagnostic, treatment, and swallow function data pre- and postoperatively. A follow-up survey was distributed to assess current swallow status. RESULTS: One hundred twenty-five patients were included. Preoperatively, 68.8% of patients reported dysphagia. Median functional oral intake score (FOIS) was 4.0 [interquartile range, IQR: 1.0-6.75]. The SL group had lower preop FOIS [2.0; IQR: 1.0-4.75] that did not reach significance compared to the PL group [4.5; IQR: 1.0-7.0] (P = .052). 73.4% of patients had a feeding tube. The PL group was more likely to have the tube removed [odds ratio, OR: 2.4; confidence interval, CI: 1.0-5.7]. The SL group was more likely to require feeding tube placement more than 6 months postop [OR: 6.9; CI: 1.65-32.6]. SL FOIS scores improved by 3 months postop to 5 (SL ΔFOIS = 3, P = .0150). PL scores improved to 7 [PL ΔFOIS = 2, P = .0005] at 12 to 15 months. Sixty-nine patients were contacted for a follow-up survey and 16 completed this survey. 30.4% patients reported dietary restrictions (mean 4.4 years postop). CONCLUSION: Patients undergoing SL appear to obtain similar swallow outcomes compared to PL at 3 to 6 months postlaryngectomy, but plateau. The PL group continues to improve up to 1 year postoperatively. Fifty percent of patients report on-going dysphagia after 5 years.
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Trastornos de Deglución , Neoplasias Laríngeas , Laringectomía , Terapia Recuperativa , Humanos , Laringectomía/métodos , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Neoplasias Laríngeas/cirugía , Terapia Recuperativa/métodos , Trastornos de Deglución/etiología , Anciano , Deglución/fisiología , Carcinoma de Células Escamosas/cirugía , Complicaciones PosoperatoriasRESUMEN
Differentiation of murine epidermal stem/progenitor cells involves the permanent withdrawal from the cell cycle, the synthesis of various protein and lipid components for the cornified envelope, and the controlled dissolution of cellular organelles and nuclei. Deregulated epidermal differentiation contributes to the development of various skin diseases, including skin cancers. With a genome-wide shRNA screen, we identified vesicle-associated membrane protein 2 (VAMP2) as a critical factor involved in skin differentiation. Deletion of VAMP2 leads to aberrant skin stratification and enucleation in vivo. With quantitative proteomics, we further identified an autophagy protein, focal adhesion kinase family interacting protein of 200 kDa (FIP200), as a binding partner of VAMP2. Additionally, we showed that both VAMP2 and FIP200 are critical for murine keratinocyte enucleation and epidermal differentiation. Loss of VAMP2 or FIP200 enhances cutaneous carcinogenesis in vivo. Together, our findings identify important molecular mechanisms underlying epidermal differentiation and skin tumorigenesis.
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Proteínas Relacionadas con la Autofagia , Autofagia , Carcinogénesis , Diferenciación Celular , Epidermis , Queratinocitos , Proteína 2 de Membrana Asociada a Vesículas , Animales , Ratones , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Queratinocitos/metabolismo , Queratinocitos/citología , Epidermis/metabolismo , Epidermis/patología , Proteína 2 de Membrana Asociada a Vesículas/metabolismo , Proteína 2 de Membrana Asociada a Vesículas/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinogénesis/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/genética , Células Epidérmicas/metabolismo , Núcleo Celular/metabolismo , Ratones NoqueadosRESUMEN
Unhealthy alcohol use and sexually transmitted infections (STIs) are significant public health concerns for US college students. Because alcohol use and condomless sex often co-occur in this population, alcohol-associated condomless sex has been identified as a behavioral intervention target. Existing theoretical frameworks have not garnered sufficient empirical support to serve as the foundation for interventions. The primary goal of the current study was to use a mixed-methods approach to develop a model of college student alcohol-associated condomless sex that combines elements from well-established health behavior theories. In Aim 1, multilevel modeling was used to predict condomless vaginal sex in a sample of heterosexual college student drinkers (N = 53). Aim 2 consisted of in-depth interviews (n = 18) to gather perceptions about the role of alcohol in sexual activity and identify supplemental constructs omitted from theories in Aim 1. The multilevel model explained a significant proportion of variance in condomless vaginal sex at the between- and within-person level. Themes derived from the in-depth interviews identified complementary elements of condom use decision-making. Findings from both aims were synthesized to construct a combined model of alcohol-associated condomless sex. This model can be further refined and ultimately serve as the foundation of an alcohol-STI prevention-intervention.
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Infecciones por VIH , Enfermedades de Transmisión Sexual , Femenino , Humanos , Sexo Inseguro/prevención & control , Conducta Sexual , Enfermedades de Transmisión Sexual/prevención & control , Enfermedades de Transmisión Sexual/epidemiología , Sexo Seguro , Estudiantes , Condones , Infecciones por VIH/epidemiologíaRESUMEN
Surgical palliative care (PC) facilitates communication between surgeons and patients/family about prognosis, symptom control, and therapeutic goals. Surgical critical care (SCC) fellows are at the forefront of the intensive care team; thus, we aim to assess previous and ongoing experiences in delivering PC by surveying fellows at a large academic center. Seventeen surveys were completed in which 59% of fellows reported no previous PC education. Six fellows (35%) reported participating in goals of care/end-of-life (GOC/EOL) discussions "a few times a year" during residency, while 41% responded the same for transitioning patients to comfort-focused care (CFC). When asked if respondents felt comfortable facilitating GOC/EOL discussions prior to fellowship, 7 (41%) answered "disagree" or "strongly disagree." Most fellows reported that more training in navigating GOC/EOL discussions (88%) and transitioning patients to CFC (76%) is needed. This assessment demonstrates variability in fellows' prior PC exposure and a strong desire for more structured training.
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Centros Médicos Académicos , Cuidados Críticos , Becas , Evaluación de Necesidades , Cuidados Paliativos , Humanos , Encuestas y Cuestionarios , Educación de Postgrado en Medicina/métodos , Internado y Residencia , Femenino , Cirugía General/educación , Masculino , Cirugía de Cuidados IntensivosRESUMEN
Unplanned admission to an intensive care unit (ICU) is a trauma quality improvement indicator associated with increased morbidity, mortality, and hospital resource usage. We identified demographics, injuries, and other clinical factors between early ICU admission, <72 hrs after admission (EAd), and delayed admission, >72 hrs (DelAd) from a medical/surgical floor. 146 trauma patients admitted to ICU at a level 1 trauma center from January 2020 to March 2023 met inclusion criteria and were divided into EAd and DelAd. No statistical differences in injury mechanism or severity were observed. Delayed admission demonstrated higher mortality (P = .001), more frequent decline in GCS (P = .045), and initiation of anticoagulation (P = .002). Abnormal EKG, orthopedic surgery during admission, and home anticoagulant and antidepressant use were statistically significant in identifying patients requiring early ICU admission.