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1.
J Biol Chem ; 296: 100383, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33556373

RESUMEN

The rhomboid protease PARL is a critical regulator of mitochondrial homeostasis through its cleavage of substrates such as PINK1, PGAM5, and Smac/Diablo, which have crucial roles in mitochondrial quality control and apoptosis. However, the catalytic properties of PARL, including the effect of lipids on the protease, have never been characterized in vitro. To address this, we isolated human PARL expressed in yeast and used FRET-based kinetic assays to measure proteolytic activity in vitro. We show that PARL activity in detergent is enhanced by cardiolipin, a lipid enriched in the mitochondrial inner membrane. Significantly higher turnover rates were observed for PARL reconstituted in proteoliposomes, with Smac/Diablo being cleaved most rapidly at a rate of 1 min-1. In contrast, PGAM5 is cleaved with the highest efficiency (kcat/KM) compared with PINK1 and Smac/Diablo. In proteoliposomes, a truncated ß-cleavage form of PARL, a physiological form known to affect mitochondrial fragmentation, is more active than the full-length enzyme for hydrolysis of PINK1, PGAM5, and Smac/Diablo. Multiplex profiling of 228 peptides reveals that PARL prefers substrates with a bulky side chain such as Phe in P1, which is distinct from the preference for small side chain residues typically found with bacterial rhomboid proteases. This study using recombinant PARL provides fundamental insights into its catalytic activity and substrate preferences that enhance our understanding of its role in mitochondrial function and has implications for specific inhibitor design.


Asunto(s)
Metaloproteasas/metabolismo , Metaloproteasas/fisiología , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/fisiología , Proteínas Reguladoras de la Apoptosis/metabolismo , Dominio Catalítico , Endopeptidasas/metabolismo , Células HEK293 , Células HeLa , Humanos , Metaloproteasas/genética , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Péptido Hidrolasas/metabolismo , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Proteolisis
2.
AIDS Behav ; 23(Suppl 3): 304-312, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31456198

RESUMEN

Client-level data from two Tennessee-based PrEP navigation demonstration projects reported to the Tennessee Department of Health from January to December 2017 were evaluated to determine the proportion of clients who accepted, were linked to, and were prescribed PrEP. Disparities by age, race, transmission risk, and geographic region as well as trends over time were examined via bivariate and multivariable modified Poisson regression models accounting for potential confounders. Among 1385 PrEP-eligible individuals, 50.5% accepted, 33.4% were linked, and 27.3% were prescribed PrEP. PrEP uptake varied by age, race, and HIV transmission risk, and most disparities persisted across Tennessee throughout evaluation period. Multivariable regression models revealed significant independent associations between age, race/ethnicity, transmission risk, and region and PrEP acceptance and linkage. While differences in PrEP acceptance by race narrowed over time, success among black MSM was limited, underscoring a significant need to improve upstream PrEP continuum outcomes for this important population.


Asunto(s)
Infecciones por VIH/etnología , Infecciones por VIH/prevención & control , Aceptación de la Atención de Salud/psicología , Profilaxis Pre-Exposición/estadística & datos numéricos , Adulto , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Distribución por Edad , Infecciones por VIH/transmisión , Conocimientos, Actitudes y Práctica en Salud , Homosexualidad Masculina/etnología , Homosexualidad Masculina/psicología , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Aceptación de la Atención de Salud/estadística & datos numéricos , Profilaxis Pre-Exposición/métodos , Distribución por Sexo , Tennessee , Población Blanca/psicología , Población Blanca/estadística & datos numéricos
3.
MMWR Morb Mortal Wkly Rep ; 67(15): 447-450, 2018 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-29672477

RESUMEN

The Alabama Department of Public Health (ADPH) conducts an annual community assessment to evaluate household preparedness and local public health concerns. In June 2017, ADPH conducted a Community Assessment for Public Health Emergency Response (CASPER), focusing on indoor air pollutants in seven neighborhoods in Madison County, Alabama, where a large percentage of homes were built before 1980. Local health partners had concerns about indoor air quality and environmental risks such as radon; however, limited information was available regarding community awareness, prevention, and mitigation measures related to potential exposures. Weighted response frequencies were calculated from assessment responses. Among 192 household interview respondents, 78.4% were aware of potential indoor lead exposures, but only 12.6% of respondents living in houses built before 1978 reported that the house had been tested for lead. Similarly, respondents in 70.2% of households had heard of radon; however, only 7.3% of houses had been tested for radon. Smoking was reported by residents of 45.7% of households; among those, 48.4% reported that smoking occurred inside the house. Identified gaps in exposure prevention and mitigation, including low lead and radon testing rates and a high prevalence of indoor smoking, were shared with the local health department, and recommendations for timely interventions and policy guidance (e.g., targeted education campaigns and smoking cessation programs) were presented. Results of this CASPER demonstrated its usefulness and efficiency in gathering community-level data to help guide public health policies and timely interventions.


Asunto(s)
Contaminación del Aire Interior , Conocimientos, Actitudes y Práctica en Salud , Características de la Residencia , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/análisis , Alabama , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Humanos , Plomo/efectos adversos , Plomo/análisis , Práctica de Salud Pública , Radón/efectos adversos , Radón/análisis , Enfermedades Respiratorias/inducido químicamente , Encuestas y Cuestionarios
4.
J Trauma Nurs ; 23(4): 194-201, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27414141

RESUMEN

Children who sustain injuries are at risk for experiencing traumatic stress reactions. Few studies have obtained detailed, qualitative information regarding children's and parents' own understanding of their experiences during the peritrauma period. Understanding children's injury and early hospital experiences is crucial to inform the development of early interventions during the peritrauma period, which speak to these concerns. The primary purpose of this study was to understand child and parent views of the stressors experienced by children hospitalized for an injury. A secondary aim was to identify children's feelings and thoughts about injury- and hospital-related stressors. Ten children and their parents participated in semistructured interviews. Interviews were audio-recorded, transcribed, and coded. Stressors were classified into 5 domains: procedural concerns, uncertainty, sleep and nutrition challenges, being confined to the hospital, and home preparation. Children and parents were more likely to articulate feelings about stressors than thoughts about stressors. Feelings reported by children and parents were predominantly negative. Children and parents may have an easier time expressing feelings than thoughts, which has implications for communicating with medical teams as well as for psychological treatment. Future research should examine how children's perceptions of their injury- and hospital-related experiences relate to later outcomes such as traumatic stress reactions.


Asunto(s)
Padres/psicología , Calidad de la Atención de Salud , Estrés Psicológico , Heridas y Lesiones/terapia , Adolescente , Niño , Conducta Infantil , Emociones , Estudios de Evaluación como Asunto , Femenino , Hospitalización , Hospitales Pediátricos , Humanos , Puntaje de Gravedad del Traumatismo , Entrevistas como Asunto , Masculino , Relaciones Padres-Hijo , Resultado del Tratamiento , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/psicología
5.
Can J Respir Ther ; 52(1): 7-11, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26909008

RESUMEN

BACKGROUND: Percutaneous tracheostomy is a common procedure in the intensive care unit and, on patient transfer to the wards, there is a gap in ongoing tracheostomy management. There is some evidence that tracheostomy teams can shorten weaning to decannulation times. In response to lengthy weaning to decannulation times at Trillium Health Partners - Credit Valley Hospital site (Mississauga, Ontario), an interprofessional tracheostomy team, led by respiratory therapists and consisting of speech-language pathologists and intensive care physicians, was implemented. OBJECTIVE: To evaluate the interprofessional tracheostomy team and its impact on time from weaning off mechanical ventilation to decannulation; and time from weaning to speech-language pathology referral. METHODS: Performance metrics were collected retrospectively through chart review pre- and post-team implementation. The primary metrics evaluated were the time from weaning off mechanical ventilation to decannulation, and time to referral to speech-language pathology. RESULTS: Following implementation of the interprofessional tracheostomy team, there was no improvement in decannulation times or time from weaning to speech-language pathology referral. A significant improvement was noted in the average time to first tracheostomy tube change (36.2 days to 22.9 days; P=0.01) and average time to speech-language pathology referral following initial tracheostomy insertion (51.8 days to 26.3 days; P=0.01). CONCLUSION: An interprofessional tracheostomy team can improve the quality of tracheostomy care through earlier tracheostomy tube changes and swallowing assessment referrals. The lack of improved weaning to decannulation time was potentially due to poor adherence with established protocols as well as a change in mechanical ventilation practices. To validate the findings from this particular institution, a more rigorous quality improvement methodology should be considered in addition to strategies to improve protocol compliance.


HISTORIQUE: La trachéostomie percutanée est une intervention fréquente dans l'unité de soins intensifs. Au transfert des patients au service d'hospitalisation, la continuité de la prise en charge de la trachéostomie pose un problème. Selon certaines données, les équipes de trachéostomie peuvent réduire le temps accordé au sevrage avant la décanulation. En réponse au long temps accordé sevrage avant la décanulation du Credit Valley Hospital des Trillium Health Partners (Mississauga, Ontario), une équipe interprofessionnelle de trachéostomie, dirigée par des inhalothérapeutes et composée d'orthophonistes et d'intensivistes, a été formée. OBJECTIF: Évaluer l'équipe interprofessionnelle de trachéostomie et ses effets lors du temps accordé entre le sevrage de la ventilation mécanique et la décanulation ainsi que sur le temps accordé entre le sevrage et l'orientation vers l'orthophonie. MÉTHODOLOGIE: Les chercheurs ont recueilli rétrospectivement les mesures de performance par une analyse des dossiers avant et après la formation de l'équipe. Les mesures primaires évaluées étaient le temps accordé entre le sevrage de la ventilation mécanique et la décanulation, et le temps accordé avant l'orientation vers un l'orthophonie. RÉSULTATS: Après la formation de l'équipe interprofessionnelle de trachéostomie, il n'y avait pas de réduction du temps accordé avant la décanulation ou l'orientation vers l'orthophonie. Le temps accordé, en moyenne, avant le premier changement de canule de trachéostomie a considérablement diminué (passant de 36,2 jours à 22,9 jours; P=0,01), de même que le temps accordé, en moyenne, avant l'orientation vers une orthophonie après l'insertion de la première trachéostomie (passant de 51,8 jours à 26,3 jours; P=0,01). CONCLUSION: Une équipe interprofessionnelle de trachéostomie peut améliorer la qualité des soins de trachéostomie grâce au changement plus rapide de la canule de trachéostomie et à l'orientation vers une évaluation de la déglutition. L'absence de réduction du temps accordé entre le sevrage et la décanulation pouvait être causée par une mauvaise compliance aux protocoles établis et à un changement aux pratiques de ventilation mécanique. Pour valider les observations provenant de cet établissement, il faudrait envisager une méthodologie d'amélioration de la qualité plus rigoureuse en plus de stratégies pour améliorer la compliance au protocole.

6.
MMWR Morb Mortal Wkly Rep ; 64(39): 1121-2, 2015 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-26447715

RESUMEN

On April 2, 2015, four patients were evaluated at the University of Mississippi Medical Center (UMMC) in Jackson, Mississippi, for agitated delirium after using synthetic cannabinoids. Over the next 3 days, 24 additional persons went to UMMC with illnesses suspected to be related to synthetic cannabinoid use; one patient died. UMMC notified the Mississippi State Department of Health, which issued a statewide alert via the Health Alert Network on April 5, requesting that health care providers report suspected cases of synthetic cannabinoid intoxication to the Mississippi Poison Control Center (MPCC). A suspected case was defined as the occurrence of at least two of the following symptoms: sweating, severe agitation, or psychosis in a person with known or suspected synthetic cannabinoid use. A second statewide alert was issued on April 13, instructing all Mississippi emergency departments to submit line lists of suspected patients to MPCC each day. By April 21, 16 days after the first alert was issued, MPCC had received reports of approximately 400 cases, including eight deaths possibly linked to synthetic cannabinoid use; in contrast, during April 2012­March 2015, the median number of telephone calls to MPCC regarding synthetic cannabinoid use was one per month (range = 0­11). The Mississippi State Department of Health, with the assistance of CDC, initiated an investigation to better characterize the outbreak, identify risk factors associated with severe illness, and prevent additional illnesses and deaths.


Asunto(s)
Cannabinoides/envenenamiento , Drogas de Diseño/envenenamiento , Brotes de Enfermedades , Trastornos Relacionados con Sustancias/epidemiología , Centros Médicos Académicos , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mississippi/epidemiología , Centros de Control de Intoxicaciones , Índice de Severidad de la Enfermedad , Adulto Joven
7.
J Public Health Manag Pract ; 20(6): 632-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24253404

RESUMEN

CONTEXT: In 2008, a lightning strike caused a leak of tert-butyl mercaptan from its storage tank at the Gulf South Natural Gas Pumping Station in Prichard, Alabama. On July 27, 2012, the Alabama Department of Public Health requested Centers for Disease Control and Prevention epidemiologic assistance investigating possible health effects resulting from airborne exposure to mercaptan from a contaminated groundwater spring, identified in January 2012. OBJECTIVE: To assess the self-reported health effects in the community, to determine the scope of the reported medical services received, and to develop recommendations for prevention and response to future incidents. DESIGN: In September 2012, we performed a representative random sampling design survey of households, comparing reported exposures and health effects among residents living in 2 circular zones located within 1 and 2 miles from the contaminated source. SETTING: Eight Mile community, Prichard, Alabama. PARTICIPANTS: We selected 204 adult residents of each household (≥ 18 years) to speak for all household members. MAIN OUTCOME MEASURES: Self-reported mercaptan odor exposure, physical and mental health outcomes, and medical-seeking practices, comparing residents in the 1- and 2-mile zones. RESULTS: In the past 6 months, 97.9% of respondents in the 1-mile zone and 77.6% in the 2-mile zone reported mercaptan odors. Odor severity was greater in the 1-mile zone, in which significantly more subjects reported exposures aggravating their physical and mental health including shortness of breath, eye irritations, and agitated behavior. Overall, 36.5% sought medical care for odor-related symptoms. CONCLUSIONS: Long-term odorous mercaptan exposures were reportedly associated with physical and psychological health complaints. Communication messages should include strategies to minimize exposures and advise those with cardiorespiratory conditions to have medications readily available. Health care practitioners should be provided information on mercaptan health effects and approaches to prevent exacerbating existing chronic diseases.


Asunto(s)
Liberación de Peligros Químicos/estadística & datos numéricos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Salud Pública/estadística & datos numéricos , Compuestos de Sulfhidrilo/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alabama , Niño , Preescolar , Femenino , Encuestas Epidemiológicas , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Medición de Riesgo , Adulto Joven
8.
Front Mol Neurosci ; 17: 1341808, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38544523

RESUMEN

Introduction: Patients who suffer a traumatic brain injury (TBI) often experience chronic and sometimes debilitating sequelae. Recent reports have illustrated both acute and long-term dysbiosis of the gastrointestinal microbiome with significant alterations in composition and predicted functional consequences. Methods: Working with participants from past research, metagenomic stability of the TBI- associated fecal microbiome (FMB) was evaluated by custom qPCR array comparing a fecal sample from 2015 to one collected in 2020. Metatranscriptomics identified differently expressed bacterial genes and biochemical pathways in the TBI FMB. Microbiota that contributed the largest RNA amounts identified a set of core bacteria most responsible for functional consequences of the TBI FMB. Results: A remarkably stable FMB metagenome with significant similarity (two-tail Spearman nonparametric correlation p < 0.001) was observed between 2015 and 2020 fecal samples from subjects with TBI. Comparing the 2020 TBI FMB metagenome to FMBs from healthy controls confirmed and extended the dysbiotic genera and species. Abundance differences between average TBI and healthy FMBs revealed Bacteroides caccae, B. uniformis, Blautia spp., Collinsella spp., Dialister spp., and Ordoribacter spp. were significantly different. Functionally, the Parabacteroides genus contributed the highest percentage of RNA sequences in control FMBs followed by the Bacteroides genus as the second highest contributor. In the TBI FMB, the Corynebacterium genus contributed the most RNA followed by the Alistipes genus. Corynebacterium and Pseudomonas were distinct in the top 10 contributing genera in the TBI FMB while Parabacteroides and Ruminococcus were unique to the top 10 in controls. Comparing RNA profiles, TBI samples had ∼1.5 fold more expressed genes with almost 700 differently expressed genes (DEGs) mapped to over 100 bacterial species. Bioinformatic analysis associated DEGs with pathways led identifying 311 functions in the average TBI FMB profile and 264 in the controls. By average profile comparison, 30 pathways had significantly different abundance (p < 0.05, t-test) or were detected in >80% of the samples in only one of the cohorts (binary distinction). Discussion: Functional differences between TBI and healthy control FMBs included amino acid metabolism, energy and carbon source usage, fatty acid metabolism, bacterial cell wall component production and nucleic acid synthesis and processing pathways. Together these data shed light on the functional consequences of the dysbiotic TBI FMB decades after injury.

9.
Med Sci Educ ; 33(6): 1399-1403, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38188380

RESUMEN

Documentation of performance provides feedback to medical trainees on their progress and is required by Programs as a record for monitoring whether trainees are achieving expectations against accepted standards. Despite the importance of performance documentation and the focus on improving feedback delivery in medical education, there has been little written in the literature on documentation best practices. Documentation is an essential skill that cannot be learned solely by observation, as most is confidential. However, teaching documentation of learner performance is rarely discussed. This article describes the authors' experience in teaching the skill of effective documentation of trainee performance for the purpose of providing feedback, monitoring progress, and recording evaluations.

10.
Prehosp Disaster Med ; 27(6): 496-502, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23010443

RESUMEN

BACKGROUND: On April 20, 2010, the Deepwater Horizon drilling unit exploded off the coast of Louisiana, resulting in 11 deaths and the largest marine petroleum release in history. Previous oil spill disasters have been associated with negative mental health outcomes in affected communities. In response to requests from Mississippi and Alabama, potential mental health issues resulting from this event were identified by implementing a novel use of a Community Assessment for Public Health Emergency Response (CASPER) in the months immediately following the Gulf Coast oil spill. PURPOSE: This assessment was repeated one year later to determine long-term mental health needs and changes. METHODS: A two-stage sampling method was used to select households, and a questionnaire including the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System (BRFSS) questions was administered. Weighted cluster analysis was conducted, and BRFSS questions were compared to the most recent BRFSS reports and the 2010 results. RESULTS: In 2011, 8.8%-15.1% of individuals reported depressive symptoms compared to 15.4%-24.5% of individuals in 2010, with 13.2%-20.3% reporting symptoms consistent with an anxiety disorder compared to 21.4%-31.5% of individuals in 2010. Respondents reporting decreased income following the oil spill were more likely to report mental health symptoms compared to respondents reporting no change in income. CONCLUSIONS: Overall, mental health symptoms were higher in the three assessment areas compared to BRFSS reports, but lower than 2010 surveys. These results suggest that mental health services are still needed, particularly in households experiencing decreased income since the oil spill.


Asunto(s)
Servicios de Salud Mental/estadística & datos numéricos , Evaluación de Necesidades , Salud Pública , Alabama , Depresión/epidemiología , Estado de Salud , Humanos , Trastornos Mentales/epidemiología , Mississippi , Contaminación por Petróleo/efectos adversos , Vigilancia en Salud Pública , Estrés Psicológico/epidemiología
11.
Prehosp Disaster Med ; 27(5): 401-8, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22985680

RESUMEN

INTRODUCTION: Previous oil spills and disasters from other human-made events have shown that mental health effects to the affected population are widespread and can be significant. HYPOTHESIS/PROBLEM: There has been concern regarding the likelihood that existing public health surveillance was not capturing the mental health effects to the population affected by the Gulf Coast oil spill. The objectives of this study were to assess the mental health needs of coastal communities in the states of Alabama and Mississippi following the Deepwater Horizon oil spill. METHODS: A cluster sampling methodology was used to assess the mental health status of coastal residents in three counties in Alabama four months following the 2010 Deepwater Horizon oil spill, and in the Gulf Coast counties in Mississippi 5.5 months after the oil spill. RESULTS: A total of 469 residents of the selected areas were interviewed. Between 15.4 and 24.5% of the respondents reported depressive symptoms, with 21.4-31.5% reporting symptoms consistent with an anxiety disorder, and 16.3-22.8% reporting ≥14 mentally unhealthy days within the past 30 days. Overall, there were more negative quality of life indicators and negative social context outcomes than in the state's Behavioral Risk Factor Surveillance System (BRFSS) survey. Between 32.1% and 35.7% of all households reported decreased income since the oil spill, and 35.5-38.2% of all households reported having been exposed to oil. CONCLUSION: The proportion of respondents reporting negative mental health parameters in the affected Alabama and Mississippi coastal communities is higher than the proportion reported in the 2008 and 2009 BRFSS state reports, suggesting that the public health response to the Deepwater Horizon oil spill should focus on mental health services in these communities.


Asunto(s)
Desastres , Salud Mental , Contaminación por Petróleo/efectos adversos , Vigilancia en Salud Pública/métodos , Alabama/epidemiología , Análisis por Conglomerados , Depresión/epidemiología , Femenino , Estado de Salud , Humanos , Entrevistas como Asunto , Masculino , Mississippi/epidemiología , Evaluación de Necesidades , Muestreo , Conducta Social , Apoyo Social , Factores Socioeconómicos , Estrés Psicológico/epidemiología
12.
Pulm Circ ; 12(1): e12003, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35506067

RESUMEN

Mortality in pulmonary arterial hypertension (PAH) remains high and referral to palliative or supportive care (P/SC) specialist services is recommended when appropriate. However, access to P/SC is frequently a challenge for patients with a noncancer diagnosis and few patients living with PAH report P/SC involvement in their care. A modified Delphi process of three questionnaires completed by a multidisciplinary panel (N = 15) was used to develop expert consensus statements regarding the use of P/SC to support patients with PAH. Panelists rated their agreement with each statement on a Likert scale. There was a strong consensus that patients should be referred to P/SC when disease symptoms become unmanageable or for end-of-life care. Services that achieved consensus were pain management techniques, end-of-life care, and psychosocial recommendations. Palliative or supportive care should be discussed with patients, preferably in-person, when disease symptoms become unmanageable, when starting treatment, when treatment-related adverse events occur or become refractory to initial intervention. Care partners and patient support groups were considered important in improving a patient's overall health outcomes, treatment adherence, and perception of care. Most patients with PAH experience cognitive and/or psychosocial changes and those who receive psychosocial management have better persistence and/or compliance with their treatment. These consensus statements provide guidance to healthcare providers on the "who and when" of referral to palliative care services, as well as the importance of focusing on the psychosocial aspects of patient care and quality of life.

13.
Methods Mol Biol ; 2302: 1-20, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33877619

RESUMEN

Rhomboid proteases are a ubiquitous superfamily of serine intramembrane peptidases that play a role in a wide variety of cellular processes. The mammalian mitochondrial rhomboid protease, Presenilin-Associated Rhomboid Like (PARL), is a critical regulator of mitochondrial homeostasis through the cleavage of its substrates, which have roles in mitochondrial quality control and apoptosis. However, neither structural nor functional information for this important protease is available, because the expression of eukaryotic membrane proteins to sufficient levels in an active form often represents a major bottleneck for in vitro studies. Here we present an optimized protocol for expression and purification of the human PARL protease using the eukaryotic expression host Pichia pastoris. The PARL gene construct was generated in tandem with green fluorescent protein (GFP), which allowed for the selection of high expressing clones and monitoring during the large-scale expression and purification steps. We discuss the production protocol with precise details for each step. The protocol yields 1 mg of pure PARL per liter of yeast culture.


Asunto(s)
Metaloproteasas/aislamiento & purificación , Proteínas Mitocondriales/aislamiento & purificación , Saccharomycetales/crecimiento & desarrollo , Expresión Génica , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Metaloproteasas/genética , Proteínas Mitocondriales/genética , Proteínas Recombinantes/aislamiento & purificación , Saccharomycetales/genética , Transformación Genética
14.
Pediatrics ; 148(3)2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34452981

RESUMEN

OBJECTIVES: To determine if the Integrated Community-Based Health Systems-Strengthening (ICBHSS) initiative was effective in expanding health coverage, improving care quality, and reducing child mortality in Togo. METHODS: Population-representative cross-sectional household surveys adapted from the Demographic Household Survey and Multiple Indicator Cluster Surveys were conducted at baseline (2015) and then annually (2016-2020) in 4 ICBHSS catchment sites in Kara, Togo. The primary outcome was under-5 mortality, with health service coverage and health-seeking behavior as secondary outcomes. Costing analyses were calculated by using "top-down" methodology with audited financial statements and programmatic data. RESULTS: There were 10 022 household surveys completed from 2015 to 2020. At baseline (2015), under-5 mortality was 51.1 per 1000 live births (95% confidence interval [CI]: 35.5-66.8), and at the study end period (2020), under-5 mortality was 35.8 (95% CI: 23.4-48.2). From 2015 to 2020, home-based treatment by a community health worker increased from 24.1% (95% CI: 21.9%-26.4%) to 45.7% (95% CI: 43.3%-48.2%), and respondents reporting prenatal care in the first trimester likewise increased (37.5% to 50.1%). Among respondents who sought care for a child with fever, presenting for care within 1 day increased from 51.9% (95% CI: 47.1%-56.6%) in 2015 to 80.3% (95% CI: 74.6%-85.0%) in 2020. The estimated annual additional intervention cost was $8.84 per person. CONCLUSIONS: Our findings suggest that the ICBHSS initiative, a bundle of evidence-based interventions implemented with a community-based strategy, improves care access and quality and was associated with reduction in child mortality.


Asunto(s)
Servicios de Salud del Niño/organización & administración , Atención Primaria de Salud/organización & administración , Adolescente , Adulto , Mortalidad del Niño , Preescolar , Agentes Comunitarios de Salud , Estudios Transversales , Femenino , Accesibilidad a los Servicios de Salud , Encuestas Epidemiológicas , Humanos , Persona de Mediana Edad , Aceptación de la Atención de Salud/estadística & datos numéricos , Atención Prenatal , Calidad de la Atención de Salud , Togo , Adulto Joven
15.
BMJ Glob Health ; 6(12)2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34876458

RESUMEN

INTRODUCTION: Despite ongoing maternal health interventions, maternal deaths in Tanzania remain high. One of the main causes of maternal mortality includes postoperative infections. Surgical site infection (SSI) rates are higher in low/middle-income countries (LMICs), such as Tanzania, compared with high-income countries. We evaluated the impact of a multicomponent safe surgery intervention in Tanzania, hypothesising it would (1) increase adherence to safety practices, such as the WHO Surgical Safety Checklist (SSC), (2) reduce SSI rates following caesarean section (CS) and (3) reduce CS-related perioperative mortality rates (POMRs). METHODS: We conducted a pre-cross-sectional/post-cross-sectional study design to evaluate WHO SSC utilisation, SSI rates and CS-related POMR before and 18 months after implementation. Our interventions included training of inter-professional surgical teams, promoting use of the WHO SSC and introducing an infection prevention (IP) bundle for all CS patients. We assessed use of WHO SSC and SSI rates through random sampling of 279 individual CS patient files. We reviewed registers and ward round reports to obtain the number of CS performed and CS-related deaths. We compared proportions of individuals with a characteristic of interest during pre-implementation and post implementation using the two-proportion z-test at p≤0.05 using STATA V.15. RESULTS: The SSC utilisation rate for CS increased from 3.7% (5 out of 136) to 95.1% (136 out of 143) with p<0.001. Likewise, the proportion of women with SSI after CS reduced from 14% during baseline to 1% (p=0.002). The change in SSI rate after the implementation of the safe surgery interventions is statistically significant (p<0.001). The CS-related POMR decreased by 38.5% (p=0.6) after the implementation of safe surgery interventions. CONCLUSION: Our findings show that our intervention led to improved utilisation of the WHO SSC, reduced SSIs and a drop in CS-related POMR. We recommend replication of the interventions in other LMICs.


Asunto(s)
Cesárea , Infección de la Herida Quirúrgica , Cesárea/efectos adversos , Estudios Transversales , Femenino , Humanos , Mortalidad Materna , Embarazo , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control , Tanzanía/epidemiología
16.
J Neurotrauma ; 37(8): 1037-1051, 2020 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-31868094

RESUMEN

Patients with chronic traumatic brain injury (TBI) requiring long-term, permanent care suffer a myriad of clinical symptoms (i.e., impaired cognition, fatigue, and other conditions) that persist for years beyond the acute brain injury. In addition to these comorbid clinical symptoms, chronic TBI patients exhibit altered amino acid and hormonal profiles with distinct cytokine patterns suggesting chronic inflammation. This metabolic link suggests a role of the gut-brain axis in chronic TBI. Thus, we utilized a two-site trial to investigate the role of the gut-brain axis in comorbidities of chronic TBI. The fecal microbiome profile of 22 moderate/severe TBI patients residing in permanent care facilities in Texas and California was compared to 18 healthy age-matched control subjects working within the participating facilities. Each fecal microbiome was characterized by 16S(V4) ribosomal RNA (rRNA) gene sequencing and metagenomic genome sequencing approaches followed by confirmatory full 16S rRNA gene sequencing or focused tuf gene speciation and specific quantitative polymerase chain reaction evaluation of selected genera or species. The average chronic TBI patient fecal microbiome structure was significantly different compared to the control cohort, and these differences persisted after group stratification analysis to identify any unexpected confounders. Notably, the fecal microbiome of the chronic TBI cohort had absent or reduced Prevotella spp. and Bacteroidies spp. Conversely, bacteria in the Ruminococcaceae family were higher in abundance in TBI compared to control profiles. Previously reported hypoaminoacidemia, including significantly reduced levels of l-tryptophan, l-sarcosine, ß-alanine, and alanine, positively correlated with the reduced levels of Prevotella spp. in the TBI cohort samples compared to controls. Although the sequelae of gut-brain axis disruption after TBI is not fully understood, characterizing TBI-related alterations in the fecal microbiome may provide biomarkers and therapeutic targets to address patient morbidity.


Asunto(s)
Lesiones Traumáticas del Encéfalo/microbiología , Microbioma Gastrointestinal/fisiología , Adulto , Anciano , Bacterias/genética , Bacterias/metabolismo , Heces/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo , Adulto Joven
17.
Clin Toxicol (Phila) ; 57(1): 10-18, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29989463

RESUMEN

STUDY OBJECTIVES: In April 2015, a multistate outbreak of illness linked to synthetic cannabinoid (SC) use was unprecedented in magnitude and severity. We identified Mississippi cases in near-real time, collected information on cases to characterize the outbreak, and identified the causative SC. METHODS: A case was defined as any patient of a Mississippi healthcare facility who was suspected of SC use and presenting with ≥2 of the following symptoms: sweating, severe agitation, or psychosis during April 2-May 3, 2015. Clinicians reported cases to the Mississippi Poison Control Center (MPCC). We used MPCC data to identify cases at the University of Mississippi Medical Center (UMMC) to characterize in further detail, including demographics and clinical findings. Biologic samples were tested for known and unknown SCs by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). RESULTS: Clinicians reported 721 cases (11 deaths) statewide; 119 (17%) were UMMC patients with detailed data for further analysis. Twelve (10%) were admitted to an intensive care unit and 2 (2%) died. Aggression (32%), hypertension (33%), and tachycardia (42%) were common. SCs were identified in serum from 39/56 patients (70%); 33/39 patients (85%) tested positive for MAB-CHMINACA (N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide) or its metabolites. Compared to all patients tested for SCs, those positive for MAB-CHMINACA were more likely to have altered mental status on examination (OR = 3.3, p = .05). CONCLUSION: SC use can cause severe health effects. MAB-CHMINACA was the most commonly detected SC in this outbreak. As new SCs are created, new strategies to optimize surveillance and patient care are needed to address this evolving public health threat.


Asunto(s)
Cannabinoides/toxicidad , Drogas Ilícitas/toxicidad , Trastornos Relacionados con Sustancias/epidemiología , Drogas Sintéticas/toxicidad , Adolescente , Adulto , Centers for Disease Control and Prevention, U.S. , Brotes de Enfermedades , Femenino , Humanos , Masculino , Persona de Mediana Edad , Centros de Control de Intoxicaciones/estadística & datos numéricos , Salud Pública , Estados Unidos , Adulto Joven
18.
N Engl J Med ; 352(14): 1436-44, 2005 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-15814879

RESUMEN

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection has emerged in patients who do not have the established risk factors. The national burden and clinical effect of this novel presentation of MRSA disease are unclear. METHODS: We evaluated MRSA infections in patients identified from population-based surveillance in Baltimore and Atlanta and from hospital-laboratory-based sentinel surveillance of 12 hospitals in Minnesota. Information was obtained by interviewing patients and by reviewing their medical records. Infections were classified as community-associated [correction] MRSA disease if no established risk factors were identified. RESULTS: From 2001 through 2002, 1647 cases of community-associated [correction] MRSA infection were reported, representing between 8 and 20 percent of all MRSA isolates. The annual disease incidence varied according to site (25.7 cases per 100,000 population in Atlanta vs. 18.0 per 100,000 in Baltimore) and was significantly higher among persons less than two years old than among those who were two years of age or older (relative risk, 1.51; 95 percent confidence interval, 1.19 to 1.92) and among blacks than among whites in Atlanta (age-adjusted relative risk, 2.74; 95 percent confidence interval, 2.44 to 3.07). Six percent of cases were invasive, and 77 percent involved skin and soft tissue. The infecting strain of MRSA was often (73 percent) resistant to prescribed antimicrobial agents. Among patients with skin or soft-tissue infections, therapy to which the infecting strain was resistant did not appear to be associated with adverse patient-reported outcomes. Overall, 23 percent of patients were hospitalized for the MRSA infection. CONCLUSIONS: Community-associated MRSA infections are now a common and serious problem. These infections usually involve the skin, especially among children, and hospitalization is common.


Asunto(s)
Resistencia a la Meticilina , Infecciones Estafilocócicas/epidemiología , Staphylococcus aureus , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Baltimore/epidemiología , Población Negra , Niño , Preescolar , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/terapia , Drenaje , Enfermedades Endémicas/estadística & datos numéricos , Georgia/epidemiología , Humanos , Incidencia , Lactante , Persona de Mediana Edad , Minnesota/epidemiología , Vigilancia de la Población , Factores de Riesgo , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/terapia , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Población Blanca
19.
Public Health Rep ; 133(2_suppl): 43S-51S, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30457951

RESUMEN

OBJECTIVES: Tennessee was 1 of 8 states that received funding from the Care and Prevention in the United States Demonstration Project, which aimed to reduce HIV-related morbidity and mortality among racial/ethnic and sexual minority populations. The objective of this study was to describe implementation of a social network strategy (SNS) program, which leverages personal connections in social networks, to reach people with undiagnosed HIV infection for HIV testing. We targeted young black men who have sex with men (MSM) at 3 agencies in Memphis and Nashville, Tennessee, during 2013-2016. METHODS: Specialists at the 3 agencies identified MSM with and without diagnosed HIV infection (ie, recruiters) who could recruit members from their social networks for HIV testing (ie, network associates). Both recruiters and network associates received OraQuick rapid and confirmatory HIV tests. We used χ2 and Fisher exact tests to assess differences in demographic characteristics, HIV testing, and care engagement status by agency. RESULTS: Of 1752 people who were tested for HIV in the SNS program, 158 (9.0%) tested positive; of these, 80 (50.6%) were newly diagnosed with HIV. Forty-seven of the 78 (60.3%) people who were previously diagnosed with HIV were not in care in the previous 12 months; of these, 27 (57.4%) were reengaged in medical care. Of 80 people newly diagnosed with HIV, 44 (55.0%) were linked to care. CONCLUSIONS: The SNS program ascertained HIV status among a high-risk population in a heavily burdened region. Further program evaluation is needed to understand how to improve linkage to care among people with newly diagnosed HIV.


Asunto(s)
Negro o Afroamericano , Infecciones por VIH/diagnóstico , Homosexualidad Masculina , Tamizaje Masivo/organización & administración , Red Social , Adolescente , Adulto , Anciano , Humanos , Masculino , Tamizaje Masivo/economía , Persona de Mediana Edad , Selección de Paciente , Evaluación de Programas y Proyectos de Salud , Factores de Riesgo , Factores Socioeconómicos , Tennessee , Estados Unidos , Adulto Joven
20.
Public Health Rep ; 133(2_suppl): 60S-74S, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30457958

RESUMEN

OBJECTIVES: The Care and Prevention in the United States Demonstration Project included implementation of a Data to Care strategy using surveillance and other data to (1) identify people with HIV infection in need of HIV medical care or other services and (2) facilitate linkages to those services to improve health outcomes. We present the experiences of 4 state health departments: Illinois, Louisiana, Tennessee, and Virginia. METHODS: The 4 state health departments used multiple databases to generate listings of people with diagnosed HIV infection (PWH) who were presumed not to be in HIV medical care or who had difficulty maintaining viral suppression from October 1, 2013, through September 29, 2016. Each health department prioritized the listings (eg, by length of time not in care, by viral load), reviewed them for accuracy, and then disseminated the listings to staff members to link PWH to HIV care and services. RESULTS: Of 16 391 PWH presumed not to be in HIV medical care, 9852 (60.1%) were selected for follow-up; of those, 4164 (42.3%) were contacted, and of those, 1479 (35.5%) were confirmed to be not in care. Of 794 (53.7%) PWH who accepted services, 694 (87.4%) were linked to HIV medical care. The Louisiana Department of Health also identified 1559 PWH as not virally suppressed, 764 (49.0%) of whom were eligible for follow-up. Of the 764 PWH who were eligible for follow-up, 434 (56.8%) were contacted, of whom 269 (62.0%) had treatment adherence issues. Of 153 PWH who received treatment adherence services, 104 (68.0%) showed substantial improvement in viral suppression. CONCLUSIONS: The 4 health departments established procedures for using surveillance and other data to improve linkage to HIV medical care and health outcomes for PWH. To be effective, health departments had to enhance coordination among surveillance, care programs, and providers; develop mechanisms to share data; and address limitations in data systems and data quality.


Asunto(s)
Infecciones por VIH/terapia , Accesibilidad a los Servicios de Salud/organización & administración , Aceptación de la Atención de Salud , Administración en Salud Pública , Vigilancia en Salud Pública/métodos , Humanos , Estados Unidos
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