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1.
Immunol Rev ; 305(1): 152-164, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34820863

RESUMEN

Micronutrients are essential small molecules required by organisms in minute quantity for survival. For instance, vitamins and minerals, the two major categories of micronutrients, are central for biological processes such as metabolism, cell replication, differentiation, and immune response. Studies estimated that around two billion humans worldwide suffer from micronutrient deficiencies, also known as "hidden hunger," linked to weakened immune responses. While micronutrients affect the immune system at multiple levels, recent studies showed that micronutrients potentially impact the differentiation and function of immune cells as cofactors for epigenetic enzymes, including the 2-oxoglutarate-dependent dioxygenase (2OGDD) family involved in histone and DNA demethylation. Here, we will first provide an overview of the role of DNA methylation in T cells and B cells, followed by the micronutrients ascorbate (vitamin C) and iron, two critical cofactors for 2OGDD. We will discuss the emerging evidence of these micronutrients could regulate adaptive immune response by influencing epigenetic remodeling.


Asunto(s)
Epigénesis Genética , Micronutrientes , Humanos , Inmunidad/genética , Micronutrientes/metabolismo , Minerales/metabolismo , Vitaminas
2.
Am J Addict ; 32(5): 433-441, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37551638

RESUMEN

BACKGROUND AND OBJECTIVES: Alcohol use disorder (AUD) is a significant public health concern, with underutilized effective treatments, particularly in special populations. This article summarizes the current evidence and guidelines for treating AUD in special populations. METHODS: This article is a literature review that synthesizes the latest research on AUD treatment for special populations. We screened 242 articles and included 57 in our final review. RESULTS: There are four food and Drug Administration-approved medications for AUD (MAUD): disulfiram, oral naltrexone, extended-release injectable naltrexone (XR-NTX), and acamprosate. Naltrexone and disulfiram have the potential to cause liver toxicity, and acamprosate should be avoided in patients with severe kidney disease. Psychosocial treatments should be considered first-line for pregnant and nursing patients. Naltrexone is contraindicated in patients on opioids, as it may precipitate acute withdrawal. For patients experiencing homelessness, nonabstinent treatment goals may be more practical, and XR-NTX should be considered to improve adherence. Limited evidence suggests medication can improve AUD treatment outcomes in adolescents and young adults. For patients with poor treatment response despite adequate medication adherence, switching to a different medication and augmentation with psychosocial treatments should be considered. DISCUSSION AND CONCLUSIONS: Understanding the unique considerations for special populations with AUD is crucial, and addressing their special needs may improve their treatment outcomes. SCIENTIFIC SIGNIFICANCE: Our study significantly contributes to the existing literature by summarizing crucial information for the treatment of AUD in special populations, highlighting distinct challenges, and emphasizing tailored approaches to improve overall health and well-being.


Asunto(s)
Alcoholismo , Humanos , Adolescente , Alcoholismo/tratamiento farmacológico , Naltrexona/uso terapéutico , Acamprosato/uso terapéutico , Disulfiram/efectos adversos , Analgésicos Opioides/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico
3.
Camb Q Healthc Ethics ; 31(4): 482-486, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36398513

RESUMEN

Substantial advancement in the diagnosis and treatment of psychiatric disorders may come from assembling diverse data streams from clinical notes, neuroimaging, genetics, and real-time digital footprints from smartphones and wearable devices. This is called "deep phenotyping" and often involves machine learning. We argue that incidental findings arising in deep phenotyping research have certain special, morally and legally salient features: They are specific, actionable, numerous, and probabilistic. We consider ethical and legal implications of these features and propose a practical ethics strategy for managing them.


Asunto(s)
Trastornos Mentales , Psiquiatría , Humanos , Hallazgos Incidentales , Principios Morales , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Neuroimagen
4.
Emerg Radiol ; 28(3): 557-563, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33428045

RESUMEN

PURPOSE: This study evaluates clinical and laboratory parameters, as well as extravasation and hematoma size on CTA as potential predictors of conventional angiogram (CA) results. METHODS: This is a retrospective study of 380 adult patients presenting with pelvic trauma over a 9-year period. Of these patients, 91 were found to have active arterial extravasation on initial CTA. Statistical analysis between the two groups +CA versus -CA was performed to determine whether clinical and laboratory parameters, as well as extravasation size and hematoma size could predict CA results. RESULTS: There were no significant differences in all clinical and laboratory data, including hemodynamic instability (defined as systolic blood pressure < 90 mmHg) on presentation (22.2% vs. 21.4%), except for Glasgow Coma Scale (p = 0.015) when comparing the two groups. Extravasation size and hematoma size as continuous or categorical variables were not predictive of subsequent positive CA. Secondary analysis demonstrated no association between select parameters (i.e., hematocrit, systolic blood pressure, and lactate) and subsequent positive CA while controlling for extravasation size or hematoma size. CONCLUSION: Clinical and laboratory parameters in blunt pelvic trauma with arterial hemorrhage were not significantly associated with subsequent conventional angiography results, once accounting for degree of hemorrhage. The area of the foci of active extravasation and hematoma size in the axial plane were not significantly associated with the need for embolization. We conclude from these findings that catheter angiography should be considered in patients with blunt pelvic trauma found to have active arterial extravasation, regardless of size of bleed or the patient's clinical or laboratory values.


Asunto(s)
Fracturas Óseas , Huesos Pélvicos , Adulto , Angiografía , Humanos , Laboratorios , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
5.
J Prosthodont ; 28(4): 436-443, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30737975

RESUMEN

PURPOSE: To study the effects of altering condylar settings and pin openings on the trueness and precision of virtual articulators vs. mechanical articulators. MATERIALS AND METHODS: Maxillary and mandibular typodonts with fiducial markers were mounted on a mechanical Artex-CR articulator, and the mandibular teeth were prepared to allow guidance solely by the posterior determinants of the articulator and the incisal table. The relationship of the mounted typodonts was preserved digitally by scanning using manufacturer transfer plate adaptors. On the mechanical articulator, pattern resin was allowed to set between the maxillary and mandibular occlusal surfaces (area #25-30) at the endpoints of dynamic movements at 3 condylar inclinations (SCI): 10°, 30°, and 45°, n = 12/inclination, or at 3 incisal pin openings (2, 5, and 10 mm, n = 12/opening). All other articulator settings were kept constant. Resin specimens attached to the typodonts were scanned within 5 minutes of setting, then removed, and the articulated typodonts rescanned. Fixed dental prostheses (FDPs) #25-30 were designed on the virtual articulator using identical parameters to the mechanical articulator. Dynamic virtual movements were used to sculpt the design, and a file of the design was saved. The files of both types of samples were aligned and overlaid. Interocclusal separation was measured in triplicate at the indentation created by the mesiolabioincisal point angle on the incisal edge of #8 and the mesiobucco-occlusal point angle of #3. Trueness and precision of both types of articulators were calculated and compared using one-way ANOVA, followed by the Tukey HSD test (α = 0.05). RESULTS: There was no statistically significant difference at altered pin openings in either trueness (F = 0.202, p = 0.37) or precision (F = 3.134, p = 0.09) for the majority of measurements. The only significant difference was in the precision between the 2 types of articulators at 5 mm incisal opening, and only at the anterior measurement point (F = 15.134, p = 0.0008); however, these differences were less than 100 µm. When the SCI was altered, there was no statistically significant difference (F = 3.624, p > 0.05) between the virtual and mechanical articulators in trueness for 5 of the 6 measurements obtained (F = 3.624, p = 0.07) or for all of the precision measurements (F = 3.529, p = 0.07). The one trueness measurement that was significantly different (F = 9.237, p = 0.006) occured at SCI of 10°, and it was less than 100 µm. CONCLUSIONS: Dynamic movements on the virtual articulator were shown to be as true and precise as to the mechanical articulator. When there were deviations, these deviations were less than 100 µm and thus, these deviations may not be clinically relevant.


Asunto(s)
Articuladores Dentales , Diente , Registro de la Relación Maxilomandibular , Mandíbula , Maxilar
6.
Brain Inj ; 32(13-14): 1725-1730, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30230916

RESUMEN

OBJECTIVES: The purpose of this study was to assess whether study population definition influences the effect of age on outcomes after blunt head trauma. We hypothesized that examining 'all comers' receiving head computerized tomography after blunt head trauma, fewer older individuals would meet Veterans Administration and Department of Defense (VA/DoD) criteria for traumatic brain injury (TBI), and would, therefore, display better outcomes than younger cohorts. However, restricting to participants meeting VA/DoD criteria for TBI, we hypothesized that older individuals would have worse outcomes. METHODS: Data from a recently completed prospective cohort study were analysed with age dichotomized at 65 years. Logistic regression modelling, controlled for potential confounders including head trauma severity, was estimated to measure the effect of age on functional recovery, post-concussion symptoms (PCS), and depressive symptoms at 1-month post-TBI. RESULTS: Fewer older than younger individuals met VA/DoD criteria for TBI. Older individuals had better functional, PCS, and depressive outcomes at 1 month. Restricting to those meeting VA/DoD criteria for TBI, older individuals continued to have better functional and PCS outcomes but had outcomes comparable to younger on depressive symptoms. CONCLUSIONS: Contrary to our hypothesis, there was a tendency for older adults to have better outcomes than younger, independent of the diagnostic criteria applied.


Asunto(s)
Factores de Edad , Lesiones Traumáticas del Encéfalo/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico , Estudios de Cohortes , Depresión/etiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Tomógrafos Computarizados por Rayos X , Índices de Gravedad del Trauma , Estados Unidos/epidemiología , United States Department of Defense , United States Department of Veterans Affairs
9.
Crit Care Med ; 44(12): 2182-2191, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27513358

RESUMEN

OBJECTIVE: The Lung Injury Prediction Score identifies patients at risk for acute respiratory distress syndrome in the emergency department, but it has not been validated in non-emergency department hospitalized patients. We aimed to evaluate whether Lung Injury Prediction Score identifies non-emergency department hospitalized patients at risk of developing acute respiratory distress syndrome at the time of critical care contact. DESIGN: Retrospective study. SETTING: Five academic medical centers. PATIENTS: Nine hundred consecutive patients (≥ 18 yr old) with at least one acute respiratory distress syndrome risk factor at the time of critical care contact. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Lung Injury Prediction Score was calculated using the worst values within the 12 hours before initial critical care contact. Patients with acute respiratory distress syndrome at the time of initial contact were excluded. Acute respiratory distress syndrome developed in 124 patients (13.7%) a median of 2 days (interquartile range, 2-3) after critical care contact. Hospital mortality was 22% and was significantly higher in acute respiratory distress syndrome than non-acute respiratory distress syndrome patients (48% vs 18%; p < 0.001). Increasing Lung Injury Prediction Score was significantly associated with development of acute respiratory distress syndrome (odds ratio, 1.31; 95% CI, 1.21-1.42) and the composite outcome of acute respiratory distress syndrome or death (odds ratio, 1.26; 95% CI, 1.18-1.34). A Lung Injury Prediction Score greater than or equal to 4 was associated with the development of acute respiratory distress syndrome (odds ratio, 4.17; 95% CI, 2.26-7.72), composite outcome of acute respiratory distress syndrome or death (odds ratio, 2.43; 95% CI, 1.68-3.49), and acute respiratory distress syndrome after accounting for the competing risk of death (hazard ratio, 3.71; 95% CI, 2.05-6.72). For acute respiratory distress syndrome development, the Lung Injury Prediction Score has an area under the receiver operating characteristic curve of 0.70 and a Lung Injury Prediction Score greater than or equal to 4 has 90% sensitivity (misses only 10% of acute respiratory distress syndrome cases), 31% specificity, 17% positive predictive value, and 95% negative predictive value. CONCLUSIONS: In a cohort of non-emergency department hospitalized patients, the Lung Injury Prediction Score and Lung Injury Prediction Score greater than or equal to 4 can identify patients at increased risk of acute respiratory distress syndrome and/or death at the time of critical care contact but it does not perform as well as in the original emergency department cohort.


Asunto(s)
Lesión Pulmonar/diagnóstico , Síndrome de Dificultad Respiratoria/diagnóstico , Índice de Severidad de la Enfermedad , Anciano , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Síndrome de Dificultad Respiratoria/etiología , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad
10.
J Vasc Interv Radiol ; 27(6): 905-12, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27103145

RESUMEN

PURPOSE: To characterize thermal changes induced by rheolytic thrombectomy (RT) within an ex vivo venous model and evaluate resultant changes of endothelial and vessel wall injury. MATERIALS AND METHODS: Patent human saphenous vein segments without thrombus were mounted in an ex vivo perfusion system with a temperature probe apposed to the adventitial surface. RT was performed over a guide wire to facilitate device centering. Continuous RT was performed for 4 minutes with temperature recorded every 10 seconds. Pulsed RT was performed for eight cycles of 30 seconds followed by 10 seconds of deactivation. Mean temperature increase, maximum temperature (Tmax), intimal/medial thickness, endothelial cell staining (CD31), and heat shock protein 90 (HSP90) expression were compared between untreated and RT-treated venous segments. RESULTS: Continuous RT produced a mean 7.6°C increase in temperature above baseline with mean Tmax of 44.1°C. Pulsed RT produced a mean 7.3°C increase in temperature and mean Tmax of 43.8°C. Differences in mean temperature increase (P = .66) and Tmax (P = .71) between the two groups were not statistically significant. RT-treated segments showed intima/media thinning (0.32 mm before RT and 0.18 mm after RT; P = .004) and reduction in intact endothelium (38.8% before RT and 13.8% after RT; P = .002). Staining for HSP90 showed a 3.1% increase in expression after RT (P = .31). CONCLUSIONS: RT in this venous model showed reproducible increases in vessel temperature and evidence of endothelial and vessel wall injury. Avoiding prolonged RT application to a focal vascular segment during clinical use may be beneficial.


Asunto(s)
Endotelio Vascular/cirugía , Vena Safena/cirugía , Temperatura , Trombectomía/métodos , Endotelio Vascular/lesiones , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Técnicas In Vitro , Perfusión , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Vena Safena/lesiones , Vena Safena/metabolismo , Vena Safena/patología , Trombectomía/efectos adversos , Factores de Tiempo , Lesiones del Sistema Vascular/etiología , Lesiones del Sistema Vascular/metabolismo , Lesiones del Sistema Vascular/patología
11.
Muscle Nerve ; 51(2): 268-75, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24895229

RESUMEN

INTRODUCTION: A device has been developed to apply freezing temperatures to temporarily impede nerve conduction, resulting in inhibition of voluntary skeletal muscle contraction. This device was designed as an alternative to the neurotoxins usually used to treat movement disorders. METHODS: We evaluated the effects of single and 3 repeat treatments with a cryoprobe device (-55°C) on a sciatic nerve rat model. Long-term effects of repeated treatment were evaluated through assessments of physiological function and histological analysis. RESULTS: There was consistent weakening of physiological function after each treatment, with recovery of normal function by 8 weeks posttreatment. Histological findings showed axonal degeneration with no disruption to the epineurial or perineurial structures. Progressive axonal regeneration was followed by normal recovery by 24 weeks post-treatment. CONCLUSIONS: Low-temperature treatment of motor nerves did not result in permanent or long-term changes to nerve function or structure.


Asunto(s)
Crioterapia/métodos , Recuperación de la Función/fisiología , Nervio Ciático/fisiopatología , Degeneración Walleriana/patología , Degeneración Walleriana/fisiopatología , Degeneración Walleriana/terapia , Animales , Modelos Animales de Enfermedad , Femenino , Estudios de Seguimiento , Lateralidad Funcional , Actividad Motora/fisiología , Ratas , Ratas Sprague-Dawley , Proteínas S100/metabolismo , Células de Schwann/metabolismo , Células de Schwann/patología , Factores de Tiempo
12.
J Vasc Interv Radiol ; 26(3): 366-71, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25638749

RESUMEN

PURPOSE: To determine the impact of the introduction of aerostatic sheaths on air embolism (AE) events during tunneled dialysis catheter (TDC) insertion and to characterize such events occurring during over-the-wire exchange (OTWE). MATERIALS AND METHODS: Between July 2001 and April 2013, 5,789 TDCs were placed, including 3,963 de novo placements, 1,811 OTWEs, and 15 tract recanalizations. There were 15 AE events reported, and the medical records of these patients were reviewed. The effect of aerostatic sheaths, introduced in July 2005, was compared with the period before their introduction; the same TDC design was used throughout. RESULTS: Of the 15 AE events, 10 occurred during de novo placement (10 of 3,963 placement; 0.25%), 4 occurred during OTWE (4 of 1,811 placements; 0.22%), and 1 occurred during tract recanalization. With regard to aerostatic sheaths in de novo TDC placement, 4 of 1,174 (0.34%) AE events occurred before aerostatic sheath introduction, and 6 of 2,789 (0.22%) AE events occurred after aerostatic sheath introduction. These rates did not differ statistically (P = .5). CONCLUSIONS: Use of aerostatic sheaths trended toward reducing AE events during de novo TDC placement. This trend was not statistically significant, probably owing to the rarity of AE despite the large sample size. Air embolism occurs during OTWE at a rate similar to de novo placement with aerostatic sheaths as well as during tract recanalization.


Asunto(s)
Cateterismo/estadística & datos numéricos , Catéteres de Permanencia/estadística & datos numéricos , Embolia Aérea/epidemiología , Embolia Aérea/prevención & control , Diálisis Renal/instrumentación , Diálisis Renal/estadística & datos numéricos , Adulto , Anciano , Cateterismo/efectos adversos , Catéteres de Permanencia/efectos adversos , Remoción de Dispositivos/efectos adversos , Remoción de Dispositivos/estadística & datos numéricos , Embolia Aérea/etiología , Análisis de Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pennsylvania/epidemiología , Prevalencia , Diseño de Prótesis , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
13.
Dermatol Surg ; 41(2): 232-41, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25654195

RESUMEN

BACKGROUND: Approximately 25% of patients exploring treatments for wrinkle reduction, have reservations about toxins. Therefore, a nonsurgical, minimally invasive, and toxin-free approach to eliminate facial hyperdynamic lines is desirable. OBJECTIVE: To assess the clinical safety and effectiveness of focused cold therapy (FCT) for the reduction of hyperdynamic forehead wrinkles. METHODS: Forty-one subjects received FCT to temporal branches of the facial nerve. Hyperdynamic forehead wrinkles were assessed by the investigator and subject before treatment, immediately after procedure, and at 7, 30, 60, 90, and 120 days after treatment. A validated 5-point wrinkle scale and a 9-point global improvement scale were used to measure line severity. RESULTS: Five subjects received a lower treatment dose and were therefore excluded from analysis. In the remaining 36 subjects, 91% had at least a 1-point improvement in forehead line severity at 30 days after treatment and 70% had at least a 2-point improvement. There were no serious adverse events. CONCLUSION: Subjects treated for forehead wrinkles showed significant clinical improvement with high subject satisfaction and no serious adverse events. Focused cold therapy seems to be an effective, safe nontoxic alternative to popular wrinkle-reducing treatments.


Asunto(s)
Crioterapia/métodos , Frente , Envejecimiento de la Piel , Adulto , Anciano , Contusiones/etiología , Crioterapia/efectos adversos , Edema/etiología , Traumatismos del Nervio Facial/etiología , Femenino , Humanos , Persona de Mediana Edad , Dolor/etiología , Satisfacción del Paciente , Estudios Prospectivos , Lóbulo Temporal , Resultado del Tratamiento
14.
J Neural Transm (Vienna) ; 121(1): 15-20, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23917804

RESUMEN

Application of freezing temperatures to the temporal branch of the facial nerve can temporarily inhibit motor nerve conduction, resulting in inhibition of voluntary contraction of the frontalis and glabella muscle groups. This feasibility study demonstrates the reduction in motility of muscle groups through application of low temperatures to nerves in a rat model. Twenty-seven adult female Sprague-Dawley rats received cryotreatment to the tibial nerve of the hind limb, and the contralateral limb was left untreated as a negative control. The use of a cold temperature application (-59 ± 8 °C for 60 s) onto the rat tibial nerve resulted in temporary reduction of physiological function of the hind limb. Histological observations of the nerve revealed demyelination and axonal degeneration by 2 weeks post-treatment followed by complete axonal regeneration and remyelination at 16 weeks. Application of low temperatures to peripheral motor nerves resulted in temporary denervation and loss of function of the treated hind limb. Low temperature treatment on motor nerves did not result in any permanent or long-term changes to function and structure of the nerves.


Asunto(s)
Crioterapia , Regeneración Nerviosa/fisiología , Conducción Nerviosa/fisiología , Nervio Tibial/fisiología , Animales , Femenino , Miembro Posterior , Ratas , Ratas Sprague-Dawley
16.
Nature ; 454(7203): 528-32, 2008 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-18552838

RESUMEN

Adult skeletal muscle robustly regenerates throughout an organism's life, but as the muscle ages, its ability to repair diminishes and eventually fails. Previous work suggests that the regenerative potential of muscle stem cells (satellite cells) is not triggered in the old muscle because of a decline in Notch activation, and that it can be rejuvenated by forced local activation of Notch. Here we report that, in addition to the loss of Notch activation, old muscle produces excessive transforming growth factor (TGF)-beta (but not myostatin), which induces unusually high levels of TGF-beta pSmad3 in resident satellite cells and interferes with their regenerative capacity. Importantly, endogenous Notch and pSmad3 antagonize each other in the control of satellite-cell proliferation, such that activation of Notch blocks the TGF-beta-dependent upregulation of the cyclin-dependent kinase (CDK) inhibitors p15, p16, p21 and p27, whereas inhibition of Notch induces them. Furthermore, in muscle stem cells, Notch activity determines the binding of pSmad3 to the promoters of these negative regulators of cell-cycle progression. Attenuation of TGF-beta/pSmad3 in old, injured muscle restores regeneration to satellite cells in vivo. Thus a balance between endogenous pSmad3 and active Notch controls the regenerative competence of muscle stem cells, and deregulation of this balance in the old muscle microniche interferes with regeneration.


Asunto(s)
Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/metabolismo , Mioblastos Esqueléticos/metabolismo , Receptores Notch/metabolismo , Proteína smad3/metabolismo , Animales , Proliferación Celular , Técnicas de Cocultivo , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Mioblastos Esqueléticos/citología , Mioblastos Esqueléticos/efectos de los fármacos , Miostatina , Regiones Promotoras Genéticas/genética , Unión Proteica , Receptores Notch/antagonistas & inhibidores , Células Satélite del Músculo Esquelético/citología , Células Satélite del Músculo Esquelético/efectos de los fármacos , Células Satélite del Músculo Esquelético/metabolismo , Proteína smad3/genética , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/farmacología
17.
J Subst Use Addict Treat ; 157: 209216, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37981243

RESUMEN

BACKGROUND: Achieving equitable access to medications for opioid use disorder (MOUD) such as buprenorphine is a pressing issue. Evidence suggests disparities in MOUD access based on race and socioeconomic status, further exacerbated by the COVID-19 pandemic. However, the drivers behind this access gap remain poorly understood. This study explores barriers to treatment access among individuals with opioid use disorder (OUD) experiencing homelessness. METHODS: We interviewed 28 individuals in and around the Boston Public Health Commission (BPHC) Engagement Center, an area known for its high density of active substance use and homelessness. We asked about people's experiences, perceptions, and attitudes toward OUD treatment. We conducted a thematic analysis of our interview data. RESULTS: Fifty-four percent of participants sampled were not prescribed MOUD. None of the participants reported having an active prescription of sublingual buprenorphine or buprenorphine/naloxone. White participants were more likely to have been prescribed buprenorphine in the past compared to participants of other races even in this socioeconomically homogeneous sample. Themes that emerged in our data included challenges to accessing MOUD due to reduced services during the COVID-19 pandemic, lost or stolen medications, fewer inpatient withdrawal management beds for women, transportation challenges, fear of adverse effects of MOUD, the perception that taking MOUD replaces one addiction for another, and community disapproval of MOUD. Participants also reported stigma and discrimination based on race, gender, and socioeconomic status. CONCLUSION: Systems and individual-level factors contribute to the MOUD treatment gap across race and socioeconomic status. The COVID-19 pandemic posed additional access challenges. This study provides important, actionable insights about the barriers faced by a particularly vulnerable population of individuals with OUD experiencing homelessness.


Asunto(s)
Buprenorfina , COVID-19 , Personas con Mala Vivienda , Trastornos Relacionados con Opioides , Femenino , Humanos , Pandemias , Buprenorfina/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico
18.
Stem Cell Res Ther ; 15(1): 11, 2024 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-38185673

RESUMEN

BACKGROUND: Mesenchymal stem cells in the adult corneal stroma (named corneal stromal stem cells, CSSCs) inhibit corneal inflammation and scarring and restore corneal clarity in pre-clinical corneal injury models. This cell therapy could alleviate the heavy reliance on donor materials for corneal transplantation to treat corneal opacities. Herein, we established Good Manufacturing Practice (GMP) protocols for CSSC isolation, propagation, and cryostorage, and developed in vitro quality control (QC) metric for in vivo anti-scarring potency of CSSCs in treating corneal opacities. METHODS: A total of 24 donor corneal rims with informed consent were used-18 were processed for the GMP optimization of CSSC culture and QC assay development, while CSSCs from the remaining 6 were raised under GMP-optimized conditions and used for QC validation. The cell viability, growth, substrate adhesion, stem cell phenotypes, and differentiation into stromal keratocytes were assayed by monitoring the electric impedance changes using xCELLigence real-time cell analyzer, quantitative PCR, and immunofluorescence. CSSC's conditioned media were tested for the anti-inflammatory activity using an osteoclastogenesis assay with mouse macrophage RAW264.7 cells. In vivo scar inhibitory outcomes were verified using a mouse model of anterior stromal injury caused by mechanical ablation using an Algerbrush burring. RESULTS: By comparatively assessing various GMP-compliant reagents with the corresponding non-GMP research-grade chemicals used in the laboratory-based protocols, we finalized GMP protocols covering donor limbal stromal tissue processing, enzymatic digestion, primary CSSC culture, and cryopreservation. In establishing the in vitro QC metric, two parameters-stemness stability of ABCG2 and nestin and anti-inflammatory ability (rate of inflammation)-were factored into a novel formula to calculate a Scarring Index (SI) for each CSSC batch. Correlating with the in vivo scar inhibitory outcomes, the CSSC batches with SI < 10 had a predicted 50% scar reduction potency, whereas cells with SI > 10 were ineffective to inhibit scarring. CONCLUSIONS: We established a full GMP-compliant protocol for donor CSSC cultivation, which is essential toward clinical-grade cell manufacturing. A novel in vitro QC-in vivo potency correlation was developed to predict the anti-scarring efficacy of donor CSSCs in treating corneal opacities. This method is applicable to other cell-based therapies and pharmacological treatments.


Asunto(s)
Lesiones de la Cornea , Opacidad de la Córnea , Limbo de la Córnea , Adulto , Humanos , Cicatriz , Antiinflamatorios , Inflamación
19.
J Clin Med Res ; 16(2-3): 46-55, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38550549

RESUMEN

Background: Emerging research indicates buprenorphine, used in management of opioid use disorder, has attracted interest for its potential in treating a variety of psychiatric conditions. This meta-analysis aimed to determine the efficacy of buprenorphine in treating symptoms of depression. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a search was conducted of several databases until April 25, 2022, for English language articles related to buprenorphine and its use in treating various mental health conditions. Standardized mean differences (SMDs) and its 95% confidence intervals (CIs) were reported for the Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS) scores. Statistical analyses were performed using Cochrane RevMan 5. Results: Of the 1,347 identified studies, six clinical trials were included. MADRS-10 least square mean difference (LSMD) inter-group assessment favored buprenorphine over placebo, but it lacked statistical significance. Similarly, MADRS scores as well as HAM-D inter-group assessment were in favor of buprenorphine, however, were not statistically significant. These findings suggest a potential therapeutic role for buprenorphine in treating depression, albeit with caution due to the observed lack of statistical significance and the potential for confounding factors. Conclusions: Preliminary evidence suggests potential efficacy of buprenorphine at lower doses in improving improving outcomes specifically related to depression. However, due to limitations in statistical significance and possible confounding factors, entail cautious interpretation. Further rigorous research is needed to investigate the long-term effects, optimal dosing, and determine the role of adjuvant drug therapy.

20.
Front Public Health ; 11: 1084259, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37089496

RESUMEN

Objectives: This study aimed to assess the extent of alcohol use and misuse among clinical therapists working in psychiatric hospitals in China during the early COVID-19 Pandemic, and to identify associated factors. Methods: An anonymous nationwide survey was conducted in 41 tertiary psychiatric hospitals. We collected demographic data as well as alcohol use using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and burnout using the Maslach Burnout Inventory Human Services Survey. Results: In total, 396 clinical therapists completed the survey, representing 89.0% of all potential participants we targeted. The mean age of participants was 33.8 years old, and more than three-quarters (77.5%) were female. Nearly two-fifths (39.1%) self-reported as current alcohol users. The overall prevalence of alcohol misuse was 6.6%. Nearly one-fifth (19.9%) reported symptoms of burnout with high emotional exhaustion in 46 (11.6%), and high depersonalization in 61 (15.4%). Multiple logistic regression showed alcohol use was associated with male gender (OR = 4.392; 95% CI =2.443-7.894), single marital status (OR = 1.652; 95% CI =0.970-2.814), smoking habit (OR = 3.847; 95%CI =1.160-12.758) and regular exercise (OR = 2.719; 95%CI =1.490-4.963). Alcohol misuse was associated with male gender (OR = 3.367; 95% CI =1.174-9.655), a lower education level (OR = 3.788; 95%CI =1.009-14.224), smoking habit (OR = 4.626; 95%CI =1.277-16.754) and high burnout (depersonalization, OR = 4.848; 95%CI =1.433-16.406). Conclusion: During the COVID-19 pandemic, clinical therapists' alcohol consumption did not increase significantly. Male gender, cigarette smoking, and burnout are associated with an increased risk of alcohol misuse among clinical therapists. Targeted intervention is needed when developing strategies to reduce alcohol misuse and improve clinical therapists' wellness and mental health.


Asunto(s)
Alcoholismo , COVID-19 , Hospitales Psiquiátricos , Personal de Hospital , Adulto , Femenino , Humanos , Masculino , Alcoholismo/epidemiología , Agotamiento Profesional/epidemiología , COVID-19/epidemiología , Conductas Relacionadas con la Salud , Pandemias , Encuestas y Cuestionarios , China/epidemiología , Factores de Riesgo , Personal de Hospital/psicología , Personal de Hospital/estadística & datos numéricos , Estudios Transversales , Persona de Mediana Edad , Centros de Atención Terciaria
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