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1.
Indian Pacing Electrophysiol J ; 23(6): 183-188, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37739312

RESUMEN

INTRODUCTION: Annual healthcare expenditures associated with atrial fibrillation (AF) in the United States (US) continue to grow as more symptomatic patients present to emergency departments (ED). Predictors of spontaneous conversion to normal sinus rhythm (ScNSR) remain poorly understood, as well as the timeline of ScNSR remains unclear. We sought to 1) to assess the association of key demographics, anthropometric, and clinical factors to ScNSR and 2) to evaluate the timeline of ScNSR, and 3) determine clinical predictors of ScNSR. METHODS: This single center, retrospective cohort study analyzed patients aged ≥18 years with symptomatic AF as diagnosed and evaluated through the ED of a rural tertiary care center in West Virginia from September 2015 to December 2018. RESULTS: Our cohort consisted of 375 AF patients (mean age 65 years, 54% male). A total of 177 patients attained ScNSR either in the ED or after hospital admission with a mean conversion time of 14.7 h (±12). Onset of symptoms <24 hrs has strong positive association to ScNSR 3.97 (95% CI: 2.24-7.05; p < 0.0001). Male gender 0.55 (95% CI: 0.35-0.85; p = 0.007) and hypertension 0.48 (95% CI: 0.31-0.76; p = 0.002), showed a strong negative association to ScNSR. Of the patients that converted spontaneously (177), the majority, 136 (76.8%) achieved ScNSR within 24 h of ED triage without use of electrical or chemical cardioversion. CONCLUSION: Most patients with AF in the ED converted spontaneously to sinus rhythm within the first 24 h which underscores the importance of earlier watchful waiting over interventions to achieve normal sinus rhythm (NSR).

2.
Ann Surg Oncol ; 29(10): 6215-6221, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35857199

RESUMEN

BACKGROUND: Abbreviated magnetic resonance imaging (Ab-MRI) has been evaluated for elevated breast cancer risk or dense breasts but has not been evaluated across all risk profiles. METHODS: Patients selected underwent Ab-MRI from February 2020 to September 2021. Women were older than aged 30 years, up to date with screening mammography, and paid $299 cash. RESULTS: A total of 93 patients were identified with a mean age of 52 years; 92.5% were Caucasian, 0% black, and 97.9% were from high socioeconomic status. Mean Gail score was 14.2, and 83.3% had a lifetime risk of breast cancer <20%. Reasons for Ab-MRI: dense breasts (36.6%); family history (24.7%); palpable mass (12.9%). Providers ordering: OBGYN (49.5%); breast surgeon (39.1%); primary care (6.6%). Thirteen biopsies (14%) detected one breast cancer. 31.1% had a change in follow-up screening: 58.6% 6-month MRI, 20.7% 6-month mammogram, and 10.3% 6-month ultrasound. Negative predictive value was 100% (95% confidence interval [CI]: 95-100%, p < 0.0001). Sensitivity was 100% (95% CI: 2.5-100%, p < 0.0001), and specificity was 87% (95% CI: 78.3-93.1%, p < 0.0001) compared with 77.6% and 98.8% for mammography. Only one cancer was detected: cost of $27,807 plus cost of 13 MRI or ultrasound (US)-guided biopsies and additional follow-up imaging. Historically 20% of abnormalities detected on full MRI are malignant; however, 7.7% of ab-MRI abnormalities were malignant CONCLUSIONS: One third of women were recommended a change in follow-up, which predominantly included a 6-month MRI. Ab-MRI may introduce average risk women to unnecessary follow-up and increased biopsies with a lower cancer detection rate. Ab-MRI should be evaluated closely before implementation.


Asunto(s)
Densidad de la Mama , Neoplasias de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Detección Precoz del Cáncer/métodos , Femenino , Humanos , Biopsia Guiada por Imagen , Imagen por Resonancia Magnética/métodos , Mamografía/métodos , Tamizaje Masivo/métodos , Persona de Mediana Edad , Sensibilidad y Especificidad
3.
Breast Cancer Res Treat ; 186(1): 53-63, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33389405

RESUMEN

INTRODUCTION: Metabolic syndrome (MS) is defined by having at least 3 of 4 components: obesity, dyslipidemia, hypertension (HTN), and diabetes. Prior studies analyzed the individual components of MS for all breast cancers which are predominantly hormone positive. Our study is the first to evaluate MS in triple-negative breast cancer (TNBC). METHODS: A retrospective review of TNBC from 2007 to 2013 identified 177 patients with complete information for statistical analysis. Cox proportional hazards models were used to test the association between MS, disease-free survival (DFS), and overall survival (OS). RESULTS: 48 (27%) patients had MS. After controlling for age, race, pathologic stage, surgery type, and additional comorbidities outside of MS, MS was significantly associated with poorer DFS (adjusted HR: 2.24, p = 0.030), but not associated with OS (adjusted HR: 1.92, p = 0.103). HTN was significantly associated with poorer DFS (adjusted HR: 3.63, p = 0.006) and OS (adjusted HR: 3.45, p = 0.035) in the univariable and multivariable analyses. Diabetes was not associated with worse OS or DFS. The 5-year age-adjusted OS rates for 60-year-old patients with and without diabetes were 85.8% and 87.3%, respectively. The age-adjusted 5-year OS rate for 60-year old patients was higher in patients with a body mass index (BMI) > 30 (90.2%) versus BMIs of 25-29.9 (88.2%) or < 25 (83.5%). CONCLUSION: In the TNBC population, MS was significantly associated with poorer DFS, but not associated with OS. HTN was the only component of MS that was significantly associated with both DFS and OS. Obesity has a potential small protective benefit in the TNBC population.


Asunto(s)
Neoplasias de la Mama , Síndrome Metabólico , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/epidemiología , Neoplasias de la Mama Triple Negativas/terapia
4.
Ann Surg Oncol ; 28(9): 5071-5081, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33547514

RESUMEN

BACKGROUND: Philadelphia and its suburbs were an epicenter for the initial COVID-19 outbreak. Accordingly, alterations were made in breast cancer care at a community hospital. METHODS: The authors developed a prospective database of all the patients with invasive or in situ breast cancer between March 1 and June 15 at their breast center. Any change in a breast cancer plan due to the pandemic was documented, and the patients were grouped into two cohorts according to whether a change was made (CTX) or no change was made (NC) in their care. The patients were asked a series of questions about their care, including those in the Generalized Anxiety Disorder two-item questionnaire (GAD-2), via telephone. RESULTS: The study enrolled 73 patients: 41 NC patients (56%) and 32 CTX patients (44%). The two cohorts did not differ in terms of age, race, or stage. Changes included delay in therapy (15.1%) and use of neoadjuvant endocrine therapy (NET, 28.8%). The median time to surgery was 24 days (interequartile range [IQR], 16-45 days) for the NC patients and 82 day s (IQR, 52-98 days) for the CTX patients (p ≤ 0.001). The median duration of NET was 78 days. The GAD-2 showed anxiety positivity to be 29.6% for the CTX patients and 32.4% for the NC patients (p = 1.00). More than half (55.6%) of the CTX patients believed COVID-19 affected their treatment outlook compared with 25.7% of the NC patients (p = 0.021). CONCLUSIONS: A prospective database captured changes in breast cancer care at a community academic breast center during the initial phase of the COVID-19 pandemic. 44% of patients experienced a change in breast cancer care due to COVID-19. The same level of anxiety and depression was seen in both change in therapy (CTX) and no change (NC). 55.6% of CTX cohort believed COVID-19 affected their treatment outlook.


Asunto(s)
COVID-19 , Pandemias , Ansiedad , Humanos , Percepción , SARS-CoV-2
5.
Prev Chronic Dis ; 16: E116, 2019 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-31469071

RESUMEN

Obesity rates in the United States are trending upward, and disadvantaged populations continue to have disproportionate rates of obesity. In Alabama, the ALProHealth initiative used community-based participatory research to work with community coalitions to implement research-based interventions that addressed issues related to the lack of opportunities for physical activity in 14 counties whose populations are at high risk of obesity. Coalitions developed work plans and timelines for implementing interventions on the basis of issues discussed during focus groups at the beginning of the ALProHealth initiative. These 14 coalitions implemented 101 interventions related to physical activity in 16 communities. In this evaluation, we measured potential reach and improvements in amenities. The largest reach for an intervention was achieved through marketing and communication efforts, while the most popular intervention, undertaken by the largest number of communities, centered on installing or repairing playground equipment at community parks. Community-based participatory research is an effective method for addressing health issues at the local level, as interventions are developed and readily adopted through active partnerships with community leaders and residents.


Asunto(s)
Ejercicio Físico , Promoción de la Salud , Obesidad , Recreación , Alabama/epidemiología , Investigación Participativa Basada en la Comunidad/estadística & datos numéricos , Promoción de la Salud/métodos , Promoción de la Salud/organización & administración , Humanos , Obesidad/epidemiología , Obesidad/prevención & control , Evaluación de Programas y Proyectos de Salud , Salud Pública/normas , Mejoramiento de la Calidad/organización & administración , Recreación/fisiología , Recreación/psicología , Factores de Riesgo , Población Rural/estadística & datos numéricos , Poblaciones Vulnerables/estadística & datos numéricos
6.
J Gastroenterol Hepatol ; 33(10): 1717-1721, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29514412

RESUMEN

BACKGROUND AND AIM: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications worldwide, with dramatic efficacy for upper gastrointestinal acid-related disorders. In recent years, however, the safety of long-term PPI use has been questioned. One issue based on scant and conflicting literature is the possibility of PPI-related hypomagnesemia. Our purpose was to assess for any clinically significant alteration in serum magnesium levels in large groups of patients taking different PPIs in varying doses, with or without diuretics. METHODS: This was a retrospective review of patient records at time of hospitalization, from February 2012 to December 2014. Two thousand four hundred patients were randomly selected from a pool of 12 058 magnesium levels performed at or within 24 h of hospital admission. Patients were categorized in six groups based on outpatient PPI and/or diuretic use. The main outcome studied was hypomagnesemia, defined as serum magnesium level < 1.6 mg/dL. RESULTS: Mean magnesium levels were normal in PPI users (1.84 ± 0.29 mg/dL [normal 1.6 to 2.5 mg/dL]) and PPI nonusers (1.85 ± 0.30 mg/dL), P = 0.40, and there was no statistical difference in the prevalence of hypomagnesemia (14.7% vs 15.1%, P = 0.77). In separate groups, there were also no significant differences in serum magnesium levels between those taking PPIs of varying doses, with or without concomitant diuretics, and those not taking PPIs or diuretics. CONCLUSION: Regardless of PPI dosage or concomitant diuretics prescribed, magnesium levels were unaffected. Routine screening of serum magnesium in PPI patients appears unnecessary.


Asunto(s)
Diuréticos/administración & dosificación , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Quimioterapia Combinada , Femenino , Humanos , Hipercalciuria/inducido químicamente , Hipercalciuria/diagnóstico , Magnesio/sangre , Masculino , Persona de Mediana Edad , Nefrocalcinosis/inducido químicamente , Nefrocalcinosis/diagnóstico , Defectos Congénitos del Transporte Tubular Renal/inducido químicamente , Defectos Congénitos del Transporte Tubular Renal/diagnóstico , Estudios Retrospectivos
8.
Pediatr Radiol ; 47(5): 606-612, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28213626

RESUMEN

BACKGROUND: Minimizing the ionizing radiation dose to children is fundamental to pediatric radiology. The most widely accepted imaging examination for evaluating craniosynostosis is computed tomography (CT) of the head, an examination that involves ionizing radiation. OBJECTIVE: To determine if sonography of the cranial sutures is an adequate screening examination for the diagnosis of craniosynostosis in patients with abnormal skull shape. MATERIALS AND METHODS: A retrospective review of all cranial suture ultrasound (US) examinations performed during the course of a 3-year period (July 2012 - September 2015) was undertaken. Results were compared with clinical follow-up and/or head CT to evaluate the accuracy of this modality as a screening tool to determine the presence or absence of craniosynostosis. Fifty-two sonographic exams were adequate for inclusion. RESULTS: Forty-five of the examinations did not reveal synostosis. In each of these instances, follow-up physical exam findings and/or CT imaging confirmed that no abnormal premature suture closure was present. US findings demonstrated synostosis in seven cases. CT exam or operative reports of these cases confirmed all seven findings of premature suture closure. Statistical analysis demonstrated a sensitivity of 100% (95% confidence interval [CI]: 56.1-100.0%), a specificity of 100% (95% CI: 90.2-100.0%), and a negative predictive value of 100% (95% CI: 90.2-100.0%). CONCLUSION: Cranial US is a reliable screening tool to rule out craniosynostosis in patients with abnormal head shape.


Asunto(s)
Suturas Craneales/diagnóstico por imagen , Craneosinostosis/diagnóstico por imagen , Ultrasonografía/métodos , Humanos , Lactante , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad
9.
Am J Pathol ; 184(4): 1062-1072, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24486326

RESUMEN

Toll-like receptors (TLRs) are highly conserved type 1 membrane proteins that initiate a multiplicity of transient gene transcriptions, resulting in innate and adaptive immune responses. These essential immune responses are triggered by common TLR pattern recognition receptors of microbial products expressed through the cytoplasmic carboxy-terminal Toll/IL-1 domain. Toll/IL-1 adapter protein cascades are induced by an activated Toll/IL-1 to induce transient transcription responses. All TLRs, with the exception of TLR3, use an MyD88 adapter to Toll/IL-1 to initiate a proinflammatory cascade. TLR3 uses the toll receptor 3/4 induction factor adapter to initiate a different cytosolic adapter cascade with double-stranded RNA agonists. This non-MyD88 pathway induces both NF-κB and type 1 interferon responses. By using a TLR3-restricted double-stranded RNA agonist, rintatolimod, we demonstrate significant unexpected differences in toxic responses between rats and primates. The mechanism of this differential response is consistent with a relative down-regulation of the NF-κB inflammatory cytokine induction pathway in the cynomolgus monkey and humans, but not observed systemically in rat. Our findings suggest evaluation of TLR3 agonists in drug therapy.


Asunto(s)
Inflamación/metabolismo , Poli I-C/farmacología , Poli U/farmacología , Especificidad de la Especie , Receptor Toll-Like 3/antagonistas & inhibidores , Secuencia de Aminoácidos , Animales , Perros , Síndrome de Fatiga Crónica/tratamiento farmacológico , Humanos , Inflamación/inmunología , Macaca fascicularis , Dosis Máxima Tolerada , Datos de Secuencia Molecular , Conejos , Ratas , Ratas Sprague-Dawley
10.
Environ Sci Technol ; 49(24): 14195-203, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26544021

RESUMEN

Organic nitrates are an important aerosol constituent in locations where biogenic hydrocarbon emissions mix with anthropogenic NOx sources. While regional and global chemical transport models may include a representation of organic aerosol from monoterpene reactions with nitrate radicals (the primary source of particle-phase organic nitrates in the Southeast United States), secondary organic aerosol (SOA) models can underestimate yields. Furthermore, SOA parametrizations do not explicitly take into account organic nitrate compounds produced in the gas phase. In this work, we developed a coupled gas and aerosol system to describe the formation and subsequent aerosol-phase partitioning of organic nitrates from isoprene and monoterpenes with a focus on the Southeast United States. The concentrations of organic aerosol and gas-phase organic nitrates were improved when particulate organic nitrates were assumed to undergo rapid (τ = 3 h) pseudohydrolysis resulting in nitric acid and nonvolatile secondary organic aerosol. In addition, up to 60% of less oxidized-oxygenated organic aerosol (LO-OOA) could be accounted for via organic nitrate mediated chemistry during the Southern Oxidants and Aerosol Study (SOAS). A 25% reduction in nitrogen oxide (NO + NO2) emissions was predicted to cause a 9% reduction in organic aerosol for June 2013 SOAS conditions at Centreville, Alabama.


Asunto(s)
Aerosoles/análisis , Aerosoles/química , Contaminantes Atmosféricos/análisis , Nitratos/análisis , Alabama , Butadienos/química , Hemiterpenos/química , Modelos Químicos , Modelos Teóricos , Monoterpenos/química , Nitratos/química , Óxidos de Nitrógeno/análisis , Óxidos de Nitrógeno/química , Pentanos/química , Sudeste de Estados Unidos
11.
J Air Waste Manag Assoc ; 65(10): 1171-84, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26452014

RESUMEN

UNLABELLED: The development of a database for making model species assignments when preparing total organic gas (TOG) emissions input for atmospheric models is described. This database currently has assignments of model species for 12 different gas-phase chemical mechanisms for over 1700 chemical compounds and covers over 3000 chemical categories used in five different anthropogenic TOG profile databases or output by two different biogenic emissions models. This involved developing a unified chemical classification system, assigning compounds to mixtures, assigning model species for the mechanisms to the compounds, and making assignments for unknown, unassigned, and nonvolatile mass. The comprehensiveness of the assignments, the contributions of various types of speciation categories to current profile and total emissions data, inconsistencies with existing undocumented model species assignments, and remaining speciation issues and areas of needed work are also discussed. The use of the system to prepare input for SMOKE, the Speciation Tool, and for biogenic models is described in the supplementary materials. The database, associated programs and files, and a users manual are available online at http://www.cert.ucr.edu/~carter/emitdb . IMPLICATIONS: Assigning air quality model species to the hundreds of emitted chemicals is a necessary link between emissions data and modeling effects of emissions on air quality. This is not easy and makes it difficult to implement new and more chemically detailed mechanisms in models. If done incorrectly, it is similar to errors in emissions speciation or the chemical mechanism used. Nevertheless, making such assignments is often an afterthought in chemical mechanism development and emissions processing, and existing assignments are usually undocumented and have errors and inconsistencies. This work is designed to address some of these problems.


Asunto(s)
Contaminantes Atmosféricos/análisis , Bases de Datos Factuales , Compuestos Orgánicos Volátiles/análisis , Modelos Teóricos , Estados Unidos
12.
W V Med J ; 111(2): 18-21, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25842701

RESUMEN

Long-term survival in patients with complete aortic coarctation (AC) without surgical repair has not been well characterized and is rarely documented. We report a case of an 84 year old male with complete aortic coarctation with history of hypertension for more than 40 years. Since the diagnosis was made in early 1950's medical treatment to control hypertension was initiated as patient was deemed high risk for surgical intervention. He has survived to the age of 84 years with minimal medical problems. This report also reviews the few documented cases of prolonged survival in patients with aortic coarctation. This report demonstrates that prolonged survival is possible in patients with documented complete coarctation and awareness of this report may influence the decision to use medical treatment for selected elderly patients with high risk of mortality associated with surgical repair.


Asunto(s)
Antihipertensivos/uso terapéutico , Aorta Torácica , Coartación Aórtica/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Anciano de 80 o más Años , Aorta Torácica/diagnóstico por imagen , Coartación Aórtica/complicaciones , Coartación Aórtica/diagnóstico por imagen , Humanos , Hipertensión/etiología , Masculino , Radiografía
13.
J Periodontol ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605536

RESUMEN

BACKGROUND: Periodontal diseases (PD) have been increasingly associated with several systemic conditions such as cardiovascular disease (CVD), diabetes mellitus (DM), rheumatoid arthritis (RA), and Alzheimer's disease (AD). This study aimed to gain insight into patients' awareness of the association between PD and systemic diseases. METHODS: A survey was developed to analyze patient awareness of the association between PD and systemic diseases. Descriptive and categorical variables were summarized with counts and percentages. Chi-squared tests were used to evaluate differences between variables. A linear logistical regression model was used to assess the simultaneous, independent association between each variable. RESULTS: Data from 161 completed surveys were analyzed. The majority of the participants (61.49%) reported awareness of symptoms of PD, but only 36.36% identified all its major symptoms. Individuals reporting awareness of the association between PD and systemic diseases was 48.4%, 31.7%, 14.9%, and 9.9% for CVD, DM, RA, and AD, respectively. Patients aged ≥51 years and males were more aware of the association between PD and CVD. Increased awareness of an association between PD and DM was observed among patients who had a higher frequency of dental visits and those with a self-reported history of DM. CONCLUSIONS: This study provides insight that, even with the vast amount of scientific knowledge on the inter-relationships that exist between PD and systemic diseases, most patients are still unaware of these associations. This research identified that improvement of health literacy surrounding PD, their symptoms, and their association with systemic diseases may be warranted.

14.
Open Biol ; 14(6): 240025, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38862021

RESUMEN

Faithful transmission of genetic material is crucial for the survival of all organisms. In many eukaryotes, a feedback control mechanism called the spindle checkpoint ensures chromosome segregation fidelity by delaying cell cycle progression until all chromosomes achieve proper attachment to the mitotic spindle. Kinetochores are the macromolecular complexes that act as the interface between chromosomes and spindle microtubules. While most eukaryotes have canonical kinetochore proteins that are widely conserved, kinetoplastids such as Trypanosoma brucei have a seemingly unique set of kinetochore proteins including KKT1-25. It remains poorly understood how kinetoplastids regulate cell cycle progression or ensure chromosome segregation fidelity. Here, we report a crystal structure of the C-terminal domain of KKT14 from Apiculatamorpha spiralis and uncover that it is a pseudokinase. Its structure is most similar to the kinase domain of a spindle checkpoint protein Bub1. In addition, KKT14 has a putative ABBA motif that is present in Bub1 and its paralogue BubR1. We also find that the N-terminal part of KKT14 interacts with KKT15, whose WD40 repeat beta-propeller is phylogenetically closely related to a direct interactor of Bub1/BubR1 called Bub3. Our findings indicate that KKT14-KKT15 are divergent orthologues of Bub1/BubR1-Bub3, which promote accurate chromosome segregation in trypanosomes.


Asunto(s)
Cinetocoros , Proteínas Protozoarias , Cinetocoros/metabolismo , Cinetocoros/química , Proteínas Protozoarias/metabolismo , Proteínas Protozoarias/química , Proteínas Protozoarias/genética , Trypanosoma brucei brucei/metabolismo , Trypanosoma brucei brucei/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/genética , Modelos Moleculares , Secuencia de Aminoácidos , Filogenia , Unión Proteica , Cristalografía por Rayos X , Segregación Cromosómica , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética
15.
bioRxiv ; 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38746313

RESUMEN

Schwann cells are vital to development and maintenance of the peripheral nervous system and their dysfunction has been implicated in a range of neurological and neoplastic disorders, including NF2 -related schwannomatosis. We have developed a novel human induced pluripotent stem cell (hiPSC) model for the study of Schwann cell differentiation in health and disease. We performed transcriptomic, immunofluorescence, and morphological analysis of hiPSC derived Schwann cell precursors (SPCs) and terminally differentiated Schwann-like cells (SLCs) representing distinct stages of development. To further validate our findings, we performed integrated, cross-species analyses across multiple external datasets at bulk and single cell resolution. Our hiPSC model of Schwann cell development shared overlapping gene expression signatures with human amniotic mesenchymal stem cell (hAMSCs) derived SLCs and in vivo mouse models, but also revealed unique features that may reflect species-specific aspects of Schwann cell biology. Moreover, we have identified gene co-expression modules that are dynamically regulated during hiPSC to SLC differentiation associated with ear and neural development, cell fate determination, the NF2 gene, and extracellular matrix (ECM) organization. By cross-referencing results between multiple datasets and analyses, we have identified potential new genes that are related to NF2 for further study including: ANXA1, CDH6, COL1A1, COL8A1, MFAP5, IGFBP5, FGF1, AHNAK, CDKN2B, LOX, CAV1 , and CAV2 . Our hiPSC model further provides a tractable platform for studying Schwann cell development in the context of human disease.

16.
Front Neurol ; 14: 1254760, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37808500

RESUMEN

Objective: To examine the combined effects of neuromuscular electrical stimulation-resistance training (NMES-RT) and functional electrical stimulation-lower extremity cycling (FES-LEC) compared to passive movement training (PMT) and FES-LEC in adults with SCI on (1) oxygen uptake (VO2), insulin sensitivity and glucose disposal in adults with SCI; (2) Metabolic and inflammatory biomarkers; (3) skeletal muscle, intramuscular fat (IMF) and visceral adipose tissue (VAT) cross-sectional areas (CSAs). Materials and methods: Thirty-three participants with chronic SCI (AIS A-C) were randomized to 24 weeks of NMES-RT + FES or PMT + FES. The NMES-RT + FES group underwent 12 weeks of evoked surface NMES-RT using ankle weights followed by an additional 12 weeks of progressive FES-LEC. The control group, PMT + FES performed 12 weeks of passive leg extension movements followed by an additional 12 weeks of FES-LEC. Measurements were performed at baseline (BL; week 0), post-intervention 1 (P1; week 13) and post-intervention 2 (P2; week 25) and included FES-VO2 measurements, insulin sensitivity and glucose effectiveness using the intravenous glucose tolerance test; anthropometrics and whole and regional body composition assessment using dual energy x-ray absorptiometry (DXA) and magnetic resonance imaging to measure muscle, IMF and VAT CSAs. Results: Twenty-seven participants completed both phases of the study. NMES-RT + FES group showed a trend of a greater VO2 peak in P1 [p = 0.08; but not in P2 (p = 0.25)] compared to PMT + FES. There was a time effect of both groups in leg VO2 peak. Neither intervention elicited significant changes in insulin, glucose, or inflammatory biomarkers. There were modest changes in leg lean mass following PMT + FES group. Robust hypertrophy of whole thigh muscle CSA, absolute thigh muscle CSA and knee extensor CSA were noted in the NMES-RT + FES group compared to PMT + FES at P1. PMT + FES resulted in muscle hypertrophy at P2. NMES-RT + FES resulted in a decrease in total VAT CSA at P1. Conclusion: NMES-RT yielded a greater peak leg VO2 and decrease in total VAT compared to PMT. The addition of 12 weeks of FES-LEC in both groups modestly impacted leg VO2 peak. The addition of FES-LEC to NMES-RT did not yield additional increases in muscle CSA, suggesting a ceiling effect on signaling pathways following NMES-RT. Clinical trial registration: identifier NCT02660073.

17.
Lancet Infect Dis ; 23(10): e418-e430, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37295453

RESUMEN

Analytical treatment interruptions (ATIs) have become a key methodological approach to evaluate the effects of experimental HIV cure-related research interventions. During ATIs, sex partners of trial participants might be at risk of acquiring HIV. This risk raises both ethical and feasibility concerns about ATI trials. We propose a partner protection package (P3) approach to address these concerns. A P3 approach would provide guidance to investigators, sponsors, and those who are designing and implementing context-specific partner protections in HIV cure-related trials involving ATIs. The approach would also help assure institutional review boards, trial participants, and communities that ATI trials with a P3 would provide appropriate partner protections. We offer a prototype P3 framework that delineates three basic considerations for protecting participants' sex partners during ATI trials: (1) ensuring the scientific and social value of the ATI and the trial, (2) reducing the likelihood of unintended HIV transmission, and (3) ensuring prompt management of any acquired HIV infection. We outline possible ways of implementing these basic considerations.


Asunto(s)
Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Ensayos Clínicos como Asunto
18.
HIV Res Clin Pract ; 24(1): 2267825, 2023 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-37837376

RESUMEN

BACKGROUND: A feature of HIV cure trials is the need to interrupt treatment to test the efficacy of experimental interventions-a process known as analytical treatment interruptions (ATIs). OBJECTIVES: We report the experiences of participants after they completed an extended ATI. METHODS: From April to November 2022, we conducted post-ATI in-depth interviews with BEAT2 clinical trial (NCT03588715) participants who stopped ART while receiving an immunotherapy regimen. We used conventional content analysis to code the data. RESULTS: We conducted interviews with 11 Black/African American and three White/Caucasian participants (11 males, two females, and one transgender woman). The mean ATI was 38 weeks. Participants noted several significant experiences surrounding the interventions' side effects, ATI, and returning to medication. Some participants had positive experiences with their ATI. Other participants were nervous during the ATI. Rising viral loads led some to feel a sense of failure. Although trial experiences were heterogeneous, participants unanimously had positive interactions with the clinical trial staff which facilitated their retention in the trial. Participants shared their experiences with the trial, including changes in expectations, experiences with experimental interventions and procedures, compensation as a measure of respect, effort, transportation, and effects of COVID-19 during the trial. Based on these results, we provide considerations for the conduct of future HIV cure-directed clinical trials involving ATIs. CONCLUSIONS: Managing expectations, focusing on participants' contributions, and providing support to reduce feelings of having failed the research team and/or the HIV community following viral rebound should be part of HIV cure trial design. Discussing the mental health impact of rebound during consent, distinct from risk, is needed. Continued efforts to understand how people with HIV experience ATIs will improve future designs of HIV cure clinical trials.


Asunto(s)
COVID-19 , Infecciones por VIH , Femenino , Humanos , Masculino , Infecciones por VIH/tratamiento farmacológico , Inmunoterapia , Philadelphia , Estados Unidos , Carga Viral , Ensayos Clínicos como Asunto
19.
Fed Pract ; 40(Suppl 3): S50-S57, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38021100

RESUMEN

Background: Prostate-specific antigen (PSA) testing remains controversial due to the debate about overdetection and overtreatment. Given the lack of published data regarding PSA testing rates in the population with spinal cord injury (SCI) within the US Department of Veterans Affairs (VA), there is concern for potential disparities and overtesting in this patient population. In this study, we sought to identify and evaluate national PSA testing rates in veterans with SCI. Methods: Using the VA Informatics and Computing Infrastructure Corporate Data Warehouse, we extracted PSA testing data for all individuals with a diagnosis of SCI. Testing rates were calculated, analyzed by race and age, and stratified according to published American Urological Association guideline groupings for PSA testing. Results: We identified 45,274 veterans at 129 VA medical centers with a diagnosis of SCI who had records of PSA testing in 2000 through 2017. Veterans who were only tested prior to SCI diagnosis were excluded. Final cohort data analysis included 37,243 veterans who cumulatively underwent 261,125 post-SCI PSA tests during the given time frame. Significant differences were found between African American veterans and other races veterans for all age groups (0.47 vs 0.46 tests per year, respectively, aged ≤ 39 years; 0.83 vs 0.77 tests per year, respectively, aged 40-54 years; 1.04 vs 1.00 tests per year, respectively, aged 55-69 years; and 1.08 vs 0.90 tests per year, respectively, aged ≥ 70 years; P < .001). Conclusions: Significant differences exist in rates of PSA testing in persons with SCI based on age and race. High rates of testing were found in all age groups, especially for African American veterans aged ≥ 70 years.

20.
Res Involv Engagem ; 9(1): 39, 2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-37291622

RESUMEN

INTRODUCTION: Achieving effective community engagement has been an objective of U.S. National Institutes of Health-funded HIV research efforts, including participation of persons with HIV. Community Advisory Boards (CABs) have remained the predominant model for community engagement since their creation in 1989. As HIV cure-directed research efforts have grown into larger academic-industry partnerships directing resources toward both basic and clinical research under the Martin Delaney Collaboratories (MDC), community input models have also evolved. The BEAT-HIV MDC Collaboratory, based at The Wistar Institute in Philadelphia, United States, implemented a three-part model for community engagement that has shown success in providing greater impact for community engagement across basic, biomedical, and social sciences research efforts. DISCUSSION: In this paper, we review the case study of the formation of the BEAT-HIV Community Engagement Group (CEG) model, starting with the historical partnership between The Wistar Institute as a basic research center and Philadelphia FIGHT as a not-for-profit community-based organization (CBO), and culminating with the growth of community engagement under the BEAT-HIV MDC. Second, we present the impact of a cooperative structure including a Community Advisory Board (CAB), CBO, and researchers through the BEAT-HIV CEG model, and highlight collaborative projects that demonstrate the potential strengths, challenges, and opportunities of this model. We also describe challenges and future opportunities for the use of the CEG model. CONCLUSIONS: Our CEG model integrating a CBO, CAB and scientists could help move us towards the goal of effective, equitable and ethical engagement in HIV cure-directed research. In sharing our lessons learned, challenges and growing pains, we contribute to the science of community engagement into biomedical research efforts with an emphasis on HIV cure-directed research. Our documented experience with implementing the CEG supports greater discussion and independent implementation efforts for this model to engage communities into working teams in a way we find a meaningful, ethical, and sustainable model in support of basic, clinical/biomedical, social sciences and ethics research.


HIV biomedical research groups have prioritized community support and representation as exemplified by the creation of Community Advisory Boards (CABs). Most CABs bring diverse stakeholders to advise on research objectives as part of their activities. The BEAT-HIV Delaney Collaboratory, based at The Wistar Institute in Philadelphia, is a research program created in 2016 to advance HIV cure research. To better engage communities beyond the CAB, the BEAT-HIV Delaney Collaboratory created a Community Engagement Group (CEG) model composed of three distinct components. First, the involvement of a community-based organization (CBO) introduces the historical know-how and relationship with the community. Philadelphia FIGHT fulfills the CBO role as a provider of primary care, education, advocacy, and research support for persons with HIV. Second, the BEAT-HIV CAB provides individual experiences and community input into HIV cure research and gives updates to the broader community about the status of research. Third, basic, clinical/biomedical, and social scientists implement the scientific goals of the BEAT-HIV Collaboratory. In this paper, we aimed to highlight the strengths, challenges, lessons learned, and opportunities of the BEAT-HIV CEG model. We also present examples of collaborative community engagement projects. Our paper contributes to the literature on novel community engagement approaches beyond the CAB. Based on our experience to date using the CEG, a multi-part community engagement model could help move us towards the goal of inclusive, effective, equitable, and ethical engagement in HIV cure research.

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