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1.
BMC Genomics ; 25(1): 437, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698335

RESUMO

BACKGROUND: Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation). RESULTS: We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, suggesting acceptability from a molecular standpoint. Liver metabolic functional genes were similarly upregulated, and extracellular matrix genes were similarly downregulated in the accepted and rejected-2 groups compared to rejected-1. The transcriptomic pattern of the rejected-2 subset was enriched for a gene expression signature of graft success post-transplantation. Serum AST, ALT, and total bilirubin levels showed similar overlapping patterns. Additional histopathological filtering identified cases with borderline scores and extensive molecular overlap with accepted donor livers. CONCLUSIONS: Our integrated approach identified a subset of rejected donor livers that are likely suitable for transplantation, demonstrating the potential to expand the pool of transplantable livers.


Assuntos
Perfilação da Expressão Gênica , Transplante de Fígado , Fígado , Doadores de Tecidos , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Feminino , Transcriptoma , Rejeição de Enxerto/genética , Adulto
2.
AIDS Behav ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916689

RESUMO

Experiencing HIV and intersectional stigmas in healthcare settings may affect antiretroviral treatment (ART) adherence among people with HIV (PWH), given their need for frequent interactions with clinical settings and healthcare providers. Considering the importance of reducing stigmas to promote well-being and the need to elucidate how stigma influences health across various settings, we examined how experienced HIV stigma in Dominican Republic healthcare settings impacts ART adherence through internalized HIV stigma and whether race or sexual orientation stigma moderates this relationship. Participants were 471 PWH (aged 17-71) who were recruited from two HIV clinics in the Dominican Republic in 2021-2022. Results revealed a significant mediation effect (B=-0.10, SE = 0.05, CI [-0.234, - 0.014]) after adjusting for effect of age and time since HIV diagnosis, suggesting that experienced HIV stigma in healthcare settings was associated with more internalized HIV stigma (B = 0.39, SE = 0.11, p = .001), subsequently linked to lower ART adherence (B=-0.26, SE = 0.11, p = .016). The indirect effect was significant at low levels of race stigma (B=-0.16, SE = 0.09, CI [-0.369, - 0.001]) but not at high levels of race stigma (B=-0.06, SE = 0.05, CI [-0.175, 0.038]). This indirect effect was also significant at low levels of sexual orientation stigma (B=-0.19, SE = 0.10, CI [-0.401, - 0.023]) but not at high levels of sexual orientation stigma (B=-0.04, SE = 0.06, CI [-0.160, 0.074]). These findings suggest that addressing experienced HIV stigma in Dominican Republic healthcare settings, along with various dimensions of HIV-related stigma (e.g., internalized stigma) and intersecting stigmas (e.g., race, sexual orientation), is vital for improving health outcomes, such as optimal ART adherence.


RESUMEN: Experimentar estigmas relacionados con el VIH e interseccionales en entornos de atención médica puede afectar la adherencia al tratamiento antirretroviral (TAR) entre las personas que viven con VIH (PVVIH), dado que necesitan interacciones frecuentes con entornos clínicos y proveedores de atención médica. Considerando la importancia de reducir los estigmas para promover el bienestar y la necesidad de esclarecer cómo el estigma influye en la salud en diversos contextos, examinamos cómo el estigma del VIH experimentado en entornos de atención médica en la República Dominicana impacta la adherencia al TAR a través del estigma internalizado del VIH y si el estigma racial o de orientación sexual modera esta relación. Los participantes fueron 471 PVVIH (de 17 a 71 años) que fueron reclutados de dos clínicas de VIH en la República Dominicana en 2021­2022. Los resultados revelaron un efecto de mediación significativo (B=-0.10, SE = 0.05, CI [-0.234, − 0.014]) después de ajustar por el efecto de la edad y el tiempo desde el diagnóstico de VIH, sugiriendo que el estigma del VIH experimentado en entornos de atención médica estaba asociado con un mayor estigma internalizado del VIH (B = 0.39, SE = 0.11, p = .001), vinculado posteriormente a una menor adherencia al TAR (B=-0.26, SE = 0.11, p = .016). El efecto indirecto fue significativo en niveles bajos de estigma racial (B=-0.16, SE = 0.09, CI [-0.369, − 0.001]) pero no en niveles altos de estigma racial (B=-0.06, SE = 0.05, CI [-0.175, 0.038]). Este efecto indirecto también fue significativo en niveles bajos de estigma por orientación sexual (B=-0.19, SE = 0.10, CI [-0.401, − 0.023]) pero no en niveles altos de estigma por orientación sexual (B=-0.04, SE = 0.06, CI [-0.160, 0.074]). Estos hallazgos sugieren que abordar el estigma del VIH experimentado en entornos de atención médica en la República Dominicana, junto con diversas dimensiones del estigma relacionado con el VIH (por ejemplo, estigma internalizado) y estigmas interseccionales (por ejemplo, raza, orientación sexual), es vital para mejorar los resultados de salud, como la adherencia óptima al TAR.

3.
Mol Cell Proteomics ; 21(7): 100252, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35636728

RESUMO

Changes in the abundance of individual proteins in the proteome can be elicited by modulation of protein synthesis (the rate of input of newly synthesized proteins into the protein pool) or degradation (the rate of removal of protein molecules from the pool). A full understanding of proteome changes therefore requires a definition of the roles of these two processes in proteostasis, collectively known as protein turnover. Because protein turnover occurs even in the absence of overt changes in pool abundance, turnover measurements necessitate monitoring the flux of stable isotope-labeled precursors through the protein pool such as labeled amino acids or metabolic precursors such as ammonium chloride or heavy water. In cells in culture, the ability to manipulate precursor pools by rapid medium changes is simple, but for more complex systems such as intact animals, the approach becomes more convoluted. Individual methods bring specific complications, and the suitability of different methods has not been comprehensively explored. In this study, we compare the turnover rates of proteins across four mouse tissues, obtained from the same inbred mouse strain maintained under identical husbandry conditions, measured using either [13C6]lysine or [2H2]O as the labeling precursor. We show that for long-lived proteins, the two approaches yield essentially identical measures of the first-order rate constant for degradation. For short-lived proteins, there is a need to compensate for the slower equilibration of lysine through the precursor pools. We evaluate different approaches to provide that compensation. We conclude that both labels are suitable, but careful determination of precursor enrichment kinetics in amino acid labeling is critical and has a considerable influence on the numerical values of the derived protein turnover rates.


Assuntos
Lisina , Proteoma , Aminoácidos/metabolismo , Animais , Marcação por Isótopo/métodos , Lisina/metabolismo , Camundongos , Proteólise , Proteoma/metabolismo
4.
Curr Oncol Rep ; 24(3): 375-385, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35142974

RESUMO

PURPOSE OF THE REVIEW: Esophageal cancer is the sixth most common cause of cancer death globally. Squamous cell carcinoma of the esophagus (ESCC) is the predominant histologic type in the world. Treatment strategies have evolved in the last decade and new paradigms are replacing traditional approaches at all stages of cancer. This review will summarize the epidemiology, diagnosis, staging, and treatment of esophageal squamous cell carcinoma. RECENT FINDINGS: Novel approaches to screening may be cost-effective in regions with a high incidence of ESCC. Multi-disciplinary evaluation and treatment has become the standard of care. Endoscopic resection may be an option for early stage ESCC. Minimally invasive esophagectomy can be performed safely as a primary therapy or after-induction chemoradiation. Several recent studies have found a survival benefit to immunotherapy for patients with metastatic or persistent disease. Multi-disciplinary evaluation and multi-modal therapy including cytotoxic chemotherapy, radiation, surgery, and immunotherapy have improved survival compared to surgery alone.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Células Epiteliais/patologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia/efeitos adversos , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
5.
World J Surg ; 46(7): 1567-1574, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35368235

RESUMO

Esophagectomy for achalasia is reserved for patients with end-stage disease for whom prior treatment has failed. Esophagectomy can be performed safely through a variety of techniques. Conduit options include stomach, colon, and small intestine. There are many potential complications following esophagectomy. Outcomes of esophagectomy for achalasia are good when performed in experienced surgical centers.


Assuntos
Acalasia Esofágica , Esofagectomia , Colo , Acalasia Esofágica/cirurgia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Humanos , Estômago
6.
Semin Diagn Pathol ; 39(6): 383-388, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35123831

RESUMO

Intraoperative cytopathology for thoracic surgeons is a service that has not been utilized to its full potential in most institutions. It has the advantage of a rapid turnaround time, low costs, high accuracy, real time communication with the surgeon, on-site visualization of the lesion before excision, simplicity, and safety. Our experience, common cytologic findings of the most frequent thoracic tumors encountered during ICTS, hints about the service, and models for implementation and maintenance are presented. This review is aimed to present our experience and perspective about intraoperative cytopathology for thoracic surgeons.


Assuntos
Cirurgia Torácica , Humanos
7.
J Pathol ; 243(3): 390-400, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28815607

RESUMO

Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GECs), podocytes, and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFß, which has been implicated as an important mediator of glomerulosclerosis. GECs form a lumenized vascular network, which regresses in response to TGFß. MCs respond to TGFß by forming glomerulosclerotic-like nodules with matrix deposition. TGFß treatment of podocytes does not alter cell morphology but increases connective tissue growth factor (CTGF) expression. BMP7 prevents TGFß-induced GEC network regression, whereas TGFß-induced MC nodule formation is prevented by SMAD3 siRNA knockdown or ALK5 inhibitors but not BMP7, and increased phospho-SMAD3 was observed in human glomerulosclerosis. In 3D tri-culture, GECs, podocytes, and MCs form a vascular network in which GECs and podocytes interact intimately within a matrix containing MCs. TGFß treatment induces formation of nodules, but combined inhibition of ALK5 and CTGF is required to prevent TGFß-induced nodule formation in tri-cellular cultures. Identification of therapeutic targets for glomerulosclerosis depends on the 3D culture of all three glomerular cells. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Glomérulos Renais/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Matriz Extracelular/metabolismo , Humanos , Nefropatias/patologia , Glomérulos Renais/metabolismo , Células Mesangiais/citologia , Receptor do Fator de Crescimento Transformador beta Tipo I
8.
Nano Lett ; 16(1): 629-36, 2016 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-26612060

RESUMO

Superconducting layered transition metal dichalcogenides (TMDs) stand out among other superconductors due to the tunable nature of the superconducting transition, coexistence with other collective electronic excitations (charge density waves), and strong intrinsic spin-orbit coupling. Molybdenum disulfide (MoS2) is the most studied representative of this family of materials, especially since the recent demonstration of the possibility to tune its critical temperature, Tc, by electric-field doping. However, just one of its polymorphs, band-insulator 2H-MoS2, has so far been explored for its potential to host superconductivity. We have investigated the possibility to induce superconductivity in metallic polytypes, 1T- and 1T'-MoS2, by potassium (K) intercalation. We demonstrate that at doping levels significantly higher than that required to induce superconductivity in 2H-MoS2, both 1T and 1T' phases become superconducting with Tc = 2.8 and 4.6 K, respectively. Unusually, K intercalation in this case is responsible both for the structural and superconducting phase transitions. By adding new members to the family of superconducting TMDs, our findings open the way to further manipulate and enhance the electronic properties of these technologically important materials.


Assuntos
Dissulfetos/química , Molibdênio/química , Nanoestruturas/química , Potássio/química , Catálise , Calcogênios/química , Condutividade Elétrica , Temperatura
9.
J Pathol ; 230(2): 132-47, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23460469

RESUMO

TNF signals through two distinct receptors, designated TNFR1 and TNFR2, which initiate diverse cellular effects that include cell survival, activation, differentiation, and proliferation and cell death. These cellular responses can promote immunological and inflammatory responses that eradicate infectious agents, but can also lead to local tissue injury at sites of infection and harmful systemic effects. Defining the molecular mechanisms involved in TNF responses, the effects of natural and experimental genetic diversity in TNF signalling and the effects of therapeutic blockade of TNF has increased our understanding of the key role that TNF plays in infectious disease.


Assuntos
Doenças Transmissíveis/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Morte Celular , Doenças Transmissíveis/genética , Regulação da Expressão Gênica , Humanos , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo II do Fator de Necrose Tumoral/genética , Transdução de Sinais , Fator de Necrose Tumoral alfa/antagonistas & inibidores
10.
J Pathol ; 230(3): 241-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23460481

RESUMO

Tumour necrosis factor (TNF) was originally described as a circulating factor that can induce haemorrhagic necrosis of tumours. It is now clear that TNF has many different functions in cancer biology. In addition to causing the death of cancer cells, TNF can activate cancer cell survival and proliferation pathways, trigger inflammatory cell infiltration of tumours and promote angiogenesis and tumour cell migration and invasion. These effects can be explained by the diverse cellular responses TNF can initiate through distinct signal transduction pathways, opening the way for more selective targeting of TNF signalling in cancer therapy.


Assuntos
Neoplasias/patologia , Fatores de Necrose Tumoral/fisiologia , Animais , Morte Celular , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Humanos , Modelos Biológicos , Neoplasias/irrigação sanguínea , Neoplasias/imunologia , Neoplasias/terapia , Neovascularização Patológica , Transdução de Sinais , Fatores de Necrose Tumoral/genética , Fatores de Necrose Tumoral/uso terapêutico
11.
Ann Thorac Surg ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38777248

RESUMO

BACKGROUND: The current guidelines for the treatment of esophageal cancer recommend a multimodal approach that includes chemotherapy, targeted therapy and immunotherapy, radiation, and surgery. Despite advances in treatment, rates of treatment failure, pathologic incomplete response, tumor metastasis, and death remain unacceptably high. METHODS: This study was a narrative literature review using the terms "resectable esophageal cancer" and "multimodal therapy" to identify prospective trials of neoadjuvant radiation and chemotherapy, individually or combined with surgery, for esophageal cancer. Trials performed between 1984 and 2022 were identified and analyzed. CLINICALTRIALS: gov was queried to identify ongoing studies. RESULTS: Twenty-one clinical studies were identified: 15 randomized controlled trials and 6 prospective nonrandomized trials. The results of the randomized trials suggest that multimodal therapy-in the form of neoadjuvant chemotherapy in combination with radiation or chemotherapy alone, followed by surgery-is associated with better rates of local disease control and partial clinical response and, potentially, longer survival than is surgery alone. Immunotherapy is an emerging option for the treatment of patients with esophageal cancer. CONCLUSIONS: The treatment of patients with resectable esophageal cancer is rapidly evolving. Although previous treatment options have had only limited benefits for patients, significant progress has been made during last 3 decades. The results of the available studies suggest that advances in the treatment of esophageal cancer have the potential to improve survival in these patients; however, questions remain regarding mechanisms of action, patient selection, and the use of personalized approaches that are based on genetics.

12.
J Surg Case Rep ; 2024(2): rjae040, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38344140

RESUMO

Treatment of long-segment tracheal defects remains a challenge in thoracic surgery with no standard surgical option. Aortic allografts have been used for this purpose with varying degrees of success. In a patient that suffered anastomotic dehiscence after tracheal resection with primary anastomosis, we performed complete tracheal resection and replacement using a stented circumferential aortic allograft. Currently, this patient is able to breathe normally without tracheostomy assistance 22 months postoperatively. Our report is the first in the English literature of long-term survival without tracheostomy dependence and close interval follow-up after circumferential tracheal resection and replacement with a cryopreserved aortic allograft.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38836609

RESUMO

ABSTRACT: Medical school curricula across the United States fail to adequately prepare students to provide high-quality care to and advocate for patients with disabilities. To address this shortcoming at one large, urban medical school, the Curriculum Committee at Sidney Kimmel Medical College (SKMC) formed a taskforce of students and faculty to evaluate the degree and quality of disability representation in its undergraduate medical education (UME) curriculum. Taskforce members solicited input from five community members in various fields of disability advocacy to craft recommendations that reflected this community's vision for disability education in UME. Community partners suggested areas of focus including clinical skills, accessibility of healthcare facilities, awareness of intersectionality with other identities, acknowledgment of bias, and respect for the patient's autonomy via their "right to risk." The taskforce report to the Curriculum Committee included 9 recommendations for curricular revision based on community partner suggestions, 6 of which were accepted and are being implemented into the curricular content for the class of 2026 and beyond. This novel approach to implementing curricular change could encourage other medical schools to evaluate their own curricula through the lens of disability and prompt curricular revision with the input of community partners with disabilities, students, and, faculty.

14.
Eur J Cardiothorac Surg ; 65(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38011656

RESUMO

OBJECTIVES: A study of tumour metabolic reprogramming has revealed disease biomarkers and avenues for therapeutic intervention. Metabolic reprogramming in thymoma is currently understudied and largely unknown. This study utilized metabolomics and isotope tracing with 13C-glucose to metabolically investigate thymomas, adjacent thymic tissue and benign thymic lesions. METHODS: From 2017 to 2021, 20 patients with a suspected thymoma were recruited to this prospective Institutional Review Board approved clinical trial. At the time of surgery, 11 patients were infused with 13C-glucose, a stable, non-radioactive tracer which reports the flow of carbon through metabolic pathways. Samples were analysed by mass spectrometry to measure the abundance of >200 metabolites.13C enrichment was measured in patients who received 13C-glucose infusions. RESULTS: Histological analysis showed that 9 patients had thymomas of diverse subtypes and 11 patients had benign cysts. In our metabolomic analysis, thymomas could be distinguished from both adjacent thymus tissue and benign lesions by metabolite abundances. Metabolites in pyrimidine biosynthesis and glycerophospholipid metabolism were differentially expressed across these tissues.13C-glucose infusions revealed differential labelling patterns in thymoma compared to benign cysts and normal thymus tissue. The lactate/3PG labelling ratio, a metabolic marker in aggressive lung tumours correlated with lactate uptake, was increased in thymomas (1.579) compared to normal thymus (0.945) and benign masses (0.807) (thymic tissue versus tumour P = 0.021, tumour versus benign P = 0.013). CONCLUSIONS: We report metabolic biomarkers, including differential 13C labelling of metabolites from central metabolism, that distinguish thymomas from benign tissues. Altered glucose and lactate metabolism warrant further investigation and may provide novel therapeutic targets for thymoma.


Assuntos
Cistos , Timoma , Neoplasias do Timo , Humanos , Timoma/diagnóstico , Timoma/cirurgia , Timoma/patologia , Estudos Prospectivos , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/cirurgia , Neoplasias do Timo/patologia , Biomarcadores , Glucose , Lactatos
15.
Eur J Cardiothorac Surg ; 65(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38547389

RESUMO

OBJECTIVES: Spontaneous sternoclavicular joint infection (SSCJI) is a rare and poorly understood disease process. This study aims to identify factors guiding effective management strategies for SSCJI by using data mining. METHODS: An Institutional Review Board-approved retrospective review of patients from 2 large hospitals (2010-2022) was conducted. SSCJI is defined as a joint infection without direct trauma or radiation, direct instrumentation or contiguous spread. An interdisciplinary team consisting of thoracic surgeons, radiologists, infectious disease specialists, orthopaedic surgeons, hospital information experts and systems engineers selected relevant variables. Small set data mining algorithms, utilizing systems engineering, were employed to assess the impact of variables on patient outcomes. RESULTS: A total of 73 variables were chosen and 54 analysed against 11 different outcomes. Forty-seven patients [mean age 51 (22-82); 77% male] met criteria. Among them, 34 underwent early joint surgical resection (<14 days), 5 patients received delayed surgical intervention (>14 days) and 8 had antibiotic-only management. The antibiotic-only group had comparable outcomes. Indicators of poor outcomes were soft tissue fluid >4.5 cm, previous SSCJI, moderate/significant bony fragments, HgbA1c >13.9% and moderate/significant bony sclerosis. CONCLUSIONS: This study suggests that targeted antibiotic-only therapy should be considered initially for SSCJI cases while concurrently managing comorbidities. Patients displaying indicators of poor outcomes or no symptomatic improvement after antibiotic-only therapy should be considered for surgical joint resection.


Assuntos
Artrite Infecciosa , Articulação Esternoclavicular , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Articulação Esternoclavicular/diagnóstico por imagem , Articulação Esternoclavicular/cirurgia , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Antibacterianos/uso terapêutico
16.
Cureus ; 15(1): e34111, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36843809

RESUMO

Enlarged cisterna chyli is an infrequently encountered entity and is most often an asymptomatic, incidental finding on imaging for other reasons. The pathogenesis of cisterna chyli enlargement is not well elucidated and includes infectious, inflammatory, and idiopathic causes. In this report, we present the rare case of an asymptomatic, markedly dilated "mega" cisterna chyli in a 60-year-old female.

17.
Front Physiol ; 14: 1102393, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969577

RESUMO

Liver resection is an important surgical technique in the treatment of cancers and transplantation. We used ultrasound imaging to study the dynamics of liver regeneration following two-thirds partial hepatectomy (PHx) in male and female rats fed via Lieber-deCarli liquid diet protocol of ethanol or isocaloric control or chow for 5-7 weeks. Ethanol-fed male rats did not recover liver volume to the pre-surgery levels over the course of 2 weeks after surgery. By contrast, ethanol-fed female rats as well as controls of both sexes showed normal volume recovery. Contrary to expectations, transient increases in both portal and hepatic artery blood flow rates were seen in most animals, with ethanol-fed males showing higher peak portal flow than any other experimental group. A computational model of liver regeneration was used to evaluate the contribution of physiological stimuli and estimate the animal-specific parameter intervals. The results implicate lower metabolic load, over a wide range of cell death sensitivity, in matching the model simulations to experimental data of ethanol-fed male rats. However, in the ethanol-fed female rats and controls of both sexes, metabolic load was higher and in combination with cell death sensitivity matched the observed volume recovery dynamics. We conclude that adaptation to chronic ethanol intake has a sex-dependent impact on liver volume recovery following liver resection, likely mediated by differences in the physiological stimuli or cell death responses that govern the regeneration process. Immunohistochemical analysis of pre- and post-resection liver tissue validated the results of computational modeling by associating lack of sensitivity to cell death with lower rates of cell death in ethanol-fed male rats. Our results illustrate the potential for non-invasive ultrasound imaging to assess liver volume recovery towards supporting development of clinically relevant computational models of liver regeneration.

18.
Contemp Clin Trials Commun ; 29: 100980, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36060154

RESUMO

Background: This protocol details the adaptation and pilot testing of the Finding Respect and Ending Stigma around HIV (FRESH) intervention in Dominican Republic. FRESH is a healthcare setting stigma-reduction intervention designed to reduce stigmas affecting people living with HIV (PLHIV), focusing on HIV and intersectional stigmas experienced by sexual and gender minority (SGM) people living with HIV. After the successful adaptation of the FRESH intervention, it will be pilot-tested through the conduct of a pilot stepped wedge cluster randomized controlled trial. Methods: Three aims are included in this study; Aim 1 includes exploratory qualitative assessment, specifically the conduct four focus groups with men who have sex with men (MSM) living with HIV (n = 24-32) and in-depth interviews with transgender women living with HIV to explore their experiences with stigma in clinics (n = 9-12). In-depth interviews will also be held with HIV healthcare workers to elucidate their perceptions and behaviors towards their SGM clients (n = 9-12). In Aim 2, informed by Aim 1 data, we will use the sequential phases of the ADAPT-ITT framework to iteratively adapt the FRESH intervention for the Dominican Republic. In Aim 3, the adapted intervention will be pilot-tested via a cluster stepped wedge randomized controlled trial to assess feasibility and acceptability of the intervention and study protocols. Conclusions: If this pilot trial is successful, next steps will include testing the adapted intervention across Dominican Republic or in similar Spanish-speaking Caribbean nations in a larger trial to assess effectiveness in reducing stigma in clinical settings towards PLHIV.

19.
Adv Physiol Educ ; 35(2): 227-36, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21652509

RESUMO

This study examined the effect of different anatomic representations on student learning in a human anatomy class studying the muscular system. Specifically, we examined the efficacy of using dissected cats (with and without handouts) compared with clay sculpting of human structures. Ten undergraduate laboratory sections were assigned to three treatment groups: cat dissection only, cat dissection with handouts, and human clay sculpting with handouts. Exams included higher-order questions that presented novel anatomic images and scenarios that the students did not practice in class. The higher-order anatomy exam questions varied the degree to which students in the different treatments had to transform the anatomic representation studied during laboratory activities to match the representation used in the exam questions. In this respect, exam questions manipulated the similarity between the surface features of the anatomic representations used in the classroom versus the exam. When identifying anatomic structures presented in a photograph or diagram, student performance improved significantly when transformation demands decreased, i.e., students in the human clay sculpting treatment group performed best on human anatomy questions and students in the cat dissection treatment group performed better on cat anatomy questions (independent of the use of handouts). There were similar, but nonsignificant, trends when students were asked functional anatomy questions presented in human and cat contexts. On survey questions designed to measure student attitudes about dissection versus nonanimal alternatives, students typically preferred the method used in their treatment group, suggesting that student preference is too fluid to factor into curricular decisions. When designing curricula, instructors must choose anatomic representations that support their course goals. Human representations are most effective when teaching the human muscular system.


Assuntos
Anatomia/educação , Dissecação/métodos , Avaliação Educacional/métodos , Modelos Animais , Adolescente , Adulto , Silicatos de Alumínio , Animais , Gatos , Argila , Currículo , Coleta de Dados , Escolaridade , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pennsylvania , Estatística como Assunto , Análise e Desempenho de Tarefas , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-34957464

RESUMO

In this brief report, we aim to assess levels of HIV mis-information among cisgender Haitian female sex workers engaged in sex work at the Haiti and Dominican Republic border. We conducted bivariate analyses on the 2014 Border Study on Sex Workers comparing responses from female sex workers on the Haiti side of the border to those from their peers on the Dominican Republic side (N=212). Prevention of HIV acquisition by correct and consistent condom use with each sex act was correctly endorsed by 90.5% of female sex workers in Haiti but only 57.0% of their peers in Dominican Republic (χ2=32.28, p<0.001); 84.1% of respondents in Haiti correctly identified that HIV can be transmitted through a single unprotected sexual act, compared to 52.3% in Dominican Republic (χ2=25.2, p<0.001). Significantly higher percentages of female sex workers in Dominican Republic correctly responded that HIV can be transmitted in pregnancy, compared to respondents in Haiti (96.5% vs. 71.4%; χ2=21.42, p<0.001). Higher percentages of respondents in Dominican Republic correctly answered that HIV can be transmitted through needle sharing, relative to respondents in Haiti (100.0% vs 89.7%; χ2=9.45, p<0.01). Respondents in Dominican Republic more accurately rejected the possibility of transmission through food or through mosquito bites, compared to respondents in Haiti (95.4% vs. 81.8%, χ2=8.51, p<0.01; 97.7% vs. 86.5%, χ2=7.81, p<0.01, respectively). Findings indicate that if HIV knowledge is examined aggregating responses to individual questions, then elements of misinformation may remain unaddressed. For example, we found significant differences in correct answers ranging from 16.7% to 100.0%.

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