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1.
J Immunother Cancer ; 12(5)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754916

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and refractory B-cell malignancies. If CAR-T cell therapy for non-hematological malignancies is to achieve the same stage of clinical development, then iterative early-phase clinical testing can add value to the clinical development process for evaluating CAR-T cell products containing different CAR designs and manufactured under differing conditions. METHODS: We conducted a phase 1 trial of third-generation GD2-specific CAR-T cell therapy, which has previously been tested in neuroblastoma patients. In this study, the GD2-CAR-T therapy was evaluated for the first time in metastatic melanoma patients in combination with BRAF/MEK inhibitor therapy, and as a monotherapy in patients with colorectal cancer and a patient with fibromyxoid sarcoma. Feasibility and safety were determined and persistence studies, multiplex cytokine arrays on sera and detailed immune phenotyping of the original CAR-T products, the circulating CAR-T cells, and, in select patients, the tumor-infiltrating CAR-T cells were performed. RESULTS: We demonstrate the feasibility of manufacturing CAR-T products at point of care for patients with solid cancer and show that a single intravenous infusion was well tolerated with no dose-limiting toxicities or severe adverse events. In addition, we note significant improvements in CAR-T cell immune phenotype, and expansion when a modified manufacturing procedure was adopted for the latter 6 patients recruited to this 12-patient trial. We also show evidence of CAR-T cell-mediated immune activity and in some patients expanded subsets of circulating myeloid cells after CAR-T cell therapy. CONCLUSIONS: This is the first report of third-generation GD2-targeting CAR-T cells in patients with metastatic melanoma and other solid cancers such as colorectal cancer, showing feasibility, safety and immune activity, but limited clinical effect. TRIAL REGISTRATION NUMBER: ACTRN12613000198729.


Assuntos
Imunoterapia Adotiva , Melanoma , Receptores de Antígenos Quiméricos , Humanos , Melanoma/imunologia , Melanoma/terapia , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Receptores de Antígenos Quiméricos/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Gangliosídeos/imunologia , Adulto , Idoso , Linfócitos T/imunologia , Resultado do Tratamento
2.
Soc Sci Med ; 352: 117015, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38788530

RESUMO

This study investigates the intersection of race, gender, and criminality in the language surrounding mental health and illness. Applying computational methods of word embeddings to full text data from major American newspapers between 2000 and 2023, I show that the landscape of mental health is broadly racialized as black, challenging the notion of mental illness as a predominantly white phenomenon. Cultural ideas about mental illness are gendered such that women are medicalized and men are criminalized, yet certain terms blur the boundary between illness and criminality. I highlight how stereotypes embedded in mental health language perpetuate stigma around men's mental health and justify social control with notable implications for black men. I conclude with recommendations for the mental health movement by advocating for more inclusive discussions around men's mental health and revised person-centric language.

3.
Nurse Res ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770593

RESUMO

BACKGROUND: The evidence base for hydration practice in care homes is underdeveloped. High-quality research is therefore needed to determine what practices support older people with dementia in drinking sufficient fluid. However, methodological developments are needed to be able to do this. AIM: To highlight the methodological issues researchers encountered during a feasibility cluster, randomised controlled trial of ThinkDrink, a hydration care guide for people with dementia living in UK care homes. DISCUSSION: This is a challenging area because of the complexity of recruitment, participation and data collection in care homes. Researchers must pay extra attention to rigour and quality in the design of their studies. There may be multiple challenges, so various strategies may be required. CONCLUSION: It is important that researchers continue to reflect on rigorous approaches to develop evidence in a crucial area of care, despite these challenges. IMPLICATIONS FOR PRACTICE: Researchers working in complex environments face a variety of challenges to complete methodologically rigorous research. It is important for researchers to be critical of research processes and data, to mitigate and overcome these challenges.

4.
J Exp Biol ; 227(9)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38738313

RESUMO

A hydrostatic skeleton allows a soft body to transmit muscular force via internal pressure. A human's tongue, an octopus' arm and a nematode's body illustrate the pervasive presence of hydrostatic skeletons among animals, which has inspired the design of soft engineered actuators. However, there is a need for a theoretical basis for understanding how hydrostatic skeletons apply mechanical work. We therefore modeled the shape change and mechanics of natural and engineered hydrostatic skeletons to determine their mechanical advantage (MA) and displacement advantage (DA). These models apply to a variety of biological structures, but we explicitly consider the tube feet of a sea star and the body segments of an earthworm, and contrast them with a hydraulic press and a McKibben actuator. A helical winding of stiff, elastic fibers around these soft actuators plays a critical role in their mechanics by maintaining a cylindrical shape, distributing forces throughout the structure and storing elastic energy. In contrast to a single-joint lever system, soft hydrostats exhibit variable gearing with changes in MA generated by deformation in the skeleton. We found that this gearing is affected by the transmission efficiency of mechanical work (MA×DA) or, equivalently, the ratio of output to input work. The transmission efficiency changes with the capacity to store elastic energy within helically wrapped fibers or associated musculature. This modeling offers a conceptual basis for understanding the relationship between the morphology of hydrostatic skeletons and their mechanical performance.


Assuntos
Oligoquetos , Animais , Fenômenos Biomecânicos , Oligoquetos/fisiologia , Modelos Biológicos , Cifozoários/fisiologia , Cifozoários/anatomia & histologia , Esqueleto/fisiologia
5.
bioRxiv ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38766165

RESUMO

Ferroptosis is a form of cell death caused by lipid peroxidation that is emerging as a target for cancer therapy, highlighting the need to identify factors that govern ferroptosis susceptibility. Lipid peroxidation occurs primarily on phospholipids containing polyunsaturated fatty acids (PUFAs). Here, we show that even though extracellular lipid limitation reduces cellular PUFA levels, lipid-starved cancer cells are paradoxically more sensitive to ferroptosis. Using mass spectrometry-based lipidomics with stable isotope fatty acid labeling, we show that lipid limitation induces a fatty acid trafficking pathway in which PUFAs are liberated from triglycerides to synthesize highly unsaturated PUFAs such as arachidonic acid and adrenic acid. These PUFAs then accumulate in phospholipids, particularly ether phospholipids, to promote ferroptosis sensitivity. Therefore, PUFA levels within cancer cells do not necessarily correlate with ferroptosis susceptibility. Rather, how cancer cells respond to extracellular lipid levels by trafficking PUFAs into proper phospholipid pools dictates their sensitivity to ferroptosis.

6.
Skin Health Dis ; 4(2): e324, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577057

RESUMO

Background: Alopecia describes a group of dermatological conditions characterised by hair loss, which are either non-scarring or scarring in nature, and range from bald patches to complete body hair loss, to general thinning. In the UK, the General Practitioner (GP) is typically the first point of contact, and some patients are referred for specialist dermatology consultation. However, little is known about how individuals with alopecia in the UK experience the care provided by the National Health Service. Objectives: We aimed to understand patients' perceptions of primary healthcare and dermatology provision. Further, we aimed to investigate how care provision and patients' overall patient journey might be improved in the UK, and how these lessons may apply internationally. Methods: An online mixed methods survey was distributed by Alopecia UK to UK-based individuals with alopecia. Open-ended text responses were analysed using qualitative content analysis. Quantitative data were analysed using descriptive analyses and dependent measures t-tests. Results: A total of 291 participants completed the survey. They reported neutral-to-partial dissatisfaction with their GP appointments, with greater satisfaction in their most recent compared to their first appointment. Participants highlighted positive experiences with GPs and dermatologists as well as areas for improvement. Participants also expressed a desire for a greater degree of support and understanding about the psychological impact of alopecia. Conclusions: Results highlight the importance of being empathic and caring healthcare professionals for patients with alopecia, the need for training for GPs on alopecia, as well as a simplified and joined up pathway between primary and secondary healthcare.

7.
Acad Pediatr ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631476

RESUMO

OBJECTIVE: Oral pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission. However, oral PrEP uptake is low, particularly among sexual and gender minority youth who are vulnerable to HIV infection. Alternative methods of PrEP delivery, such as long-acting injectable (LAI) PrEP may overcome barriers and be preferred. However, attitudes and preferences of younger sexual and gender minorities towards LAI PrEP have not been well studied. The purpose of this study is to describe preferences for initiating LAI PrEP among sexual and gender minority youth. METHODS: We analyzed data collected as part of an HIV prevention randomized trial from January 2022 to February 2023, using multiple regression to identify factors associated with a preference for LAI PrEP. RESULTS: The study sample (N = 265) was 50% youth of color, mean age 25 years (SD=3.4, range=18-31), and primarily identified as gay (71%) and male (91%). Forty two percent had heard of LAI PrEP and 31% preferred LAI PrEP over other prevention methods. In multiple regression analysis, LAI PrEP preference was associated with identifying as White, previous PrEP experience, and perceived LAI PrEP efficacy. CONCLUSIONS: We conclude that gaps in awareness exist for LAI PrEP, however it may be preferred over other prevention methods especially in White youth, those with PrEP experience and higher perceptions of its efficacy. More education and outreach are needed to prevent extension of existing race and ethnicity disparities in use of oral daily PrEP to LAI PrEP.

8.
Cutis ; 113(3): E6-E9, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38648592

RESUMO

Carpet beetle larvae of the family Dermestidae have been documented to cause both acute and delayed hypersensitivity reactions in susceptible individuals. These larvae have specialized horizontal rows of spear-shaped hairs called hastisetae, which detach easily into the surrounding environment and are small enough to travel by air. Exposure to hastisetae has been tied to adverse effects ranging from dermatitis to rhinoconjunctivitis and acute asthma, with treatment being mostly empiric and symptom based. Due to the pervasiveness of carpet beetles in homes, improved awareness of dermestid-induced manifestations is valuable for clinicians.


Assuntos
Besouros , Larva , Animais , Humanos
9.
Artigo em Inglês | MEDLINE | ID: mdl-38541366

RESUMO

It is well known that parental depression is correlated to adverse child mental health outcomes; but what is the effect of treating parental depression on the child? This narrative review aims to explore this question, and how certain specific interventions designed to help depressed parents affect mental health outcomes in their children. The academic database APA PsychInfo was searched for articles that broadly included interventions for parents with depression as well as child wellbeing or outcomes as of October 2023. Additional searches were conducted in the academic database PubMed in December 2023 and January 2024. Forty-nine articles met the inclusion criteria and were examined closely for this review. The studies included were divided into the following categories: psychotherapy, psychopharmacology, parenting support, and paternal interventions. We discuss the implications of our review on clinical practice and recommend further research in this area.


Assuntos
Depressão , Psicoterapia , Criança , Masculino , Humanos , Depressão/terapia , Poder Familiar/psicologia , Pai , Cicatrização
10.
Front Pharmacol ; 15: 1358393, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495100

RESUMO

Introduction: The development of bioconjugates for the targeted delivery of anticancer agents is gaining momentum after recent success of antibody drug conjugates (ADCs) in the clinic. Smaller format conjugates may have several advantages including better tumor penetration; however, cellular uptake and trafficking may be substantially different from ADCs. To fully leverage the potential of small molecule drug conjugates (SMDCs) with potent binding molecules mediating tumor homing, novel linker chemistries susceptible for efficient extracellular activation and payload release in the tumor microenvironment (TME) need to be explored. Methods: We designed a novel class of SMDCs, which target αvß3 integrins for tumor homing and are cleaved by neutrophil elastase (NE), a serine protease active in the TME. A peptidomimetic αvß3 ligand was attached via optimized linkers composed of substrate peptide sequences of NE connected to different functional groups of various payload classes, such as camptothecins, monomethyl auristatin E, kinesin spindle protein inhibitors (KSPi) and cyclin-dependent kinase 9 inhibitors (CDK-9i). Results: NE-mediated cleavage was found compatible with the diverse linker attachments via hindered ester bonds, amide bonds and sulfoximide bonds. Efficient and traceless release of the respective payloads was demonstrated in biochemical assays. The newly designed SMDCs were highly stable in buffer as well as in rat and human plasma. Cytotoxicity of the SMDCs in cancer cell lines was clearly dependent on NE. IC50 values were in the nanomolar or sub-nanomolar range across several cancer cell lines reaching similar potencies as compared to the respective payloads only in the presence of NE. In vivo pharmacokinetics evaluating SMDC and free payload exposures in rat and particularly the robust efficacy with good tolerability in triple negative breast and small cell lung cancer murine models demonstrate the utility of this approach for selective delivery of payloads to the tumor. Discussion: These results highlight the broad scope of potential payloads and suitable conjugation chemistries paving the way for future SMDCs harnessing the safety features of targeted delivery approaches in combination with NE cleavage in the TME.

11.
Frontline Gastroenterol ; 15(1): 42-49, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38487555

RESUMO

Alcohol-related hepatitis (AH) is the most florid presentation of alcohol-related liver disease and carries a high short-term and long-term mortality rate. Specific treatment options remain inadequate. The current management approach for AH focuses on early identification, careful screening and treatment of infection, as well as identification of those patients who may benefit from corticosteroid therapy based on validated prognostic scoring systems. In recent years, there has been growing interest in exploring novel therapies for AH, which may offer alternative treatment options beyond the traditional approaches. Additionally, early liver transplantation (LT) has emerged as a promising option in selected cases with growing evidence supporting its role. In this review, we will discuss the current evidence base for the assessment and treatment of AH, and how these advances are shaping practice to improve outcomes in the UK.

12.
PLoS One ; 19(3): e0300540, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38483939

RESUMO

Automated algorithms for identifying potential pre-exposure prophylaxis (PrEP) candidates are effective among men, yet often fail to detect cisgender women (hereafter referred to as "women") who would most benefit from PrEP. The emergency department (ED) is an opportune setting for implementing automated identification of PrEP candidates, but there are logistical and practical challenges at the individual, provider, and system level. In this study, we aimed to understand existing processes for identifying PrEP candidates and to explore determinants for incorporating automated identification of PrEP candidates within the ED, with specific considerations for ciswomen, through a focus group and individual interviews with ED staff. From May to July 2021, we conducted semi-structured qualitative interviews with 4 physicians and a focus group with 4 patient advocates working in a high-volume ED in Chicago. Transcripts were coded using Dedoose software and analyzed for common themes. In our exploratory study, we found three major themes: 1) Limited PrEP knowledge among ED staff, particularly regarding its use in women; 2) The ED does not have a standardized process for assessing HIV risk; and 3) Perspectives on and barriers/facilitators to utilizing an automated algorithm for identifying ideal PrEP candidates. Overall, ED staff had minimal understanding of the need for PrEP among women. However, participants recognized the utility of an electronic medical record (EMR)-based automated algorithm to identify PrEP candidates in the ED. Facilitators to an automated algorithm included organizational support/staff buy-in, patient trust, and dedicated support staff for follow-up/referral to PrEP care. Barriers reported by participants included time constraints, hesitancy among providers to prescribe PrEP due to follow-up concerns, and potential biases or oversight resulting from missing or inaccurate information within the EMR. Further research is needed to determine the feasibility and acceptability of an EMR-based predictive HIV risk algorithm within the ED setting.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Masculino , Humanos , Feminino , Profilaxia Pré-Exposição/métodos , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Pesquisa Qualitativa , Serviço Hospitalar de Emergência
13.
Proc Natl Acad Sci U S A ; 121(9): e2306554121, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38377187

RESUMO

The national context of deportation threat, defined as the federal government's approach to deportation and/or deportation's salience to the US public, fluctuated between 2011 and 2018. US Latinos across citizenship statuses may have experienced growing psychological distress associated with these changes, given their disproportionate personal or proximal vulnerabilities to deportation. Drawing on 8 y of public- and restricted-access data from the National Health Interview Survey (2011 to 2018), this article examines trends in psychological distress among Latinos who are US-born citizens, naturalized citizens, and noncitizens. It then seeks to explain these trends by considering two theoretical pathways through which the national context of deportation threat could distress Latinos: 1) through discrete dramatic societal events that independently signal a change to the country's approach to deportation and/or that render deportation temporarily more salient to the public or 2) through more gradual changes to the country's everyday institutional (i.e., quotidian efforts to detain and deport noncitizens) and social (i.e., deportation's ongoing salience to a concerned public) environment of deportation threat. We find that, though both pathways matter to some degree, there is more consistent evidence that the gradual changes are associated with Latino US citizens and noncitizens' overall experiences of psychological distress. The article highlights how, even absent observable spillover effects of dramatic societal events bearing on deportation threat, the institutional and social environment in which they occur implicates Latinos' well-being.


Assuntos
Emigrantes e Imigrantes , Angústia Psicológica , Humanos , Estados Unidos , Deportação , Hispânico ou Latino/psicologia , Inquéritos e Questionários , Meio Social
14.
Clin Nutr ESPEN ; 59: 118-125, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38220364

RESUMO

INTRODUCTION: Variation in access to parenteral nutrition (PN) in patients with intestinal failure secondary to malignant bowel obstruction (MBO) exists due to differing practice, beliefs and resource access. We aimed to examine differences in nutritional care pathways and outcomes, by referral to nutrition team for PN in patients with MBO. METHODS: This is a retrospective cohort study of MBO adults admitted to eight UK hospitals within a year and 1 year follow-up. Demographic, nutritional and medical data were analysed by comparing patients referred (R) or not referred (NR) for PN. Differences between groups were tested by Kruskal-Wallis, Chi-Squared tests and multi-level regression and survival using Cox regression. RESULTS: 232 patients with 347 MBO admissions [median 66yr, (IQR: 55-74yrs), 67 % female], 79/232 patients were referred for PN (R group). Underlying primary malignancies of gynaecological and gastrointestinal origin predominated (71 %) and 78 % with metastases. Those in the NR group were found to be older, weigh more on admission, and more likely to be treated conservatively compared to those in the R group. For 123 (35 %) admissions, patients were referred to a nutrition team, and for 204 (59 %) admissions, patients were reviewed by a dietician. Multi-disciplinary team discussion and dietetic contact were more likely to occur in the R group-123/347 admissions (R vs NR group: 27 % vs. 7 %, P = 0.001; 95 % vs 39 %, P < 0.0001). Median admission weight loss was 8 % (IQR: 0 to 14). 43/123 R group admissions received inpatient PN only, with 32 patients discharged or already established on home parenteral nutrition. Overall survival was 150 days (126-232) with no difference between R/NR groups. CONCLUSION: In this multi-centre study evaluating nutritional care management of patients with malignant bowel obstruction, only 1 in 3 admissions resulted in a referral to the nutrition team for PN, and just over half were reviewed by a dietician. Further prospective research is required to evaluate possible consequences of these differential care pathways on clinical outcomes and quality of life.


Assuntos
Obstrução Intestinal , Neoplasias , Nutrição Parenteral no Domicílio , Feminino , Humanos , Masculino , Procedimentos Clínicos , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia , Neoplasias/complicações , Neoplasias/terapia , Qualidade de Vida , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso
15.
BMC Public Health ; 24(1): 56, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166881

RESUMO

BACKGROUND: Sex workers, those who trade sex for monetary or nonmonetary items, experience high rates of HIV transmission but have not been adequately included in HIV prevention and Pre-Exposure Prophylaxis (PrEP) adherence program development research. Community-empowered (C.E.) approaches have been the most successful at reducing HIV transmission among sex workers. Centering Healthcare (Centering) is a C.E. model proven to improve health outcomes and reduce health disparities in other populations, such as pregnant women, people with diabetes, and sickle cell disease. However, no research exists to determine if Centering can be adapted to meet the unique HIV prevention needs of sex workers. OBJECTIVE: We aim to explain the process by which we collaboratively and iteratively adapted Centering to meet the HIV prevention and PrEP retention needs of sex workers. METHODS: We utilized the Assessment, Decision, Adaptation, Production, Topical Experts, Integration, Training, Testing (ADAPT-ITT) framework, a model for adapting evidence-based interventions. We applied phases one through six of the ADAPT-ITT framework (Assessment, Decision, Adaptation, Production, Topical Experts, Integration) to the design to address the distinct HIV prevention needs of sex workers in Chicago. Study outcomes corresponded to each phase of the ADAPT-ITT framework. Data used for adaptation emerged from collaborative stakeholder meetings, individual interviews (n = 36) and focus groups (n = 8) with current and former sex workers, and individual interviews with care providers (n = 8). In collaboration with our community advisory board, we used a collaborative and iterative analytical process to co-produce a culturally adapted 3-session facilitator's guide for the Centering Pre-exposure Prophylaxis (C-PrEP +) group healthcare model. RESULTS: The ADAPT-ITT framework offered structure and facilitated this community-empowered innovative adaptation of Centering Healthcare. This process culminated with a facilitator's guide and associated materials ready for pilot testing. CONCLUSIONS: In direct alignment with community empowerment, we followed the ADAPT-ITT framework, phases 1-6, to iteratively adapt Centering Healthcare to suit the stated HIV Prevention and PrEP care needs of sex workers in Chicago. The study represents the first time the first time Centering has been adapted to suit the HIV prevention and PrEP care needs of sex workers. Addressing a gap in HIV prevention care for sex workers, Centering PrEP harnesses the power of community as it is an iteratively adapted model that can be piloted and replicated regionally, nationally, and internationally.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Profissionais do Sexo , Humanos , Feminino , Gravidez , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Chicago , Atenção à Saúde , Fármacos Anti-HIV/uso terapêutico
16.
J Vet Intern Med ; 38(2): 1207-1213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38205913

RESUMO

BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses. HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses. ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November 2010 and March 2022. METHODS: Case-control study using biobanked samples was performed and commercial competitive ELISA kit (Highly Sensitive 8-OHdG Check ELISA) utilized. Concentration of 8-OHdG was quantitated in both CSF and serum and compared between groups. RESULTS: No correlation was established between the measures of 8-OHdG in serum and CSF and group. CSF median [8-OHdG] for NAD/DM was 169.9 pg/mL (IQR25-75 : 67.18-210.6), CVSM 157.1 pg/mL (IQR25-75 : 132.1-229.1), EPM 131.4 pg/mL (IQR25-75 : 102.1-193.2), and control 149.8 pg/mL (IQR25-75 : 113.3-196.4). Serum median [8-OHdG] for NAD/DM was 130 pg/mL (IQR25-75 : 51.73-157.2), CVSM 125.8 pg/mL (IQR25-75 : 62.8-170.8), EPM 120.6 pg/mL (IQR25-75 : 87.23-229.7), and control 157.6 pg/mL (IQR25-75 : 97.15-245.6). Poisson regression analysis showed no difference established once confounding variables were considered. CONCLUSIONS: Eight-OHdG did not aid in antemortem diagnosis of NAD/DM in this cohort of horses. At the time of diagnosis horses with NAD/DM do not have ongoing oxidative stress.


Assuntos
Doenças dos Cavalos , Distrofias Neuroaxonais , Doenças Neurodegenerativas , Humanos , Animais , Cavalos , 8-Hidroxi-2'-Desoxiguanosina , Doenças Neurodegenerativas/veterinária , Estudos de Casos e Controles , NAD , Doenças dos Cavalos/diagnóstico , Distrofias Neuroaxonais/veterinária , Ataxia/veterinária
17.
J Vet Intern Med ; 38(1): 431-439, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38095342

RESUMO

BACKGROUND: Adult horses with proprioceptive ataxia and behavior changes that have histologic lesions consistent with neurodegenerative disease have been increasingly recognized. HYPOTHESIS/OBJECTIVES: Describe the history, clinical findings and histopathologic features of horses presented to a referral institution with neuroaxonal degeneration. ANIMALS: One hundred horses with a necropsy diagnosis of neuroaxonal degeneration compatible with neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM). METHODS: Retrospective study of horses presented to the University of Pennsylvania, New Bolton Center, between 2017 and 2021 with a necropsy diagnosis of eNAD/EDM. RESULTS: Affected horses had a median age of 8 years (range, 1-22), and the majority were Warmbloods (72). Sixty-eight horses had behavioral changes, and all 100 had proprioceptive ataxia (median grade, 2/5). Fifty-seven horses had abnormal findings on cervical vertebral radiographs, and 14 had myelographic findings consistent with compressive myelopathy. No antemortem diagnostic test results were consistently associated with necropsy diagnosis of neurodegenerative disease. All 100 horses had degenerative lesions characteristic of eNAD in the brainstem gray matter, and 24 had concurrent degenerative features of EDM in the spinal cord white matter. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical and histopathologic findings in this large group of horses with neurodegenerative disease were most consistent with eNAD/EDM, but with a different signalment and clinical presentation from earlier descriptions. The increasing occurrence of neurodegenerative disease in horses and the safety risk posed emphasize the importance of focused research in affected horses.


Assuntos
Doenças dos Cavalos , Distrofias Neuroaxonais , Doenças Neurodegenerativas , Compressão da Medula Espinal , Cavalos , Animais , Doenças Neurodegenerativas/veterinária , Estudos Retrospectivos , Distrofias Neuroaxonais/veterinária , Compressão da Medula Espinal/veterinária , Ataxia/veterinária , Doenças dos Cavalos/diagnóstico
18.
Sex Transm Dis ; 51(3): 139-145, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38100791

RESUMO

BACKGROUND: The incidence of sexually transmitted infections (STIs) has been increasing in the United States, and this trend has continued alongside expanding/changing human immunodeficiency virus (HIV) prevention strategies, moving from reliance solely on behavioral interventions like condoms to biomedical methods like oral and injectable antiretroviral preexposure prophylaxis (PrEP). In 2019, the Ending the HIV Epidemic (EHE) initiative was released to prioritize resource allocation to the 50 jurisdictions in the United States with the highest HIV incidence, providing an opportunity to monitor STI incidence in a national group of discrete, geographic units and identify trends and differences across jurisdictions. OBJECTIVES AND DESIGN: Using existing data from the US CDC and Census Bureau, a retrospective analysis was conducted to examine the incidence of STIs in 49 of the 50 EHE priority counties between 2005 and 2019. This timeframe was divided into 2 periods representing a before and after entry into the biomedical era of HIV prevention: P1 (2005-2011) and P2 (2012-2019). KEY RESULTS: A total of 49 EHE counties were included in this analysis, representing 27.4% of the total US population. Entry into the biomedical HIV prevention era was associated with an increase in STI incidence in 28 EHE counties and a decrease in 14 EHE counties. The greatest percent increase in total STI incidence was in the District of Columbia (+12.1%; incidence rate ratio = 1.121 [1.115, 1.127]; P < 0.001) and the greatest percent decrease was identified in Orleans Parish, LA (-8.7%; incidence rate ratio = 0.913 [0.908, 0.919]; P < 0.001). CONCLUSIONS: Rising STI rates in the biomedical era of HIV prevention represent missed opportunities for comprehensive sexual and preventive healthcare. County-level data provide actionable insight for reducing STI incidence. The EHE counties that have experienced decreases in STI incidence while being in the biomedical era may provide models of best practice, which may be scaled in other jurisdictions.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Infecções Sexualmente Transmissíveis , Humanos , Estados Unidos/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Incidência , HIV , Estudos Retrospectivos , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Profilaxia Pré-Exposição/métodos , District of Columbia
19.
Front Psychol ; 14: 1339578, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38144979

RESUMO

[This corrects the article DOI: 10.3389/fpsyg.2023.1122277.].

20.
BMC Infect Dis ; 23(1): 781, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946103

RESUMO

BACKGROUND: Ciswomen constitute a disproportionately low percentage of pre-exposure prophylaxis for HIV prevention (PrEP) users compared to men. Despite PrEP's effectiveness, women are 5.25 times less likely to take PrEP than men. Identifying women who have increased reasons for HIV prevention and educating and offering PrEP to these women is crucial to reducing HIV transmission and overall health equity. However, the best method of identifying women at highest risk of acquiring HIV remains unknown. This study aimed to identify common HIV risk factors and data sources for identifying these common factors (e.g., electronic medical record data, open source neighborhood data), as well as potential intervention points and missed opportunities for PrEP linkage. METHODS: We conducted an evaluation of multiple data sources: semi-structured qualitative interviews, electronic medical record (EMR) chart abstraction, and open source data abstraction. We accessed EMRs for enrolled participants and all participants signed a standard release of medical information (ROI) form for all institutions at which they had received medical care for the five-year period preceding their HIV diagnosis. Data were abstracted using a standardized procedure. Both structured and unstructured fields (i.e., narrative text of free notes) within the EMR were examined and included for analysis. Finally, open data sources (e.g., STI cases, HIV prevalence) were examined by community area of Chicago. Open data sources were used to examine several factors contributing to the overall Economic Hardship Index (EHI) score. We used these calculated scores to assess the economic hardship within participants' neighborhoods. RESULTS: A total of 18 cisgender women with HIV participated in our study. Participants were mostly Black/African American (55.6%) and young (median age of 34). Our analysis identified two main themes influencing HIV risk among participants: contextual factors and relationship factors. Further, potential pre-diagnosis intervention points and missed opportunities were identified during reproductive health/prenatal visits, behavioral/mental health visits, and routine STI testing. Our evaluation of multiple data sources included investigating the presence or absence of information in the EMR (STI history, HIV testing, substance use, etc.) as well as whether pertinent information could be gathered from open access sources. CONCLUSION: Ciswomen recently diagnosed with HIV identified many shared experiences, including syndemic conditions like mental illness and substance abuse, sex with men who have sex with men, and frequent moving in areas with high HIV incidence prior to their diagnosis. It is imperative that providers ask patients about social history, information about partners, and other key variables, in addition to the standardized questions. Findings can be used to better recognize ciswomen most vulnerable to HIV and offer PrEP to them, reducing HIV transmission.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Humanos , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Fonte de Informação , Fármacos Anti-HIV/uso terapêutico
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