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1.
JBI Evid Implement ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39291714

RESUMO

BACKGROUND: Heart failure affects thousands of patients annually, often resulting in hospitalization, emergency room visits, and decreased quality of life. The scientific evidence indicates that disease management programs using a multidisciplinary approach improve outcomes for heart failure patients. AIM: The overarching aim of this evidence implementation project was to establish a disease management program for heart failure patients. Specifically, the project sought to promote compliance with best practices for the early identification of heart failure exacerbation symptoms to prevent emergency room visits and hospitalizations, thereby reducing morbidity and mortality. METHODS: This project was guided by the JBI Evidence Implementation Framework, which is grounded in an audit, feedback, and re-audit strategy. A baseline audit was conducted, revealing the need for a heart failure disease management program. A policy was developed to implement a disease management program and virtual relationships were established to create a multidisciplinary team. A follow-up audit was conducted to determine whether the implemented interventions closed the gap in practice identified by the baseline audit. RESULTS: The baseline audit revealed 0% compliance with best practices for the management of patients with heart failure, while the follow-up audit revealed 93.3% compliance. CONCLUSIONS: This project enhanced best practices by implementing a protocol in a rural health clinic to ensure that all heart failure patients were enrolled in a disease management program. Recommendations include using the electronic health record to quickly identify heart failure patients and their status in a disease management program. Chart audits should be performed every 6 months to ensure the program's sustainability and to determine heart failure patients' enrollment status. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A270.

2.
Womens Health (Lond) ; 20: 17455057241277974, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39245949

RESUMO

BACKGROUND: Awareness and uptake of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) remains low among Black/African American cisgender women, partly due to low self-reported PrEP knowledge and comfort among primary care providers. Ensuring providers are trained on PrEP is crucial, as increased PrEP knowledge is associated with higher rates of PrEP prescription. OBJECTIVE: We aimed to develop a PrEP training for providers to improve their self-efficacy in discussing and prescribing PrEP for Black women, with the ultimate goal of increasing PrEP awareness and utilization among Black women. DESIGN: In this qualitative study, we conducted focus groups with medical providers at three federally qualified health centers in the Southern and Midwestern United States to identify themes informing the development of a provider PrEP training. METHODS: Providers were asked for input on content/design of PrEP training. Transcripts underwent rapid qualitative analysis using the Stanford Lightning Report Method. Themes were identified and presented under the domains of the Consolidated Framework for Implementation Research. RESULTS: Ten providers completed four focus groups. Themes included the individual characteristics of providers (low comfort initiating PrEP discussions, particularly among White providers) and the outer setting of client attitudes (perceptions of potential provider bias/racism, varying levels of concern about HIV acquisition). Opportunities were identified to maximize the benefit of training design (e.g., developing case scenarios to enhance providers' cultural competency with Black women and PrEP knowledge). CONCLUSION: This comprehensive PrEP training features both didactic material and interactive role-plays to equip providers with the clinical knowledge for prescribing PrEP while building their competency discussing PrEP with Black women. This training is particularly important for providers who have racial or gender discordance with Black women and express lower comfort discussing PrEP with these clients. Provider training could lead to minimizing racial- and gender-based inequities in PrEP use.


Increasing the use of pre-exposure prophylaxis (PrEP) among Black women: a study to improve provider knowledge through PrEP trainingWhy was the study done? Use of pre-exposure prophylaxis (PrEP), a medication that can prevent the transmission of human immunodeficiency virus (HIV), is low among Black/African American women. Part of the reason why is because primary care providers (PCPs) report lower knowledge about PrEP and lower comfort talking about PrEP with clients. Making sure PCPs are trained on PrEP could help increase PrEP use among Black women. What did the researchers do? The research team held focus groups, during which they asked medical providers at federally qualified health centers (FQHCs) in the Southern and Midwestern United States questions about their experiences with discussing PrEP and what information should be included in a training about PrEP for providers to make sure the training would be helpful for them. What did the researchers find? A total of ten providers completed four focus groups. Important points mentioned in the focus groups included low comfort among providers when bringing up PrEP to clients, especially among White providers, as well as different levels of concern about HIV and feelings of potential provider bias/racism among clients. These points helped the researchers design a PrEP training that addresses providers' needs (such as creating case scenarios that help providers practice discussing PrEP with Black women and answering common questions about PrEP). What do the findings mean? A PrEP training for providers should have both information about prescribing PrEP and interactive role-plays to build providers' PrEP knowledge while improving their confidence and skill in talking about PrEP with Black women. This training is particularly important for providers who are a different race or gender than Black women and express lower rates of comfort discussing PrEP with these clients. Provider training could eventually lead to higher PrEP use among Black women.


Assuntos
Negro ou Afro-Americano , Infecções por HIV , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Profilaxia Pré-Exposição , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Competência Clínica , Pessoal de Saúde/educação , Infecções por HIV/prevenção & controle , Estados Unidos
3.
Healthcare (Basel) ; 12(17)2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39273793

RESUMO

Black women continue to be disproportionally burdened by HIV. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention option, which is underused by Black women. While social network interventions (SNIs) have been widely researched and implemented among some groups vulnerable to HIV, little is known about social network characteristics among Black women. To learn more about the social networks of Black women vulnerable to HIV and their knowledge of and interest in PrEP, we conducted a cross-sectional survey among 109 Black women aged 18-45 years attending a family planning clinic in Chicago, Illinois. In our study, 44% of women reported that they were moderately to extremely concerned about HIV. Over half of participants (53%) had a small personal network size (i.e., less than two). No statistically significant associations between having larger network sizes and having previously heard of PrEP, having an interest in starting PrEP, or having good PrEP knowledge were detected. Open-ended responses revealed high levels of trust in network connections with matters related to sexual health. Additionally, nearly all (94%) of women reported that SNIs were a good idea to promote PrEP. Future network studies are needed to inform the development of effective intervention strategies for women.

4.
J Am Vet Med Assoc ; : 1-9, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39241798

RESUMO

OBJECTIVE: Evaluate the incidence of Borrelia burgdorferi in cases of equine nuchal bursitis (NB) and investigate the relationship between elevated serum outer surface protein A (OspA) antibodies and the molecular identification of B burgdorferi in bursal tissue or synovial fluid. Additionally, describe clinical cases and compare the histologic changes in NB with and without detection of B burgdorferi. METHODS: This was a retrospective multicenter cohort study (2013 to 2022). Medical records from horses with a diagnosis of NB and B burgdorferi PCR testing on NB tissue or synovial fluid were reviewed. The study population included 11 horses with a postmortem diagnosis of NB, 19 horses from the northeastern US with an antemortem diagnosis of B burgdorferi PCR-positive NB, and 15 healthy controls without evidence of NB and unvaccinated for B burgdorferi. Where serum was available, Lyme multiplex assay results were compared with controls and ELISAs targeting individual B burgdorferi antigens were performed. Histologic findings in nuchal bursa tissue were compared between NB cases with and without B burgdorferi PCR detection. RESULTS: Serum OspA antibody values in B burgdorferi-positive NB cases (n = 13) were significantly elevated (P < .001) compared to controls (15), and OspA was the predominant antigen detected by ELISA (8). Histopathology did not vary between NB cases with (n = 9) and without (6) B burgdorferi PCR detection. CONCLUSIONS: The presence of B burgdorferi in the nuchal bursa of horses is associated with increased serum OspA antibodies. CLINICAL RELEVANCE: The role of B burgdorferi in equine NB may be underestimated, and targeted therapy requires investigation.

5.
Nat Commun ; 15(1): 5796, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987243

RESUMO

Metabolite extraction is the critical first-step in metabolomics experiments, where it is generally regarded to inactivate and remove proteins. Here, arising from efforts to improve extraction conditions for polar metabolomics, we discover a proteomic landscape of over 1000 proteins within metabolite extracts. This is a ubiquitous feature across several common extraction and sample types. By combining post-resuspension stable isotope addition and enzyme inhibitors, we demonstrate in-extract metabolite interconversions due to residual transaminase activity. We extend these findings with untargeted metabolomics where we observe extensive protein-mediated metabolite changes, including in-extract formation of glutamate dipeptide and depletion of total glutathione. Finally, we present a simple extraction workflow that integrates 3 kDa filtration for protein removal as a superior method for polar metabolomics. In this work, we uncover a previously unrecognized, protein-mediated source of observer effects in metabolomics experiments with broad-reaching implications across all research fields using metabolomics and molecular metabolism.


Assuntos
Metabolômica , Proteoma , Proteômica , Proteoma/metabolismo , Metabolômica/métodos , Proteômica/métodos , Humanos , Animais , Glutationa/metabolismo , Metaboloma , Transaminases/metabolismo
6.
Anim Biotelemetry ; 12(1): 18, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022453

RESUMO

The study of animal movement provides insights into underlying ecological processes and informs analyses of behaviour and resource use, which have implications for species management and conservation. The tools used to study animal movement have evolved over the past decades, allowing for data collection from a variety of species, including those living in remote environments. Satellite-linked radio and GPS collars have been used to study polar bear (Ursus maritimus) ecology and movements throughout the circumpolar Arctic for over 50 years. However, due to morphology and growth constraints, only adult female polar bears can be reliably collared. Collars have proven to be safe, but there has been opposition to their use, resulting in a deficiency in data across much of the species' range. To bolster knowledge of movement characteristics and behaviours for polar bears other than adult females, while also providing an alternative to collars, we tested the use of fur- and ear-mounted telemetry tags that can be affixed to polar bears of any sex and age. We tested three fur tag designs (SeaTrkr, tribrush and pentagon tags), which we affixed to 15 adult and 1 subadult male polar bears along the coast of Hudson Bay during August-September 2021-2022. Fur tags were compared with ear tags deployed on 42 subadult and adult male polar bears captured on the coast or the sea ice between 2016 and 2022. We used data from the tags to quantify the amount of time subadult and adult males spent resting versus traveling while on land. Our results show the three fur tag designs remained functional for shorter mean durations (SeaTrkr = 58 days; tribrush = 47 days; pentagon = 22 days) than ear tags (121 days), but positional error estimates were comparable among the Argos-equipped tags. The GPS/Iridium-equipped SeaTrkr fur tags provided higher resolution and more frequent location data. Combined, the tags provided sufficient data to model different behavioural states. Furthermore, as hypothesized, subadult and adult male polar bears spent the majority of their time resting while on land, increasing time spent traveling as temperatures cooled. Fur tags show promise as a short-term means of collecting movement data from free-ranging polar bears. Supplementary Information: The online version contains supplementary material available at 10.1186/s40317-024-00373-2.

7.
bioRxiv ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38979360

RESUMO

The progressive decline of CD8 T cell effector function-also known as terminal exhaustion-is a major contributor to immune evasion in cancer. Yet, the molecular mechanisms that drive CD8 T cell dysfunction remain poorly understood. Here, we report that the Kelch-like ECH-associated protein 1 (KEAP1)-Nuclear factor erythroid 2-related factor 2 (NRF2) signaling axis, which mediates cellular adaptations to oxidative stress, directly regulates CD8 T cell exhaustion. Transcriptional profiling of dysfunctional CD8 T cells from chronic infection and cancer reveals enrichment of NRF2 activity in terminally exhausted (Texterm) CD8 T cells. Increasing NRF2 activity in CD8 T cells (via conditional deletion of KEAP1) promotes increased glutathione production and antioxidant defense yet accelerates the development of terminally exhausted (PD-1+TIM-3+) CD8 T cells in response to chronic infection or tumor challenge. Mechanistically, we identify PTGIR, a receptor for the circulating eicosanoid prostacyclin, as an NRF2-regulated protein that promotes CD8 T cell dysfunction. Silencing PTGIR expression restores the anti-tumor function of KEAP1-deficient T cells. Moreover, lowering PTGIR expression in CD8 T cells both reduces terminal exhaustion and enhances T cell effector responses (i.e. IFN-γ and granzyme production) to chronic infection and cancer. Together, these results establish the KEAP1-NRF2 axis as a metabolic sensor linking oxidative stress to CD8 T cell dysfunction and identify the prostacyclin receptor PTGIR as an NRF2-regulated immune checkpoint that regulates CD8 T cell fate decisions between effector and exhausted states.

8.
AIDS Educ Prev ; 36(3): 155-167, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38917300

RESUMO

Transgender women are disproportionately impacted by HIV infection. We report herein the findings of a pre-post evaluation of the TransLife Care (TLC) project in Chicago, Illinois, on behaviors associated with HIV transmission among transgender women. Participants who received any TLC component versus those who did not were compared using mixed-effects logistic regression with random intercepts across follow-up time points. Ninety-seven participants aged 18 to 59 (median age 24) enrolled; 76.3% were transgender women of color. There was a decrease in condomless sex without consistent PrEP use at 8 months, which was not significantly different between those who did and did not receive the TLC intervention, controlling for calendar time. Evidence does not indicate that the TLC reduces condomless sex without PrEP protection among urban transgender women. However, given the preponderance of evidence of the influence of structural barriers on condomless sex, future research should continue to test the efficacy of structural interventions.


Assuntos
Infecções por HIV , Pessoas Transgênero , Humanos , Feminino , Pessoas Transgênero/psicologia , Pessoas Transgênero/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Chicago , Adulto , Masculino , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Profilaxia Pré-Exposição/métodos , Sexo sem Proteção/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde , Preservativos/estatística & dados numéricos , Comportamento Sexual , Conhecimentos, Atitudes e Prática em Saúde , Modelos Logísticos
9.
Nurse Res ; 32(3): 18-25, 2024 Sep 11.
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.


Assuntos
Demência , Casas de Saúde , Humanos , Reino Unido , Casas de Saúde/organização & administração , Demência/enfermagem , Idoso , Hidratação/métodos , Projetos de Pesquisa , Pesquisa em Enfermagem/métodos
10.
Soc Sci Med ; 352: 117015, 2024 Jul.
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.


Assuntos
Transtorno Bipolar , Negro ou Afro-Americano , Transtornos Psicóticos , Brancos , Feminino , Humanos , Masculino , Transtorno Bipolar/psicologia , Transtorno Bipolar/etnologia , Negro ou Afro-Americano/psicologia , Saúde Mental , Estigma Social , Estereotipagem , Terminologia como Assunto , Estados Unidos , Brancos/psicologia , Transtornos Psicóticos/etnologia , Transtornos Psicóticos/psicologia
11.
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
12.
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.

13.
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
14.
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.

15.
Acad Pediatr ; 24(7): 1110-1115, 2024.
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.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Pessoas Transgênero , Humanos , Masculino , Feminino , Infecções por HIV/prevenção & controle , Adolescente , Adulto Jovem , Minorias Sexuais e de Gênero/estatística & dados numéricos , Adulto , Preferência do Paciente , Preparações de Ação Retardada , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Injeções , Conhecimentos, Atitudes e Prática em Saúde
16.
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
17.
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.

18.
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.

19.
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
20.
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
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