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1.
Artículo en Inglés | MEDLINE | ID: mdl-39078280

RESUMEN

OBJECTIVE: The All of Us Research Program aims to return value to participants by developing research capacity in communities. We describe a novel set of introductory exercises (Data Sandboxes) and specialized trainings to orient researchers to the Researcher Workbench to foster health equity research. MATERIALS AND METHODS: We developed a tailored training to familiarize researchers with the All of Us Research Program: (1) orientation, (2) tailored "data treasure hunt" using the Public Data Browser, and (3) overview of the analyses tools and platform. RESULTS: Participants' pre- and post-knowledge of the contents and structure of the All of Us dataset scores increased significantly after training. These trainings effectively engaged researchers in exploring this rich dataset. CONCLUSION: We describe ways of orienting and familiarizing a wide variety of researchers with the All of Us Research Program dataset, sparking their interest, and "jump-starting" their research.

2.
J Autoimmun ; 147: 103263, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38851089

RESUMEN

RATIONALE: In inflammatory diseases such as rheumatoid arthritis (RA), steroid metabolism is a central component mediating the actions of immuno-modulatory glucocorticoids and sex steroids. However, the regulation and function of cellular steroid metabolism within key leukocyte populations such as macrophages remain poorly defined. In this study, the inflammatory regulation of global steroid metabolism was assessed in RA macrophages. METHODS: Bulk RNA-seq data from RA synovial macrophages was used to assess transcripts encoding key enzymes in steroid metabolism and signalling. Changes in metabolism were assessed in synovial fluids, correlated to measures of disease activity and functionally validated in primary macrophage cultures. RESULTS: RNA-seq revealed a unique pattern of differentially expressed genes, including changes in genes encoding the enzymes 11ß-HSD1, SRD5A1, AKR1C2 and AKR1C3. These correlated with disease activity, favouring increased glucocorticoid and androgen levels. Synovial fluid 11ß-HSD1 activity correlated with local inflammatory mediators (TNFα, IL-6, IL-17), whilst 11ß-HSD1, SRD5A1 and AKR1C3 activity correlated with systemic measures of disease and patient pain (ESR, DAS28 ESR, global disease activity). Changes in enzyme activity were evident in inflammatory activated macrophages in vitro and revealed a novel androgen activating role for 11ß-HSD1. Together, increased glucocorticoids and androgens were able to suppress inflammation in macrophages and fibroblast-like-synoviocytes. CONCLUSIONS: This study underscores the significant increase in androgen and glucocorticoid activation within inflammatory polarized macrophages of the synovium, contributing to local suppression of inflammation. The diminished profile of inactive steroid precursors in postmenopausal women may contribute to disturbances in this process, leading to increased disease incidence and severity.


Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1 , Artritis Reumatoide , Inflamación , Macrófagos , Humanos , Artritis Reumatoide/metabolismo , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Macrófagos/metabolismo , Macrófagos/inmunología , Inflamación/metabolismo , Inflamación/inmunología , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/genética , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/metabolismo , Líquido Sinovial/metabolismo , Líquido Sinovial/inmunología , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/metabolismo , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Masculino , Femenino , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Membrana Sinovial/inmunología , Células Cultivadas , Glucocorticoides/metabolismo , Esteroides/metabolismo , Regulación de la Expresión Génica , Hidroxiesteroide Deshidrogenasas
3.
J Small Anim Pract ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38742752

RESUMEN

OBJECTIVES: The goals of this retrospective study were to assess the clinical and radiographic outcomes in dogs with proximal femoral fractures, other than capital physeal fractures, treated via total hip arthroplasty. MATERIALS AND METHODS: Medical records as well as pre-operative, immediate post-operative and 2 to 3 months post-operative radiographs of 14 dogs with femoral head and neck fractures treated via total hip arthroplasty were reviewed. A Liverpool Osteoarthritis in Dogs questionnaire was completed by owners to assess long-term outcomes. RESULTS: Seven femoral head fractures, and seven femoral neck fractures were included. Four of the femoral head fractures were acute in nature, the three remaining femoral head fractures and all seven femoral neck fracture cases were chronic fractures. Malorientation of the femoral stem was more common in the chronic femoral fracture cases when compared to the acute femoral fracture cases. Two of the acute fracture cases and five chronic fracture cases experienced a change in femoral stem position post-operatively. One femoral fissure fracture occurred and was repaired intraoperatively. One case had a post-operative complication that resulted in implant removal. All dogs had good to excellent owner-perceived outcome. CLINICAL SIGNIFICANCE: Femoral head and neck fractures, and in particular the chronic cases, represented a challenging subset of cases presenting for total hip arthroplasty, resulting in suboptimal stem alignment in many cases. However, clinical outcomes were considered good to excellent in all dogs in the study, indicating that total hip arthroplasty is a viable treatment option for these types of fractures.

4.
Ann R Coll Surg Engl ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38746984

RESUMEN

INTRODUCTION: Therapeutic mammaplasty (TM) facilitates large tumour resection while maintaining optimal aesthetic outcome. It carries higher wound complication risks, which may delay adjuvant therapy initiation. Whether this delay affects oncological outcome requires evaluation. METHODS: Data were collected for consecutive patients receiving TM at the Leeds breast unit (2009-2017). A prospectively maintained database was used to determine tumour characteristics, wound complication rates, receipt of adjuvant therapy and breast cancer recurrence or death. RESULTS: In total 112 patients (median age of 54 years) underwent 114 TM procedures. The most common histological subtypes were invasive ductal carcinoma (61.4%), invasive lobular carcinoma (13.2%) and ductal carcinoma in situ (13.2%). Of the patients, 88.2% had oestrogen receptor-positive cancer and 14% had human epidermal growth factor receptor-positive cancer; 26.3% had multifocal cancer. The median tumour size was 30mm. The median Nottingham Prognostic Index was 4.2. The local recurrence rate was 3.5% (median follow-up of 8.6 years). The 5- and 10-year disease-free survival (DFS) was 88.5% and 83.5%, and the equivalent overall survival (OS) rates were 94% and 83.5%. Wound complication rate was 23.6% (n=27), the commonest being wound infection (11.4%; n=13) and T-junction wound breakdown (10.5%; n=12). The median time to adjuvant therapy was 72 days (interquartile range [IQR] 56-90) for patients with wound complications, and 51 days (IQR 42-58) for those without. However, this delay did not affect DFS or OS (log-rank test; p=0.58 and p=0.94, respectively). This was confirmed on Cox regression analysis. CONCLUSION: Our study finding demonstrates that although wound complications after TM leads to a modest delay to adjuvant therapy, the long-term oncological outcomes were comparable with those in patients without wound complications.

5.
Eur J Orthop Surg Traumatol ; 34(5): 2629-2638, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38733543

RESUMEN

AIMS: To assess the pre- and postoperative responses to each of the 12 individual Oxford Knee Score (OKS) questions and percentages of those that were better, same or worse after primary knee arthroplasty (KA). METHODS: A single centre retrospective cohort study conducted over a 24-month period which included 3259 patients with completed OKS preoperatively and 1-year after KA. There were 1286 males and 1973 females, with an overall mean age of 70.0 (range 34-94). The mean scores for each question of the OKS were compared between baseline and 1-year. The percentage of patients who reported better, the same or worse postoperative symptoms for each question were calculated and represented on a heatmap. RESULTS: There were significant (p < 0.001) improvements in all 12 questions, all of which demonstrated moderate (Q2, Q7) or large effect sizes. Improvements in individual question responses varied. Symptoms of pain and limping demonstrated the greatest improvement, with 86% of patients enjoying a positive change in their symptoms. Despite this improvement 1067 (41.4%) continued to have mild to severe pain in their knee, and 442 (17.3%) patients limped often to all the time when walking postoperatively. Whereas other questions that did not improve to the same extent for example washing and drying only improved in 53% of patients but only 347 (13.5%) had moderate/extreme trouble or found it impossible to do this postoperatively. Preoperatively four questions (Q1, Q6, Q7, Q8) demonstrated floor effects, postoperatively all questions apart from question 7 (kneeling) demonstrated ceiling effects. CONCLUSION: The mean improvement and outcome at 1-year for each of the 12 questions varied according to the patient's preoperative response. As a clinical tool, the heatmap (improvement, same and worse) will enable communication to patients about their potential change in their knee specific symptoms according to their preoperative responses. LEVEL OF EVIDENCE: Retrospective study, Level III.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Femenino , Masculino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Adulto , Periodo Posoperatorio , Periodo Preoperatorio , Osteoartritis de la Rodilla/cirugía , Encuestas y Cuestionarios , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/fisiopatología , Resultado del Tratamiento , Dimensión del Dolor
6.
Parasit Vectors ; 17(1): 186, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605395

RESUMEN

Starting in October 2021, quarterly malacological surveys have been undertaken in Malawi, with the sampling of 12 specified freshwater habitats throughout a calendar year. Each survey monitors the presence of aquatic intermediate snail hosts of medical and veterinary importance. In March 2023, the alien lymnaeid species Pseudosuccinea columella was encountered for the first time in the surveys, in Nsanje District. This species identity was later confirmed upon DNA analysis of mitochondrial ribosomal 16S sequences. In July 2023, P. columella was also noted at single sites within Mangochi and Chikwawa Districts, and again in Nsanje District, with an additional location observed. Of particular importance, our sampled location in Mangochi District was directly connected to Lake Malawi, which expands the species list of invasive molluscs in this lake. While P. columella is a well-known intermediate snail host for human and animal fascioliasis, screening collected snails for trematode cercariae, alongside molecular xenomonitoring, did not yield equivocal evidence of active fluke infection. However, the newly recognized presence of this alien intermediate snail host within Lake Malawi, and along the Shire River Valley, flags a new concern in altered local transmission potential for human and animal fascioliasis.


Asunto(s)
Fasciola hepatica , Fascioliasis , Animales , Humanos , Fasciola hepatica/genética , Fascioliasis/veterinaria , Malaui , Caracoles
7.
Int J Parasitol Parasites Wildl ; 23: 100919, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38495311

RESUMEN

The freshwater amphibious snail Orientogalba viridis commonly occurs in eastern Asia, on certain Pacific islands and more importantly has recently dispersed into Europe. Since this snail is now considered an invasive species, its distribution is of growing parasitological interest as an alien intermediate host for various trematodes, particularly liver flukes. As part of ongoing surveillance for snail-borne diseases in Malawi, a population of O. viridis was first observed in May 2023, alongside an alarming presence of a human schistosome cercaria. This snail population later underwent detailed morphological characterisation with both snail and parasite identities confirmed upon DNA barcoding. This seminal observation triggered more extensive local snail surveys, finding 3 further populations in separated rice paddies, with further field-caught snails (n = 465) screened for infection and a selection used for repeated experimental challenges with miracidia from Schistosoma haematobium and Schistosoma mattheei. Although no field-caught (and experimentally exposed) snail was seen to shed schistosome cercariae, molecular xenomonitoring for schistosomiasis provided tangible evidence of putative transmission potential. Our first report of O. viridis here in Malawi, and more broadly in Africa, flags a need for increased vigilance for this invasive species alongside local clarification(s) of its transmission potential for trematodiases of either medical and/or veterinary importance.

8.
World J Pediatr Congenit Heart Surg ; 15(2): 155-159, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38263637

RESUMEN

BACKGROUND: Ebstein anomaly is a rare congenital anomaly of the tricuspid valve which presents challenges to cardiac surgeons due to the spectrum of the disease and the technical difficulty of valve repair. The natural history of the anomaly differs between patients presenting in the neonatal period to those presenting in adulthood. METHODS: A retrospective review of all patients >15 years of age with Ebstein anomaly, undergoing surgery on the tricuspid valve at 6 centers across Australia and New Zealand was performed. Patients from 1985 to 2019 were included in the study. RESULTS: A total of 125 patients were included in the study, 76 patients (60%) undergoing tricuspid valve repair, of which 23 patients underwent a Cone repair and 49 (40%) had a tricuspid valve replacement. The mean follow-up was 7.9 ± 7.3 years. Postoperatively, early mortality was 3 patients (2%) and 10-year survival was 91.5%. A postoperative pacemaker was required in 24 patients (19%). Reoperation was required in 21 patients (17%). There was no statistically significant difference in survival or reoperation between patients who underwent repair or replacement of the tricuspid valve; however, with a small number of patients in long-term follow-up. CONCLUSION: Older children and adult patients undergoing surgery for Ebstein anomaly in Australia and New Zealand experience good medium-term postoperative survival. Repair of the valve is achieved in a significant proportion of patients with increasing use and success with the Cone repair technique.


Asunto(s)
Anomalía de Ebstein , Niño , Recién Nacido , Adulto , Humanos , Adolescente , Anomalía de Ebstein/cirugía , Nueva Zelanda , Resultado del Tratamiento , Válvula Tricúspide/cirugía , Australia
9.
Anaesthesia ; 79(5): 465-468, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38214405
10.
Aging Ment Health ; 28(2): 197-206, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37667896

RESUMEN

OBJECTIVES: Hospices are regarded as gold standard providers of end-of-life care. The term hospice, however, is broadly used, and can describe a type of care offered in a variety of health care services (e.g. nursing homes). It thus becomes complex for families to decide between services. We aimed to review the evidence around the experience of family carers of people with dementia accessing in-patient hospice settings for end-of-life care. METHOD: We registered the review protocol on PROSPERO. We used PerSPE(C)TiF to systematically organise our search strategy. The evidence was reviewed across six databases: PubMed, EMBASE, PsycINFO, ASSIA, ISI Web, and CINAHL. We used meta-ethnography as per the eMERGe guidance for data interpretation. RESULTS: Four studies were included. Two third-order constructs were generated through meta-ethnography: expectations of care and barriers to quality of care. We found that carers had expectations of care, and these could change over time. If discussion was not held with hospice staff early on, the carers could experience reduced care quality due to unmatched expectations. Unmatched expectations acted as barriers to care and these were found in terms of carers not feeling adequately supported, and/or having the person discharged from hospice, which would entail increased care responsibility for carers. CONCLUSION: In view of an increase in new dementia cases over time and with hospice services being under pressure, integrating palliative care services within community-based models of care is key to reducing the risk of having inadequate and under resourced services for people with dementia.


Asunto(s)
Demencia , Hospitales para Enfermos Terminales , Cuidado Terminal , Humanos , Cuidadores , Antropología Cultural , Demencia/terapia
11.
J Chemother ; 36(3): 198-201, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37800850

RESUMEN

Isatuximab is a CD38-directed antibody indicated for the treatment of relapsed or refractory multiple myeloma. The Division of Pharmacovigilance at the U.S. Food and Drug Administration (FDA) reviewed case reports from postmarketing sources, including the FDA Adverse Event Reporting System (FAERS), PubMed, and Embase, to investigate a potential association between isatuximab and the risk of varicella zoster virus (VZV) reactivation. We identified 20 reports of which 15 met our case definition and causality criteria. All 15 patients (80% male, median age = 60 years) received isatuximab for a hematologic neoplasm; eight (53%) for previously untreated multiple myeloma. All cases described additional risk factors for VZV reactivation, including concomitant proteasome inhibitor and/or immunomodulatory drug (n = 10, 67%) use. Based on this postmarket analysis, the U.S. Prescribing Information for isatuximab was updated to include this new safety information, including recommendations for antiviral prophylaxis.


Asunto(s)
Herpes Zóster , Mieloma Múltiple , Humanos , Masculino , Persona de Mediana Edad , Femenino , Herpesvirus Humano 3 , Mieloma Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Herpes Zóster/inducido químicamente , Herpes Zóster/tratamiento farmacológico
13.
PLoS One ; 18(11): e0286493, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37930977

RESUMEN

BACKGROUND: Nearly 50 million people worldwide have dementia and the increasing numbers requiring end-of-life and palliative care, has led to national efforts to define standards of care for this patient group. Little research, however, has been done to date about the experience of hospice care for people with dementia accessing these services. This study explores the views of hospice dementia care for bereaved carers of people with dementia and hospice clinicians. METHODS: We used purposive sampling for participant recruitment. Semi-structured qualitative interviews were conducted with bereaved carers and hospice clinical staff. Interviews were audio recorded and the transcriptions were analysed through thematic analysis. A total of 12 participants were interviewed from one service in the Northwest region in the UK. All were female and white British. RESULTS: Participants described their experience of hospice dementia care in three main themes: Pre-access to service, roles and responsibility within hospice care, ease and difficulty of last period of end-of-life care. CONCLUSION: Rapid response teams delivering hospice home care could represent a better option to inpatient care and may be preferred by patients. This type of service, however, may require joined-up care with other community services, and this type of care needs to be considered and planned. Future studies should evaluate this type of community care.


Asunto(s)
Demencia , Cuidados Paliativos al Final de la Vida , Hospitales para Enfermos Terminales , Humanos , Femenino , Masculino , Cuidadores , Cuidados Paliativos , Investigación Cualitativa
14.
J Am Med Inform Assoc ; 31(1): 70-78, 2023 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-37847653

RESUMEN

OBJECTIVE: Apply natural language processing (NLP) to Amazon consumer reviews to identify adverse events (AEs) associated with unapproved over the counter (OTC) homeopathic drugs and compare findings with reports to the US Food and Drug Administration Adverse Event Reporting System (FAERS). MATERIALS AND METHODS: Data were extracted from publicly available Amazon reviews and analyzed using JMP 16 Pro Text Explorer. Topic modeling identified themes. Sentiment analysis (SA) explored consumer perceptions. A machine learning model optimized prediction of AEs in reviews. Reports for the same time interval and product class were obtained from the FAERS public dashboard and analyzed. RESULTS: Homeopathic cough/cold products were the largest category common to both data sources (Amazon = 616, FAERS = 445) and were analyzed further. Oral symptoms and unpleasant taste were described in both datasets. Amazon reviews describing an AE had lower Amazon ratings (X2 = 224.28, P < .0001). The optimal model for predicting AEs was Neural Boosted 5-fold combining topic modeling and Amazon ratings as predictors (mean AUC = 0.927). DISCUSSION: Topic modeling and SA of Amazon reviews provided information about consumers' perceptions and opinions of homeopathic OTC cough and cold products. Amazon ratings appear to be a good indicator of the presence or absence of AEs, and identified events were similar to FAERS. CONCLUSION: Amazon reviews may complement traditional data sources to identify AEs associated with unapproved OTC homeopathic products. This study is the first to use NLP in this context and lays the groundwork for future larger scale efforts.


Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Estados Unidos , Humanos , Procesamiento de Lenguaje Natural , Programas Informáticos , United States Food and Drug Administration , Tos
15.
Nature ; 621(7980): 716-722, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37758891

RESUMEN

Einstein's general theory of relativity from 19151 remains the most successful description of gravitation. From the 1919 solar eclipse2 to the observation of gravitational waves3, the theory has passed many crucial experimental tests. However, the evolving concepts of dark matter and dark energy illustrate that there is much to be learned about the gravitating content of the universe. Singularities in the general theory of relativity and the lack of a quantum theory of gravity suggest that our picture is incomplete. It is thus prudent to explore gravity in exotic physical systems. Antimatter was unknown to Einstein in 1915. Dirac's theory4 appeared in 1928; the positron was observed5 in 1932. There has since been much speculation about gravity and antimatter. The theoretical consensus is that any laboratory mass must be attracted6 by the Earth, although some authors have considered the cosmological consequences if antimatter should be repelled by matter7-10. In the general theory of relativity, the weak equivalence principle (WEP) requires that all masses react identically to gravity, independent of their internal structure. Here we show that antihydrogen atoms, released from magnetic confinement in the ALPHA-g apparatus, behave in a way consistent with gravitational attraction to the Earth. Repulsive 'antigravity' is ruled out in this case. This experiment paves the way for precision studies of the magnitude of the gravitational acceleration between anti-atoms and the Earth to test the WEP.

16.
Poult Sci ; 102(10): 102841, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37480657

RESUMEN

Necrotic enteritis (NE) is a widespread infectious disease caused by Clostridium perfringens that inflicts major economic losses on the global poultry industry. Due to regulations on antibiotic use in poultry production, there is an urgent need for alternative strategies to mitigate the negative effects of NE. This paper presents a passive immunization technology that utilizes hyperimmune egg yolk immunoglobulin Y (IgY) specific to the major immunodominant antigens of C. perfringens. Egg yolk IgYs were generated by immunizing hens with 4 different recombinant C. perfringens antigens, and their protective effects against NE were evaluated in commercial broilers. Six different spray-dried egg powders were produced using recombinant C. perfringens antigens: α-toxin, NE B-like toxin (NetB; EB), elongation factor-Tu (ET), pyruvate:ferredoxin oxidoreductase, a mixture of 4 antigens (EM-1), and a nonimmunized control (EC). The challenged groups were either provided with different egg powders at a 1% level or no egg powders (EN). The NE challenge model based on Eimeria maxima and C. perfringens dual infection was used. In Experiments 1 and 2, the EB and ET groups exhibited increased body weight gain (BWG; P < 0.01), decreased NE lesion scores (P < 0.001), and reduced serum NetB levels (P < 0.01) compared to the EN and EC groups. IgY against NetB significantly reduced Leghorn male hepatocellular cytotoxicity in an in vitro test (P < 0.01). In Experiment 3, the protective effect of the IgYs mixture (EM-2) against C. perfringens antigens (NetB and EFTu) and Eimeria antigens (elongation factor-1-alpha: EF1α and Eimeria profilin: 3-1E) was tested. The EM-2 group showed similar body weight, BWG, and feed intake from d 7 to 22 compared to the NC group (P < 0.05). On d 20, the EM-2 group showed comparable intestinal permeability, NE lesion scores, and jejunal NetB and collagen adhesion protein levels to the NC group (P < 0.05). In conclusion, dietary mixture containing antibodies to NetB and EFTu provides protection against experimental NE in chickens through passive immunization.


Asunto(s)
Toxinas Bacterianas , Infecciones por Clostridium , Eimeria , Enteritis , Enfermedades de las Aves de Corral , Animales , Femenino , Masculino , Clostridium perfringens , Pollos/metabolismo , Toxinas Bacterianas/metabolismo , Infecciones por Clostridium/prevención & control , Infecciones por Clostridium/veterinaria , Yema de Huevo/metabolismo , Enteritis/prevención & control , Enteritis/veterinaria , Anticuerpos Antibacterianos , Peso Corporal , Factores de Elongación de Péptidos/metabolismo , Enfermedades de las Aves de Corral/prevención & control , Necrosis/veterinaria
17.
Genes Brain Behav ; 22(6): e12847, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37461188

RESUMEN

Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/-) were used in this study. First, using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol-naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/- rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two-bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/- rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/- males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD).


Asunto(s)
Proteínas de Transporte de Dopamina a través de la Membrana Plasmática , Etanol , Humanos , Ratas , Masculino , Animales , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Dopamina , Ratas Wistar , Consumo de Bebidas Alcohólicas/genética , Núcleo Accumbens
18.
Sci Justice ; 63(4): 477-484, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37453779

RESUMEN

The Body Fluid Forum of the Association of Forensic Science Providers recognised concerns raised by forensic practitioners regarding the lack of data to inform on the incidence of significant AP (Acid Phosphatase) reactions from vaginal and oral samples, i.e. those which might be misinterpreted as indicating the presence of semen. This is particularly relevant in the light of appeal court rulings regarding the need for data to support evaluations. This paper presents collaborative data on the nature and incidence of AP reactions from vaginal and oral swabs provided by donors. The results demonstrate that caution is required with mid to strong purple AP reactions from direct testing of oral swabs and with mid purple reactions from vaginal swabs. The use of a Bayesian approach to assist with the provision of opinions regarding the presence of seminal fluid is highlighted.


Asunto(s)
Fosfatasa Ácida , Líquidos Corporales , Femenino , Humanos , Teorema de Bayes , Semen , Vagina
19.
J Adolesc Health ; 73(4): 746-752, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37410007

RESUMEN

PURPOSE: Despite the fact that adolescence represents a distinct developmental period wherein dating and sexual relationships are emergent, much of what is known about substance use, sexual agreements, and sexual risk behaviors among adolescent sexual minority males (ASMM) is extrapolated from research on adults. This study tested associations between substance use and sexual risk behaviors among ASMM and examined whether relationship status and sexual agreements moderated these associations. METHODS: Cross-sectional online survey data were collected from 2,892 HIV negative ASMM aged 13-17 years between November 2017 and March 2020. All were sexually active with male partners and not on pre-exposure prophylaxis. A multigroup hurdle model predicted the occurrence and frequency of condomless anal sex (CAS) with casual partners. RESULTS: Non-monogamous ASMM were more likely to use illicit drugs and more likely to have CAS with casual partners compared with single ASMM and those in monogamous relationships. Among ASMM who had CAS at least once, those in relationships (both monogamous and nonmonogamous) had CAS more frequently than single ASMM. Binge drinking (odds ratio (OR) = 1.47, p < .001), cannabis (OR = 1.30, p < .001), and illicit drug use (including prescription drug misuse) (OR = 1.77, p < .001) were associated with the occurrence of CAS with casual partners but only binge drinking (rate ratio (RR) = 1.23, p = .027) and illicit drugs (RR = 1.75, p < .001) were associated with its frequency. DISCUSSION: While results aligned with adult studies in many respects, unlike adult sexual minority males, these findings suggest partnered ASMM-particularly those in nonmonogamous relationships-were at highest risk of substance use and associated sexual HIV transmission risk.


Asunto(s)
Consumo Excesivo de Bebidas Alcohólicas , Infecciones por VIH , Drogas Ilícitas , Minorías Sexuales y de Género , Trastornos Relacionados con Sustancias , Adulto , Masculino , Humanos , Adolescente , Estados Unidos/epidemiología , Homosexualidad Masculina , Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Estudios Transversales , Conducta Sexual , Trastornos Relacionados con Sustancias/epidemiología , Asunción de Riesgos , Infecciones por VIH/prevención & control , Parejas Sexuales
20.
Drug Alcohol Depend ; 249: 109946, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37354584

RESUMEN

BACKGROUND: We use national surveillance data to evaluate race/ethnicity by sex/gender differences and trends in substance use treatment admissions and overdose deaths involving opioid and stimulant use. METHODS: We used data (1992-2019) from the Treatment Episode Dataset-Admissions to identify treatment admissions and the Center for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (1999-2020) to identify overdose deaths. We assessed treatment admissions and related drug overdose deaths per 100,000 adults by sex and race/ethnicity for opioid and stimulant groups: cocaine, opioid, methamphetamines, cocaine and opioid use, cocaine and methamphetamines, and opioid and methamphetamines. RESULTS: We found significant variations in treatment admissions and deaths by race/ethnicity and sex/gender. Cocaine-related treatment admissions and deaths were most prevalent among Non-Hispanic Black individuals over the study years, yet lower rates were evident among individuals from other racial/ethnic groups. Notably, Non-Hispanic Black men experienced larger increases in cocaine-only admissions than men of other racial/ethnic groups between 1992 and 2019. Men had higher opioid and stimulant treatment admissions and overdose deaths than women. We observed skyrocketing methamphetamine deaths among American Indian/Native Alaskan men and women from 1992 to 2019. DISCUSSION: Steep increases in overdose deaths fueled by methamphetamines among Non-Hispanic Native Americans and cocaine among Non-Hispanic Black individuals suggest a need for more effective interventions to curb stimulant use. Variations by race/ethnicity and sex/gender also suggest interventions should be developed through an intersectionality lens.


Asunto(s)
Cocaína , Sobredosis de Droga , Metanfetamina , Trastornos Relacionados con Opioides , Adulto , Masculino , Humanos , Femenino , Analgésicos Opioides , Sobredosis de Droga/epidemiología , Etnicidad , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/terapia
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