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1.
Front Psychol ; 15: 1382614, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39118851

RESUMEN

Introduction: Public safety personnel (PSP) are at increased risk for posttraumatic stress injuries (PTSI). Before Operational Stress (BOS) is a mental health program for PSP with preliminary support mitigating PTSI. The current study compared the effectiveness of delivering BOS in-person by a registered clinician (i.e., Intensive) to virtually delivery by a trained clinician (i.e., Classroom). Methods: Canadian PSP completed the Intensive (n = 118; 61.9% male) or Classroom (n = 149; 50.3% male) program, with self-report surveys at pre-, post-, 1 month, and 4 months follow-ups. Results: Multilevel modelling evidenced comparable reductions in anxiety (p < 0.05, ES = 0.21) and emotional regulation difficulties (ps < 0.05, ESs = 0.20, 0.25) over time with no significant difference between modalities. Participants discussed benefits of the delivery modality they received. Discussion: The results support virtual delivery of the BOS program (Classroom) as an accessible mental health training option for PSP, producing effects comparable to in-person delivery by clinicians.

2.
Brain Behav Immun ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39097202

RESUMEN

Immune cells are critical in promoting neuroinflammation and neuropathic pain and in facilitating pain resolution, depending on their inflammatory and immunoregulatory cytokine response. Interleukin (IL)-35, secreted by regulatory immune cells, is a member of the IL-12 family with a potent immunosuppressive function. In this study, we investigated the effects of IL-35 on pain behaviors, spinal microglia phenotype following peripheral nerve injury, and in vitro microglial cultures in male and female mice. Intrathecal recombinant IL-35 treatment alleviated mechanical pain hypersensitivity prominently in male mice, with only a modest effect in female mice after sciatic nerve chronic constriction injury (CCI). IL-35 treatment resulted in sex-specific microglial changes following CCI, reducing inflammatory microglial markers and upregulating anti-inflammatory markers in male mice. Spatial transcriptomics analysis revealed that IL-35 suppressed microglial complement activation in the superficial dorsal horn in male mice after CCI. Moreover, in vitro studies showed that IL-35 treatment of cultured inflammatory microglia mitigated their hypertrophied morphology, increased their cell motility, and decreased their phagocytic activity, indicating a phenotypic shift towards homeostatic microglia. Further, IL-35 altered microglial cytokines/chemokines in vitro, suppressing the release of IL-9 and monocyte-chemoattractant protein-1 and increasing IL-10 in the supernatant of male microglial cultures. Our findings indicate that treatment with IL-35 modulates spinal microglia and alleviates neuropathic pain in male mice, suggesting IL-35 as a potential sex-specific targeted immunomodulatory treatment for neuropathic pain.

3.
Anal Chem ; 96(32): 12973-12982, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39089681

RESUMEN

There is increasing interest in developing in-depth proteomic approaches for mapping tissue heterogeneity in a cell-type-specific manner to better understand and predict the function of complex biological systems such as human organs. Existing spatially resolved proteomics technologies cannot provide deep proteome coverage due to limited sensitivity and poor sample recovery. Herein, we seamlessly combined laser capture microdissection with a low-volume sample processing technology that includes a microfluidic device named microPOTS (microdroplet processing in one pot for trace samples), multiplexed isobaric labeling, and a nanoflow peptide fractionation approach. The integrated workflow allowed us to maximize proteome coverage of laser-isolated tissue samples containing nanogram levels of proteins. We demonstrated that the deep spatial proteomics platform can quantify more than 5000 unique proteins from a small-sized human pancreatic tissue pixel (∼60,000 µm2) and differentiate unique protein abundance patterns in pancreas. Furthermore, the use of the microPOTS chip eliminated the requirement for advanced microfabrication capabilities and specialized nanoliter liquid handling equipment, making it more accessible to proteomic laboratories.


Asunto(s)
Péptidos , Proteoma , Proteómica , Humanos , Proteoma/análisis , Proteómica/métodos , Péptidos/análisis , Péptidos/química , Páncreas/metabolismo , Páncreas/química , Nanotecnología , Técnicas Analíticas Microfluídicas/instrumentación , Captura por Microdisección con Láser/métodos
4.
Proc Natl Acad Sci U S A ; 121(34): e2413366121, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39141350
5.
Arterioscler Thromb Vasc Biol ; 44(8): 1833-1851, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38957986

RESUMEN

BACKGROUND: Tight control of cytoplasmic Ca2+ concentration in endothelial cells is essential for the regulation of endothelial barrier function. Here, we investigated the role of Cavß3, a subunit of voltage-gated Ca2+ (Cav) channels, in modulating Ca2+ signaling in brain microvascular endothelial cells (BMECs) and how this contributes to the integrity of the blood-brain barrier. METHODS: We investigated the function of Cavß3 in BMECs by Ca2+ imaging and Western blot, examined the endothelial barrier function in vitro and the integrity of the blood-brain barrier in vivo, and evaluated disease course after induction of experimental autoimmune encephalomyelitis in mice using Cavß3-/- (Cavß3-deficient) mice as controls. RESULTS: We identified Cavß3 protein in BMECs, but electrophysiological recordings did not reveal significant Cav channel activity. In vivo, blood-brain barrier integrity was reduced in the absence of Cavß3. After induction of experimental autoimmune encephalomyelitis, Cavß3-/- mice showed earlier disease onset with exacerbated clinical disability and increased T-cell infiltration. In vitro, the transendothelial resistance of Cavß3-/- BMEC monolayers was lower than that of wild-type BMEC monolayers, and the organization of the junctional protein ZO-1 (zona occludens-1) was impaired. Thrombin stimulates inositol 1,4,5-trisphosphate-dependent Ca2+ release, which facilitates cell contraction and enhances endothelial barrier permeability via Ca2+-dependent phosphorylation of MLC (myosin light chain). These effects were more pronounced in Cavß3-/- than in wild-type BMECs, whereas the differences were abolished in the presence of the MLCK (MLC kinase) inhibitor ML-7. Expression of Cacnb3 cDNA in Cavß3-/- BMECs restored the wild-type phenotype. Coimmunoprecipitation and mass spectrometry demonstrated the association of Cavß3 with inositol 1,4,5-trisphosphate receptor proteins. CONCLUSIONS: Independent of its function as a subunit of Cav channels, Cavß3 interacts with the inositol 1,4,5-trisphosphate receptor and is involved in the tight control of cytoplasmic Ca2+ concentration and Ca2+-dependent MLC phosphorylation in BMECs, and this role of Cavß3 in BMECs contributes to blood-brain barrier integrity and attenuates the severity of experimental autoimmune encephalomyelitis disease.


Asunto(s)
Barrera Hematoencefálica , Señalización del Calcio , Encefalomielitis Autoinmune Experimental , Células Endoteliales , Animales , Femenino , Masculino , Ratones , Barrera Hematoencefálica/metabolismo , Calcio/metabolismo , Canales de Calcio/metabolismo , Canales de Calcio/genética , Permeabilidad Capilar , Células Cultivadas , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/genética , Células Endoteliales/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Cadenas Ligeras de Miosina/metabolismo , Quinasa de Cadena Ligera de Miosina/metabolismo , Quinasa de Cadena Ligera de Miosina/genética , Fosforilación
6.
West J Emerg Med ; 25(4): 557-564, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39028241

RESUMEN

Introduction: Optimizing the performance of emergency department (ED) teams impacts patient care, but the utility of current, team-based performance assessment tools to comprehensively measure this impact is underexplored. In this study we aimed to 1) evaluate ED team performance using current team-based assessment tools during an interprofessional in situ simulation and 2) identify characteristics of effective ED teams. Methods: This mixed-methods study employed case study methodology based on a constructivist paradigm. Sixty-three eligible nurses, technicians, pharmacists, and postgraduate year 2-4 emergency medicine residents at a tertiary academic ED participated in a 10-minute in situ simulation of a critically ill patient. Participants self-rated performance using the Team Performance Observation Tool (TPOT) 2.0 and completed a brief demographic form. Two raters independently reviewed simulation videos and rated performance using the TPOT 2.0, Team Emergency Assessment Measure (TEAM), and Ottawa Crisis Resource Management Global Rating Scale (Ottawa GRS). Following simulations, we conducted semi-structured interviews and focus groups with in situ participants. Transcripts were analyzed using thematic analysis. Results: Eighteen team-based simulations took place between January-April 2021. Raters' scores were on the upper end of the tools for the TPOT 2.0 (R1 4.90, SD 0.17; R2 4.53, SD 0.27, IRR [inter-rater reliability] 0.47), TEAM (R1 3.89, SD 0.19; R2 3.58, SD 0.39, IRR 0.73), and Ottawa GRS (R1 6.6, SD 0.56; R2 6.2, SD 0.54, IRR 0.68). We identified six themes from our interview data: team member entrustment; interdependent energy; leadership tone; optimal communication; strategic staffing; and simulation empowering team performance. Conclusion: Current team performance assessment tools insufficiently discriminate among high performing teams in the ED. Emergency department-specific assessments that capture features of entrustability, interdependent energy, and leadership tone may offer a more comprehensive way to assess an individual's contribution to a team's performance.


Asunto(s)
Competencia Clínica , Servicio de Urgencia en Hospital , Grupo de Atención al Paciente , Humanos , Masculino , Relaciones Interprofesionales , Femenino , Medicina de Emergencia/educación , Entrenamiento Simulado , Adulto , Grupos Focales , Simulación de Paciente
7.
Front Mol Biosci ; 11: 1420691, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38993838

RESUMEN

Conformational diseases, such as Alzheimer's, Parkinson's and Huntington's diseases as well as ataxias and fronto-temporal disorders, are part of common class of neurological disorders characterised by the aggregation and progressive accumulation of mutant proteins which display aberrant conformation. In particular, Huntington's disease (HD) is caused by mutations leading to an abnormal expansion in the polyglutamine (poly-Q) tract of the huntingtin protein (HTT), leading to the formation of inclusion bodies in neurons of affected patients. Furthermore, recent experimental evidence is challenging the conventional view of the disease by revealing the ability of mutant HTT to be transferred between cells by means of extracellular vesicles (EVs), allowing the mutant protein to seed oligomers involving both the mutant and wild type forms of the protein. There is still no successful strategy to treat HD. In addition, the current understanding of the biological processes leading to the oligomerization and aggregation of proteins bearing the poly-Q tract has been derived from studies conducted on isolated poly-Q monomers and oligomers, whose structural properties are still unclear and often inconsistent. Here we describe a standardised biochemical approach to analyse by isopycnic ultracentrifugation the oligomerization of the N-terminal fragment of mutant HTT. The dynamic range of our method allows one to detect large and heterogeneous HTT complexes. Hence, it could be harnessed for the identification of novel molecular determinants responsible for the aggregation and the prion-like spreading properties of HTT in the context of HD. Equally, it provides a tool to test novel small molecules or bioactive compounds designed to inhibit the aggregation of mutant HTT.

8.
Int J Legal Med ; 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-38997516

RESUMEN

Despite the improvements in forensic DNA quantification methods that allow for the early detection of low template/challenged DNA samples, complicating stochastic effects are not revealed until the final stage of the DNA analysis workflow. An assay that would provide genotyping information at the earlier stage of quantification would allow examiners to make critical adjustments prior to STR amplification allowing for potentially exclusionary information to be immediately reported. Specifically, qPCR instruments often have dissociation curve and/or high-resolution melt curve (HRM) capabilities; this, coupled with statistical prediction analysis, could provide additional information regarding STR genotypes present. Thus, this study aimed to evaluate Qiagen's principal component analysis (PCA)-based ScreenClust® HRM® software and a linear discriminant analysis (LDA)-based technique for their abilities to accurately predict genotypes and similar groups of genotypes from HRM data. Melt curves from single source samples were generated from STR D5S818 and D18S51 amplicons using a Rotor-Gene® Q qPCR instrument and EvaGreen® intercalating dye. When used to predict D5S818 genotypes for unknown samples, LDA analysis outperformed the PCA-based method whether predictions were for individual genotypes (58.92% accuracy) or for geno-groups (81.00% accuracy). However, when a locus with increased heterogeneity was tested (D18S51), PCA-based prediction accuracy rates improved to rates similar to those obtained using LDA (45.10% and 63.46%, respectively). This study provides foundational data documenting the performance of prediction modeling for STR genotyping based on qPCR-HRM data. In order to expand the forensic applicability of this HRM assay, the method could be tested with a more commonly utilized qPCR platform.

9.
Cureus ; 16(6): e61731, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38975392

RESUMEN

The use of dentures and dental plates is widespread in the adult population. Accidental ingestion of these foreign objects is not uncommon, with the majority of patients having an uneventful passage of the object through the gastrointestinal tract. Of those patients requiring intervention, endoscopy is the most common, followed by surgical removal. We discuss a case of a patient with prior pelvic surgery and diverticulosis causing severe angulation of the bowel, resulting in non-passage of the foreign object requiring surgical intervention.

10.
Assessment ; : 10731911241260233, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39054848

RESUMEN

The present series of studies aimed to develop and provide initial validation of the Ease of Imagery Questionnaire (EIQ)-a measure assessing ease of imaging different positive and negative imagery content reflective of valence and engaging or disengaging in adverse situations. Five studies were conducted to collectively examine the questionnaire's factor structure and concurrent validity. Study 1 (N = 336) and Study 2 (N = 207) informed the development of 16 items of the EIQ, with a four-factor structure supported in Studies 3 (N = 219), 4 (N = 135), and 5 (N = 184) using confirmatory factor analysis. Study 3 also supported concurrent validity with significant bivariate correlations (p < .05) with the similar Sport Imagery Ability Questionnaire subscales, while studies 4 and 5 demonstrated criterion validity in the EIQ's prediction of challenge and threat appraisal tendencies, perceived stress, stress mindset, and anxiety and depressive symptoms. Overall, the EIQ demonstrates a replicable four-factor structure and appears to assess ability to image content associated with positive and negative emotions as well as demanding stress-evoking situations.

11.
Artículo en Inglés | MEDLINE | ID: mdl-39013167

RESUMEN

Mass spectrometry is broadly employed to study complex molecular mechanisms in various biological and environmental fields, enabling 'omics' research such as proteomics, metabolomics, and lipidomics. As study cohorts grow larger and more complex with dozens to hundreds of samples, the need for robust quality control (QC) measures through automated software tools becomes paramount to ensure the integrity, high quality, and validity of scientific conclusions from downstream analyses and minimize the waste of resources. Since existing QC tools are mostly dedicated to proteomics, automated solutions supporting metabolomics are needed. To address this need, we developed the software PeakQC, a tool for automated QC of MS data that is independent of omics molecular types (i.e., omics-agnostic). It allows automated extraction and inspection of peak metrics of precursor ions (e.g., errors in mass, retention time, arrival time) and supports various instrumentations and acquisition types, from infusion experiments or using liquid chromatography and/or ion mobility spectrometry front-end separations and with/without fragmentation spectra from data-dependent or independent acquisition analyses. Diagnostic plots for fragmentation spectra are also generated. Here, we describe and illustrate PeakQC's functionalities using different representative data sets, demonstrating its utility as a valuable tool for enhancing the quality and reliability of omics mass spectrometry analyses.

13.
Int J Gynecol Cancer ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862154

RESUMEN

OBJECTIVES: Primary mucinous ovarian carcinoma represents 3% of ovarian cancers and is typically diagnosed early, yielding favorable outcomes. This study aims to identify risk factors, focussing on the impact of age and ethnicity on survival from primary mucinous ovarian cancer. METHODS: A retrospective observational study of patients treated at Sandwell and West Birmingham Hospitals NHS Trust and University Hospital Coventry and Warwickshire. Patients included were women aged ≥16 years, with primary mucinous ovarian cancer confirmed by specialist gynecological histopathologist and tumor immunohistochemistry, including cytokeratin-7, cytokeratin-20, and CDX2. Statistical analyses were performed using R integrated development environment, with survival assessed by Cox proportional hazards models and Kaplan-Meier plots. RESULTS: A total of 163 patients were analyzed; median age at diagnosis was 58 years (range 16-92), 145 (89%) were International Federation of Gynecology and Obstetrics stage I and 43 (26%) patients had infiltrative invasion. Women aged ≤45 years were more likely to have infiltrative invasion (RR=1.38, 95% CI 0.78 to 2.46), with increased risk of death associated with infiltrative invasion (HR=2.29, 95% CI 1.37 to 5.83). Compared with White counterparts, South Asian women were more likely to undergo fertility-sparing surgery (RR=3.52, 95% CI 1.48 to 8.32), and have infiltrative invasion (RR=1.25, 95% CI 0.60 to 2.58). South Asian women undergoing fertility-sparing surgery had worse prognosis than those undergoing traditional staging surgery (HR=2.20, 95% CI 0.39 to 13.14). In FIGO stage I disease, 59% South Asian and 37% White women received adjuvant chemotherapy (p=0.06). South Asian women exhibited a worse overall prognosis than White women (HR=2.07, 95% CI 0.86 to 4.36), particularly pronounced in those aged ≤45 years (HR=8.75, 95% CI 1.22 to 76.38). CONCLUSION: This study identified young age as a risk factor for diagnosis of infiltrative invasion. Fertility-sparing surgery in South Asian women is a risk factor for poorer prognosis. South Asian women exhibit poorer overall survival than their White counterparts.

14.
Air Med J ; 43(4): 313-320, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38897694

RESUMEN

OBJECTIVE: Given the recommendations against the use of critical incident stress debriefing, the emergency medical services (EMS) Code Lavender program was created as a mechanism to consistently recognize and reach out to EMS clinicians after acute crisis events, offer nonintrusive informal peer support and acts of kindness, and provide stepwise support via mental health professionals as needed. The study aimed to assess program utilization and evaluate the program's impact on EMS clinicians' perceptions of support and resources available to them after an acute crisis event. METHODS: Anonymous surveys were distributed before program implementation and 18 months later. Program utilization was tracked using REDCap (Vanderbilt University, Nashville, TN). Fisher exact tests and logistic regression were used to analyze the survey results. RESULTS: Within 30 months, 87 referrals were made. Seventy-seven preprogram (59% response rate) and 104 intraprogram (88% response rate) surveys were collected. There were no differences between respondents by sex or role. There were significant improvements in knowing where to go for help (from 40% to 85%, P < .001) and willingness to seek help if needed (from 40% to 59%, P = .02). CONCLUSION: The implementation of an EMS Code Lavender program led to significant increases in EMS clinician self-reported knowledge of where to go and willingness to seek help after acute crisis events.


Asunto(s)
Servicios Médicos de Urgencia , Humanos , Masculino , Femenino , Adulto , Intervención en la Crisis (Psiquiatría) , Grupo Paritario , Encuestas y Cuestionarios , Persona de Mediana Edad , Auxiliares de Urgencia/psicología , Apoyo Social
15.
Air Med J ; 43(4): 333-339, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38897697

RESUMEN

OBJECTIVE: Emergency medical services (EMS) Code Lavender was developed to support EMS clinicians after stressful events via consistent recognition of events, informal peer support, and intentional acts of kindness. This study evaluated changes in burnout screening tool responses of EMS clinicians in response to program implementation and the coincidental start of coronavirus disease 2019. METHODS: Anonymous surveys with demographic questions and 2 burnout screening tools were distributed before program implementation (spring 2020) and 20 months later (fall 2021). Analysis included t-tests, Fisher exact tests, and multivariable linear regression. RESULTS: Seventy-seven preprogram (59% response rate) and 108 intraprogram (88% response rate) survey responses were included. No changes existed between preprogram and intraprogram responses across all subscale scores. Sex was associated with depersonalization subscale scores, with men having scores 1.53 (95% confidence interval [CI] 0.11-2.95) higher than women. Compared with emergency medical technicians, paramedics had higher compassion satisfaction (OR 3.50; 95% CI 1.79-5.70) and personal accomplishment scores (OR 2.40; 95% CI 1.08-3.71). Transport nurses had higher personal accomplishment (OR 3.29; 95% CI 1.18-5.40), depersonalization (OR 3.73; 95% CI 1.19-6.26), and rates of burnout symptoms (OR 0.54; 95% CI 0.09-0.98) than emergency medical technicians. CONCLUSION: The organizational commitment, peer support, and authentic leadership of EMS Code Lavender may attenuate work-related stressors among EMS clinicians.


Asunto(s)
Agotamiento Profesional , COVID-19 , Auxiliares de Urgencia , Empatía , Humanos , Agotamiento Profesional/psicología , Masculino , Femenino , Adulto , Auxiliares de Urgencia/psicología , COVID-19/psicología , Encuestas y Cuestionarios , Grupo Paritario , Persona de Mediana Edad , Servicios Médicos de Urgencia , Satisfacción en el Trabajo , Estrés Laboral/psicología , Desgaste por Empatía/psicología
16.
bioRxiv ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38915495

RESUMEN

Inverted formin-2 (INF2) gene mutations are among the most common causes of genetic focal segmental glomerulosclerosis (FSGS) with or without Charcot-Marie-Tooth (CMT) disease. Recent studies suggest that INF2, through its effects on actin and microtubule arrangement, can regulate processes including vesicle trafficking, cell adhesion, mitochondrial calcium uptake, mitochondrial fission, and T-cell polarization. Despite roles for INF2 in multiple cellular processes, neither the human pathogenic R218Q INF2 point mutation nor the INF2 knock-out allele is sufficient to cause disease in mice. This discrepancy challenges our efforts to explain the disease mechanism, as the link between INF2-related processes, podocyte structure, disease inheritance pattern, and their clinical presentation remains enigmatic. Here, we compared the kidney responses to puromycin aminonucleoside (PAN) induced injury between R218Q INF2 point mutant knock-in and INF2 knock-out mouse models and show that R218Q INF2 mice are susceptible to developing proteinuria and FSGS. This contrasts with INF2 knock-out mice, which show only a minimal kidney phenotype. Co-localization and co-immunoprecipitation analysis of wild-type and mutant INF2 coupled with measurements of cellular actin content revealed that the R218Q INF2 point mutation confers a gain-of-function effect by altering the actin cytoskeleton, facilitated in part by alterations in INF2 localization. Differential analysis of RNA expression in PAN-stressed heterozygous R218Q INF2 point-mutant and heterozygous INF2 knock-out mouse glomeruli showed that the adhesion and mitochondria-related pathways were significantly enriched in the disease condition. Mouse podocytes with R218Q INF2, and an INF2-mutant human patient's kidney organoid-derived podocytes with an S186P INF2 mutation, recapitulate the defective adhesion and mitochondria phenotypes. These results link INF2-regulated cellular processes to the onset and progression of glomerular disease. Thus, our data demonstrate that gain-of-function mechanisms drive INF2-related FSGS and explain the autosomal dominant inheritance pattern of this disease.

17.
PLoS One ; 19(6): e0303894, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38941338

RESUMEN

OBJECTIVE: This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented. METHODS: Initially, the RCT randomized participants 1:1 to either ECT plus usual care or simulated ECT plus usual care (S-ECT) groups. As patients were enrolled, data were collected from both ECT and simulated ECT (S-ECT) patients. The study now continues in an open-label study design where all patients receive actual ECT, reducing the targeted sample size from 200 to 50 participants. RESULTS: Study is ongoing and open to enrollment. CONCLUSION: The transition of the ECT-AD study design from an RCT to open-label design exemplifies adaptive research methodologies in response to real-world challenges. Data from both the RCT and open-label phases of the study will provide a unique perspective on the role of ECT in managing severe treatment-refractory agitation in dementia, potentially influencing future clinical practices and research approaches.


Asunto(s)
Demencia , Terapia Electroconvulsiva , Agitación Psicomotora , Humanos , Terapia Electroconvulsiva/métodos , Agitación Psicomotora/terapia , Demencia/terapia , Demencia/complicaciones , Método Simple Ciego , Femenino , Masculino , Resultado del Tratamiento , Anciano , Conducta Motora Aberrante en la Demencia
18.
Genes (Basel) ; 15(6)2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38927704

RESUMEN

Although guidelines exist for identifying mixtures, these measures often occur at the end-point of analysis and are protracted. To facilitate early mixture detection, we integrated a high-resolution melt (HRM) mixture screening assay into the qPCR step of the forensic workflow, producing the integrated QuantifilerTM Trio-HRM assay. The assay, when coupled with a prediction tool, allowed for 75.0% accurate identification of the contributor status of a sample (single source vs. mixture). To elucidate the limitations of the developed qPCR-HRM assay, developmental validation studies were conducted assessing the reproducibility and samples with varying DNA ratios, contributors, and quality. From this work, it was determined that the integrated QuantifilerTM Trio-HRM assay is capable of accurately identifying mixtures with up to five contributors and mixtures at ratios up to 1:100. Further, the optimal performance concentration range was found to be between 0.025 and 0.5 ng/µL. With these results, evidentiary-like DNA samples were then analyzed, resulting in 100.0% of the mixture samples being accurately identified; furthermore, every time a sample was predicted as a single source, it was true, giving confidence to any single-source calls. Overall, the integrated QuantifilerTM Trio-HRM assay has exhibited an enhanced ability to discern mixture samples from single-source samples at the qPCR stage under commonly observed conditions regardless of the contributor's sex.


Asunto(s)
Genética Forense , Humanos , Genética Forense/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , ADN/genética , Dermatoglifia del ADN/métodos , Reproducibilidad de los Resultados , Repeticiones de Microsatélite/genética
19.
J Viral Hepat ; 31(8): 490-499, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38798022

RESUMEN

Chronic hepatitis B infection (CHB) affects 300 million people worldwide and is being targeted by the United Nations 2030 Sustainable Development Goals (SDGs) and the World Health Organisation (WHO), working towards elimination of hepatitis B virus (HBV) as a public health threat. In this piece, we explore the evidence and potential impact of peer support to enhance and promote interventions for people living with CHB. Peer support workers (PSWs) are those with lived experience of an infection, condition or situation who work to provide support for others, aiming to improve education, prevention, treatment and other clinical interventions and to reduce the physical, psychological and social impacts of disease. Peer support has been shown to be a valuable tool for improving health outcomes for people living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), but to date has not been widely available for communities affected by HBV. HBV disproportionately affects vulnerable and marginalised populations, who could benefit from PSWs to help them navigate complicated systems and provide advocacy, tackle stigma, improve education and representation, and optimise access to treatment and continuity of care. The scale up of peer support must provide structured and supportive career pathways for PSWs, account for social and cultural needs of different communities, adapt to differing healthcare systems and provide flexibility in approaches to care. Investment in peer support for people living with CHB could increase diagnosis, improve retention in care, and support design and roll out of interventions that can contribute to global elimination goals.


Asunto(s)
Hepatitis B Crónica , Grupo Paritario , Apoyo Social , Humanos , Hepatitis B Crónica/terapia , Hepatitis B Crónica/psicología
20.
Int J Clin Exp Hypn ; 72(3): 254-273, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38753818

RESUMEN

Perceived stress is a significant problem among female college students that can impact psychological distress, sleep, and overall well-being. Mindful self-hypnosis (MSH) and resistance training (RT) have both been shown to reduce perceived stress. The rationale for the present study was to investigate whether MSH combined with RT could be more effective at reducing perceived stress as measured by the Perceived Stress Scale than RT alone due to synergistic effects achieved by combining the interventions. Forty-four female college students were randomized to one of the three groups: MSH+RT, RT only, or a wait-list control (WLC). Results indicated that, compared to RT only, the addition of MSH led to pronounced improvements in perceived stress which was significantly greater than WLC. Also, MSH+RT resulted in significant increases in mindfulness, sleep, strength, and well-being in comparison to WLC. MSH+RT was shown to be feasible with highly satisfactory participant ratings. Future research should examine the MSH+RT intervention with a larger population and with older women who are more at risk for stress and declining strength.


Asunto(s)
Atención Plena , Entrenamiento de Fuerza , Estrés Psicológico , Estudiantes , Humanos , Femenino , Atención Plena/métodos , Estudiantes/psicología , Estrés Psicológico/psicología , Adulto Joven , Entrenamiento de Fuerza/métodos , Universidades , Adulto , Adolescente
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