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1.
J Affect Disord ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38754598

RESUMO

BACKGROUND: Bipolar disorder remains a disabling mental health condition despite the availability of effective treatments. Collaborative chronic care models (CCMs) represent an evidence-based way to structure care for conditions like bipolar disorder. Life Goals Collaborative Care (LGCC) was designed specifically for bipolar disorder, featuring psychoeducation alongside collaborative components (e.g. nurse care management or expert psychiatric consultation). Despite the use of Life Goals across health systems, a systematic review summarizing its effectiveness has never been conducted. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) of LGCC through December 2023 to help guide the field in treating bipolar disorder (PROSPERO: #404581). We evaluated study quality and outcomes in several symptom and quality of life domains. RESULTS: Ten articles describing eight studies met inclusion criteria. All studies featured group-based LGCC; most were compared to treatment as usual (TAU). Three of eight studies found LGCC to be associated with statistically significant effects for the prevention of manic episodes. Most studies finding positive effects featured additional collaborative care components beyond psychoeducation and were conducted in capitated healthcare systems. LIMITATIONS: Limitations include: several types of potential bias in included studies; exclusion of observational studies of LGCC; lack of generalizability to pediatric populations; insufficient studies to conduct subgroup analyses; and low confidence in the quality of the evidence. CONCLUSIONS: In this systematic review, group-based LGCC demonstrated some positive effects for reducing mania recurrence; results for other outcome domains were equivocal. Future studies should investigate one-on-one LGCC, both in person and virtually, to enhance well-being for people with bipolar disorder.

2.
Psychoanal Q ; : 1-35, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776426

RESUMO

King Lear is a timeless exposition of humankind's attempt to find meaning amidst the ceaseless turbulence of existence. This entails navigating the disintegrating pulls of nature and harmful human action that exist alongside affiliative, life-promoting gestures shown toward one another. As the predictability and safety afforded by social and two-dimensional psychic constructs collapse, several characters in this play are forced to reckon with the untamed, less organized realms of the mind and natural world. This leads to movements toward psychic paralysis and disintegration, as well as toward growth and interpersonal healing, dynamics that hinge on the characters' internal structuring.

3.
Glob Implement Res Appl ; 20242024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38765294

RESUMO

Transferring successful implementation strategies from research to practice requires approaches for assessing fidelity to the strategy's core components. Implementation facilitation (IF) is a strategy involving an interactive process of problem-solving, enabling, and supporting individuals in efforts to implement clinical innovations that occurs in the context of a recognized need for improvement and supportive interpersonal relationships. Because IF is a dynamic strategy involving numerous activities, our objective was to conduct a rigorous consensus development process to identify core activities for monitoring fidelity to IF when applied in clinical settings. We first conducted a scoping literature review to identify the range of activities used when IF has been applied in clinical settings, searching multiple citation databases for English-language articles including "facilitation" or other commonly-used terms for the strategy published from 1996-2015. Through multi-stage screening, 135 articles (from 94 studies) were identified for data extraction on IF activities, frequency with which IF activities were identified as 'core' by study authors, and study outcomes. From the literature review, we identified 32 distinct IF activities and developed definitions/examples for each. Next, we conducted a 3-stage, modified-Delphi expert panel consensus development process to identify core IF activities across three implementation phases (i.e., Pre-Implementation, Implementation, Sustainment). The expert panel identified 8 core activities for the Pre-Implementation Phase, 8 core activities for the Implementation Phase, and 4 core activities for the Sustainment Phase. This work provides an important foundation for developing measures/tools to assess use of core IF activities to ensure the strategy is delivered with fidelity.

4.
Arch Dermatol Res ; 316(5): 174, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758250

RESUMO

Understanding patient non-adherence to prescribed antibiotics can inform clinical practices, patient counseling, and antibiotic efficacy study design in dermatology. The primary objective was to determine the rate of and reasons for antibiotic non-adherence in the dermatologic surgery setting. The secondary objective was to test the applicability of previously studied survey questions for antibiotic non-adherence screening in the dermatologic surgery setting. Five academic outpatient dermatologic surgery centers across the United States conducted one multicenter prospective cohort study. Dermatologic surgery patients ≥ 18 years of age who were prescribed an antibiotic were included as part of this study. 15.2% (42/276) of patients did not adhere to their antibiotic regimen after dermatologic surgery. Most common reasons for incomplete antibiotic courses included forgotten antibiotics (42.9%,18/42) and side effects (28.6%, 12/42). Previously evaluated questions to identify and predict non-adherence had modest performance in the dermatologic surgery setting (Area under the curve of 0.669 [95% CI (0.583-0.754)]). Antibiotic non-adherence after skin surgery is prevalent and commonly due to reasons that physicians can address with patients.


Assuntos
Antibacterianos , Adesão à Medicação , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Estudos Prospectivos , Feminino , Pessoa de Meia-Idade , Masculino , Adesão à Medicação/estatística & dados numéricos , Idoso , Procedimentos Cirúrgicos Dermatológicos/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Estados Unidos , Inquéritos e Questionários/estatística & dados numéricos
5.
Dermatol Surg ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38754124

RESUMO

BACKGROUND AND OBJECTIVE: Large defects of the nose after Mohs surgery pose a significant reconstructive challenge to both dermatologic and reconstructive surgeons. The authors present their 12-year experience utilizing acellular dermal matrices for nasal reconstruction. METHODS: A retrospective review of patients undergoing Mohs surgery and alloplastic nasal reconstruction with acellular dermal matrices between 2010 and 2022 was performed. Patients who underwent single-stage reconstruction and dual-stage reconstruction with skin graft with at least 90 days of follow-up were included. RESULTS: Fifty-one patients met criteria with a median age of 77 years. Fifty-three lesions were reconstructed with acellular dermal matrices. The most common lesion location was nasal sidewall (50%) with a mean defect size of 10.8 cm 2 . 30.8% underwent same-day acellular dermal matrix reconstruction, with 69.2% undergoing two-stage reconstruction. Acellular dermal matrices successfully reconstructed acquired defects in 94.2% of lesions. Average time to re-epithelialization was 27.6 + 6.2 days. Average time to repigmentation was 145.35 + 86 days. No recurrences were recorded. Total complication rate was 9.62%. Average size for successful healing was 10.8 cm 2 . Average defect size for complication or failure was 14.7 cm 2 . Seven sites (13.46%) underwent aesthetic improvement procedures. CONCLUSION: Acellular bilayer wound matrix is an adequate reconstructive option for single or dual-stage reconstruction of the nose with low complication and revision rates.

6.
Dermatol Surg ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38574349

RESUMO

BACKGROUND: Mohs surgery of eyelid skin cancers requires detailed knowledge of anatomy for precise surgery and accurate evaluation of histology. OBJECTIVE: To review the histology of the peritarsal eyelid using frozen sections as encountered intraoperatively by Mohs surgeons. METHODS: The authors review the literature describing the anatomy and histology of the peritarsal eyelid from the lens of a Mohs surgeon. Histology from select Mohs cases is used to frame the discussion of the microanatomy of this region. RESULTS: The peritarsal eyelids contain a unique mixture of skin, muscle, tarsus, glandular tissue, and conjunctiva. The histologic appearance of many of these structures differs from skin found outside of this anatomic region. Tumors of the eyelid and periocular region may mimic normal histologic structures found within the peritarsal eyelid. CONCLUSION: The peritarsal eyelids have unique anatomy and associated histologic structures. Knowledge of the detailed histoanatomy is required for confident execution of Mohs surgery in this anatomic region.

7.
Proc Natl Acad Sci U S A ; 121(18): e2317690121, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38648485

RESUMO

The underlying mechanism(s) by which the PML::RARA fusion protein initiates acute promyelocytic leukemia is not yet clear. We defined the genomic binding sites of PML::RARA in primary mouse and human hematopoietic progenitor cells with V5-tagged PML::RARA, using anti-V5-PML::RARA chromatin immunoprecipitation sequencing and CUT&RUN approaches. Most genomic PML::RARA binding sites were found in regions that were already chromatin-accessible (defined by ATAC-seq) in unmanipulated, wild-type promyelocytes, suggesting that these regions are "open" prior to PML::RARA expression. We found that GATA binding motifs, and the direct binding of the chromatin "pioneering factor" GATA2, were significantly enriched near PML::RARA binding sites. Proximity labeling studies revealed that PML::RARA interacts with ~250 proteins in primary mouse hematopoietic cells; GATA2 and 33 others require PML::RARA binding to DNA for the interaction to occur, suggesting that binding to their cognate DNA target motifs may stabilize their interactions. In the absence of PML::RARA, Gata2 overexpression induces many of the same epigenetic and transcriptional changes as PML::RARA. These findings suggested that PML::RARA may indirectly initiate its transcriptional program by activating Gata2 expression: Indeed, we demonstrated that inactivation of Gata2 prior to PML::RARA expression prevented its ability to induce self-renewal. These data suggested that GATA2 binding creates accessible chromatin regions enriched for both GATA and Retinoic Acid Receptor Element motifs, where GATA2 and PML::RARA can potentially bind and interact with each other. In turn, PML::RARA binding to DNA promotes a feed-forward transcriptional program by positively regulating Gata2 expression. Gata2 may therefore be required for PML::RARA to establish its transcriptional program.


Assuntos
Fator de Transcrição GATA2 , Células-Tronco Hematopoéticas , Proteínas de Fusão Oncogênica , Animais , Humanos , Camundongos , Sítios de Ligação , Autorrenovação Celular , Cromatina/metabolismo , DNA/metabolismo , Fator de Transcrição GATA2/metabolismo , Fator de Transcrição GATA2/genética , Células-Tronco Hematopoéticas/metabolismo , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patologia , Proteínas de Fusão Oncogênica/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteína da Leucemia Promielocítica/metabolismo , Proteína da Leucemia Promielocítica/genética , Ligação Proteica , Receptor alfa de Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico/genética
9.
Water Res ; 254: 121413, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489850

RESUMO

A long-term field trial of membrane capacitive deionization (MCDI) was conducted in a remote community in the Northern Territory of Australia, with the aim of producing safe palatable drinking water from groundwater that contains high concentrations of salt and hardness ions and other contaminants. This trial lasted for 1.5 years, which, to our knowledge, is one of the longest reported studies of pilot-scale MCDI field trials. The 8-module MCDI pilot unit reduced salt concentration to below the Australian Drinking Water Guideline value of 600 mg/L total dissolved solids (TDS) concentration with a relatively high water recovery of 71.6 ± 8.7 %. During continuous constant current operation and electrode discharging at near zero volts, a rapid performance deterioration occurred that was primarily attributed to insufficient desorption of multivalent ions from the porous carbon electrodes. Performance could be temporarily recovered using chemical cleaning and modified operating procedures however these approaches could not fundamentally resolve the issue of insufficient electrode performance regeneration. Constant current discharging of the electrodes to a negative cell cut-off voltage was hence employed to enhance the stability and overall performance of the MCDI unit during the continuous operation. An increase in selectivity of monovalent ions over divalent ions was also attained by implementing negative voltage discharging. The energy consumption of an MCDI system with a capacity of 1000 m3/day was projected to be 0.40∼0.53 kWh/m3, which is comparable to the energy consumption of electrodialysis reversal (EDR) and brackish water reverse osmosis (BWRO) systems of the same capacity. The relatively low maintenance requirements of the MCDI system rendered it the most cost-efficient water treatment technology for deployment in remote locations. The LCOW of an MCDI system with a capacity of 1000 m3/day was projected to be AU$1.059/m3 and AU$1.146/m3 under two operational modes, respectively. Further investigation of particular water-energy trade-offs amongst MCDI performance metrics is required to facilitate broader application of this promising water treatment technology.


Assuntos
Água Potável , Purificação da Água , Adsorção , Austrália , Carbono , Cloreto de Sódio , Íons , Purificação da Água/métodos , Eletrodos
10.
J Appl Physiol (1985) ; 136(5): 1105-1112, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38482574

RESUMO

During spaceflight, fluids shift headward, causing internal jugular vein (IJV) distension and altered hemodynamics, including stasis and retrograde flow, that may increase the risk of thrombosis. This study's purpose was to determine the effects of acute exposure to weightlessness (0-G) on IJV dimensions and flow dynamics. We used two-dimensional (2-D) ultrasound to measure IJV cross-sectional area (CSA) and Doppler ultrasound to characterize venous blood flow patterns in the right and left IJV in 13 healthy participants (6 females) while 1) seated and supine on the ground, 2) supine during 0-G parabolic flight, and 3) supine during level flight (at 1-G). On Earth, in 1-G, moving from seated to supine posture increased CSA in both left (+62 [95% CI: +42 to 81] mm2, P < 0.0001) and right (+86 [95% CI: +58 to 113] mm2, P < 0.00012) IJV. Entry into 0-G further increased IJV CSA in both left (+27 [95% CI: +5 to 48] mm2, P = 0.02) and right (+30 [95% CI: +0.3 to 61] mm2, P = 0.02) relative to supine in 1-G. We observed stagnant flow in the left IJV of one participant during 0-G parabolic flight that remained during level flight but was not present during any imaging during preflight measures in the seated or supine postures; normal venous flow patterns were observed in the right IJV during all conditions in all participants. Alterations to cerebral outflow dynamics in the left IJV can occur during acute exposure to weightlessness and thus, may increase the risk of venous thrombosis during any duration of spaceflight.NEW & NOTEWORTHY The absence of hydrostatic pressure gradients in the vascular system and loss of tissue weight during weightlessness results in altered flow dynamics in the left internal jugular vein in some astronauts that may contribute to an increased risk of thromboembolism during spaceflight. Here, we report that the internal jugular veins distend bilaterally in healthy participants and that flow stasis can occur in the left internal jugular vein during acute weightlessness produced by parabolic flight.


Assuntos
Veias Jugulares , Ausência de Peso , Humanos , Feminino , Veias Jugulares/fisiologia , Veias Jugulares/diagnóstico por imagem , Masculino , Adulto , Ausência de Peso/efeitos adversos , Voo Espacial/métodos , Hemodinâmica/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Decúbito Dorsal/fisiologia , Adulto Jovem
11.
Foot Ankle Int ; : 10711007241238221, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501747

RESUMO

BACKGROUND: We aim to compare early surgical results between groups who underwent minimally invasive surgery (MIS) vs open first metatarsophalangeal (MTP) arthrodesis to treat end-stage hallux rigidus. METHODS: We conducted a retrospective cohort review of 65 patients who underwent a first MTP fusion procedure at an academic medical center between 2015 and 2023. Success of fusion was determined radiographically. Postoperative complications were identified through medical record review. RESULTS: Sixty-seven first MTP fusion surgeries (41 open and 26 MIS) were performed on 65 patients with a primary diagnosis of hallux rigidus. Open surgery and MIS groups had similarly high fusion rates: 95% (39/41) and 96% (25/26), respectively (P = .84). We identified no difference in overall complication rates: 20% for open surgery and 23% for MIS (P = .73). CONCLUSION: This retrospective analysis of 67 first MTP arthrodesis procedures showed no significant differences in fusion success or complications in the short term when comparing MIS to open surgery. Further studies are needed to elucidate potential differences between MIS vs open surgery. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

13.
Implement Sci ; 19(1): 16, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373979

RESUMO

BACKGROUND: Sustaining evidence-based practices (EBPs) is crucial to ensuring care quality and addressing health disparities. Approaches to identifying factors related to sustainability are critically needed. One such approach is Matrixed Multiple Case Study (MMCS), which identifies factors and their combinations that influence implementation. We applied MMCS to identify factors related to the sustainability of the evidence-based Collaborative Chronic Care Model (CCM) at nine Department of Veterans Affairs (VA) outpatient mental health clinics, 3-4 years after implementation support had concluded. METHODS: We conducted a directed content analysis of 30 provider interviews, using 6 CCM elements and 4 Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) domains as codes. Based on CCM code summaries, we designated each site as high/medium/low sustainability. We used i-PARIHS code summaries to identify relevant factors for each site, the extent of their presence, and the type of influence they had on sustainability (enabling/neutral/hindering/unclear). We organized these data into a sortable matrix and assessed sustainability-related cross-site trends. RESULTS: CCM sustainability status was distributed among the sites, with three sites each being high, medium, and low. Twenty-five factors were identified from the i-PARIHS code summaries, of which 3 exhibited strong trends by sustainability status (relevant i-PARIHS domain in square brackets): "Collaborativeness/Teamwork [Recipients]," "Staff/Leadership turnover [Recipients]," and "Having a consistent/strong internal facilitator [Facilitation]" during and after active implementation. At most high-sustainability sites only, (i) "Having a knowledgeable/helpful external facilitator [Facilitation]" was variably present and enabled sustainability when present, while (ii) "Clarity about what CCM comprises [Innovation]," "Interdisciplinary coordination [Recipients]," and "Adequate clinic space for CCM team members [Context]" were somewhat or less present with mixed influences on sustainability. CONCLUSIONS: MMCS revealed that CCM sustainability in VA outpatient mental health clinics may be related most strongly to provider collaboration, knowledge retention during staff/leadership transitions, and availability of skilled internal facilitators. These findings have informed a subsequent CCM implementation trial that prospectively examines whether enhancing the above-mentioned factors within implementation facilitation improves sustainability. MMCS is a systematic approach to multi-site examination that can be used to investigate sustainability-related factors applicable to other EBPs and across multiple contexts.


Assuntos
Serviços de Saúde Mental , Saúde Mental , Humanos , Pacientes Ambulatoriais , Assistência de Longa Duração , Qualidade da Assistência à Saúde
14.
Implement Res Pract ; 5: 26334895231226197, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322803

RESUMO

Background: Sustaining healthcare interventions once they have been implemented is a pivotal public health endeavor. Achieving sustainability requires context-sensitive adaptations to evidence-based practices (EBPs) or the implementation strategies used to ensure their adoption. For replicability of adaptations beyond the specific setting in question, the underlying logic needs to be clearly described, and adaptations themselves need to be plainly documented. The goal of this project was to describe the process by which implementation facilitation was adapted to improve the uptake of clinical care practices that are consistent with the collaborative chronic care model (CCM). Method: Quantitative and qualitative data from a prior implementation trial found that CCM-consistent care practices were not fully sustained within outpatient general mental health teams that had received 1 year of implementation facilitation to support uptake. We undertook a multistep consensus process to identify adaptations to implementation facilitation based on these results, with the goal of enhancing the sustainability of CCM-based care in a subsequent trial. The logic for these adaptations, and the resulting adaptations themselves, were documented using two adaptation-oriented implementation frameworks (the iterative decision-making for evaluation of adaptations [IDEA] and the framework for reporting adaptations and modifications to evidence-based implementation strategies [FRAME-IS], respectively). Results: Three adaptations emerged from this process and were documented using the FRAME-IS: (a) increasing the scope of implementation facilitation within the medical center, (b) having the internal facilitator take a greater role in the implementation process, and (c) shortening the implementation timeframe from 12 to 8 months, while increasing the intensity of facilitation support during that time. Conclusions: EBP sustainability may require careful adaptation of EBPs or the implementation strategies used to get them into routine practice. Recently developed frameworks such as the IDEA and FRAME-IS may be used to guide decision-making and document resulting adaptations themselves. An ongoing funded study is investigating the utility of the resulting adaptations for improving healthcare.


Evidence-based treatments may not be sustained after they have been implemented in healthcare settings. To address this, treatments and implementation strategies may need to be adapted to fit the local context or the patient population. Maximizing the usefulness of such adaptations requires documenting the decision-making process. Understanding how an implementation strategy has been adapted for a given study or setting is crucial to ensuring that adaptations don't compromise fidelity to the implementation strategy while enabling its replicability in similar settings. This article uses two adaptation frameworks to describe the process by which implementation facilitation, a common implementation strategy, was adapted to help establish and sustain effective mental health clinical teams in VA medical centers. It is our hope that our description of this process may help healthcare researchers, administrators, and policymakers to describe and document adaptations to implementation strategies in their own settings.

15.
J Neurosurg ; : 1-7, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38306646

RESUMO

OBJECTIVE: The number of women graduating from United States medical schools has reached parity with that of men. However, persistent inequalities and barriers have slowed the pace toward equity in application and representation in neurosurgery residency despite initiatives to increase female representation. The objective of the present study was to assess the advancement of gender parity within neurosurgery residency programs. Additionally, the study aimed to analyze the pipeline dynamics by investigating the effects of attrition on women in neurosurgery, as well as exploring the patterns of female applications to neurosurgery residency programs versus other surgical specialties. METHODS: Data on the number of active female neurosurgery residents and female applicants to neurosurgery were collected from the Accreditation Council for Graduate Medical Education Data Resource Book from 2007 to 2021 and Electronic Residency Application Service from 2014 to 2022. Linear regression analysis was used to predict the percent of active female residents based on academic year (AY). A Pearson chi-square test was used to determine the odds of a female applying to neurosurgery. RESULTS: The percent of active female residents in neurosurgery increased from 11.0% in 2007 to 21.8% in 2021. Bivariate linear regression analysis using AY as a predictor of the percent of active females showed a statistically significant correlation. On average, the percent of active female residents increased by 0.65% per year. If trends persist, parity for females in neurosurgery will not be reached until 2069. Linear regression analysis of the overall rate of attrition in neurosurgery as a predictor of the percent of active female residents revealed that for every 1% increase in the rate of attrition, the percent of active female residents decreased by 2.91% (p = 0.001). The percent of female applicants to neurosurgery increased from 19.6% in 2014 to 29.8% in 2022 (p = 0.009), yet the odds of a female applying to neurosurgery remain low. CONCLUSIONS: Neurosurgery continues to struggle with the recruitment of female medical students even as parity has been reached for female medical school matriculants. Greater effort is needed to recruit and retain female applicants to neurosurgery, including increased transparency in match and attrition metrics.

16.
Acta Neuropathol Commun ; 12(1): 32, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395965

RESUMO

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are clinically linked major neurodegenerative diseases. Notably, TAR DNA-binding protein-43 (TDP43) accumulations are hallmark pathologies of FTD/ALS and mutations in the gene encoding TDP43 cause familial FTD/ALS. There are no cures for FTD/ALS. FTD/ALS display damage to a broad range of physiological functions, many of which are regulated by signaling between the endoplasmic reticulum (ER) and mitochondria. This signaling is mediated by the VAPB-PTPIP51 tethering proteins that serve to recruit regions of ER to the mitochondrial surface so as to facilitate inter-organelle communications. Several studies have now shown that disrupted ER-mitochondria signaling including breaking of the VAPB-PTPIP51 tethers are features of FTD/ALS and that for TDP43 and other familial genetic FTD/ALS insults, this involves activation of glycogen kinase-3ß (GSK3ß). Such findings have prompted suggestions that correcting damage to ER-mitochondria signaling and the VAPB-PTPIP51 interaction may be broadly therapeutic. Here we provide evidence to support this notion. We show that overexpression of VAPB or PTPIP51 to enhance ER-mitochondria signaling corrects mutant TDP43 induced damage to inositol 1,4,5-trisphosphate (IP3) receptor delivery of Ca2+ to mitochondria which is a primary function of the VAPB-PTPIP51 tethers, and to synaptic function. Moreover, we show that ursodeoxycholic acid (UDCA), an FDA approved drug linked to FTD/ALS and other neurodegenerative diseases therapy and whose precise therapeutic target is unclear, corrects TDP43 linked damage to the VAPB-PTPIP51 interaction. We also show that this effect involves inhibition of TDP43 mediated activation of GSK3ß. Thus, correcting damage to the VAPB-PTPIP51 tethers may have therapeutic value for FTD/ALS and other age-related neurodegenerative diseases.


Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Doenças Neurodegenerativas , Proteínas de Transporte Vesicular , Humanos , Esclerose Lateral Amiotrófica/patologia , Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Demência Frontotemporal/genética , Demência Frontotemporal/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Sinapses/patologia , Proteinopatias TDP-43/metabolismo , Proteínas de Transporte Vesicular/genética
17.
Nat Sci Sleep ; 16: 63-74, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318264

RESUMO

Purpose: We aimed to adapt the Turkish Sleep Condition Indicator (SCI) version and examine its psychometric properties among the general population. Methods: This study was a cross-sectional study. The item-total correlation, standard error of measurement, Cronbach's α, and McDonald's ω were used for internal consistency. We ran confirmatory factor analysis (CFA) and network analysis to confirm the factor structure. Multigroup CFA was run to assess the measurement invariance across gender, whether clinical insomnia or not, and poor sleep quality. We correlated SCI scores with Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) scores to evaluate construct validity. A receiver operating characteristic (ROC) curve analysis was conducted to calculate the cut-off score of the SCI. The temporal stability was examined with the intraclass correlation coefficient. Results: Eight hundred thirty-four participants attended. Over half of the participants were women (63.2% n = 527); the mean age was 36.15 ± 9.64. Confirmatory factor and network analysis results show that the two-factor correlated model had a good model fit for the SCI. The SCI had scalar level invariance across gender, having clinical insomnia and poor sleep quality in the Multigroup CFA. ROC curve analysis shows that the SCI has good sensitivity (90.3%) and specificity (91.8%) for cut-off ≤ 15. The intraclass correlation coefficient computed between the first and second SCI total scores was significant (r=0.80 with a 95% confidence interval from 0.78 to 0.87; p < 0.001). Conclusion: The Turkish SCI is a practical self-reported insomnia scale with good psychometric properties that can be used to screen for insomnia disorder.

18.
Epidemiol Rev ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38324739

RESUMO

For lethal means safety counseling interventions (LMSC) to reduce population-level suicide rates, interventions must be deployed across many settings and populations. We conducted a systematic search in six databases to review the current state of LMSC interventions across study designs, settings, messengers, populations, and injury prevention levels (e.g., universal). Eligibility criteria were: any individual or group receiving a LMSC intervention involving a human-to-human component aiming to influence adult behaviors related to lethal suicide methods, and outcome assessment of storage behaviors and/or suicidal self-directed violence (SDV). Risk of bias was assessed using the Effective Public Health Practice Project (EPHPP) quality assessment tool. A descriptive synthesis approach was used for analysis. Twenty-two studies were included that reported medication and/or firearm storage behaviors and/or SDV following LMSC. Fourteen of the 19 studies assessing behavioral change reported a significant improvement in safe storage behaviors, and all studies measuring acceptability reported that participants found the interventions favorable. Quality of evidence was limited. No studies were rated low risk of bias, and 77% were rated high risk of bias. There was substantial heterogeneity in the settings, populations, injury prevention levels, delivery methods, and intervention elements. Many included studies focused on caregivers of pediatric populations, and few studies assessed SDV outcomes. Higher quality trials conducted across a variety of settings, particularly those focusing on adults at risk of suicide, are needed. There was no funding for this review, and it was preregistered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42021230668).

19.
J Infect Dis ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38213276

RESUMO

Definitive data demonstrating the utility of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) for treating immunocompromised patients remains elusive. To better understand the mechanism of action of CCP, we studied viral replication and disease progression in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected hamsters treated with CCP obtained from recovered COVID-19 patients that were also vaccinated with an mRNA vaccine, hereafter referred to as Vaxplas. Vaxplas transiently enhanced disease severity and lung pathology in hamsters treated near peak viral replication due to immune complex and activated complement deposition in pulmonary endothelium, and recruitment of M1 proinflammatory macrophages into the lung parenchyma. However, aside from one report, transient enhanced disease has not been reported in CCP recipient patients, and the transient enhanced disease in Vaxplas hamsters may have been due to mismatched species IgG-FcR interactions, infusion timing, or other experimental factors. Despite transient disease enhancement, Vaxplas dramatically reduced virus replication in lungs and improved infection outcome in SARS-CoV-2-infected hamsters.

20.
ESC Heart Fail ; 11(2): 1022-1029, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38232976

RESUMO

AIMS: Population-wide, person-level, linked electronic health record data are increasingly used to estimate epidemiology, guide resource allocation, and identify events in clinical trials. The accuracy of data from NHS Digital (now part of NHS England) for identifying hospitalization for heart failure (HHF), a key HF standard, is not clear. This study aimed to evaluate the accuracy of NHS Digital data for identifying HHF. METHODS AND RESULTS: Patients experiencing at least one HHF, as determined by NHS Digital data, and age- and sex-matched patients not experiencing HHF, were identified from a prospective cohort study and underwent expert adjudication. Three code sets commonly used to identify HHF were applied to the data and compared with expert adjudication (I50: International Classification of Diseases-10 codes beginning I50; OIS: Clinical Commissioning Groups Outcomes Indicator Set; and NICOR: National Institute for Cardiovascular Outcomes Research, used as the basis for the National Heart Failure Audit in England and Wales). Five hundred four patients underwent expert adjudication, of which 10 (2%) were adjudicated to have experienced HHF. Specificity was high across all three code sets in the first diagnosis position {I50: 96.2% [95% confidence interval (CI) 94.1-97.7%]; NICOR: 93.3% [CI 90.8-95.4%]; OIS: 95.6% [CI 93.3-97.2%]} but decreased substantially as the number of diagnosis positions expanded. Sensitivity [40.0% (CI 12.2-73.8%)] and positive predictive value (PPV) [highest with I50: 17.4% (CI 8.1-33.6%)] were low in the first diagnosis position for all coding sets. PPV was higher for the National Heart Failure Audit criteria, albeit modestly [36.4% (CI 16.6-62.2%)]. CONCLUSIONS: NHS Digital data were not able to accurately identify HHF and should not be used in isolation for this purpose.


Assuntos
Insuficiência Cardíaca , Medicina Estatal , Humanos , Estudos Prospectivos , Insuficiência Cardíaca/diagnóstico , Hospitalização , Valor Preditivo dos Testes
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