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1.
JAMA Netw Open ; 7(8): e2425822, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39102266

RESUMEN

Importance: Use of herbal and dietary supplements (HDSs) accounts for an increasing proportion of drug hepatotoxicity cases. Turmeric or curcumin, green tea extract, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha are the most frequently reported hepatoxic botanicals, but their prevalence and reasons for use in the general population are unknown. Objective: To assess the prevalence and clinical characteristics of adult consumers of 6 potentially hepatoxic botanicals. Design, Setting, and Participants: This survey study analyzed nationally representative data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative, cross-sectional survey of the general US population. Prescription drug and HDS exposure data in the past 30 days were analyzed, and 2020 US Census data were used for population estimates. Data were analyzed July 1, 2023, to February 1, 2024. Exposures: Adult NHANES participants enrolled between January 2017 and March 2020. Main Outcomes and Measures: Baseline weighted characteristics of HDS users and users of 6 potentially hepatotoxic botanical products were compared with non-HDS users. Multivariable analysis was undertaken to identify factors associated with HDS use or at-risk botanical use. Results: Among 9685 adults enrolled in this NHANES cohort, the mean (SE) age was 47.5 (0.5) years, and 51.8% (95% CI, 50.2%-53.4%) were female. The overall prevalence of HDS product use was 57.6% (95% CI, 55.9%-59.4%), while the prevalence of using the 6 botanicals of interest was 4.7% (95% CI, 3.9%-5.7%). Turmeric-containing botanicals were most commonly used (n = 236), followed by products containing green tea (n = 92), ashwagandha (n = 28), Garcinia cambogia (n = 20), red yeast rice (n = 20), and black cohosh (n = 19). Consumers of these 6 botanicals were significantly older (adjusted odds ratio [AOR], 2.36 [95% CI, 1.06-5.25]; P = .04 for 40-59 years of age and AOR, 3.96 [95% CI, 1.93-8.11]; P = .001 for ≥60 years of age), had a higher educational level (AOR, 4.78 [95% CI, 2.62-8.75]; P < .001), and were more likely to have arthritis (AOR, 2.27 [95% CI, 1.62-3.29]; P < .001) compared with non-HDS users. An estimated 15 584 599 (95% CI, 13 047 571-18 648 801) US adults used at least 1 of the 6 botanical products within the past 30 days, which was similar to the estimated number of patients prescribed potentially hepatotoxic drugs, including simvastatin (14 036 024 [95% CI, 11 202 460-17 594 452]) and nonsteroidal anti-inflammatory drugs (14 793 837 [95% CI, 13 014 623-16 671 897]). The most common reason for consuming turmeric and green tea was to improve or maintain health. Conclusions and Relevance: In this survey study, an estimated 15.6 million US adults consumed at least 1 botanical product with liver liability within the past 30 days, comparable with the number of people who consumed nonsteroidal anti-inflammatory drugs and a commonly prescribed hypolipidemic drug. Given a lack of regulatory oversight on the manufacturing and testing of botanical products, clinicians should be aware of possible adverse events from consumption of these largely unregulated products.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Suplementos Dietéticos , Encuestas Nutricionales , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Estados Unidos/epidemiología , Estudios Transversales , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Suplementos Dietéticos/efectos adversos , Curcuma , Anciano , Extractos Vegetales/efectos adversos , Adulto Joven , Garcinia cambogia , Prevalencia , Preparaciones de Plantas/efectos adversos , Cimicifuga/efectos adversos
2.
Health Res Policy Syst ; 22(1): 105, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39135114

RESUMEN

BACKGROUND: It is vital that health service delivery and health interventions address patients' needs or preferences, are relevant for practice and can be implemented. Involving those who will use or deliver healthcare in priority-setting can lead to health service delivery and research that is more meaningful and impactful. This is particularly crucial in rural communities, where limited resources and disparities in healthcare and health outcomes are often more pronounced. The aim of this study was to determine the health and healthcare priorities in rural communities using a region-wide community engagement approach. METHODS: This multi-methods study was conducted in five rural communities in the Grampians region, Western Victoria, Australia. It involved six concept mapping steps: (1) preparation, (2) generation (brainstorming statements and identifying rating criteria), (3) structuring statements (sorting and rating statements), (4) representation of statements, (5) interpretation of the concept map and (6) utilization. Community forums, surveys and stakeholder consultations with community members and health professionals were used in Step 2. An innovative online group concept mapping platform, involving consumers, health professionals and researchers was used in Step 3. RESULTS: Overall, 117 community members and 70 health professionals identified 400 health and healthcare issues. Six stakeholder consultation sessions (with 16 community members and 16 health professionals) identified three key values for prioritizing health issues: equal access for equal need, effectiveness and impact (number of people affected). Actionable priorities for healthcare delivery were largely related to access issues, such as the challenges navigating the healthcare system, particularly for people with mental health issues; the lack of sufficient general practitioners and other health providers; the high travel costs; and poor internet coverage often impacting technology-based interventions for people in rural areas. CONCLUSIONS: This study identified actionable health and healthcare priorities from the perspective of healthcare service users and providers in rural communities in Western Victoria. Issues related to access, such as the inequities in healthcare costs, the perceived lack of quality and availability of services, particularly in mental health and disability, were identified as priorities. These insights can guide future research, policy-making and resource allocation efforts to improve healthcare access, quality and equity in rural communities.


Asunto(s)
Personal de Salud , Prioridades en Salud , Población Rural , Humanos , Victoria , Femenino , Masculino , Servicios de Salud Rural/organización & administración , Atención a la Salud , Participación de la Comunidad , Adulto , Investigadores , Persona de Mediana Edad , Participación de los Interesados , Accesibilidad a los Servicios de Salud , Anciano , Investigación sobre Servicios de Salud
3.
Br J Ophthalmol ; 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033014

RESUMEN

AIMS: To develop and externally test deep learning (DL) models for assessing the image quality of three-dimensional (3D) macular scans from Cirrus and Spectralis optical coherence tomography devices. METHODS: We retrospectively collected two data sets including 2277 Cirrus 3D scans and 1557 Spectralis 3D scans, respectively, for training (70%), fine-tuning (10%) and internal validation (20%) from electronic medical and research records at The Chinese University of Hong Kong Eye Centre and the Hong Kong Eye Hospital. Scans with various eye diseases (eg, diabetic macular oedema, age-related macular degeneration, polypoidal choroidal vasculopathy and pathological myopia), and scans of normal eyes from adults and children were included. Two graders labelled each 3D scan as gradable or ungradable, according to standardised criteria. We used a 3D version of the residual network (ResNet)-18 for Cirrus 3D scans and a multiple-instance learning pipline with ResNet-18 for Spectralis 3D scans. Two deep learning (DL) models were further tested via three unseen Cirrus data sets from Singapore and five unseen Spectralis data sets from India, Australia and Hong Kong, respectively. RESULTS: In the internal validation, the models achieved the area under curves (AUCs) of 0.930 (0.885-0.976) and 0.906 (0.863-0.948) for assessing the Cirrus 3D scans and Spectralis 3D scans, respectively. In the external testing, the models showed robust performance with AUCs ranging from 0.832 (0.730-0.934) to 0.930 (0.906-0.953) and 0.891 (0.836-0.945) to 0.962 (0.918-1.000), respectively. CONCLUSIONS: Our models could be used for filtering out ungradable 3D scans and further incorporated with a disease-detection DL model, allowing a fully automated eye disease detection workflow.

4.
bioRxiv ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39005346

RESUMEN

Star-PAP is a noncanonical poly(A) polymerase that controls gene expression. Star-PAP was previously reported to bind the phosphatidylinositol 4-phosphate 5-kinase PIPKI⍺ and its product phosphatidylinositol 4,5-bisphosphate, which regulate Star-PAP poly(A) polymerase activity and expression of specific genes. Recent studies have revealed a nuclear PI signaling pathway in which the PI transfer proteins PITP⍺/ß, PI kinases and phosphatases bind p53 to sequentially modify protein-linked phosphatidylinositol phosphates and regulate its function. Here we demonstrate that multiple phosphoinositides, including phosphatidylinositol 4-monophosphate and phosphatidylinositol 3,4,5-trisphosphate are also coupled to Star-PAP in response to stress. This is initiated by PITP⍺/ß binding to Star-PAP, while the Star-PAP-linked phosphoinositides are modified by PI4KII⍺, PIPKI⍺, IPMK, and PTEN recruited to Star- PAP. The phosphoinositide coupling enhances the association of the small heat shock proteins HSP27/⍺B-crystallin with Star-PAP. Knockdown of the PITPs, kinases, or HSP27 reduce the expression of Star-PAP targets. Our results demonstrate that the PITPs generate Star-PAP-PIPn complexes that are then modified by PI kinases/phosphatases and small heat shock proteins that regulate the linked phosphoinositide phosphorylation and Star-PAP activity in response to stress.

5.
J Am Chem Soc ; 146(29): 19649-19653, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38976364

RESUMEN

The attractive electronic properties of metal-pyrazine materials─electrical conductivity, magnetic order, and strong magnetic coupling─can be tuned in a wide range depending on the metal employed, as well as its ligand-imposed redox environment. Using solvent-directed synthesis to control the dimensionality of such systems, a discrete tetranuclear chromium(III) complex, exhibiting a rare example of bridging radical pyrazine, has been prepared from chromium(II) triflate and neutral pyrazine. The strong antiferromagnetic interaction between CrIII (S = 3/2) and radical pyrazine (S = 1/2) spins, theoretically estimated at about -932 K, leads to a thermally isolated ST = 4 ground state, which remains the only populated state observable even at room temperature.

7.
CASE (Phila) ; 8(5): 317-319, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38947189
8.
CASE (Phila) ; 8(6): 349-350, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38983647
10.
Life Sci Alliance ; 7(9)2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38981683

RESUMEN

Collagenopathies are a group of clinically diverse disorders caused by defects in collagen folding and secretion. For example, mutations in the gene encoding collagen type-II, the primary collagen in cartilage, can lead to diverse chondrodysplasias. One example is the Gly1170Ser substitution in procollagen-II, which causes precocious osteoarthritis. Here, we biochemically and mechanistically characterize an induced pluripotent stem cell-based cartilage model of this disease, including both hetero- and homozygous genotypes. We show that Gly1170Ser procollagen-II is notably slow to fold and secrete. Instead, procollagen-II accumulates intracellularly, consistent with an endoplasmic reticulum (ER) storage disorder. Likely owing to the unique features of the collagen triple helix, this accumulation is not recognized by the unfolded protein response. Gly1170Ser procollagen-II interacts to a greater extent than wild-type with specific ER proteostasis network components, consistent with its slow folding. These findings provide mechanistic elucidation into the etiology of this disease. Moreover, the easily expandable cartilage model will enable rapid testing of therapeutic strategies to restore proteostasis in the collagenopathies.


Asunto(s)
Colágeno Tipo II , Retículo Endoplásmico , Procolágeno , Respuesta de Proteína Desplegada , Retículo Endoplásmico/metabolismo , Humanos , Procolágeno/metabolismo , Colágeno Tipo II/metabolismo , Mutación , Células Madre Pluripotentes Inducidas/metabolismo , Cartílago/metabolismo , Cartílago/patología , Pliegue de Proteína , Artritis/metabolismo , Artritis/genética , Osteoartritis/metabolismo , Osteoartritis/genética , Osteoartritis/patología , Animales , Condrocitos/metabolismo
11.
Rural Remote Health ; 24(3): 8316, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39075776

RESUMEN

CONTEXT: There is growing evidence supporting a shift towards 'grow your own' approaches to recruiting, training and retaining health professionals from and for rural communities. To achieve this, there is a need for sound methodologies by which universities can describe their area of geographic focus in a precise way that can be utilised to recruit students from their region and evaluate workforce outcomes for partner communities. In Australia, Deakin University operates a Rural Health Multidisciplinary Training (RHMT) program funded Rural Clinical School and University Department of Rural Health, with the purpose of producing a graduate health workforce through the provision of rural clinical placements in western and south-western Victoria. The desire to establish a dedicated Rural Training Stream within Deakin's Doctor of Medicine course acted as a catalyst for us to describe our 'rural footprint' in a way that could be used to prioritise local student recruitment as well as evaluate graduate workforce outcomes specifically for this region. ISSUE: In Australia, selection of rural students has relied on the Australian Statistical Geography Standard Remoteness Areas (ASGS-RA) or Modified Monash Model (MMM) to assign rural background status to medical course applicants, based on a standard definition provided by the RHMT program. Applicants meeting rural background criteria may be preferentially admitted to any medical school according to admission quotas or dedicated rural streams across the country. Until recently, evaluations of graduate workforce outcomes have also used these rurality classifications, but often without reference to particular geographic areas. Growing international evidence supports the importance of place-based connection and training, with medical graduates more likely to work in a region that they are from or in which they have trained. For universities to align rural student recruitment more strategically with training in specific geographic areas, there is a need to develop precise geographical definitions of areas of rural focus that can be applied during admissions processes. LESSONS LEARNED: As we strived to describe our rural activity area precisely, we modelled the application of several geographical and other frameworks, including the MMM, ASGS-RA, Primary Healthcare Networks (PHN), Local Government Areas (LGAs), postcodes and Statistical Areas. It became evident that there was no single geographical or rural framework that (1) accurately described our area of activity, (2) accurately described our desired workforce focus, (3) was practical to apply during the admissions process. We ultimately settled on a bespoke approach using a combination of the PHN and MMM to achieve the specificity required. This report provides an example of how a rural activity footprint can be accurately described and successfully employed to prioritise students from a geographical area for course admission. Lessons learned about the strengths and limitations of available geographical measures are shared. Applications of a precise footprint definition are described including student recruitment, evaluation of workforce outcomes for a geographic region, benefits to stakeholder relationships and an opportunity for more nuanced RHMT reporting.


Asunto(s)
Servicios de Salud Rural , Facultades de Medicina , Recursos Humanos , Humanos , Servicios de Salud Rural/organización & administración , Facultades de Medicina/organización & administración , Selección de Personal , Criterios de Admisión Escolar , Ubicación de la Práctica Profesional , Selección de Profesión , Área sin Atención Médica , Australia , Victoria , Fuerza Laboral en Salud/organización & administración
12.
BMJ Open Sport Exerc Med ; 10(2): e002070, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38882206

RESUMEN

Exercise can produce transient elevations of cardiac troponin (cTn) concentrations, which may resemble the cTn release profile of myocardial infarction. Consequently, clinical interpretation of postexercise cTn elevations (ie, values above the 99th percentile upper reference limit) remains challenging and may cause clinical confusion. Therefore, insight into the physiological versus pathological nature of postexercise cTn concentrations is warranted. We aim to (1) establish resting and postexercise reference values for recreational athletes engaged in walking, cycling or running exercise; (2) compare the prevalence of (sub)clinical coronary artery disease in athletes with high versus low postexercise cTn concentrations and (3) determine the association between postexercise cTn concentrations and the incidence of major adverse cardiovascular events (MACE) and mortality during long-term follow-up. For this purpose, the prospective TRoponin concentrations following Exercise and the Association with cardiovascular ouTcomes (TREAT) observational cohort study was designed to recruit 1500 recreational athletes aged ≥40 to <70 years who will participate in Dutch walking, cycling and running events. Baseline and postexercise high-sensitivity cTnT and cTnI concentrations will be determined. The prevalence and magnitude of coronary atherosclerosis on computed tomography (eg, coronary artery calcium score, plaque type, stenosis degree and CT-derived fractional flow reserve) will be compared between n=100 athletes with high postexercise cTn concentrations vs n=50 age-matched, sex-matched and sport type-matched athletes with low postexercise cTn concentrations. The incidence of MACE and mortality will be assessed in the entire cohort up to 20 years follow-up. The TREAT study will advance our understanding of the clinical significance of exercise-induced cTn elevations in middle-aged and older recreational athletes. Trial registration number NCT06295081.

13.
Aliment Pharmacol Ther ; 60(3): 378-388, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38828940

RESUMEN

BACKGROUND AND AIMS: The objective of the study was to analyse the prevalence, incidence, and death of alcohol-associated liver disease (ALD) among adolescents and young adults globally, continentally, and nationally, focusing on trends over time. METHODS: The study analysed data from the Global Burden of Disease (GBD) study between 2000 and 2019. It examined ALD's prevalence, incidence, and death in adolescents and young adults aged 15-29, segmented by region, nation, and sociodemographic index. The analysis utilised Joinpoint regression modelling to calculate the annual per cent change (APC) in the rate of these parameters over time. RESULTS: In 2019, there were 281,450 ALD prevalences, 18,930 incidences, and 3190 deaths among adolescents and young adults globally. From 2000 to 2019, the age-adjusted prevalence rate per 100,000 increased in the 25-29 age group (APC: +0.6%, p = 0.003), remained stable among ages 20-24 (p = 0.302) and ages 15-19 (p = 0.160). Prevalence increased significantly from age 15-19 to 20-24 (19-fold increase) and from age 20-24 to 25-29 (2.5-fold increase). ALD prevalence rates increased in all age groups in adolescents and young adults in Africa and the Eastern Mediterranean region. Around three-quarters of countries and territories experienced an increase in ALD incidence rates in young adults. CONCLUSION: Over two decades, the burden of ALD among adolescents and young adults has increased globally. The study emphasises the importance of public health policies aimed at reducing alcohol consumption and preventing ALD among younger populations.


Asunto(s)
Salud Global , Hepatopatías Alcohólicas , Humanos , Adolescente , Adulto Joven , Masculino , Femenino , Adulto , Prevalencia , Incidencia , Hepatopatías Alcohólicas/epidemiología , Carga Global de Enfermedades , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/efectos adversos
14.
Materials (Basel) ; 17(12)2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38930304

RESUMEN

Iron-nickel (Fe-Ni) batteries are renowned for their durability and resilience against overcharging and operating temperatures. However, they encounter challenges in achieving widespread adoption for energy storage applications due to their low efficiency and the need for regular maintenance and electrolyte replacement, which adds to maintenance costs. This study evaluates and demonstrates the capabilities of Fe-Ni batteries for participating in grid energy storage applications. Stable performance was observed frequency regulation (FR) testing at 100% and 50% state of charge (SOC)s, while at 50% SOC, there was a 14% increase in efficiency compared to 100% SOC. Although 25% SOC achieved higher efficiency, limited cyclability was observed due to reaching the discharge cutoff voltage. Optimal SOC selection, battery monitoring, maintenance, and appropriate charging strategies of Fe-Ni batteries seem to be crucial for their FR applications. Fe-Ni batteries exhibit stable peak shaving (PS) results, indicating their suitability and reliability under various load conditions for PS testing. Extended cycling tests confirm their potential for long-term grid-scale energy storage, enhancing their appeal for PS and FR applications.

15.
J Vasc Surg ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38906429

RESUMEN

OBJECTIVE: Although multidisciplinary clinics improve outcomes in chronic limb-threatening ischemia (CLTI), their role in addressing socioeconomic disparities is unknown. Our institution treats patients with CLTI at both traditional general vascular clinics and a multidisciplinary Limb Preservation Program (LPP). The LPP is in a minority community, providing expedited care at a single facility by a consistent team. We compared outcomes within the LPP with our institution's traditional clinics and explored patients' perspectives on barriers to care to evaluate if the LPP might address them. METHODS: All patients undergoing index revascularization for CLTI from 2014 to 2023 at our institution were stratified by clinic type (LPP or traditional). We collected clinical and socioeconomic variables, including Area Deprivation Index (ADI). Patient characteristics were compared using χ2, Student t, or Mood median tests. Outcomes were compared using log-rank and multivariable Cox analysis. We also conducted semi-structured interviews to understand patient-perceived barriers. RESULTS: From 2014 to 2023, 983 limbs from 871 patients were revascularized; 19.5% of limbs were treated within the LPP. Compared with traditional clinic patients, more LPP patients were non-White (43.75% vs 27.43%; P < .0001), diabetic (82.29% vs 61.19%; P < .0001), dialysis-dependent (29.17% vs 13.40%; P < .0001), had ADI in the most deprived decile (29.38% vs 19.54%; P = .0061), resided closer to clinic (median 6.73 vs 28.84 miles; P = .0120), and had worse Wound, Ischemia, and foot Infection (WIfI) stage (P < .001). There were no differences in freedom from death, major adverse limb event (MALE), or patency loss. Within the most deprived subgroup (ADI >90), traditional clinic patients had earlier patency loss (P = .0108) compared with LPP patients. Multivariable analysis of the entire cohort demonstrated that increasing age, heart failure, dialysis, chronic obstructive pulmonary disease, and increasing WIfI stage were independently associated with earlier death, and male sex was associated with earlier MALE. Ten traditional clinic patients were interviewed via convenience sampling. Emerging themes included difficulty understanding their disease, high visit frequency, transportation barriers, distrust of the health care system, and patient-physician racial discordance. CONCLUSIONS: LPP patients had worse comorbidities and socioeconomic deprivation yet had similar outcomes to healthier, less deprived non-LPP patients. The multidisciplinary clinic's structure addresses several patient-perceived barriers. Its proximity to disadvantaged patients and ability to conduct multiple appointments at a single visit may address transportation and visit frequency barriers, and the consistent team may facilitate patient education and improve trust. Including these elements in a multidisciplinary clinic and locating it in an area of need may mitigate some negative impacts of socioeconomic deprivation on CLTI outcomes.

16.
Artículo en Inglés | MEDLINE | ID: mdl-38829320

RESUMEN

When participants study items one-by-one and are directed to either remember or forget the respective item directly after its presentation, retention of to-be-forgotten items is regularly worse than of to-be-remembered items. We tested whether this directed forgetting effect which is regularly observed for item memory generalizes to source memory. In three experiments, participants studied items in two different source colors (N = 101) or at two different source locations (N = 64; N = 81). Sources were manipulated orthogonally to item type (remember vs. forget). At test, we asked participants to recognize all studied items and also to identify their source. We used a multinomial processing tree model to disentangle item memory, source memory, and guessing. In all three experiments, we replicated the directed forgetting effect in item memory. Source memory for to-be-forgotten items that were recognized despite the intention to forget, however, tended to be even better than source memory for to-be-remembered items that were recognized. These results suggest that the directed forgetting effect does not simply translate from item to source memory. Rather source memory seems to be disproportionally increased in to-be-forgotten items that are remembered. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

17.
Brain Commun ; 6(3): fcae175, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846536

RESUMEN

Over the first years of life, the brain undergoes substantial organization in response to environmental stimulation. In a silent world, it may promote vision by (i) recruiting resources from the auditory cortex and (ii) making the visual cortex more efficient. It is unclear when such changes occur and how adaptive they are, questions that children with cochlear implants can help address. Here, we examined 7-18 years old children: 50 had cochlear implants, with delayed or age-appropriate language abilities, and 25 had typical hearing and language. High-density electroencephalography and functional near-infrared spectroscopy were used to evaluate cortical responses to a low-level visual task. Evidence for a 'weaker visual cortex response' and 'less synchronized or less inhibitory activity of auditory association areas' in the implanted children with language delays suggests that cross-modal reorganization can be maladaptive and does not necessarily strengthen the dominant visual sense.

18.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167268, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38823460

RESUMEN

Cancers are the product of evolutionary events, where molecular variation occurs and accumulates in tissues and tumors. Sequencing of this molecular variation informs not only which variants are driving tumorigenesis, but also the mechanisms behind what is fueling mutagenesis. Both of these details are crucial for preventing premature deaths due to cancer, whether it is by targeting the variants driving the cancer phenotype or by measures to prevent exogenous mutations from contributing to somatic evolution. Here, we review tools to determine both molecular signatures and cancer drivers, and avenues by which these metrics may be linked.

19.
PLoS One ; 19(6): e0304767, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38870235

RESUMEN

People in custody are at high risk of developing depression. Accessing psychological treatments in a prison setting is a particular challenge, in part, due to difficulties accessing specialist mental health workers. Behavioural Activation (BA) may be helpful in improving health outcomes for people in custody experiencing depressive symptoms. The aim of this study is to establish the feasibility and acceptability of custodial health nurses delivering BA to improve depressive symptoms of people in custody. We will conduct a pilot randomised controlled trial with process observation examining the feasibility and acceptability of BA in treating people in custody with depressive symptoms. 60 people in custody presenting with depressive symptoms will be randomised to receive BA plus treatment as usual (TAU) or TAU provided by custodial health nurses. Eight custodial health nurses will be recruited, trained, and deliver BA. BA will be delivered twice a week for six weeks, with sessions lasting up to 30 minutes. Changes in depression and quality of life (QoL) will be assessed at baseline, 6 weeks, and 3 months post-intervention. Participants will be interviewed to understand feasibility and acceptability of BA in prison settings. The findings will inform the design of a randomised controlled trial to test the efficacy of BA for people in custody with depression. Findings will help determine whether BA for depression is suited to prison health care system and services. Improving depressive symptoms in people in custody has benefits beyond prison settings. The Central Adelaide Local Health Network Human Research Ethics Committee and University of South Australia Human Research Ethics Committee have approved the study. The trial results will be disseminated through peer-reviewed journals and scientific conferences and reported to local stakeholders and policy makers. If feasibility and acceptability is demonstrated, we will seek to progress to an effectiveness study. A potential strength of the trial model proposed, is in its scalability, with potential to increase the trial sites and locations. This trial has been prospectively registered with the Australian New Zealand Clinical Trials Registry (reference number: ACTRN12623000346673p). Trial registration ACTRN12623000346673p.


Asunto(s)
Depresión , Estudios de Factibilidad , Prisioneros , Calidad de Vida , Humanos , Depresión/terapia , Prisioneros/psicología , Masculino , Proyectos Piloto , Femenino , Adulto , Terapia Conductista/métodos , Prisiones
20.
J Vasc Surg ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38912996

RESUMEN

OBJECTIVE: Long-term outcomes for harvesting techniques for great saphenous vein (GSV) and its impact on the outcomes of infrainguinal arterial bypass remains largely unknown. Endoscopic GSV harvesting (EVH) has emerged as a less invasive alternative to conventional open techniques. Using the Vascular Quality initiative Vascular Implant Surveillance & Interventional Outcomes Network (VQI-VISION) database, we compared the long-term outcomes of infrainguinal arterial bypass using open and endoscopic GSV harvest techniques. METHODS: Patients who underwent infrainguinal GSV bypass between 2010 and 2019 were identified in the VQI-VISION Medicare linked database. Long-term outcomes of major/minor amputations, and reinterventions up to 5 years of follow-up were compared between continuous incisions, skip incision, and EVH, with continuous incisions being the reference group. Secondary outcomes included 30- and 90-day readmission, in addition to surgical site infections and patency rates at 6 months to 2 years postoperatively. Survival analysis using Kaplan-Meier curves and Cox regression hazard models were utilized to compare outcomes between groups. To adjust for multiple comparisons between the study groups, a P value of 2.5% was considered significant. RESULTS: Among the 8915 patients included in the study, continuous and skip vein harvest techniques were used in 44.4% and 43.4% of cases each, whereas 12.3% underwent EVH. The utilization of EVH remained relatively stable at around 12% throughout the study period. Compared with GSV harvest using continuous incisions, EVH was associated with higher rates of reintervention at 1 year (46.5% vs 41.3%; adjusted hazard ratio [aHR], 1.22; 95% confidence interval [CI], 1.06-1.41; P = .01]. However, no significant difference was observed between EVH and continuous incisions, and between skip and continuous incisions in terms of long-term reintervention or major and minor amputations on adjusted analysis. Compared with continuous incision vein harvest, both EVH and skip incisions were associated with lower surgical site infection rates within the first 6 months post-bypass (aHR, 0.53; 95% CI, 0.35-0.82 and aHR, 0.68; 95% CI, 0.53-0.87, respectively). Loss of primary, primary-assisted, and secondary patency was higher after EVH compared with continuous incision vein harvest. Among surgeons performing EVH, comparable long-term outcomes were observed regardless of low (<4 cases/year), medium (4-7 cases/year), or high procedural volumes (>7 cases/year). CONCLUSIONS: Despite higher 1-year reintervention rates, EVH for infrainguinal arterial bypass is not associated with a significant difference in long-term reintervention or amputation rates compared with other harvesting techniques. These outcomes are not influenced by procedural volumes for EVH technique.

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