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1.
Neurosci Biobehav Rev ; : 105871, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39222777
2.
Evol Psychol ; 22(3): 14747049241275706, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39228190

RESUMEN

We were interested in how people in a romantic relationship would perceive the intelligence of their partners who have high or low trait anger. Specifically, we referred to the tension between compassion (low anger) and competence (high intelligence) in mate choice. Some evolutionary theories suggest that mating might be considered a bargaining process between these two higher-order attributes. Our study involved 148 heterosexual couples in romantic relationships. We measured the relationship between relationship satisfaction, trait anger, objective intelligence, self-assessed intelligence, and subjectively assessed partners' intelligence. We found that angrier men were less satisfied in their romantic relationship than those men who were less angry, and their partners were also less satisfied in the relationship. Additionally, women perceived angrier men as less intelligent, an effect that remained after controlling for men's objective intelligence. Lastly, we found that women's perception of their partner's intelligence mediated the link between men's anger and relationship satisfaction for both sexes. Our findings suggest that both anger and intelligence play important roles in romantic relationship functioning, consistent with evolutionary theories that emphasize the value of competence (i.e., intelligence) and compassion (i.e., low anger) in romantic partners. Furthermore, our study highlights the importance of women's perception of their partner's intelligence in determining the quality of the relationship.


Asunto(s)
Ira , Inteligencia , Relaciones Interpersonales , Satisfacción Personal , Parejas Sexuales , Humanos , Masculino , Femenino , Ira/fisiología , Adulto , Parejas Sexuales/psicología , Adulto Joven , Inteligencia/fisiología , Empatía/fisiología , Percepción Social , Persona de Mediana Edad , Adolescente
3.
Sci Adv ; 10(36): eadn2321, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39231235

RESUMEN

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recessively inherited neurodegenerative disorder caused by intronic biallelic, nonreference CCCTT/AAGGG repeat expansions within RFC1. To investigate how these repeats cause disease, we generated patient induced pluripotent stem cell-derived neurons (iNeurons). CCCTT/AAGGG repeat expansions do not alter neuronal RFC1 splicing, expression, or DNA repair pathway function. In reporter assays, AAGGG repeats are translated into pentapeptide repeat proteins. However, these proteins and repeat RNA foci were not detected in iNeurons, and overexpression of these repeats failed to induce neuronal toxicity. CANVAS iNeurons exhibit defects in neuronal development and diminished synaptic connectivity that is rescued by CRISPR deletion of a single expanded AAGGG allele. These deficits were neither replicated by RFC1 knockdown in control iNeurons nor rescued by RFC1 reprovision in CANVAS iNeurons. These findings support a repeat-dependent but RFC1 protein-independent cause of neuronal dysfunction in CANVAS, with implications for therapeutic development in this currently untreatable condition.


Asunto(s)
Ataxia Cerebelosa , Expansión de las Repeticiones de ADN , Células Madre Pluripotentes Inducidas , Neuronas , Proteína de Replicación C , Sinapsis , Humanos , Proteína de Replicación C/genética , Proteína de Replicación C/metabolismo , Neuronas/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Expansión de las Repeticiones de ADN/genética , Ataxia Cerebelosa/genética , Ataxia Cerebelosa/patología , Ataxia Cerebelosa/metabolismo , Sinapsis/metabolismo , Sinapsis/genética , Vestibulopatía Bilateral/genética , Vestibulopatía Bilateral/metabolismo , Enfermedades Vestibulares/genética , Alelos
4.
J Commun Healthc ; : 1-9, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39140645

RESUMEN

BACKGROUND: The study explores the language barriers between two language minority populations and healthcare professionals in the Volta Region of Ghana. METHODS: An interpretive description with a qualitative approach to data collection and analysis was used. This study was carried out in the Tafi-Atome and Avatime-Vane communities, the Hohoe Municipal Hospital and the Margaret Marquart Catholic Hospital in the Kpando Municipality. In all, 46 respondents comprising 19 purposively sampled community members (patients) from the two selected communities and 27 conveniently sampled healthcare professionals from the two health facilities were interviewed. The face-to-face in-depth interviews were audio-recorded, transcribed and thematically analysed. RESULTS: The study revealed a barrier in language use between healthcare professionals and patients from the two language minority communities. While healthcare professionals preferred to use English, Akan and Ewe, the patients, on the other hand, preferred their native languages, which are Sideme and Tegbor. The services of unqualified interpreters were utilised by both healthcare professionals and patients. Study participants were aware of these challenges, which prevented the patients from receiving optimum healthcare services, and the healthcare workers from delivering client-centred healthcare services. CONCLUSIONS: The presence of communication challenges emanating from language barriers between healthcare professionals and patients should be considered as a key hindrance to the attainment of the Sustainable Development Goal Three (SDG3), which aims to promote health and well-being at all ages. Therefore, stakeholders in the healthcare delivery system in Ghana need to prioritize stronger communication and translation practices and policies.

5.
Materials (Basel) ; 17(15)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39124353

RESUMEN

Amorphous/crystalline high-entropy-alloy (HEA) composites show great promise as structural materials due to their exceptional mechanical properties. However, there is still a lack of understanding of the dynamic nanoindentation response of HEA composites at the atomic scale. Here, the mechanical behavior of amorphous/crystalline HEA composites under nanoindentation is investigated through a large-scale molecular dynamics simulation and a dislocation-based strength model, in terms of the indentation force, microstructural evolution, stress distribution, shear strain distribution, and surface topography. The results show that the uneven distribution of elements within the crystal leads to a strong heterogeneity of the surface tension during elastic deformation. The severe mismatch of the amorphous/crystalline interface combined with the rapid accumulation of elastic deformation energy causes a significant number of dislocation-based plastic deformation behaviors. The presence of surrounding dislocations inhibits the free slip of dislocations below the indenter, while the amorphous layer prevents the movement or disappearance of dislocations towards the substrate. A thin amorphous layer leads to great indentation force, and causes inconsistent stacking and movement patterns of surface atoms, resulting in local bulges and depressions at the macroscopic level. The increasing thickness of the amorphous layer hinders the extension of shear bands towards the lower part of the substrate. These findings shed light on the mechanical properties of amorphous/crystalline HEA composites and offer insights for the design of high-performance materials.

6.
J Arthroplasty ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39147074

RESUMEN

BACKGROUND: The purpose of this study was to determine implant survivorship and functional outcomes for revision total knee arthroplasty (rTKA) with contemporary rotating-hinge knee implants. METHODS: A retrospective review identified 115 rTKAs using contemporary rotating-hinge implants from 2014 to 2018 for the treatment of instability (34, 30%), reimplantation after periprosthetic joint infection (PJI) (33, 29%), aseptic loosening (25, 22%), arthrofibrosis (14, 12%), periprosthetic fracture (4, 3%), osteolysis (4, 3%), and femoral component fracture (1, 1%). There were 70 women (61%), and the mean age was 67 years (range, 27 to 94). The mean follow-up was 3 years (range, 2 to 6). Kaplan-Meier analysis and Cox proportional hazard models estimated survivorship. RESULTS: The re-revision rate was 20% (23 of 115) at an average of 18 months postoperatively. Re-revision indications included PJI (n = 14), aseptic loosening (n = 4), arthrofibrosis (n = 2), instability/malalignment (n = 1), femoral stem fracture (n = 1), and hinge mechanism disruption (n = 1). At 2 and 5 years, survivorship free from all-cause re-revision was 86% and 64%, and survivorship free from re-revision for aseptic loosening was 100% and 87%, respectively. Use of a rotating-hinge implant in reimplantation after PJI was a risk factor for subsequent re-revision (hazard ratio = 2.4, P = 0.046). On a radiographic review of unrevised rotating-hinges, there were major radiolucent lines around 2 femoral and 5 tibial components. The mean Knee Osteoarthritis Outcomes Score for Joint Replacement (KOOS JR) increased from 43 preoperatively to 60 at 1 year (P < 0.001). CONCLUSION: In patients treated with a rotating-hinge implant for rTKA, there were relatively poor 2-year (86%) and 5-year (64%) survivorship free from all-cause re-revision, most commonly due to PJI. Mid-term survivorship free from re-revision for aseptic loosening was modest (87%). There should be a goal to mitigate complications in complex rTKAs with rotating-hinge implants, namely PJI.

7.
Front Psychol ; 15: 1458388, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161686
8.
J Am Geriatr Soc ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090970

RESUMEN

BACKGROUND: High-intensity end-of-life (EOL) care, marked by admission to intensive care units (ICUs) or in-hospital death, can be costly and burdensome. Recent trends in use of ICUs, life-sustaining treatments (LSTs), and noninvasive ventilation (NIV) during EOL hospitalizations among older adults with advanced cancer and patterns of in-hospital death are unknown. METHODS: We used SEER-Medicare data (2003-2017) to identify beneficiaries with advanced solid cancer (summary stage 7) who died within 3 years of diagnosis. We identified EOL hospitalizations (within 30 days of death), classifying them by increasing intensity of care into: (1) without ICU; (2) with ICU but without LST (invasive mechanical ventilation, tracheostomy, gastrostomy, acute dialysis) or NIV; (3) with ICU and NIV but without LST; and (4) with ICU and LST use. We constructed a multinomial regression model to evaluate trends in risk-adjusted hospitalization, overall and across hospitalization categories, adjusting for sociodemographics, cancer characteristics, comorbidities, and frailty. We evaluated trends in in-hospital death across categories. RESULTS: Of 226,263 Medicare beneficiaries with advanced cancer, 138,305 (61.1%) were hospitalized at EOL [Age, Mean (SD):77.9(7.1) years; 45.5% female]. Overall, EOL hospitalizations remained high throughout, from 78.1% (95% CI: 77.4, 78.7) in 2004 to 75.5% (95% CI: 74.5, 76.2) in 2017. Hospitalizations without ICU use decreased from 49.3% (95% CI: 48.5, 50.2) to 35.0% (95% CI: 34.2, 35.9) while hospitalizations with more intensive care increased, from 23.7% (95% CI: 23.0, 24.4) to 28.7% (95% CI: 27.9, 29.5) for ICU without LST or NIV, 0.8% (95% CI: 0.6, 0.9) to 3.8% (95% CI: 3.4, 4.1) for ICU with NIV but without LST, and 4.3% (95% CI: 4.0, 4.7) to 8.0% (95% CI: 7.5, 8.5) for ICU with LST use. Among those who experienced in-hospital death, the proportion receiving ICU care increased from 46.5% to 65.0%. CONCLUSIONS: Among older adults with advanced cancer, EOL hospitalization rates remained stable from 2004-2017. However, intensity of care during EOL hospitalizations increased as evidenced by increasing use of ICUs, LSTs, and NIV.

9.
Reprod Biol Endocrinol ; 22(1): 100, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39118090

RESUMEN

BACKGROUND: Patients with endometriosis suffer with chronic pelvic pain and infertility, and from the lack of pharmacologic therapies that consistently halt disease progression. Differences in the endometrium of patients with endometriosis vs. unaffected controls are well-documented. Specifically, shed endometrial tissues (delivered to the pelvic cavity via retrograde menstruation) reveal that a subset of stromal cells exhibiting pro-inflammatory, pro-fibrotic, and pro-senescence-like phenotypes is enhanced in endometriosis patients compared to controls. Additionally, cultured biopsy-derived endometrial stromal cells from endometriosis patients exhibit impaired decidualization, a defined differentiation process required for human embryo implantation and pregnancy. Quercetin, a senolytic agent, shows therapeutic potential for pulmonary fibrosis, a disorder attributed to senescent pulmonary fibroblasts. In rodent models of endometriosis, quercetin shows promise, and quercetin improves decidualization in vitro. However, the exact mechanisms are not completely understood. Therefore, we investigated the effects of quercetin on menstrual effluent-derived endometrial stromal cells from endometriosis patients and unaffected controls to define the signaling pathways underlying quercetin's effects on endometrial stromal cells. METHODS: Menstrual effluent-derived endometrial stromal cells were collected and cultured from unaffected controls and endometriosis patients and then, low passage cells were treated with quercetin (25 µM) under basal or standard decidualization conditions. Decidualization responses were analyzed by measuring the production of IGFBP1 and PRL. Also, the effects of quercetin on intracellular cAMP levels and cellular oxidative stress responses were measured. Phosphokinase arrays, western blotting, and flow cytometry methods were performed to define the effects of quercetin on various signaling pathways and the potential mechanistic roles of quercetin. RESULTS: Quercetin significantly promotes decidualization of control- and endometriosis-endometrial stromal cells. Quercetin substantially reduces the phosphorylation of multiple signaling molecules in the AKT and ERK1/2 pathways, while enhancing the phosphorylation of p53 and total p53 levels. Furthermore, p53 inhibition blocks decidualization while p53 activation promotes decidualization. Finally, we provide evidence that quercetin increases apoptosis of endometrial stromal cells with a senescent-like phenotype. CONCLUSIONS: These data provide insight into the mechanisms of action of quercetin on endometrial stromal cells and warrant future clinical trials to test quercetin and other senolytics for treating endometriosis.


Asunto(s)
Senescencia Celular , Endometriosis , Proteínas Proto-Oncogénicas c-akt , Quercetina , Células del Estroma , Proteína p53 Supresora de Tumor , Quercetina/farmacología , Femenino , Humanos , Endometriosis/metabolismo , Endometriosis/patología , Endometriosis/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Adulto , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Senescencia Celular/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Endometrio/patología , Decidua/efectos de los fármacos , Decidua/metabolismo , Transducción de Señal/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células Cultivadas
10.
bioRxiv ; 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39091741

RESUMEN

Preferentially Expressed Antigen in Melanoma (PRAME) and Ten-Eleven Translocation (TET) dioxygenase-mediated 5-hydroxymethylcytosine (5hmC) are emerging melanoma biomarkers. We observed an inverse correlation between PRAME expression and 5hmC levels in benign nevi, melanoma in situ, primary invasive melanoma, and metastatic melanomas via immunohistochemistry and multiplex immunofluorescence: nevi exhibited high 5hmC and low PRAME, whereas melanomas showed the opposite pattern. Single-cell multiplex imaging of melanoma precursors revealed that diminished 5hmC coincides with PRAME upregulation in premalignant cells. Analysis of TCGA and GTEx databases confirmed a negative relationship between TET2 and PRAME mRNA expression in melanoma. Additionally, 5hmC levels were reduced at the PRAME 5' promoter in melanoma compared to nevi, suggesting a role for 5hmC in PRAME transcription. Restoring 5hmC levels via TET2 overexpression notably reduced PRAME expression in melanoma cell lines. These findings establish a function of TET2-mediated DNA hydroxymethylation in regulating PRAME expression and demonstrate epigenetic reprogramming as pivotal in melanoma tumorigenesis. Teaser: Melanoma biomarker PRAME expression is negatively regulated epigenetically by TET2-mediated DNA hydroxymethylation.

11.
Front Cell Neurosci ; 18: 1426231, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161786

RESUMEN

Multiple sclerosis (MS) is a frequently disabling neurological disorder characterized by symptoms, clinical signs and imaging abnormalities that typically fluctuate over time, affecting any level of the CNS. Prominent lymphocytic inflammation, many genetic susceptibility variants involving immune pathways, as well as potent responses of the neuroinflammatory component to immunomodulating drugs, have led to the natural conclusion that this disease is driven by a primary autoimmune process. In this Hypothesis and Theory article, we discuss emerging data that cast doubt on this assumption. After three decades of therapeutic experience, what has become clear is that potent immune modulators are highly effective at suppressing inflammatory relapses, yet exhibit very limited effects on the later progressive phase of MS. Moreover, neuropathological examination of MS tissue indicates that degeneration, CNS atrophy, and myelin loss are most prominent in the progressive stage, when lymphocytic inflammation paradoxically wanes. Finally, emerging clinical observations such as "progression independent of relapse activity" and "silent progression," now thought to take hold very early in the course, together argue that an underlying "cytodegenerative" process, likely targeting the myelinating unit, may in fact represent the most proximal step in a complex pathophysiological cascade exacerbated by an autoimmune inflammatory overlay. Parallels are drawn with more traditional neurodegenerative disorders, where a progressive proteopathy with prion-like propagation of toxic misfolded species is now known to play a key role. A potentially pivotal contribution of the Epstein-Barr virus and B cells in this process is also discussed.

12.
Am J Sports Med ; 52(10): 2639-2645, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39129296

RESUMEN

BACKGROUND: Previous studies have reported that spondylolysis occurs predominantly at the L5 and L4 levels, with defects at higher levels occurring in <5% of cases. However, computed tomography and radiography were the primary imaging modalities in these studies. Current evidence regarding diagnostic imaging for pediatric lumbar spondylolysis suggests that magnetic resonance imaging (MRI) is as accurate as computed tomography in detecting early stress reactions of the pars interarticularis or pedicles without fractures while avoiding radiation exposure. The early detection of spondylolysis results in a higher likelihood of bony union and a decreased likelihood of spondylolisthesis. HYPOTHESIS: The increased use of MRI may reveal a larger proportion of spondylolysis in patients who experience an injury at a higher spinal level than previously reported. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: The medical records of 902 pediatric and adolescent athletes (364 female, 538 male) diagnosed with symptomatic pars interarticularis and pedicle stress injuries at 2 academic medical centers between 2016 and 2021 were retrospectively reviewed. All patients had MRI scans taken at the time of diagnosis. Only patients with pars/pedicle edema on MRI were included. Data regarding spondylolysis stage, spinal level of injury, unilateral versus bilateral injury, sport participation, and MRI protocol over the 5-year study period were analyzed. RESULTS: Male patients presented at older ages than female patients (P < .001). Soccer was the most common sport at symptom onset and the second most common single-sport activity among those who specialized (participating in 1 sport year-round at the exclusion of others), behind gymnastics. The mean symptom duration was 4.0 months. Although most patients (83.5%) had exclusively lower lumbar stress injuries, 9.1% of injuries occurred at or above the L3 level. Over half of the patients had active single-level pars/pedicle fractures on MRI, with a mean symptom duration before presentation in this subgroup of 4.0 months. Even when pars/pedicle stress reactions were excluded from analysis, 7.1% of patients were injured at or above the L3 level. CONCLUSION: Among male and female athletes aged 8 to 21 years presenting with symptomatic pars interarticularis and pedicle stress injuries evaluated by MRI at the time of initial diagnosis, there was a higher incidence of upper lumbar stress injuries than previously reported.


Asunto(s)
Traumatismos en Atletas , Dolor de la Región Lumbar , Vértebras Lumbares , Imagen por Resonancia Magnética , Espondilólisis , Humanos , Masculino , Femenino , Adolescente , Estudios Retrospectivos , Espondilólisis/diagnóstico por imagen , Estudios Transversales , Niño , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/etiología , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/lesiones , Traumatismos en Atletas/diagnóstico por imagen , Fracturas por Estrés/diagnóstico por imagen , Atletas
13.
Protein Expr Purif ; 225: 106583, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39168394

RESUMEN

In recombinant protein purification, differences in isoelectric point (pI)/surface charge and hydrophobicity between the product and byproducts generally form the basis for separation. For bispecific antibodies (bsAbs), in many cases the physicochemical difference between product and byproducts is subtle, making byproduct removal considerably challenging. In a previous report, with a bsAb case study, we showed that partition coefficient (Kp) screening for the product and byproducts under various conditions facilitated finding conditions under which effective separation of two difficult-to-remove byproducts was achieved by anion exchange (AEX) chromatography. In the current work, as a follow-up study, we demonstrated that the same approach enabled identification of conditions allowing equally good byproduct removal by mixed-mode chromatography with remarkably improved yield. Results from the current and previous studies proved that separation factor determination based on Kp screening for product and byproduct is an effective approach for finding conditions enabling efficient and maximum byproduct removal, especially in challenging cases.

14.
J Arthroplasty ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39128782

RESUMEN

INTRODUCTION: Arthrofibrosis is a common postoperative total knee arthroplasty (TKA) complication that results in limited range of motion (ROM). There is limited literature on outcomes after revision TKA (rTKA) for arthrofibrosis based on preoperative ROM restriction. The aims of this study were to: (1) examine ROM trajectory after rTKA for arthrofibrosis patients who have severe versus non-severe limitations; (2) compare ROM gains and final arc of motion (AOM) between severe and non-severe cohorts; (2a) compare ROM gain in a severe cohort treated with a rotating hinge (RH) versus a non-rotating hinge (non-RH) construct; and (3) assess the impact of arthrofibrosis severity on patient-reported outcome measures (PROMs). METHODS: Patients were divided into 2 groups: Group A had preoperative ROM < 70o (severe), and Group B had preoperative ROM > 70o (non-severe). Patients were assessed clinically using AOM gain, absolute ROM, Knee injury and Osteoarthritis Outcomes Score for Joint Replacement (KOOS, JR), Lower Extremity Activity Scale (LEAS), and pain scores. Postoperative gains in AOM were compared between both groups. RESULTS: A total of 56 rTKAs (Group A (severe): n = 36, Group B (non-severe): n = 20) were performed for patients who have postoperative fibrosis. Group B had better ROM at the one-year timepoint (Group B: 95.9 ± 22.5 versus Group A: 83.2 ± 25.7). Group A had significantly better improvement in absolute AOM than Group B (31.1 ± 20.9 versus 11.4 ± 25.0, P < 0.01). The RH group demonstrated significantly better absolute AOM gain than the non-RH group (41.3 ± 19.4 versus 18.3 ± 15.2, P < 0.001). However, there were no significant differences in PROMs between Groups A and B or between RH and NRH groups at the final follow-up. DISCUSSION: Final ROM achieved between severe and non-severe arthrofibrosis groups were similar, and patients who have severe arthrofibrosis can expect greater absolute ROM gains and similar functional outcomes than non-severe arthrofibrosis patients. The RH rTKAs provided greater AOM gains for patients who have severe arthrofibrosis, with equivalent functional outcomes to non-RH implants. For severe arthrofibrosis patients, RH designs provided twice the overall ROM gain, however, longer follow-up is necessary to determine whether RH designs have inferior overall implant survivorship.

15.
Nucleic Acids Res ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39106168

RESUMEN

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and rodent neurons, reducing stress granule formation with nsP3 had modest impacts on lifespan even in the setting of serial stress pathway induction. In contrast, reducing stress granule formation in models of ataxia, amyotrophic lateral sclerosis and frontotemporal dementia largely exacerbated disease phenotypes. These data support a model whereby stress granules mitigate, rather than promote, neurodegenerative cascades.

16.
Intern Med J ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136359

RESUMEN

The objective of this article is to summarise the current knowledge regarding the prevalence of six rheumatological conditions in indigenous Australians - rheumatoid arthritis (RA), osteoarthritis (OA), osteoporosis (OSP), systemic lupus erythematosus (SLE), gout and musculoskeletal (MSK) pain. Online medical literature databases were searched for 'indigenous', 'Aboriginal' and 'Torres Strait Islander', as well as the names of the six conditions. Other included search terms were 'crystal', 'urate', 'arthritis' and 'arthropathy'. No limitations were placed on publication data or language. Forty-five articles examining the prevalence of the six conditions were identified. Based on the published literature, SLE appears to have a higher prevalence, while RA appears to have a lower prevalence in indigenous Australians compared to the non-indigenous community. MSK pain is prevalent, has a significant impact on indigenous people and is perceived as an important area of need. There is a paucity of data regarding these conditions in indigenous Australians. This may be impacted by the uncertainty of case ascertainment by self-report, differences in disease phenotypes and prevalence between the metropolitan compared to the rural or remote indigenous population, and difficulty with access to healthcare. Further studies in conjunction with local indigenous communities are needed to accurately determine the burden of rheumatological disease in the indigenous population. This will assist with resource and workforce planning to deliver culturally appropriate interventions. Strategies for future clinical work and research include the development and dissemination of culturally safe rheumatology resources, rheumatology training of Aboriginal Health Workers and wider integration of rheumatology clinics into community-controlled Aboriginal Health Services.

18.
Virchows Arch ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39153110

RESUMEN

Histopathology is a challenging interpretive discipline, and the level of confidence a pathologist has in their diagnosis is known to vary, which is conveyed descriptively in pathology reports. There has been little study to accurately quantify pathologists' diagnostic confidence or the factors that influence it. In this study involving sixteen pathologists from six NHS trusts, we assessed diagnostic confidence across multiple variables and four specialties. Each case was reported by four pathologists, with each pathologist reporting each case twice (on light microscopy (LM) and digital pathology (DP)). For each diagnosis, pathologists recorded their confidence on a 7-point Likert scale. This provided 16,187 diagnoses and associated confidence scores for analysis. All variables investigated were found to be significantly predictive of diagnostic confidence, except level of pathologist experience. Confidence was lower for difficult to report cases, cases where there was inter- and intra-pathologist variation in the diagnosis, and cases where the pathologist made an incorrect diagnosis. Confidence was higher, although nominally, for LM diagnoses than DP (rate ratio 1.09 (95% CI 1.01-1.18), p = 0.035), although results indicate pathologists are confident to report on DP. Lowest confidence scores were seen in areas of known diagnostic complexity and cases with quality issues. High confidence in incorrect diagnoses were almost invariably attributed to interpretive diagnostic differences which occurred across both rare and common lesions. The results highlight the value of external quality control schemes and the benefits of selective peer review when reporting.

19.
J Hand Surg Glob Online ; 6(4): 551-557, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39166189

RESUMEN

Purpose: Due to the Coronavirus Disease-19 pandemic, the fellowship application process has transitioned from in-person interviews to virtual interviews. Although several studies have assessed the impact of Coronavirus Disease-19 on residency and fellowship interviews, fewer studies have investigated the program director's perspective. Therefore, the aim of this study was to assess the experience of virtual interviews on hand fellowship program directors and understand some of the important factors that may make an applicant more competitive. Methods: A 21-question survey was conducted through Google Forms and distributed through a standardized email to hand fellowship program directors and coordinators. Questions used a 5-point Likert scale with the opportunity for respondents to answer some questions in a free-response format. Statistical analysis was conducted with significance assigned to P values < .05. Results: Ninety-three surveys were distributed, of which 35 responses were obtained, corresponding to a 37.6% survey response rate. Program directors reported that they tended to place more emphasis on applicant's curriculum vitae, calls from colleagues, and applicants that they had previously met. In addition, program directors felt that applicants were able to accurately represent themselves through the virtual format. Finally, most program directors stated that they were highly likely to continue to offer virtual interviews. Conclusions: With several parenting organizations and program directors affirming that they are comfortable with proceeding with virtual interviews, it is essential for hand fellowship applicants to understand what factors program directors may perceive as more important. It is possible that the virtual interview process may effectively achieve suitable matches between applicants and institutions. Type of study/level of evidence: Decision analysis IIIb.

20.
Int J Surg ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39172711

RESUMEN

BACKGROUND: Previous small studies investigating health-related quality of life (HRQoL) following bariatric surgery have demonstrated heterogenous effects. This study aimed to use National Bariatric Surgery Registry (NBSR) records to investigate the relationship between weight and HRQoL in people undergoing bariatric surgery in the UK. MATERIALS AND METHODS: In this observational study using United Kingdom National Bariatric Surgery Registry (NBSR) records between 1st June 2017 and 23rd November 2022, patients undergoing primary bariatric surgery with one baseline and at least one follow-up visit within one year from surgery were eligible for inclusion. Models estimated the relationship between EuroQol Five Dimension 5-level (EQ-5D) and BMI at baseline and longitudinally. Further analyses stratified by type 2 diabetes, type of operation (adjustable gastric band, sleeve, or bypass) and domain of EQ-5D. RESULTS: 5,587 observations of 2,160 patients were analysed. At baseline, mean BMI was 45.7±7.8 kg/m2 and mean EQ-5D was 0.78±0.22. A 1 kg/m2 higher BMI was associated with 0.005 (95%CI[-0.006,-0.004]) lower EQ-5D. In the month following surgery, EQ-5D increased to 0.91±0.2 while BMI decreased to 39.8±7.1 kg/m2 (P<0.001 for both); subsequently EQ-5D plateaued (0.90±0.17 at 12 months) while BMI continued to decrease (31.5±6.2 kg/m2 at 12 months, P<0.001). Each 1 kg/m2 decrease in BMI was associated with a 0.006 (95%CI [-0.007,-0.005]) increase in EQ-5D. Remission of T2D was independently associated with increase in EQ-5D (0.037, 95%CI [0.015,0.059]); type of operation was not. Decreases in BMI were associated with improvements in all five domains of EQ-5D. CONCLUSIONS: In this large dataset, greater weight loss and T2D remission were independently associated with greater improvements in HRQoL following bariatric surgery. The HRQoL-BMI relationship for people undergoing bariatric surgery differs to that which has previously been estimated following behavioural interventions. Use of the estimates generated here will be important for clinical and political decision making.

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