Heat and Acupuncture to Manage Osteoarthritis of the Knee (HARMOKnee): Protocol for an Effectiveness-Implementation Hybrid Randomized Controlled Trial.

BACKGROUND: Knee osteoarthritis (KOA) is one of most prevalent and fastest-growing causes of pain, impaired mobility, and poor quality of life in the rapidly aging population worldwide. There is a lack of high-quality evidence on the efficacy of traditional Chinese medicine (TCM), particularly acupuncture, and a lack of KOA practice guidelines that are tailored to unique population demographics and tropical climates. OBJECTIVE: Our HARMOKnee (Heat and Acupuncture to Manage Osteoarthritis of the Knee) trial aims to address these gaps by evaluating the short- and medium-term clinical and cost-effectiveness of acupuncture with heat therapy in addition to standard care, compared to standard care alone. Through a robust process and economic evaluation, we aim to inform evidence-based practice for patients with KOA to facilitate the large-scale implementation of a comprehensive and holistic model of care that harmonizes elements of Western medicine and TCM. We hypothesize that acupuncture with heat therapy as an adjunct to standard care is clinically more effective than standard care alone. METHODS: A multicenter, pragmatic, parallel-arm, single-blinded, effectiveness-implementation hybrid randomized controlled trial will be conducted. We intend to recruit 100 patients with KOA randomized to either the control arm (standard care only) or intervention arm (acupuncture with heat therapy, in addition to standard care). The inclusion criteria are being a community ambulator and having primary KOA, excluding patients with secondary arthritis or previous knee replacements. The primary outcome measure is the Knee Osteoarthritis Outcome Score at 6 weeks. Secondary outcome measures include psychological, physical, quality of life, satisfaction, and global outcome measures at 6, 12, and 26 weeks. A mixed method approach through an embedded process evaluation will facilitate large-scale implementation. An economic evaluation will be performed to assess financial sustainability. RESULTS: Patient enrollment has been ongoing since August 2022. The recruitment process is anticipated to conclude by July 2024, and the findings will be analyzed and publicized as they are obtained. As of November 6, 2023, our patient enrollment stands at 65 individuals. CONCLUSIONS: The findings of our HARMOKnee study will contribute substantial evidence to the current body of literature regarding the effectiveness of acupuncture treatment for KOA. Additionally, we aim to facilitate the creation of standardized national guidelines for evidence-based practice that are specifically tailored to our unique population demographics. Furthermore, we seek to promote the adoption and integration of acupuncture and heat therapy into existing treatment models. TRIAL REGISTRATION: ClinicalTrials.gov NCT05507619; https://clinicaltrials.gov/study/NCT05507619. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54352.

Interaction between FAK/αB-crystalline is important for viability of the glioblastoma cells

Abstract Glioblastoma multiforme is a tumor of the central nervous system. Focal Adhesion Kinase (FAK) and αB-crystalline are two proteins involved in glioblastoma development. In this study, we investigated whether the FAK/αB-crystalline interaction is important for glioblastoma cells, we aimed to investigate the interaction of these two proteins in the glioblastoma multiforme cell line U87-MG. Two peptides named FP01 peptide (derived from αB-crystalline) and FP02 peptide (derived from FAK) were synthesized for this study. Treatment of U87-MG with the peptides FP01 and FP02 in the concentration at 50 µM reduced the viability cellular to around 41% and 51%, respectively. Morphological alterations in the cells treated with the peptides when compared to the control were observed. This study suggests that the interaction between FAK and αB-crystalline is important for the viability of glioblastoma cells.

Gut commensals and their metabolites in health and disease.

Purpose of review: This review comprehensively discusses the role of the gut microbiome and its metabolites in health and disease and sheds light on the importance of a holistic approach in assessing the gut. Recent findings: The gut microbiome consisting of the bacteriome, mycobiome, archaeome, and virome has a profound effect on human health. Gut dysbiosis which is characterized by perturbations in the microbial population not only results in gastrointestinal (GI) symptoms or conditions but can also give rise to extra-GI manifestations. Gut microorganisms also produce metabolites (short-chain fatty acids, trimethylamine, hydrogen sulfide, methane, and so on) that are important for several interkingdom microbial interactions and functions. They also participate in various host metabolic processes. An alteration in the microbial species can affect their respective metabolite concentrations which can have serious health implications. Effective assessment of the gut microbiome and its metabolites is crucial as it can provide insights into one's overall health. Summary: Emerging evidence highlights the role of the gut microbiome and its metabolites in health and disease. As it is implicated in GI as well as extra-GI symptoms, the gut microbiome plays a crucial role in the overall well-being of the host. Effective assessment of the gut microbiome may provide insights into one's health status leading to more holistic care.

Study on proximal humerus evaluation of effective treatment (SPHEER) - what is the effect of rehabilitation compliance on clinical outcomes of proximal humerus fractures.

INTRODUCTION: Proximal humeral fractures (PHFs) are 3rd commonest fragility fractures and cause significant functional impairment. This paper sought to determine impact of rehabilitation compliance on the clinical outcomes for non-surgically managed PHFs, while ascertaining reasons for non-compliance which can be addressed to improve compliance. METHODS: Prospective cohort study of patients undergoing non-surgical treatment for PHFs from August 2017 to April 2020 in a tertiary trauma centre was performed. Data was collected via questionnaire: patient demographic data, PHF injury details, clinical outcome measures, therapist-reported (Sport Injury Rehabilitation Adherence Scale [SIRAS]) and patient-reported (subjective compliance, frequency of exercise) rehabilitation compliance measures. Data was analysed using multiple linear regression model to account for confounding variables. RESULTS: 107 participants attended physical therapy follow-up for mean 137.8 days. 6-week SIRAS strongly predicted 3-month Constant score (p = 0.023; 95%CI = 0.265,3.423), OSS (p = 0.038; 95%CI = 0.049,1.634), flexion ROM (p < 0.001; 95%CI = 2.872,8.982), extension ROM (p = 0.035; 95%CI = 0.097,2.614), abduction ROM (p = 0.002;95%CI = 1.995,8.466) and achievement of functional active ROM at 3-months (p = 0.049; 95%CI = 1.001,1.638). Pain was the top reason impairing rehabilitation compliance from therapist (43.9% at 6-weeks and 20.6% at 3-months) and patient-perspective (33.6% at 6-weeks, 24.3% at 3-months). Author-developed patient-reported compliance measures had good correlation with validated SIRAS score (subjective compliance: p < 0.001 frequency of exercise: p = 0.001). CONCLUSION: Rehabilitation compliance predicts short-term clinical outcomes up to 3-months and potentially 1-year outcomes. Pain control should be optimised to maximise rehabilitation compliance and improve PHF outcomes. There is lack of consensus definition for rehabilitation compliance measures; patient-reported measures used have good correlation to existing validated measures and could serve as a steppingstone for further research. LEVEL OF EVIDENCE: II, cohort study.

Detection of metastases using circulating tumour DNA in uveal melanoma.

BACKGROUND: Approximately 50% of uveal melanoma (UM) patients will develop metastatic disease depending on the genetic features of the primary tumour. Patients need 3-12 monthly scans, depending on their prognosis, which is costly and often non-specific. Circulating tumour DNA (ctDNA) quantification could serve as a test to detect and monitor patients for early signs of metastasis and therapeutic response. METHODS: We assessed ctDNA as a biomarker in three distinct UM cohorts using droplet-digital PCR: (A) a retrospective analysis of primary UM patients to predict metastases; (B) a prospective analysis of UM patients after resolution of their primary tumour for early detection of metastases; and (C) monitoring treatment response in metastatic UM patients. RESULTS: Cohort A: ctDNA levels were not associated with the development of metastases. Cohort B: ctDNA was detected in 17/25 (68%) with radiological diagnosis of metastases. ctDNA was the strongest predictor of overall survival in a multivariate analysis (HR = 15.8, 95% CI 1.7-151.2, p = 0.017). Cohort C: ctDNA monitoring of patients undergoing immunotherapy revealed a reduction in the levels of ctDNA in patients with combination immunotherapy. CONCLUSIONS: Our proof-of-concept study shows the biomarker feasibility potential of ctDNA monitoring in for the clinical management of uveal melanoma patients.

Influence of genetic polymorphisms on serum biomarkers of cardiac health.

Cardiovascular diseases (CVDs) are a leading cause of death worldwide which is why early risk prediction is crucial. Discrete Polygenic risk score (PRS) measurement using saliva or dried blood spot samples collected at home poses a convenient means for early CVD risk assessment. The present study assessed the effects of 28 disease-associated single nucleotide polymorphisms (SNPs) on 16 serological cardiac markers and also aggregated the risk alleles into a PRS to evaluate its applicability in CVD-risk prediction. The study assessed genetic and serological markers in 184 individuals. The association between serological markers and individual genetic variants was evaluated using a two-tailed t test while the associations of serum markers with the PRS was analyzed using the Pearson correlation. The comparative analysis of genotypes revealed statistically significant associations between serum markers and CVD-associated SNPs with Apo B: Apo A-1, LDL Direct, Apo B, sdLDL, hsCRP, Lp(a), NT-proBNP, and PLAC levels being significantly associated with the risk alleles of the SNPs, rs12526453, rs5186, rs10911021, rs1801131, rs670, rs10757274, and rs10757278. Increased PLAC levels were associated with rs10757274 and rs10757278 (P < .05). The SNPs, rs1801133, rs1549758, rs1799983, rs5082, and rs5186 were significantly associated with an increase in the cardioprotective markers, HDL and ApoA1 (P < .05). Furthermore, the PRS was associated with increasing levels of several serum cardiac markers (r2 > 0.6). Significant correlations were observed between high PRSs and NT-proBNP and ox-LDL levels with the r2 values being 0.82 (95% CI = 0.13-0.99; P = .03) and 0.94 (95% CI = 0.63-0.99; P = .005), respectively. The present study reports that SNPs have differential effects on serum markers with rs12526453, rs5186, rs10911021, rs1801131, rs670, rs10757274, and rs10757278 showing significant associations with elevated marker levels, which are indicators of deteriorating cardiac health. A unified PRS using several SNPs was also associated with an increase in serum markers levels, especially, NT-proBNP and ox-LDL. Genetic assessment via a convenient at-home collection to calculate the PRS can serve as an effective predictive tool for early CVD-risk assessment. This may help identify the risk groups that may require increased serological monitoring.

Avaliação e intervenção responsiva e integrativa na criança com distúrbio alimentar pediátrico com Trissomia do 21: Relato de caso / Responsive and integrative assessment and intervention in children with pediatric feeding disorder with Trisomy 21: A case report / Evaluación e intervención receptiva e integradora en un niño con trastorno alimentario pediátrico con Trisomía 21: Reporte de caso

Na criança com Trissomia do 21 a dificuldade alimentar pode estar presente. Alguns sinais são as alterações na habilidade motora-oral, no processamento sensorial, tempo elevado das refeições, recusa alimentar prolongada e falta de autonomia. Ainda pouco se discute sobre as dificuldades alimentares e seu processo terapêutico nesta população. O objetivo deste estudo foi descrever a avaliação e intervenção fonoaudiológica e da terapia ocupacional na dificuldade alimentar de uma criança com Trissomia do 21 com o uso de estratégias de alimentação responsiva e integrativa. Criança 3 anos e 2 meses, sexo masculino. Avaliação fonoaudiológica demonstrou criança com distúrbio alimentar pediátrico, caracterizado por atraso na habilidade motora-oral, baixa percepção intraoral e comportamento alimentar altamente seletivo. Na avaliação da terapia ocupacional verificou-se perfil sensorial alterado. Na fonoterapia foram trabalhados aspectos como a percepção do alimento, ritmo e o tempo de alimentação. Na terapia ocupacional, o objetivo foi adequar nível de alerta, favorecer a independência e o desenvolvimento psicomotor. Após a intervenção, a reavaliação fonoaudiológica demonstrou que houve ampliação do cardápio, melhora da percepção, da habilidade motora intraoral, aceitação de diferentes utensílios e modos de apresentação do alimento, autonomia e prazer nas refeições. A reavaliação da terapia ocupacional mostrou um nível de alerta e atenção mais adequado, uso das mãos e dedos de maneira mais funcional para se alimentar. Foram observadas evoluções positivas em relação à intervenção fonoaudiológica e da terapia ocupacional na dificuldade alimentar de uma criança com Trissomia do 21 com o uso de estratégias de alimentação responsiva e integrativa. (AU)

In children with Trisomy 21 feeding difficulty can be observed, such as changes in oral motor skills, sensory processing, longer mealtimes, food refusal, lack of autonomy and others. However, there is little discussion about feeding difficulties and rehabilitation process in this population. This study aimed to describe speech-language and occupational therapy assessment and intervention in feeding difficulties in a 3-year and 2-month-old male child with a diagnosis of Trisomy 21. Speech-language pathology assessment found that the child had feeding difficulties, delay in oral motor skills, low intraoral perception and acceptance, while the occupational therapy assessment showed an altered sensory profile. The speech-language pathology sessions included aspects such as food perception, rhythm and feeding time. In turn, occupational therapy sessions aimed to adjust the alertness level, promote independence and psychomotor development. After the intervention, the speech-language pathology reassessment showed that there was an expansion of the menu for the ingestion, improvement in perception and intraoral motor skills, acceptance of different utensils and food presentation modes, autonomy and pleasure in meals. The reassessment of occupational therapy showed a better level of alertness and attention, more functional use of hands and fingers to eat. Therefore, a positive progress was observed in the feeding difficulty of a child with Trisomy 21 after a speech-language pathology and occupational therapy intervention with the use of responsive and integrative feeding strategies. (AU)

Niños con Trisomía 21, pueden presentar dificultades de alimentación. Algunos signos son cambios en las habilidades motrices orales, procesamiento sensorial, tiempos prolongados de comida, rechazo prolongado de alimentos y falta de autonomía. Hay poca discusión sobre las dificultades de alimentación y su proceso terapéutico en esta población. El objetivo deste estudio fue describir la evaluación e intervención fonoaudiológica y de terapia ocupacional en la dificultad de alimentación de un niño con Trisomía 21 utilizando estrategias de alimentación receptiva e integradora. Niño de 3 años y 2 meses. La evaluación fonoaudiológica mostró un trastorno alimentario pediátrico, caracterizado por un retraso en las habilidades motoras orales, percepción intraoral baja y comportamiento alimentario altamente selectivo. En la evaluación de terapia ocupacional se observó un perfil sensorial alterado. En fonoaudiología se trabajaron aspectos como la percepción de alimentos, ritmo y tiempo de alimentación. En terapia ocupacional, el objetivo fue ajustar el nivel de alerta, favoreciendo la independencia y desarrollo psicomotor. Después de la intervención, la reevaluación fonoaudiológica se evidenció una ampliación del menú, mejoras en percepción, motricidad intraoral, aceptación de diferentes utensilios y formas de presentar alimentos, autonomía y placer en las comidas. La reevaluación de terapia ocupacional mostró un nivel de alerta y atención más adecuado, uso de manos y dedos de forma más funcional para alimentarse. Fueron observadas evoluciones positivas con relación a la intervención fonoaudiológica y de terapia ocupacional en la dificultad de alimentación de un niño con Trisomía 21 con el uso de estrategias de alimentación receptiva e integradora. (AU)

Discordance Between Self-Reported and Performance-Based Physical Function in Patients Who Have Knee Osteoarthritis: Associations With Pain Intensity and Negative Affect.

BACKGROUND: Although self-reported measures of physical disability are strong indication criterion for total knee arthroplasty (TKA) in painful knee osteoarthritis (OA), some patients may report greater-than-observed disability. Contributing factors to this discordance are relatively unexplored. We aimed to examine whether pain and negative affect, including anxiety and depression, were associated with the discordance of self-reported measures with performance-based measures (PPM) of physical function. METHODS: We used cross-sectional data (n = 212) from two randomized rehabilitation trials in knee OA. All patients were assessed for knee pain intensity and symptoms of anxiety and depression. Self-reported function was assessed by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical-function subscale. Objective performance-based measures (PPMs) of physical function were assessed by timed gait and stair tests. Continuous discordance scores were quantified by the difference in percentiles between WOMAC and PPMs (WOMAC-PPM), where a positive discordance, WOMAC-PPM >0, implied greater perceived than observed disability. RESULTS: Around 1 in 4 patients had >20 percentile units in WOMAC-PPM discordance. In Bayesian regression analyses, knee pain intensity had >99% posterior probability of positive associations with WOMAC-PPM discordance. Among patients awaiting TKA, anxiety intensity had approximately 99% probability of positive associations with discordance, and these associations had >65% probability of exceeding 10 percentile units. In contrast, depression had low (79% to 88%) probability of any association with discordance. CONCLUSION: In patients who have knee OA, a sizable proportion reported substantially greater physical disability than actually observed. Pain and anxiety intensity, but not depression, were meaningful predictors of this discordance. If validated, our findings may help in refining patient selection criteria for TKA.

Singapore KneE osTeoarthritis CoHort (SKETCH): protocol for a multi-centre prospective cohort study.

BACKGROUND: Knee osteoarthritis (OA) is a leading cause of global disability. The understanding of the role of psychosocial factors in knee OA outcomes is still evolving particularly in an Asian context. The primary aim of this study is to explore psychosocial factors that prognosticate short and long-term clinical outcomes, productivity, and healthcare utilization in patients with knee OA. Secondary aims are to explore the mediation and directional relationships and the role it plays in predicting the discordance between self-reported measures (SRM), physical-performance measures (PPMs) and objective clinical parameters. METHODS: A multi-centre prospective cohort study of community ambulant knee OA patients seeking treatment in the tertiary healthcare institutions in Singapore will be conducted. Patients with secondary arthritis, significant cognitive impairment, severe medical comorbidities or previous knee arthroplasty will be excluded. Primary clinical outcome measure is the Knee injury and OA Outcome Score-12 (KOOS-12). Baseline characteristics include sociodemographic status, arthritis status including symptom duration and radiographic severity, comorbidities and functional status through Charlson Comorbidities Index (CCI), Barthel Index (BI) and Parker Mobility Score (PMS). Psychosocial variables include social support, kinesiophobia, negative affect, self-efficacy, injustice, chronic illness shame and the built environment. Clinical outcomes include quality of life, physical performance, global assessment, satisfaction and physical activity levels. Productivity and healthcare utilization will be assessed by a modified OA Cost and Consequences Questionnaire (OCC-Q) and the Work Productivity and Activity Impairment Questionnaire (WPAI). Variables will be collected at baseline, 4, 12 months and yearly thereafter. Regression, mediation and structural equation modelling will be used for analysis. DISCUSSION: Results will allow contextualization, identification, and phenotyping of the critical (and potentially modifiable) psychosocial parameters that predict positive clinical outcomes in the OA population to guide optimization and refinement of healthcare and community. This will facilitate: 1. identification of high-risk knee OA subpopulations that will likely experience poor outcomes and 2. formulation of targeted multidisciplinary comprehensive approaches to address these psychosocial factors to optimize non-surgical treatment care, maximize functional outcomes and create more value-based care model for knee OA. ETHICS AND DISSEMINATION: The study has been registered under clinicaltrials.gov registry (Identifier: NCT04942236).

Integrated palliative homecare in advanced dementia: reduced healthcare utilisation and costs.

OBJECTIVES: To determine the economic benefit of an integrated home-based palliative care programme for advanced dementia (Programme Dignity), evaluation is required. This study aimed to estimate Programme Dignity's average monthly cost from a provider's perspective; and compare healthcare utilisation and costs of programme patients with controls, accounting for enrolment duration. METHODS: This was a retrospective cohort study. Home-dwelling patients with advanced dementia (stage 7 on the functional assessment staging in Alzheimer's disease) with a history of pneumonia, albumin <35 g/L or tube-feeding and known to be deceased were analysed (Programme Dignity=184, controls=139). One-year programme operational costs were apportioned on a per patient-month basis. Cumulative healthcare utilisation and costs were examined at 1, 3 and 6 months look-back from death. Between-group comparisons used Poisson, zero-inflated Poisson regressions and generalised linear models. RESULTS: The average monthly programme cost was SGD$1311 (SGD-Pounds exchange rate: 0.481) per patient. Fully enrolled programme patients were less likely to visit the emergency department (incidence rate ratios (IRRs): 1 month=0.56; 3 months=0.19; 6 months=0.10; all p<0.001), be admitted to hospital (IRRs: 1 month=0.60; 3 months=0.19; 6 months=0.15; all p<0.001), had a lower cumulative length of stay (IRRs: 1 month=0.78; 3 months=0.49; 6 months=0.24; all p<0.001) and incurred lesser healthcare utilisation costs (ß-coefficients: 1 month=0.70; 3 months=0.40; 6 months=0.43; all p<0.01) at all time-points examined. CONCLUSION: Programme Dignity for advanced dementia reduces healthcare utilisation and costs. If scalable, it may benefit more patients wishing to remain at home at the end-of-life, allowing for a potentially sustainable care model to cope with rapid population ageing. It contributes to the evidence base of advanced dementia palliative care and informs healthcare policy making. Future studies should estimate informal caregiving costs for comprehensive economic evaluation.

Bundled Payments for Hip Fracture Surgery Are Associated With Improved Access, Quality, and Health Care Utilization, but Higher Costs for Complex Cases: An Interrupted Time Series Analysis.

OBJECTIVES: To study the impact of bundled payments for surgically managed hip fractures on care access, care quality, health care resource utilization, clinical impact, and acute care cost. DESIGN: An observational retrospective cohort study using a quasi-experimental design comparing prebundled and postbundled payments through an interrupted time series analysis. SETTING: A public acute care general hospital. PATIENTS: Patients 60 years and older, with surgery for an isolated, unilateral, nonpathological hip fracture during 2014-first quarter of 2019 [diagnosis-related group codes: I03A, I03B, I08A, and I08B] and transferred to specific rehabilitation institutions were studied. INTERVENTION: Bundled payments for funder-to-provider reimbursement. MAIN OUTCOMES MEASUREMENTS: Care access, care quality, health care resource utilization, clinical impact, and cost. RESULTS: Of 1477 patients, 811 were assigned to prebundled and 666 to postbundled payments. Although there was an improving trend of ward admission waiting times during postbundled payments [odds ratio (OR) = 1.14; 95% confidence interval (CI): 1.02-1.28], ward admission waiting times were longer when compared with prebundled payments (OR = 0.45; 95% CI: 0.23-0.85). Rates of 30-day all-cause readmissions were lower (OR = 0.08; 95% CI: 0.01-0.67), and trends of reducing inpatient rehabilitation and overall episode length of stay (OR = 1.26; 95% CI: 1.16-1.37 and OR = 1.17; 95% CI: 1.07-1.28, respectively) were demonstrated during postbundled payments. Acute care cost for complex cases were higher (OR = 0.49; 95% CI: 0.26-0.92) during bundled payments, compared with prebundled payments. CONCLUSIONS: Bundled payments for surgically managed hip fractures were associated with benefits for several outcomes pertinent to clinical improvement initiatives. More work, especially concerning cost-effective surgical implants and better care cost computations, are critically needed to contain the growth of acute medical care cost for these patients. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Mediation of the meaning of work on the relationship between leadership and performance, controlling the response bias / Mediação do sentido do trabalho sobre a relação entre liderança e desempenho, controlando o viés de resposta

Objective: Researchers have investigated the relationship between the meaning of work and variables related to work well-being. This study investigated the relationships between transformational leadership and job performance, and the mediation of the meaning of work in these relationships. Method: A total of 397 professionals of a Brazilian public university participated, answerin gforced-choice questionnaire. The relationship model between variables was tested using structural equations. In addition, the parameters of indirect effects of mediation were tested using bootstrap (100 resamples). Results: The results indicated that job performance levels were explained by transformational leadership. The meaning of work explained 86% of the relationship between the variables. Conclusion: The study contributes by presenting data of acquiescence control and in explaining the impact of variables on professionals' job performance.

Objetivo: Estudiosos tem se aprofundado nas relações do sentido do trabalho com variáveis ligadas ao bem-estar laboral. O estudo investigou as relações entre a liderança transformacional e o desempenho no trabalho, e a mediação do sentido do trabalho nessas relações. Método: Participaram 397 servidores brasileiros de uma universidade pública, que responderam os instrumentos na versão de escolhas forçadas. O modelo de relação entre as variáveis foi testado por meio de equações estruturais e os parâmetros de efeitos indiretos da mediação foram testados por meio de bootstrap (100 reamostragens). Resultados: Os resultados indicaram que os níveis de desempenho no trabalho foram explicados pela liderança transformacional. O sentido do trabalho explicou 86% da relação entre as variáveis. Conclusão: O estudo contribui pela coleta de dados com controle de aquiescência e na explicação do impacto das variáveis no desempenho dos servidores públicos.

Focal adhesion kinase inhibition decreases cell viability and induces apoptosis of JAK2 V617F positive cells

Abstract Focal Adhesion Kinase (FAK) protein participates in proliferation, migration, cell survival, and apoptosis process. It has been described as overexpressed in several neoplasms being a promising target for therapy. BCR-ABL negative chronic Myeloproliferative Neoplasms (MPN) are clonal disorders characterized by the excess of proliferation and apoptosis resistance. The identification of the acquired JAK2 V617F mutation in MPN patients allowed a better understanding of pathogenesis. However, there is still no pharmacological treatment that leads all patients to molecular remission, justifying new studies. The present study aimed to evaluate FAK involvement in the viability and apoptosis of HEL and SET-2 cells, both JAK2 V617F positive cell lines. The FAK inhibitor PF 562,271 was used. Cell viability was determined using MTT assay and apoptosis verified by cleaved PARP, cleaved Caspase 3 and Annexin-V/PI staining detection. FAK inhibition significantly reduced HEL and SET-2 cells viability and induced apoptosis. Considering the role of JAK/STAT pathway in MPN, further investigation of FAK participation in the MPN cells proliferation and apoptosis resistance, as well as possible crosstalk between JAK and FAK and downstream pathways may contribute to the knowledge of MPN pathophysiology, the discovery of new molecular targets, and JAK inhibitors resistance mechanisms.

The Mediation of Harmonious Passion for Work in the Servant Leadership and Work Intentions Relationship: A Longitudinal Study / La mediación de la pasión armoniosa por el trabajo en la relación entre el liderazgo de servicio y las intenciones laborales: Un estudio longitudinal

Abstract This study evaluated the relationship between servant leadership and work intentions, mediated by passion for work, in a longitudinal study. Data were collected in three waves, with three-month intervals in between, totaling a six-month data collection period. The total sample consisted of 479 workers of both genders (70.4% women) from all Brazilian regions. The results of the cross-lagged panel analysis showed that the servant leadership positively predicted work intentions. In addition, passion for work partially mediated the relationship between servant leadership and work intentions. However, contrary to expectations, this mediation was negative. The results are discussed according to the Passion for Work Assessment Model, which provided theoretical support for the investigation.

Resumen El estudio evaluó la relación entre el liderazgo de servicio y las intenciones laborales, mediadas por la pasión por el trabajo, en un estudio longitudinal. Los datos se recopilaron en tres oleadas, con intervalos de tres meses entre ellos, totalizando un periodo de recopilación de datos de seis meses. La muestra total estuvo constituida por 479 trabajadores de todas las regiones brasileñas y de ambos sexos (70,4% mujeres). Los resultados del análisis de panel rezagado cruzado mostraron que el liderazgo de servicia predijo positivamente las intenciones de trabajo. Además, la pasión por el trabajo medió parcialmente la relación entre el liderazgo de servicia y las intenciones laborales. Sin embargo, contrariamente a lo esperado, esta mediación fue negativa. Los resultados se discuten a la luz del Modelo de Evaluación de la Pasión por el Trabajo, que brindó soporte teórico para la investigación.

Chronic low back pain and its impact on physical function, mental health, and health-related quality of life: a cross-sectional study in Singapore.

Chronic low back pain, defined as low back pain lasting more than 3 months, is a globally prevalent health problem with significantly high medical and economic burden on individuals and the society. This study aimed to estimate the prevalence of chronic low back pain and examine its association with health outcomes including physical function, mental health, and quality of life among adult population in Singapore. Cross-sectional secondary data analysis was performed using baseline data of the 1941 adults (mean age: 52.6 years, range: 21-97 years) from a representative population health survey conducted in the Central region of Singapore. Those with self-reported chronic low back pain in past six months were identified. The Late-Life Function and Disability Instrument, Patient Health Questionnaire-9, and EQ-5D-5L were used to measure physical function and limitation, mental health, and health-related quality of life, respectively. Generalized Linear Regressions were used to examine the association of chronic low back pain with physical function, limitation, depressive symptoms, and health-related quality of life. There were 8.1% (n = 180) participants reporting having chronic low back pain in past six months, among whom 80.5% sought treatments at either primary care, specialist outpatient, or Traditional Chinese Medicine clinics. Individuals with chronic low back pain reported poorer physical function, more limitations in performing major life tasks and social activities, more depressive symptoms, and lower health-related quality of life (all p < 0.01), even after adjusting for socio-demographics, lifestyle factors, and number of morbidities. The prevalence of chronic low back pain was 8.1% among the study population. Chronic low back pain was associated with poorer physical function, more limitations and depressive symptoms, and lower health-related quality of life. The findings highlight the significant impact of chronic low back pain on physical function and limitation, mental health, and health-related quality of life in a general population. Increased awareness on prevention, early and proper management of low back pain, and rehabilitation policies are required to better tackle the burden of low back pain at the population level.

Emergency department interventions for frailty (EDIFY): improving functional outcomes in older persons at the emergency department through a multicomponent frailty intervention.

OBJECTIVES: emergency department interventions for frailty (EDIFY) delivers frailty-centric interventions at the emergency department (ED). We evaluated the effectiveness of a multicomponent frailty intervention (MFI) in improving functional outcomes among older persons. DESIGN: a quasi-experimental study. SETTING: a 30-bed ED observation unit within a 1,700-bed acute tertiary hospital. PARTICIPANTS: patients aged ≥65 years, categorised as Clinical Frailty Scale 4-6, and planned for discharge from the unit. METHODS: we compared patients receiving the MFI versus usual-care. Data on demographics, function, frailty, sarcopenia, comorbidities and medications were gathered. Our primary outcome was functional status-Modified Barthel Index (MBI) and Lawton's iADL. Secondary outcomes include hospitalisation, ED re-attendance, mortality, frailty, sarcopenia, polypharmacy and falls. Follow-up assessments were at 3, 6 and 12 months. RESULTS: we recruited 140 participants (mean age 79.7 ± 7.6 years; 47% frail and 73.6% completed the study). Baseline characteristics between groups were comparable (each n = 70). For the intervention group, MBI scores were significantly higher at 6 months (mean: 94.5 ± 11.2 versus 88.5 ± 19.5, P = 0.04), whereas Lawton's iADL scores experienced less decline (change-in-score: 0.0 ± 1.7 versus -1.1 ± 1.8, P = 0.001). Model-based analyses revealed greater odds of maintaining/improving MBI in the intervention group at 6 months [odds ratio (OR) 2.51, 95% confidence interval (CI) 1.04-6.03, P = 0.04] and 12 months (OR 2.98, 95% CI 1.18-7.54, P = 0.02). This was similar for Lawton's iADL at 12 months (OR 4.01, 95% CI 1.70-9.48, P = 0.002). ED re-attendances (rate ratio 0.35, 95% CI 0.13-0.90, P = 0.03) and progression to sarcopenia (OR 0.19, 95% CI 0.04-0.94, P = 0.04) were also lower at 6 months. CONCLUSIONS: the MFI delivered to older persons at the ED can possibly improve functional outcomes and reduce ED re-attendances while attenuating sarcopenia progression.

Detection of clinical progression through plasma ctDNA in metastatic melanoma patients: a comparison to radiological progression.

BACKGROUND: The validity of circulating tumour DNA (ctDNA) as an indicator of disease progression compared to medical imaging in patients with metastatic melanoma requires detailed evaluation. METHODS: Here, we carried out a retrospective ctDNA analysis of 108 plasma samples collected at the time of disease progression. We also analysed a validation cohort of 66 metastatic melanoma patients monitored prospectively after response to systemic therapy. RESULTS: ctDNA was detected in 62% of patients at the time of disease progression. For 67 patients that responded to treatment, the mean ctDNA level at progressive disease was significantly higher than at the time of response (P < 0.0001). However, only 30 of these 67 (45%) patients had a statistically significant increase in ctDNA by Poisson test. A validation cohort of 66 metastatic melanoma patients monitored prospectively indicated a 56% detection rate of ctDNA at progression, with only two cases showing increased ctDNA prior to radiological progression. Finally, a correlation between ctDNA levels and metabolic tumour burden was only observed in treatment naïve patients but not at the time of progression in a subgroup of patients failing BRAF inhibition (N = 15). CONCLUSIONS: These results highlight the low efficacy of ctDNA to detect disease progression in melanoma when compared mainly to standard positron emission tomography imaging.

Maternal complaints about feeding problems and anthropometric parameters of children with a diagnosis of pediatric feeding disorder

ABSTRACT Purpose: to describe the anthropometric parameters of children diagnosed with pediatric feeding disorder by a multiprofessional team. Methods: a retrospective clinical study conducted on 196 children on maternal complaints of feeding difficulties and a diagnosis of pediatric feeding disorder. Children with neurological diseases or having no pediatric feeding disorder diagnosis were excluded from the study. Weight and height data were obtained and parameters such as weight-for-age, length/height-for-age and body mass index for-age were analyzed, according to the recommendations of the World Health Organization. The two-proportion equality test was used and the level of significance was set at 0.05 (5%) in all analyses. Results: results showed mean (±Standard Deviation) values of 13.09±5.1 for weight (kg), 0.61±15.53 for height (cm) and 15.37±1.56 for body mass index (kg/m²). The results also showed that 87.2% of the children were within the adequate z-score for weight-for-age, 93.4% were within the adequate z-score for length/height-for-age, and that 88.8% had a normal z-score for-age for body mass index. Conclusion: the sample of children diagnosed with pediatric feeding disorder exhibited adequate anthropometric parameters for their age range.

Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture.

(1) Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour cells (CTCs) has been proposed as a tool to avoid invasive biopsy of the primary tumour. However, the clinical utility of such liquid biopsy depends on the detection rate of CTCs. (2) Methods: The expression of melanoma, melanocyte, and stem cell markers was tested in a primary tissue microarray (TMA) and UM cell lines. Markers found to be highly expressed in primary UM were used to either immunomagnetically isolate or immunostain UM CTCs prior to treatment of the primary lesion. (3) Results: TMA and cell lines had heterogeneous expression of common melanoma, melanocyte, and stem cell markers. A multi-marker panel of immunomagnetic beads enabled isolation of CTCs in 37/43 (86%) patients with UM. Detection of three or more CTCs using the multi-marker panel, but not MCSP alone, was a significant predictor of shorter progression free (p = 0.040) and overall (p = 0.022) survival. (4) Conclusions: The multi-marker immunomagnetic isolation protocol enabled the detection of CTCs in most primary UM patients. Overall, our results suggest that a multi-marker approach could be a powerful tool for CTC separation for non-invasive prognostication of UM.

Mental health of Brazilian university students during the Covid-19 / Saúde mental dos estudantes universitários brasileiros durante a pandemia de Covid-19 / Salud mental de estudiantes universitarios brasileños durante la pandemia Covid-19

This study aimed to investigate the effects of positive and negative affects, anxiety, and obsessive and compulsive thoughts and behaviors on Brazilian university students during the Covid-19 pandemic. Participated in this study 492 students, aged 18 years or over, from all regions of the country. The survey was conducted between April and May 2020, using self-report instruments applied in the online format. The results indicated that 37% (N=182) of the students had a high level of anxiety and 46.1% (N=227) moderate levels for obsessive and compulsive thoughts and behaviors. In addition, it was found that positive affects were negatively correlated with anxiety, as well as with obsessive and compulsive thoughts and behaviors, while negative affects were positively correlated with independent variables. It is concluded that the mental health of university students must be monitored during pandemics.

Este estudo teve como objetivo investigar os efeitos dos afetos positivos e negativos, da ansiedade e dos pensamentos e comportamentos obsessivos e compulsivos nos estudantes universitários brasileiros durante a pandemia da Covid-19. Participaram deste estudo 492 estudantes de todas as regiões do país e com idades a partir de 18 anos. A pesquisa foi realizada entre os meses de abril e maio de 2020, por meio de instrumentos de autorrelatos aplicados no formato on-line. Os resultados indicaram que 37% (N = 182) dos estudantes apresentaram alto nível de ansiedade e 46,1% (N = 227) níveis moderados para os pensamentos e comportamentos obsessivos e compulsivos. Além disso, verificou-se que os afetos positivos se relacionaram negativamente à ansiedade, assim como se relacionaram negativamente aos pensamentos e comportamentos obsessivos e compulsivos, enquanto os afetos negativos se relacionaram positivamente às variáveis independentes. Conclui-se que a saúde mental dos estudantes universitários deve ser monitorada durante pandemias.

Este estudio tuvo como objetivo investigar los efectos de los afectos positivos y negativos, la ansiedad y los pensamientos y comportamientos obsesivos y compulsivos en estudiantes universitarios brasileños durante la pandemia de Covid-19. En este estudio participaron 492 estudiantes de todas las regiones del país y mayores de 18 años. La encuesta se realizó entre los meses de abril y mayo de 2020, utilizando instrumentos se autoinforme aplicados en formato online. Los resultados indicaron que el 37% (N = 182) de los estudiantes tenían niveles altos de ansiedad y el 46,1% (N = 227) niveles moderados de pensamientos y comportamientos obsesivos y compulsivos. Además, se encontró que los afectos positivos se correlacionaron negativamente con la ansiedad, así como el pensamiento y el comportamiento obsesivo y compulsivo se correlacionaron negativamente, mientras que los afectos negativos se correlacionaron positivamente con variables independientes. Se concluye que la salud mental de los estudiantes universitarios debe ser monitoreada durante las pandemias.