The Connected We St@nd programme: A feasibility pilot study of an online self-management intervention for adults on in-centre haemodialysis and family caregivers.

OBJECTIVE: The 'Connected We St@nd' is an online self-management intervention programme for people receiving in-centre haemodialysis and family caregivers that combines an educational and psychosocial support component. This study aimed to evaluate its feasibility and acceptability before proceeding to a large-scale trial. DESIGN: This was a pre-post single-arm feasibility pilot study conducted with adults undergoing in-centre haemodialysis and family caregivers. METHODS: Feasibility was based on eligibility, consent, retention, completion and intervention adherence rates, while acceptability was assessed in post-intervention focus group interviews. RESULTS: Twenty-six people (16 adults on haemodialysis and 10 family caregivers) recruited through social networks completed the intervention. Consent, retention and completion rates were excellent (>90%) and eligibility (77.5%) and intervention adherence were satisfactory (69% for the psychosocial support sessions). Qualitative findings revealed that participants shared positive feelings regarding their participation in the programme. The valuable interactions with group peers and health psychologists during the support sessions, the perception of the adequacy and coherence of the programme's contents and materials and the participants' confidence in using the platform developed to deliver the intervention were some of the aspects highlighted as facilitators of intervention acceptability. Additionally, people on haemodialysis and caregivers reported that participation in the programme brought several educational and emotional benefits (e.g., additional disease-related knowledge, improved communication and coping skills, greater confidence in managing dialysis complications or caregiving demands) that helped increase their self-management skills and psychosocial adjustment to the demands of kidney failure and renal therapies. CONCLUSIONS: The results suggested that the 'Connected We St@nd' programme is likely to be feasible and acceptable for adults on haemodialysis and family caregivers, thus representing a promising resource for the future of interdisciplinary renal rehabilitation. Suggestions were made to fine-tune the intervention design to proceed with a large-scale trial.

Predictors of improvement in community adolescents with chronic neck pain: A secondary analysis using different improvement criteria.

BACKGROUND: Interventions based on pain neuroscience education and exercise have emerged as effective in the management of chronic neck pain in adolescents. No studies have explored factors that might be associated with recovery in adolescents with neck pain. OBJECTIVE: To explore predictors of improvement after an intervention based on exercise and pain neuroscience education. DESIGN: Secondary analysis of a randomized trial. SETTING: Community. PARTICIPANTS: 127 community adolescents with neck pain. INTERVENTIONS: Blended-learning intervention based on exercise and pain neuroscience education. MAIN OUTCOME MEASURES: A set of variables including sociodemographic data, pain characteristics, physical activity, disability, sleep, catastrophizing, fear of movement, self-efficacy, symptoms of central sensitization, knowledge of pain neuroscience, pressure pain thresholds, and neck muscles endurance were used to predict a clinical response at 1 week after intervention and at 6-month follow-up. RESULTS: Different predictors of improvement and non-improvement to intervention were found, but common predictors were not found for all the improvement criteria explored and time points. CONCLUSIONS: These findings suggest that using different criteria to characterize adolescents with neck pain as improved and non-improved after pain neuroscience education and exercise have an effect on the variables associated with a response to the intervention.

Asymmetric post-translational modifications regulate the nuclear translocation of STAT3 homodimers in response to leukemia inhibitory factor.

STAT3 is a pleiotropic transcription factor overactivated in 70% of solid tumours. We have recently reported that inactivating mutations on residues susceptible to post-translational modifications (PTMs) in only one of the monomers (i.e. asymmetric) caused changes in the cellular distribution of STAT3 homodimers. Here, we used more controlled experimental conditions, i.e. without the interference of endogenous STAT3 (STAT3-/- HeLa cells) and in the presence of a defined cytokine stimulus (Leukemia Inhibitory Factor, LIF), to provide further evidence that asymmetric PTMs affect the nuclear translocation of STAT3 homodimers. Time-lapse microscopy for 20 min after LIF stimulation showed that S727 dephosphorylation (S727A) and K685 inactivation (K685R) slightly enhanced the nuclear translocation of STAT3 homodimers, while K49 inactivation (K49R) delayed STAT3 nuclear translocation. Our findings suggest that asymmetrically modified STAT3 homodimers could be a new level of STAT3 regulation and, therefore, a potential target for cancer therapy.

Physical activity in vascular cognitive impairment: Systematic review with meta-analysis.

BACKGROUND: Vascular cognitive impairment (VCI) is the second most common cause of cognitive impairment worldwide and includes a spectrum from vascular cognitive impairment no dementia (VCIND) to vascular dementia (VaD). There is no specific pharmacological treatment approved for VCI. Physical activity has been indicated to be a promising preventive measure for cognition, with direct as indirectly benefits, while improving several modifiable vascular risk factors, so potentially effective when considering VCI. Our aim was to conduct a systematic review with a meta-analysis approaching the potential preventive role of physical activity on VCI. METHODS: A systematic search was conducted in 7 databases. A total of 6786 studies were screened and assessed for eligibility, culminating in the inclusion of 9 observational prospective studies assessing physical activity impact irrespectively the type for quality assessment and qualitative and quantitative synthesis. Quantitative synthesis was performed using the reported adjusted HRs. Physical activity was handled as a dichotomous variable, with two groups created (high versus low physical activity). Subgroup analyses were done for risk of bias, VaD and length of follow-up. RESULTS: There was considerable methodological heterogeneity across studies. Only three studies reported significant associations. The overall effect was statistically significant (HR 0.68, 95%CI 0.54-0.86, I2 6.8%), with higher levels of physical activity associated with a smaller risk of VCI overtime, particularly VaD. CONCLUSIONS: These findings suggest that physical activity is a potential preventive factor for vascular dementia. Insufficient data is available on VCIND. Randomized studies are desired to confirm these results.

Exploring the Efficacy of a Set of Smart Devices for Postural Awareness for Workers in an Industrial Context: Protocol for a Single-Subject Experimental Design.

BACKGROUND: In manufacturing industries, tasks requiring poor posture, high repetition, and long duration commonly induce fatigue and lead to an increased risk of work-related musculoskeletal disorders. Smart devices assessing biomechanics and providing feedback to the worker for correction may be a successful way to increase postural awareness, reducing fatigue, and work-related musculoskeletal disorders. However, evidence in industrial settings is lacking. OBJECTIVE: This study protocol aims to explore the efficacy of a set of smart devices to detect malposture and increase postural awareness, reducing fatigue, and musculoskeletal disorders. METHODS: A longitudinal single-subject experimental design following the ABAB sequence will be developed in a manufacturing industry real context with 5 workers. A repetitive task of screw tightening of 5 screws in a standing position into a piece placed horizontally was selected. Workers will be assessed in 4 moments per shift (10 minutes after the beginning of the shift, 10 minutes before and after the break, and 10 minutes before the end of the shift) in 5 nonconsecutive days. The primary outcomes are fatigue, assessed by electromyography, and musculoskeletal symptoms assessed by the Nordic Musculoskeletal Questionnaire. Secondary outcomes include perceived effort (Borg perceived exertion scale); range of motion of the main joints in the upper body, speed, acceleration, and deceleration assessed by motion analysis; risk stratification of range of motion; and cycle duration in minutes. Structured visual analysis techniques will be conducted to observe the effects of the intervention. Results for each variable of interest will be compared among the different time points of the work shift and longitudinally considering each assessment day as a time point. RESULTS: Enrollment for the study will start in April 2023. Results are expected to be available still in the first semester of 2023. It is expected that the use of the smart system will reduce malposture, fatigue, and consequently, work-related musculoskeletal pain and disorders. CONCLUSIONS: This proposed study will explore a strategy to increase postural awareness in industrial manufacturing workers who do repetitive tasks, using smart wearables that provide real-time feedback about biomechanics. Results would showcase a novel approach for improving self-awareness of risk for work-related musculoskeletal disorders for these workers providing an evidence base support for the use of such devices. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/43637.

Impact of different automated peritoneal dialysis modalities on the inflammatory profile of elderly patients with chronic kidney disease / Impacto das diferentes modalidades de diálise peritoneal automatizada sobre o perfil inflamatório de idosos portadores de doença renal crônica

Abstract Introduction: Chronic kidney disease, more prevalent in the elderly, is considered a public health issue worldwide. Objective: To evaluate the impact of automated, peritoneal dialysis modalities, intermittent and continuous, on the inflammatory profile of elderly people with chronic kidney disease. Methods: Prospective, cross-sectional and analytical study carried out in a dialysis clinic in Brasília - Brazil, with 74 elderly people aged 60 years or older. The patients underwent rapid Peritoneal Equilibration Test, clinical assessment, blood collection for biochemical and cytokine assessments, interleukin 6 and transforming growth factor beta 1, and answered a quality-of-life questionnaire (KDQOL-SF36). We used a 5% significance level for data analysis, associations and correlations. Results: Patients in the continuous modality had higher serum values of transforming growth factor beta 1 than those in the intermittent modality, which had higher peritoneal transforming growth factor beta 1, age and residual renal function than those in continuous mode. Interleukin 6 dosage in the peritoneum was associated with age, while serum IL-6 was associated with IL-6 in the peritoneum, time on dialysis and age. There was no association between the modality and the presence of diabetes, blood volume or nutritional status. Both modalities enable good adaptation to the dialysis treatment. Conclusion: Inflammation in automated peritoneal dialysis is mainly associated with low residual renal function, advanced age and longer time on therapy, and not to the type of dialysis performed.

Resumo Introdução: A doença renal crônica, mais prevalente em idosos, é considerada um problema de saúde pública em todo o mundo. Objetivo: Avaliar o impacto das modalidades de diálise peritoneal automatizada, intermitente e contínua, no perfil inflamatório de idosos renais crônicos. Métodos: Estudo prospectivo, transversal e analítico realizado em uma clínica de diálise em Brasília, com 74 idosos com idade igual ou maior que 60 anos. Os pacientes foram submetidos ao Teste de Equilíbrio Peritoneal rápido, avaliação clínica, coleta de sangue para avaliações bioquímicas e de citocinas, interleucina 6 e fator de crescimento transformador beta 1, e questionário de qualidade de vida (KDQOL-SF36). Foram utilizadas para análise dos dados, associações e correlações com nível de significância de 5%. Resultados: Pacientes na modalidade contínua apresentaram valores séricos do fator de crescimento transformador beta 1 maiores do que os em modalidade intermitente. Estes apresentaram fator de crescimento transformador beta 1 no peritônio, idade e função renal residual maiores do que os em modalidade contínua. A dosagem da interleucina 6 no peritônio foi associada à idade, enquanto a IL-6 sérica foi associada à IL-6 no peritônio, ao tempo em diálise e à idade. Não houve associação entre a modalidade e a presença de diabetes, volemia ou estado nutricional. Ambas as modalidades permitem boa adequação à terapia dialítica. Conclusão: A inflamação na diálise peritoneal automatizada está associada principalmente à baixa função renal residual, à idade avançada e ao maior tempo em terapia, e não à modalidade de diálise realizada.

Unveiling the membrane bound dihydroorotate: Quinone oxidoreductase from Staphylococcus aureus.

Staphylococcus aureus is an opportunistic pathogen and one of the most frequent causes for community acquired and nosocomial bacterial infections. Even so, its energy metabolism is still under explored and its respiratory enzymes have been vastly overlooked. In this work, we unveil the dihydroorotate:quinone oxidoreductase (DHOQO) from S. aureus, the first example of a DHOQO from a Gram-positive organism. This protein was shown to be a FMN containing menaquinone reducing enzyme, presenting a Michaelis-Menten behaviour towards the two substrates, which was inhibited by Brequinar, Leflunomide, Lapachol, HQNO, Atovaquone and TFFA with different degrees of effectiveness. Deletion of the DHOQO coding gene (Δdhoqo) led to lower bacterial growth rates, and effected in cell morphology and metabolism, most importantly in the pyrimidine biosynthesis, here systematized for S. aureus MW2 for the first time. This work unveils the existence of a functional DHOQO in the respiratory chain of the pathogenic bacterium S. aureus, enlarging the understanding of its energy metabolism.

Impact of different automated peritoneal dialysis modalities on the inflammatory profile of elderly patients with chronic kidney disease.

INTRODUCTION: Chronic kidney disease, more prevalent in the elderly, is considered a public health issue worldwide. OBJECTIVE: To evaluate the impact of automated, peritoneal dialysis modalities, intermittent and continuous, on the inflammatory profile of elderly people with chronic kidney disease. METHODS: Prospective, cross-sectional and analytical study carried out in a dialysis clinic in Brasília - Brazil, with 74 elderly people aged 60 years or older. The patients underwent rapid Peritoneal Equilibration Test, clinical assessment, blood collection for biochemical and cytokine assessments, interleukin 6 and transforming growth factor beta 1, and answered a quality-of-life questionnaire (KDQOL-SF36). We used a 5% significance level for data analysis, associations and correlations. RESULTS: Patients in the continuous modality had higher serum values of transforming growth factor beta 1 than those in the intermittent modality, which had higher peritoneal transforming growth factor beta 1, age and residual renal function than those in continuous mode. Interleukin 6 dosage in the peritoneum was associated with age, while serum IL-6 was associated with IL-6 in the peritoneum, time on dialysis and age. There was no association between the modality and the presence of diabetes, blood volume or nutritional status. Both modalities enable good adaptation to the dialysis treatment. CONCLUSION: Inflammation in automated peritoneal dialysis is mainly associated with low residual renal function, advanced age and longer time on therapy, and not to the type of dialysis performed.

Impact of telemedicine on metabolic control and hospitalization of peritoneal dialysis patients during the COVID-19 pandemic: a national multicentric cohort study / Impacto da telemedicina no controle metabólico e hospitalização de pacientes em diálise peritoneal durante a pandemia de COVID-19: um estudo de coorte multicêntrico nacional

Abstract Introduction: The coronavirus-19 pandemic threatens the lives of all people, but results in higher mortality rates for patients with end-stage kidney disease (ESKD) including those on peritoneal dialysis (PD). Telemedicine was the main alternative to reduce exposure to the virus, but it was introduced in the Brazil without proper training. Objective: To investigate the impact of telemedicine on metabolic control, peritonitis rates, and hospitalization in PD patients during the pandemic. Methods: This was a retrospective multicenter cohort study. We included all adult patients on chronic PD from 9 clinics selected by convenience during the pandemic. The outcomes of interest were measured and compared between before and after switching to telemedicine using repeated measure analysis and multilevel Poisson regression. Results: The study included 747 patients with a mean age of 59.7±16.6 years, of whom 53.7% were male and 40.8% had diabetes. Biochemical parameters including hemoglobin, potassium, phosphate, calcium, and urea serum levels did not change significantly after transition to telemedicine. There was no association between telemedicine and peritonitis rates. In contrast, hospitalization rates increased significantly in the telemedicine period. The incidence rate ratio (IRR) for hospitalization in the telemedicine period was 1.54 (95%CI 1.10-2.17; p 0.012) and 1.57 (95%CI 1.12-2.21; p 0.009) in the mixed-effects Poisson regression before and after adjustment for the presence of confounders. Admissions for hypervolemia and infections not related to PD doubled after transition to telemedicine. Conclusion: The implementation of telemedicine without proper training may lead to an increase in adverse events in PD patients.

Resumo Introdução: A pandemia do coronavírus-19 ameaça a vida de todas as pessoas, mas resulta em uma alta taxa de mortalidade em pacientes com doença renal em estágio terminal (DRET), incluindo aqueles em diálise peritoneal (DP). A telemedicina foi a principal alternativa para reduzir a exposição ao vírus, mas foi introduzida no Brasil sem treinamento adequado. Objetivo: Investigar o impacto da telemedicina no controle metabólico, taxas de peritonite e hospitalização em pacientes em DP na pandemia. Métodos: Estudo de coorte multicêntrico retrospectivo. Incluímos todos os pacientes adultos em DP crônica de 9 clínicas selecionadas por conveniência durante a pandemia. Desfechos de interesse foram medidos e comparados entre antes e depois da mudança para telemedicina usando análise de medidas repetidas e regressão multinível de Poisson. Resultados: Incluiu-se 747 pacientes com idade média de 59,7±16,6 anos, sendo 53,7% homens e 40,8% diabéticos. Parâmetros bioquímicos, incluindo níveis séricos de hemoglobina, potássio, fosfato, cálcio e ureia não mudaram significativamente após transição para telemedicina. Não houve associação entre telemedicina e taxas de peritonite. Em contraste, taxas de hospitalização aumentaram significativamente no período de telemedicina. A razão de taxas de incidência (RTI) para internação no período de telemedicina foi 1,54 (IC95% 1,10-2,17; p 0,012) e 1,57 (IC95% 1,12-2,21; p 0,009) na regressão multinível de Poisson antes e após ajuste para presença de fatores de confusão. As internações por hipervolemia e infecções não relacionadas à DP dobraram após transição para telemedicina. Conclusão: A implementação da telemedicina sem treinamento adequado pode levar ao aumento de eventos adversos em pacientes em DP.

Physical Activity Self-Report Is Not Reliable Among Subjects with Mild Vascular Cognitive Impairment: The AFIVASC Study.

BACKGROUND: The World Health Organization (WHO) recommends a minimum of 150 minutes of moderate physical activity per week. Adherence to these recommendations is difficult to assess. OBJECTIVE: We aimed to evaluate the validity of self-reported physical activity in mild vascular cognitive impairment (mVCI) and whether physical activity was associated with cognitive status, by using baseline data from a randomized controlled trial. METHODS: A hundred and four subjects with mVCI were included (mean age 72 years; 51% women). Subjects underwent neurological, physical, and comprehensive neuropsychological assessments. Adherence to WHO physical activity recommendations was evaluated using both self-reported information and objective measures (accelerometry). RESULTS: There was poor agreement (kappa = 0.106) between self-report of following WHO recommendations and actually fulfilling them according to accelerometry. Only 16.6% of participants reported following WHO recommendations and displayed compatible values according to the accelerometer. Participants whose accelerometry values confirmed adherence to WHO recommendations had better performance in a global measure of cognition, attention, and mental speed processing. In multiple regression analyses, education and accelerometry values in accordance with WHO recommendations were independently associated with the global measure of cognition, attention, and processing speed, controlling for sex, age, and depressive symptoms. Accelerometry results were not associated with memory and executive functions. CONCLUSION: In this sample of mVCI subjects, self-reported physical activity displayed poor agreement with accelerometry values, suggesting that objective measures of physical activity are preferable. Physical activity (performed, at least, according to WHO recommendations) was associated with better cognitive performance overall.

Impact of telemedicine on metabolic control and hospitalization of peritoneal dialysis patients during the COVID-19 pandemic: a national multicentric cohort study.

INTRODUCTION: The coronavirus-19 pandemic threatens the lives of all people, but results in higher mortality rates for patients with end-stage kidney disease (ESKD) including those on peritoneal dialysis (PD). Telemedicine was the main alternative to reduce exposure to the virus, but it was introduced in the Brazil without proper training. OBJECTIVE: To investigate the impact of telemedicine on metabolic control, peritonitis rates, and hospitalization in PD patients during the pandemic. METHODS: This was a retrospective multicenter cohort study. We included all adult patients on chronic PD from 9 clinics selected by convenience during the pandemic. The outcomes of interest were measured and compared between before and after switching to telemedicine using repeated measure analysis and multilevel Poisson regression. RESULTS: The study included 747 patients with a mean age of 59.7±16.6 years, of whom 53.7% were male and 40.8% had diabetes. Biochemical parameters including hemoglobin, potassium, phosphate, calcium, and urea serum levels did not change significantly after transition to telemedicine. There was no association between telemedicine and peritonitis rates. In contrast, hospitalization rates increased significantly in the telemedicine period. The incidence rate ratio (IRR) for hospitalization in the telemedicine period was 1.54 (95%CI 1.10-2.17; p 0.012) and 1.57 (95%CI 1.12-2.21; p 0.009) in the mixed-effects Poisson regression before and after adjustment for the presence of confounders. Admissions for hypervolemia and infections not related to PD doubled after transition to telemedicine. CONCLUSION: The implementation of telemedicine without proper training may lead to an increase in adverse events in PD patients.

Crosstalk between Yeast Cell Plasma Membrane Ergosterol Content and Cell Wall Stiffness under Acetic Acid Stress Involving Pdr18.

Acetic acid is a major inhibitory compound in several industrial bioprocesses, in particular in lignocellulosic yeast biorefineries. Cell envelope remodeling, involving cell wall and plasma membrane composition, structure and function, is among the mechanisms behind yeast adaptation and tolerance to stress. Pdr18 is a plasma membrane ABC transporter of the pleiotropic drug resistance family and a reported determinant of acetic acid tolerance mediating ergosterol transport. This study provides evidence for the impact of Pdr18 expression in yeast cell wall during adaptation to acetic acid stress. The time-course of acetic-acid-induced transcriptional activation of cell wall biosynthetic genes (FKS1, BGL2, CHS3, GAS1) and of increased cell wall stiffness and cell wall polysaccharide content in cells with the PDR18 deleted, compared to parental cells, is reported. Despite the robust and more intense adaptive response of the pdr18Δ population, the stress-induced increase of cell wall resistance to lyticase activity was below parental strain levels, and the duration of the period required for intracellular pH recovery from acidification and growth resumption was higher in the less tolerant pdr18Δ population. The ergosterol content, critical for plasma membrane stabilization, suffered a drastic reduction in the first hour of cultivation under acetic acid stress, especially in pdr18Δ cells. Results revealed a crosstalk between plasma membrane ergosterol content and cell wall biophysical properties, suggesting a coordinated response to counteract the deleterious effects of acetic acid.

Security Mechanisms of a Mobile Health Application for Promoting Physical Activity among Older Adults.

Physical activity contributes to the maintenance of health conditions and functioning. However, the percentage of older adults who comply with the recommendations for physical activity levels is low when compared to the same percentages on younger groups. The SmartWalk system aims to encourage older adults to perform physical activity (i.e., walking in the city), which is monitored and adjusted by healthcare providers for best results. The study reported in this article focused on the implementation of SmartWalk security services to keep personal data safe during communications and while at rest, which were validated considering a comprehensive use case. The security framework offers various mechanisms, including an authentication system that was designed to complement the pairs of usernames and passwords with trusted execution environments and token-based features, authorization with different access levels, symmetric and asymmetric key cryptography, critical transactions review, and logging supported by blockchain technology. The resulting implementation contributes for a common understanding of the security features of trustful smart cities' applications, which conforms with existing legislation and regulations.

Dynamic interactions and Ca2+-binding modulate the holdase-type chaperone activity of S100B preventing tau aggregation and seeding.

The microtubule-associated protein tau is implicated in the formation of oligomers and fibrillar aggregates that evade proteostasis control and spread from cell-to-cell. Tau pathology is accompanied by sustained neuroinflammation and, while the release of alarmin mediators aggravates disease at late stages, early inflammatory responses encompass protective functions. This is the case of the Ca2+-binding S100B protein, an astrocytic alarmin which is augmented in AD and which has been recently implicated as a proteostasis regulator, acting over amyloid ß aggregation. Here we report the activity of S100B as a suppressor of tau aggregation and seeding, operating at sub-stoichiometric conditions. We show that S100B interacts with tau in living cells even in microtubule-destabilizing conditions. Structural analysis revealed that tau undergoes dynamic interactions with S100B, in a Ca2+-dependent manner, notably with the aggregation prone repeat segments at the microtubule binding regions. This interaction involves contacts of tau with a cleft formed at the interface of the S100B dimer. Kinetic and mechanistic analysis revealed that S100B inhibits the aggregation of both full-length tau and of the microtubule binding domain, and that this proceeds through effects over primary and secondary nucleation, as confirmed by seeding assays and direct observation of S100B binding to tau oligomers and fibrils. In agreement with a role as an extracellular chaperone and its accumulation near tau positive inclusions, we show that S100B blocks proteopathic tau seeding. Together, our findings establish tau as a client of the S100B chaperone, providing evidence for neuro-protective functions of this inflammatory mediator across different tauopathies.

Yeast adaptive response to acetic acid stress involves structural alterations and increased stiffness of the cell wall.

This work describes a coordinate and comprehensive view on the time course of the alterations occurring at the level of the cell wall during adaptation of a yeast cell population to sudden exposure to a sub-lethal stress induced by acetic acid. Acetic acid is a major inhibitory compound in industrial bioprocesses and a widely used preservative in foods and beverages. Results indicate that yeast cell wall resistance to lyticase activity increases during acetic acid-induced growth latency, corresponding to yeast population adaptation to sudden exposure to this stress. This response correlates with: (i) increased cell stiffness, assessed by atomic force microscopy (AFM); (ii) increased content of cell wall ß-glucans, assessed by fluorescence microscopy, and (iii) slight increase of the transcription level of the GAS1 gene encoding a ß-1,3-glucanosyltransferase that leads to elongation of (1→3)-ß-D-glucan chains. Collectively, results reinforce the notion that the adaptive yeast response to acetic acid stress involves a coordinate alteration of the cell wall at the biophysical and molecular levels. These alterations guarantee a robust adaptive response essential to limit the futile cycle associated to the re-entry of the toxic acid form after the active expulsion of acetate from the cell interior.

User-Centered Development of a Mobile App for Biopsychosocial Pain Assessment in Adults: Usability, Reliability, and Validity Study.

BACKGROUND: Pain-related mobile apps targeting pain assessment commonly limit pain assessment to pain behaviors and physiological aspects. However, current guidelines state that pain assessment should follow the biopsychosocial model, clearly addressing biological, psychological, and social aspects of the pain experience. Existing reviews also highlight that pain specialists and end users are not commonly involved in the development process of mobile apps for pain assessment, negatively affecting the quality of the available apps. OBJECTIVE: This study aimed to develop a mobile app for pain assessment (AvaliaDor) and assess its usability, validity, reliability, and measurement error in a sample of real patients with chronic pain recruited from a physiotherapy clinic. METHODS: This study was divided into 2 phases: phase 1-development of the AvaliaDor app; and phase 2-assessment of the apps' usability, reliability, measurement error, and validity. AvaliaDor was developed (phase 1) based on the literature and the recommendations of physiotherapists and patients with pain in cycles of evaluation, inclusion of recommendations, and reevaluation until no further changes were required. The final version of the app was then tested in patients with musculoskeletal pain attending a private physiotherapy practice (phase 2) who were asked to use the app twice on 2 consecutive days for reliability purposes. In addition, participants had to complete a set of paper-based scales (Brief Pain Inventory, painDETECT, Pain Catastrophizing Scale, and Tampa Scale for Kinesiophobia), which were used to assess the validity (criterion validity and hypothesis testing) of the app, and the Post-Study System Usability Questionnaire was used to assess its usability. RESULTS: The development process (phase 1) included 5 physiotherapists external to the research team and 5 patients with musculoskeletal pain, and it resulted in the creation of an app named AvaliaDor, which includes an assessment of pain intensity, location, and phenotype; associated disability; and the issues of pain catastrophizing and fear of movement. A total of 52 patients with pain (mean age 50.12 years, SD 11.71 years; 39 females) participated in phase 2 and used the app twice. The Pearson correlation coefficient between the scores on the paper-based scales and the app ranged between 0.81 and 0.93 for criterion validity and between 0.41 and 0.59 for hypothesis testing. Test-retest reliability was moderate to good (intraclass correlation coefficient between 0.67 and 0.90) and the score for usability was 1.16 (SD 0.27), indicating good usability. CONCLUSIONS: A mobile app named AvaliaDor was developed to assess the intensity, location, and phenotype of pain; associated disability; and the issues of pain catastrophizing and fear of movement in a user-centered design process. The app was shown to be usable, valid, and reliable for assessing pain from a biopsychosocial perspective in a heterogeneous group of patients with pain. Future work can explore the long-term use of AvaliaDor in clinical contexts and its advantages for the assessment and management of patients with pain.

Cu2+-binding to S100B triggers polymerization of disulfide cross-linked tetramers with enhanced chaperone activity against amyloid-ß aggregation.

S100B is an extracellular protein implicated in Alzheimer's Disease and a suppressor of amyloid-ß aggregation. Herein we report a mechanism tying Cu2+ binding to a change in assembly state yielding disulfide cross-linked oligomers with higher anti-aggregation activity. This chemical control of chaperone function illustrates a regulatory process relevant under metal and proteostasis dysfunction as in neurodegeneration.

Impact of dementia on informal care: a systematic review of family caregivers' perceptions.

INTRODUCTION: Caregivers play a major role in providing all the support and care in daily activities for their relatives with dementia. To fully describe the influence of dementia caregiving on family caregivers' life, we conducted a systematic review including caregivers' perceptions about the positive and negative aspects of caring and the expressed factors. MATERIALS AND METHODS: We conducted a systematic review including articles from January 1998 to July 2020. Qualitative studies reporting family caregivers' perceptions about their experiences and the effects/impact of dementia caregiving were eligible. Two authors extracted the data independently, and the analysis focused on the positive and negative aspects of dementia caregiving in caregivers' life. RESULTS: Eighty-one studies with 3347 participants were included in this review. The positive aspects of caregiving in caregivers' life encompass personal accomplishment and strengthening relationships, which were enhanced by good medical counselling/formal care support and family/friends support. The negative aspects included emotional and social aspects experienced by caregivers. Other factors such as inappropriate medical/formal care support, illness progression and the costs of dementia contributed to negative appraisal. DISCUSSION AND IMPLICATIONS: The findings provide insights into the holistic experience of caring for a person with dementia revelling the major positive and negative aspects underlying the caregiver role. The evidence emphasises the need 'to focus on positive aspects' and targeted interventions aimed at reducing the negative impact of caregiving, which has serious consequences on caregivers' quality of life. A multicomplex intervention for dementia informal caregiving should be developed, committing the society to promote mental health, address these community needs and improve the quality of life of the person with dementia and their family caregivers.

The S100B Alarmin Is a Dual-Function Chaperone Suppressing Amyloid-ß Oligomerization through Combined Zinc Chelation and Inhibition of Protein Aggregation.

Amyloid beta (Aß) aggregation and imbalance of metal ions are major hallmarks of Alzheimer's disease (AD). Indeed, amyloid plaques of AD patients are enriched in zinc and Aß42, and AD related-cognitive decline is dependent on extracellular zinc concentration. In vitro, zinc induces the formation of polymorphic Aß42 oligomers that delay the formation of amyloid fibers at the expense of increased cellular toxicity. S100B is an inflammatory alarmin and one of the most abundant proteins in the brain and is upregulated in AD and associated with amyloid plaques, where it exerts extracellular functions. Recent findings have uncovered novel neuroprotective functions for S100B as a suppressor of Aß aggregation and toxicity and in the regulation of zinc homeostasis in neurons. Here we combine biophysical and kinetic approaches to demonstrate that such S100B protective functions converge, making the protein a dual-function chaperone capable of suppressing the formation of toxic Aß oligomers through both chelation of zinc and inhibition of protein aggregation. From detailed kinetic analysis of Aß42 aggregation monitoring ThT fluorescence, we show that substoichiometric S100B prevents the formation of toxic off-pathway oligomers that are formed by monomeric Aß42 in the presence of zinc. Indeed, S100B is effective when added during the lag and transition phases of Aß42 aggregation, and its action under these circumstances results from its ability to buffer zinc, as it perfectly mimics the effect obtained with the chelating agent EDTA. Further, bioimaging analysis combining transmission electron microscopy and atomic force microscopy confirms that catalytic amounts of S100B partly revert the formation of toxic oligomers. Taken together these results indicate a new role for S100B as a dual chaperone whose distinct functions are interrelated and depend on the relative levels of zinc, S100B, and Aß, which dynamically evolve during AD.