Macromolecular condensation buffers intracellular water potential.

Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive protein folding and macromolecular interactions1. Reciprocally, macromolecules restrict the movement of 'structured' water molecules within their hydration layers, reducing the available 'free' bulk solvent and therefore the total thermodynamic potential energy of water, or water potential. Here, within concentrated macromolecular solutions such as the cytosol, we found that modest changes in temperature greatly affect the water potential, and are counteracted by opposing changes in osmotic strength. This duality of temperature and osmotic strength enables simple manipulations of solvent thermodynamics to prevent cell death after extreme cold or heat shock. Physiologically, cells must sustain their activity against fluctuating temperature, pressure and osmotic strength, which impact water availability within seconds. Yet, established mechanisms of water homeostasis act over much slower timescales2,3; we therefore postulated the existence of a rapid compensatory response. We find that this function is performed by water potential-driven changes in macromolecular assembly, particularly biomolecular condensation of intrinsically disordered proteins. The formation and dissolution of biomolecular condensates liberates and captures free water, respectively, quickly counteracting thermal or osmotic perturbations of water potential, which is consequently robustly buffered in the cytoplasm. Our results indicate that biomolecular condensation constitutes an intrinsic biophysical feedback response that rapidly compensates for intracellular osmotic and thermal fluctuations. We suggest that preserving water availability within the concentrated cytosol is an overlooked evolutionary driver of protein (dis)order and function.

CRYPTOCHROMES promote daily protein homeostasis.

The daily organisation of most mammalian cellular functions is attributed to circadian regulation of clock-controlled protein expression, driven by daily cycles of CRYPTOCHROME-dependent transcriptional feedback repression. To test this, we used quantitative mass spectrometry to compare wild-type and CRY-deficient fibroblasts under constant conditions. In CRY-deficient cells, we found that temporal variation in protein, phosphopeptide, and K+ abundance was at least as great as wild-type controls. Most strikingly, the extent of temporal variation within either genotype was much smaller than overall differences in proteome composition between WT and CRY-deficient cells. This proteome imbalance in CRY-deficient cells and tissues was associated with increased susceptibility to proteotoxic stress, which impairs circadian robustness, and may contribute to the wide-ranging phenotypes of CRY-deficient mice. Rather than generating large-scale daily variation in proteome composition, we suggest it is plausible that the various transcriptional and post-translational functions of CRY proteins ultimately act to maintain protein and osmotic homeostasis against daily perturbation.

CRYPTOCHROMES confer robustness, not rhythmicity, to circadian timekeeping.

Circadian rhythms are a pervasive property of mammalian cells, tissues and behaviour, ensuring physiological adaptation to solar time. Models of cellular timekeeping revolve around transcriptional feedback repression, whereby CLOCK and BMAL1 activate the expression of PERIOD (PER) and CRYPTOCHROME (CRY), which in turn repress CLOCK/BMAL1 activity. CRY proteins are therefore considered essential components of the cellular clock mechanism, supported by behavioural arrhythmicity of CRY-deficient (CKO) mice under constant conditions. Challenging this interpretation, we find locomotor rhythms in adult CKO mice under specific environmental conditions and circadian rhythms in cellular PER2 levels when CRY is absent. CRY-less oscillations are variable in their expression and have shorter periods than wild-type controls. Importantly, we find classic circadian hallmarks such as temperature compensation and period determination by CK1δ/ε activity to be maintained. In the absence of CRY-mediated feedback repression and rhythmic Per2 transcription, PER2 protein rhythms are sustained for several cycles, accompanied by circadian variation in protein stability. We suggest that, whereas circadian transcriptional feedback imparts robustness and functionality onto biological clocks, the core timekeeping mechanism is post-translational.

Association of healthy lifestyle behaviours with incident irritable bowel syndrome: a large population-based prospective cohort study.

OBJECTIVES: To evaluate the association between healthy lifestyle behaviours and the incidence of irritable bowel syndrome (IBS). DESIGN: Population-based prospective cohort study. SETTING: The UK Biobank. PARTICIPANTS: 64 268 adults aged 37 to 73 years who had no IBS diagnosis at baseline were enrolled between 2006 and 2010 and followed up to 2022. MAIN EXPOSURE: The five healthy lifestyle behaviours studied were never smoking, optimal sleep, high level of vigorous physical activity, high dietary quality and moderate alcohol intake. MAIN OUTCOME MEASURE: The incidence of IBS. RESULTS: During a mean follow-up of 12.6 years, 961 (1.5%) incident IBS cases were recorded. Among the 64 268 participants (mean age 55.9 years, 35 342 (55.0%) female, 7604 (11.8%) reported none of the five healthy lifestyle behaviours, 20 662 (32.1%) reported 1 behaviour, 21 901 (34.1%) reported 2 behaviours and 14 101 (21.9%) reported 3 to 5 behaviours at baseline. The multivariable adjusted hazard ratios associated with having 1, 2 and 3 to 5 behaviours for IBS incidence were 0.79 (95% confidence intervals 0.65 to 0.96), 0.64 (0.53 to 0.78) and 0.58 (0.46 to 0.72), respectively (P for trend <0.001). Never smoking (0.86, 0.76 to 0.98, P=0.02), high level of vigorous physical activity (0.83, 0.73 to 0.95, P=0.006) and optimal sleep (0.73, 0.60 to 0.88, P=0.001) demonstrated significant independent inverse associations with IBS incidence. No significant interactions were observed between these associations and age, sex, employment status, geographic location, gastrointestinal infection, endometriosis, family history of IBS or lifestyle behaviours. CONCLUSIONS: Adhering to a higher number of healthy lifestyle behaviours is significantly associated with a lower incidence of IBS in the general population. Our findings suggest the potential of lifestyle modifications as a primary prevention strategy for IBS.

The Provision and Perceptions of Telemedicine Services Among Traditional Chinese Medicine Practitioners During COVID-19: A Cross-Sectional Study in Hong Kong, China.

Objectives: Telemedicine has been widely used during the COVID-19 pandemic. Among other health care professionals, Chinese medicine practitioners (CMPs) face practical challenges in providing telemedicine consultations. This study aims to explore CMPs' experience and perceptions of telemedicine service provision before and during the pandemic. Methods: A territory-wide cross-sectional online survey was conducted in Hong Kong between April and May 2022. A structured questionnaire with open-ended questions was used to investigate the provision of and perception on telemedicine service, as well as usability of telemedicine among CMPs. Results: A total of 195 CMPs participated the survey. Before COVID-19, 42% (81/195) had been providing telemedicine services, and the proportion doubled during COVID-19. CMPs in the private sector are the main providers. Mobile apps including WhatsApp, WeChat, and Zoom were commonly used for consultations (75%, 120/161). Barriers in providing telemedicine included inability of conducting physical examination on patients (69%, 134/195), legal and ethical concerns over medical negligence (61%, 118/195), and patients' incompetence on e-literacy (50%, 98/195). Respondents urged professional and regulatory bodies to provide an explicit clinical guideline that demonstrate best practice in traditional Chinese medicine telemedicine, and to clarify legal and ethical implications of such practice. Conclusions: CMPs demonstrated their competency in telemedicine, and most of them provided telemedicine during COVID-19. Development of appropriate guidelines on the provision of telemedicine would support CMPs to continue provision after the pandemic, whereas a user-friendly and comprehensive telemedicine e-platform would enhance quality of such service. Facilitating patients with lower e-literacy to access telemedicine is key to reduce disparities.

Person-Specific Template Matching Using a Dynamic Time Warping Step-Count Algorithm for Multiple Walking Activities.

This study aimed to develop and evaluate a new step-count algorithm, StepMatchDTWBA, for the accurate measurement of physical activity using wearable devices in both healthy and pathological populations. We conducted a study with 30 healthy volunteers wearing a wrist-worn MOX accelerometer (Maastricht Instruments, NL). The StepMatchDTWBA algorithm used dynamic time warping (DTW) barycentre averaging to create personalised templates for representative steps, accounting for individual walking variations. DTW was then used to measure the similarity between the template and accelerometer epoch. The StepMatchDTWBA algorithm had an average root-mean-square error of 2 steps for healthy gaits and 12 steps for simulated pathological gaits over a distance of about 10 m (GAITRite walkway) and one flight of stairs. It outperformed benchmark algorithms for the simulated pathological population, showcasing the potential for improved accuracy in personalised step counting for pathological populations. The StepMatchDTWBA algorithm represents a significant advancement in accurate step counting for both healthy and pathological populations. This development holds promise for creating more precise and personalised activity monitoring systems, benefiting various health and wellness applications.

The Application of Artificial Intelligence in Digital Physical Activity and Falls Prevention Interventions for Older Adults.

This article discusses the practical applications of artificial intelligence in digital physical activity and falls prevention interventions for older adults. It notes the range of technologies that can be used to collect digital datasets on older adult health and how machine learning algorithms can be applied to these to improve our understanding of physical activity and falls. In particular, these advanced computational techniques could help personalize exercises, feedback, and notifications to older people, improve adherence to and reduce attrition from digital health interventions, and enhance monitoring by providing predictive analytics on the physiological and environmental conditions that contribute to physical activity and falls in aging populations.

Prognostic value of patient-reported outcome measures (PROMs) in adults with non-small cell Lung Cancer: a scoping review.

BACKGROUND: There is growing interest in the collection and use of patient-reported outcome measures (PROMs) to support clinical decision making in patients with non-small cell lung cancer (NSCLC). However, an overview of research into the prognostic value of PROMs is currently lacking. AIM: To explore to what extent, how, and how robustly the value of PROMs for prognostic prediction has been investigated in adults diagnosed with NSCLC. METHODS: We systematically searched Medline, Embase, CINAHL Plus and Scopus for English-language articles published from 2011 to 2021 that report prognostic factor study, prognostic model development or validation study. Example data charting forms from the Cochrane Prognosis Methods Group guided our data charting on study characteristics, PROMs as predictors, predicted outcomes, and statistical methods. Two reviewers independently charted the data and critically appraised studies using the QUality In Prognosis Studies (QUIPS) tool for prognostic factor studies, and the risk of bias assessment section of the Prediction model Risk Of Bias ASsessment Tool (PROBAST) for prognostic model studies. RESULTS: Our search yielded 2,769 unique titles of which we included 31 studies, reporting the results of 33 unique analyses and models. Out of the 17 PROMs used for prediction, the EORTC QLQ-C30 was most frequently used (16/33); 12/33 analyses used PROM subdomain scores instead of the overall scores. PROMs data was mostly collected at baseline (24/33) and predominantly used to predict survival (32/33) but seldom other clinical outcomes (1/33). Almost all prognostic factor studies (26/27) had moderate to high risk of bias and all four prognostic model development studies had high risk of bias. CONCLUSION: There is an emerging body of research into the value of PROMs as a prognostic factor for survival in people with NSCLC but the methodological quality of this research is poor with significant bias. This warrants more robust studies into the prognostic value of PROMs, in particular for predicting outcomes other than survival. This will enable further development of PROM-based prediction models to support clinical decision making in NSCLC.

Understanding How the Design and Implementation of Online Consultations Affect Primary Care Quality: Systematic Review of Evidence With Recommendations for Designers, Providers, and Researchers.

BACKGROUND: Online consultations (OCs) allow patients to contact their care providers on the web. Worldwide, OCs have been rolled out in primary care rapidly owing to policy initiatives and COVID-19. There is a lack of evidence regarding how OC design and implementation influence care quality. OBJECTIVE: We aimed to synthesize research on the impacts of OCs on primary care quality, and how these are influenced by system design and implementation. METHODS: We searched databases from January 2010 to February 2022. We included quantitative and qualitative studies of real-world OC use in primary care. Quantitative data were transformed into qualitative themes. We used thematic synthesis informed by the Institute of Medicine domains of health care quality, and framework analysis informed by the nonadoption, abandonment, scale-up, spread, and sustainability framework. Strength of evidence was judged using the GRADE-CERQual approach. RESULTS: We synthesized 63 studies from 9 countries covering 31 OC systems, 14 (22%) of which used artificial intelligence; 41% (26/63) of studies were published from 2020 onward, and 17% (11/63) were published after the COVID-19 pandemic. There was no quantitative evidence for negative impacts of OCs on patient safety, and qualitative studies suggested varied perceptions of their safety. Some participants believed OCs improved safety, particularly when patients could describe their queries using free text. Staff workload decreased when sufficient resources were allocated to implement OCs and patients used them for simple problems or could describe their queries using free text. Staff workload increased when OCs were not integrated with other software or organizational workflows and patients used them for complex queries. OC systems that required patients to describe their queries using multiple-choice questionnaires increased workload for patients and staff. Health costs decreased when patients used OCs for simple queries and increased when patients used them for complex queries. Patients using OCs were more likely to be female, younger, and native speakers, with higher socioeconomic status. OCs increased primary care access for patients with mental health conditions, verbal communication difficulties, and barriers to attending in-person appointments. Access also increased by providing a timely response to patients' queries. Patient satisfaction increased when using OCs owing to better primary care access, although it decreased when using multiple-choice questionnaire formats. CONCLUSIONS: This is the first theoretically informed synthesis of research on OCs in primary care and includes studies conducted during the COVID-19 pandemic. It contributes new knowledge that, in addition to having positive impacts on care quality such as increased access, OCs also have negative impacts such as increased workload. Negative impacts can be mitigated through appropriate OC system design (eg, free text format), incorporation of advanced technologies (eg, artificial intelligence), and integration into technical infrastructure (eg, software) and organizational workflows (eg, timely responses). TRIAL REGISTRATION: PROSPERO CRD42020191802; https://tinyurl.com/2p84ezjy.

Artificial intelligence for falls management in older adult care: A scoping review of nurses' role.

AIM: This study aims to synthesize evidence on nurses' involvement in artificial intelligence research for managing falls in older adults. BACKGROUND: Artificial intelligence techniques are used to analyse health datasets to aid clinical decision making, patient care and service delivery but nurses' involvement in this area of research for managing falls in older adults remains unknown. EVALUATION: A scoping review was conducted. CINAHL, the Cochrane Library, Embase, MEDLI and PubMed were searched. Results were screened against inclusion criteria. Relevant data were extracted, and studies summarized using a descriptive approach. KEY ISSUES: The evidence shows many artificial intelligence techniques, particularly machine learning, are used to identify falls risk factors and build predictive models that could help prevent falls in older adults, with nurses leading and participating in this research. CONCLUSION: Further rigorous experimental research is needed to determine the effectiveness of algorithms in predicting aspects of falls in older adults and how to implement artificial intelligence tools in gerontological nursing practice. IMPLICATIONS FOR NURSING MANAGEMENT: Nurses should pursue interdisciplinary collaborations and educational opportunities in artificial intelligence, so they can actively contribute to research on falls management. Nurses should facilitate the collection of digital falls datasets to support this emerging research agenda and the care of older adults.

The promise of artificial intelligence: a review of the opportunities and challenges of artificial intelligence in healthcare.

INTRODUCTION: Artificial intelligence (AI) and machine learning (ML) are rapidly evolving fields in various sectors, including healthcare. This article reviews AI's present applications in healthcare, including its benefits, limitations and future scope. SOURCES OF DATA: A review of the English literature was conducted with search terms 'AI' or 'ML' or 'deep learning' and 'healthcare' or 'medicine' using PubMED and Google Scholar from 2000-2021. AREAS OF AGREEMENT: AI could transform physician workflow and patient care through its applications, from assisting physicians and replacing administrative tasks to augmenting medical knowledge. AREAS OF CONTROVERSY: From challenges training ML systems to unclear accountability, AI's implementation is difficult and incremental at best. Physicians also lack understanding of what AI implementation could represent. GROWING POINTS: AI can ultimately prove beneficial in healthcare, but requires meticulous governance similar to the governance of physician conduct. AREAS TIMELY FOR DEVELOPING RESEARCH: Regulatory guidelines are needed on how to safely implement and assess AI technology, alongside further research into the specific capabilities and limitations of its medical use.

A new approach for health-oriented ozone control strategy: Adjoint-based optimization of NOx emission reductions using metaheuristic algorithms.

While levels of particulate matters in the Pearl River Delta Region (PRD) show a significant reduction, ozone (O3) has an opposite increasing trend, becoming the critical air quality target in this decade. Emission control strategies are typically formulated sector by sector, spatial variability in emissions reductions and health impacts of air pollutants may not be taken into account, affecting the overall effectiveness of control strategies. This study proposes an adjoint-based optimization framework to facilitate health-oriented O3 control over PRD. The location-specific adjoint sensitivity coefficients, which reflect the spatiotemporal influences from emissions of nitrogen dioxide (NOx) on O3 health impacts, are combined with metaheuristic algorithms to minimize the O3-related premature mortalities over receptor regions. Using the proposed optimization methodology, the regional O3 health benefits under current emission reduction policy can be increased by 16-27%. The results show that relatively larger NOx emissions reductions occurred at highly developed and populated areas. Particularly, significant reductions in NOx emissions are observed at Shenzhen and urban Guangzhou. Furthermore, implementing regional NOx emissions abatement has advantages to achieve an overall O3 health benefits for all cities. The interregional influences of NOx emissions abatement between cities indicate a promising strategy of health-oriented O3 control in PRD.

PROMs for Pain in Adult Cancer Patients: A Systematic Review of Measurement Properties.

CONTEXT: Pain is one of the most devastating symptoms for cancer patients. One third of patients who experience pain do not receive effective treatment. A key barrier to effective pain management is lack of routine measurement and monitoring of pain. Patient-reported outcome measures (PROMs) are recommended for measuring cancer pain. However, evidence to guide the selection of the most appropriate measure to identify and monitor cancer pain is limited. A systematic review of measurement properties of PROMs for pain in cancer patients is needed to identify the best validated measure for adoption to an electronic platform. OBJECTIVES: To systematically review measurement properties of PROMs used for adult cancer patients to measure pain and, as a secondary goal, to investigate the evidence of validated mobile health (mHealth) applications used to measure pain (registration number: CRD42017065575). METHODS: Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were systematically searched in March 2018 for studies examining measurement properties for PROMs for pain in adult cancer patients. The methodological quality of the studies and their results were appraised using the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and specific measurement properties criteria, respectively. RESULTS: Sixteen studies evaluating 8 instruments were included. No studies using a PROM in an mHealth application were identified. The methodological quality of the measurement properties ranged between poor and fair. No instrument showed strong positive evidence for all the evaluated measurement properties. Based on the available evidence, the Brief Pain Inventory-Short Form (BPI-SF) had the strongest evidence to support its selection for the measurement of cancer pain. CONCLUSION: The BPI-SF was the best performing measure across all properties evaluated through COSMIN. Better quality validation studies of PROMs for cancer pain are needed to explore the full range of measurement properties. Utilizing mHealth applications to measure pain in cancer patients is an innovative approach worthy of further investigation.

Intracardiac Leiomyomatosis - an Unusual Cause of Syncope in a Middle-Aged Woman.

Intracardiac leiomyomatosis is a rare complication that occurs when a uterine leiomyoma (fibroid) undergoes vascular invasion and propagates within the inferior vena cava to reach the right atrium. This article describes a case of intracardiac leiomyomatosis in a middle-aged woman, exploring the presentation, diagnosis and surgical management of this condition. In this case the presenting complaints were syncope and atrial fibrillation, illustrating the importance of performing a transthoracic echocardiogram in patients presenting with their first episode of atrial fibrillation. Clinicians should consider intracardiac leiomyomatosis when evaluating women with right heart masses, especially those with a history of uterine leiomyomas.

High reduction of ozone and particulate matter during the 2016 G-20 summit in Hangzhou by forced emission controls of industry and traffic.

Many regions in China experience air pollution episodes because of the rapid urbanization and industrialization over the past decades. Here we analyzed the effect of emission controls implemented during the G-20 2016 Hangzhou summit on air quality. Emission controls included a forced closure of highly polluting industries, and limiting traffic and construction emissions in the cities and surroundings. Particles with aerodynamic diameter lower than 2.5 µm (PM2.5) and ozone (O3) were measured. We also simulated air quality using a forecast system consisting of the two-way coupled Weather Research and Forecast and Community Multi-scale Air Quality (WRF-CMAQ) model. Results show PM2.5 and ozone levels in Hangzhou during the G-20 Summit were considerably lower than previous to the G-20 Summit. The predicted concentrations of ozone were reduced by 25.4%, whereas the predicted concentrations of PM2.5 were reduced by 56%.

Unexpected Benefits of Reducing Aerosol Cooling Effects.

Impacts of aerosol cooling are not limited to changes in surface temperature since modulation of atmospheric dynamics resulting from the increased stability can deteriorate local air quality and impact human health. Health impacts from two manifestations of the aerosol direct effects (ADE) are estimated in this study: (1) the effect on surface temperature and (2) the effect on air quality through atmospheric dynamics. Average mortalities arising from the enhancement of surface PM2.5 concentration due to ADE in East Asia, North America and Europe are estimated to be 3-6 times higher than reduced mortality from decreases of temperature due to ADE. Our results suggest that mitigating aerosol pollution is beneficial in decreasing the impacts of climate change arising from these two manifestations of ADE health impacts. Thus, decreasing aerosol pollution gets direct benefits on health, and indirect benefits on health through changes in local climate and not offsetting changes associated only with temperature modulations as traditionally thought. The modulation of air pollution due to ADE also translates into an additional human health dividend in regions (e.g., U.S. Europe) with air pollution control measures but a penalty for regions (e.g., Asia) witnessing rapid deterioration in air quality.

Depressive Symptoms Delayed Quit Attempts and Shortened Abstinence in Young Smokers of the Hong Kong Youth Quitline.

INTRODUCTION: Young smokers often report depressive symptoms while receiving smoking cessation counseling. This study examines time patterns in the quitting process among young smokers with or without notable depressive symptoms. METHODS: The quitting trajectories of young smokers aged 12 to 25 (n = 578) who called the Youth Quitline in Hong Kong between March 2006 and May 2011 were recorded and analyzed through multiple telephone sessions over periods of up to 6 months. The time patterns of young smokers who had or did not have notable depressive symptoms were compared using nonparametric Kaplan-Meier methods with log-rank tests. RESULTS: Among young smokers with low levels of nicotine dependence, those who had notable depressive symptoms were less likely to initiate a quit attempt within 28 days after their baseline telephone intervention (probability = .38 vs. .60; P value = .04). Furthermore, young smokers who had notable depressive symptoms were less likely to remain abstinent from smoking for 2 days after starting a quit attempt (probability = .50 vs. .64; P value = .012). Young adults aged 18 or above were more likely to relapse into smoking (adjusted HR = 1.50, 95% CI = 1.01, 2.22). CONCLUSIONS: Depressive symptoms may delay young smokers from initiating quit attempts and shorten their abstinence. A baseline screening process is suggested for identifying youths with co-occurring depressive disorder and nicotine dependence. Further studies should examine a collaborative model of smoking cessation that involves both counselors and physicians in preventing young smokers from rapid relapses after they make quit attempts.

A block randomized controlled trial of a brief smoking cessation counselling and advice through short message service on participants who joined the Quit to Win Contest in Hong Kong.

The present trial examined the effectiveness of brief interventions for smokers who joined the Hong Kong Quit to Win Contest to quit smoking. A block randomized controlled trial allocated 1003 adult daily smokers to three groups: (i) The TEL group (n = 338) received a 5-min nurse-led telephone counselling; (ii) The SMS group (n = 335) received eight text messages through mobile phone and (iii) The CONTROL group (n = 330) did not receive the above interventions. Participants with biochemically verified abstinence at 6-month follow-up could receive cash incentive. The primary outcome was the self-reported 7-day point prevalence (PP) of tobacco abstinence at 6-month follow-up. The abstinence rate in the TEL, SMS and CONTROL group was 22.2, 20.6 and 20.3%, respectively (P for TEL versus CONTROL = 0.32; P for SMS versus CONTROL = 0.40). When abstinence at 2-, 6- and 12-month follow-up was modelled simultaneously, the TEL group had a higher abstinence than the CONTROL group (Adjusted OR = 1.38, 95% CI = 1.01-1.88, P = 0 .04). In the Quit to Win Contest, the brief telephone counselling might have increased abstinence, but the text messages had no significant effect. Further studies on intensive intervention and interactive messaging services are warranted.