Platelet-derived microparticles and their cargos: The past, present and future.

All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Platelets form platelet-derived microparticles (PMPs) in response to activation, injury, or apoptosis. This review introduces the origin, pathway, and biological functions of PMPs and their importance in physiological and pathological processes. In addition, we review the potential applications of PMPs in cancer, vascular homeostasis, thrombosis, inflammation, neural regeneration, biomarkers, and drug carriers to achieve targeted drug delivery. In addition, we comprehensively report on the origin, biological functions, and applications of PMPs. The clinical transformation, high heterogeneity, future development direction, and limitations of the current research on PMPs are also discussed in depth. Evidence has revealed that PMPs play an important role in cell-cell communication, providing clues for the development of PMPs as carriers for relevant cell-targeted drugs. The development history and prospects of PMPs and their cargos are explored in this guidebook.

Trends in severe functional limitations among working and non-working adults in Germany: Towards an (un)-healthy working life?

We examined trends in severe functional limitations among working and non-working adults in Germany (ages 40-65). Four population-based samples of 11,615 participants were used, spanning the time periods 2002-2021. The overall prevalence of severe limitations was found to be 12.8% in the sample, but also varied from 10 to 20% according to occupational group. Over time, severe limitations were found to have increased, from 10.6% in 2002 to 13.2% in 2021. Logistic regression analysis showed that severe limitations increased significantly in certain subgroups, including working women with a low skilled white collar occupational group, working men with a low skilled blue collar occupational group and, particularly, among the whole non-working population, whereas limitations remained largely the same in the other groups, including most of the working population. In terms of expectancies, overall working life expectancy increased. Along with this increase, healthy (non-severely limited) working life expectancy increased, but this trend was accompanied by a clear increase in unhealthy working life expectancy (severely limited). Thus, although severe limitations have increased in some groups in the working-age adults, people today can expect to work more years free from severe limitations than before. In the future, potentials to increase working life expectancy may come to an end, as severe limitations increased strongly in the non-working population, which could limit the prospects for a further increase in the proportion of the population in employment. Further studies are needed to investigate the potential impact of the increasing prevalence of severe limitations on the population's ability to work.

Advances in Biosensors for the Rapid Detection of Marine Biotoxins: Current Status and Future Perspectives.

Marine biotoxins (MBs), harmful metabolites of marine organisms, pose a significant threat to marine ecosystems and human health due to their diverse composition and widespread occurrence. Consequently, rapid and efficient detection technology is crucial for maintaining marine ecosystem and human health. In recent years, rapid detection technology has garnered considerable attention for its pivotal role in identifying MBs, with advancements in sensitivity, specificity, and accuracy. These technologies offer attributes such as speed, high throughput, and automation, thereby meeting detection requirements across various scenarios. This review provides an overview of the classification and risks associated with MBs. It briefly outlines the current research status of marine biotoxin biosensors and introduces the fundamental principles, advantages, and limitations of optical, electrochemical, and piezoelectric biosensors. Additionally, the review explores the current applications in the detection of MBs and presents forward-looking perspectives on their development, which aims to be a comprehensive resource for the design and implementation of tailored biosensors for effective MB detection.

Incident Functional Limitations Among Older Adults With Diabetes During the COVID-19 Pandemic: An Analysis of Prospective Data From the Canadian Longitudinal Study on Aging.

OBJECTIVES: The objectives of this study were: 1) to examine and compare changes in functional limitations during the COVID-19 pandemic among older adults with and without diabetes; and 2): to identify key risk factors associated with developing functional limitations among older adults with and without diabetes during the pandemic. METHODS: We analyzed data collected from the Canadian Longitudinal Study on Aging. The analysis was restricted to those with no functional limitations in the follow-up 1 wave (2015 to 2018) (final sample N=6,045). Regression models were used to describe associations between diabetic status and functional limitation outcomes. We conducted stratified analyses to evaluate whether these associations varied by sociodemographic indicators. We also predicted the probability of the development of ≥1 functional limitation among those with and without diabetes for various patient profiles. RESULTS: Older adults with diabetes were 1.28-fold (95% confidence interval 1.02 to 1.60) more likely to develop ≥1 functional limitation than older adults without diabetes after controlling for relevant sociodemographic and health covariates. Risk factors for incident functional limitations among older adults, both with and without diabetes, include increasing age, low socioeconomic status, obesity, multimorbidity, and physical inactivity. CONCLUSIONS: Our findings indicate that older adults with diabetes were at an increased risk of developing functional limitations during the pandemic when compared with older adults without diabetes, even when controlling for several key risk factors. Targetting modifiable risk factors, such as physical activity, may help to reduce the risk of functional limitations among older adults with diabetes.

Craniocervical instability in patients with Ehlers­Danlos syndromes: outcomes analysis following occipito­cervical fusion of published cases.

This critique provides a critical analysis of the outcomes following occipito-cervical fusion in patients with Ehlers-Danlos syndromes (EDS) and craniocervical instability. The study examines the efficacy of the surgical intervention and evaluates its impact on patient outcomes. While the article offers valuable insights into the management of EDS-related craniocervical instability, several limitations and areas for improvement are identified, including sample size constraints, the absence of a control group, and the need for long-term follow-up data. Future research efforts should focus on addressing these concerns to optimize treatment outcomes for individuals with EDS.

Association of cancer diagnosis with disability status among older survivors of colorectal cancer: a population-based retrospective cohort study.

Background: Older cancer survivors likely experience physical function limitations due to cancer and its treatments, leading to disability and early mortality. Existing studies have focused on factors associated with surgical complications and mortality risk rather than factors associated with the development of poor disability status (DS), a proxy measure of poor performance status, in cancer survivors. We aimed to identify factors associated with the development of poor DS among older survivors of colorectal cancer (CRC) and compare poor DS rates to an age-sex-matched, non-cancer cohort. Methods: This retrospective cohort study utilized administrative data from the Texas Cancer Registry Medicare-linked database. The study cohort consisted of 13,229 survivors of CRC diagnosed between 2005 and 2013 and an age-sex-matched, non-cancer cohort of 13,225 beneficiaries. The primary outcome was poor DS, determined by Davidoff's method, using predictors from 12 months of Medicare claims after cancer diagnosis. Multivariable Cox proportional hazards regression was used to identify risk factors associated with the development of poor DS. Results: Among the survivors of CRC, 97% were 65 years or older. After a 9-year follow-up, 54% of survivors of CRC developed poor DS. Significant factors associated with future poor DS included: age at diagnosis (hazard ratio [HR] = 3.50 for >80 years old), female sex (HR = 1.50), race/ethnicity (HR = 1.34 for Hispanic and 1.21 for Black), stage at diagnosis (HR = 2.26 for distant metastasis), comorbidity index (HR = 2.18 for >1), and radiation therapy (HR = 1.21). Having cancer (HR = 1.07) was significantly associated with developing poor DS in the pooled cohorts; age and race/ethnicity were also significant factors. Conclusions: Our findings suggest that a CRC diagnosis is independently associated with a small increase in the risk of developing poor DS after accounting for other known factors. The study identified risk factors for developing poor DS in CRC survivors, including Hispanic and Black race/ethnicity, age, sex, histologic stage, and comorbidities. These findings underscore the importance of consistent physical function assessments, particularly among subsets of older survivors of CRC who are at higher risk of disability, to prevent developing poor DS.

Limitations and Complications in Treating Femoral Neck Fractures with the Femoral Neck System: A Case Report.

Introduction: The femoral neck system (FNS) represents an emerging fixation system designed for the management of femoral neck fractures. This innovative system combines the mechanical benefits of compression and anti-rotation properties in internal fixation. Biomechanical studies have demonstrated the superior axial and rotational stability of the FNS implant when compared to traditional cannulated screws and dynamic hip screw. Despite these promising mechanical advantages, there is currently a limited body of literature addressing the factors contributing to FNS failure. A thorough assessment of the safety and outcomes associated with this novel implant is essential. Case Report: In this context, we present three cases wherein FNS failure occurred, aiming to elucidate the potential causes behind these failures, and had to undergo either an implant removal or bipolar hemiarthroplasty. Conclusion: While considering the femoral neck system as the implant of choice, we should consider the age, injury to surgery time, and the location of the fracture line. However, we cannot conclusively ascertain whether age contributes independently to the risk of failure.

Time Limited Benefits of Physical and Proprioceptive Training on Physical Fitness Components in Children With Autism Spectrum Disorders.

In this study, we explored the immediate and three-month follow-up effects of physical training on physical fitness in children with autism spectrum disorder (ASD). We randomly assigned 20 children with ASD (age 8-11 years) into an experimental group (EG; n = 10) and a control group (CG; n = 10). The EG participated in an 8-week training program involving both strength and proprioceptive exercises (three 60-minute sessions/week), while the CG simply maintained their daily activities. We assessed physical fitness components for each participant at baseline, post-training, and at a 3-month follow-up. The physical training intervention significantly improved physical fitness of these children with ASD in terms of their flexibility (p < .001; 32.46%), lower limbs strength (p = .003; 36.98%), lower body power (p < .001; 41.78%) and functional mobility (p < .001; 25.56%). However, these addition training-induced gains were lost at follow-up for lower limbs strength (p < .001), flexibility (p < .001), and functional mobility (p = .034)). Physical training was effective for improving physical fitness in children with ASD, but the loss of these gains at three months follow-up underscored the need for continuous physical exercise.

Brain organoid protocols and limitations.

Stem cell-derived organoid technology is a powerful tool that revolutionizes the field of biomedical research and extends the scope of our understanding of human biology and diseases. Brain organoids especially open an opportunity for human brain research and modeling many human neurological diseases, which have lagged due to the inaccessibility of human brain samples and lack of similarity with other animal models. Brain organoids can be generated through various protocols and mimic whole brain or region-specific. To provide an overview of brain organoid technology, we summarize currently available protocols and list several factors to consider before choosing protocols. We also outline the limitations of current protocols and challenges that need to be solved in future investigation of brain development and pathobiology.

Latest updates on structure and recommendations of cardiac rehabilitation programs in chronic heart failure.

Chronic heart failure (HF) is a clinical syndrome with high morbidity and mortality worldwide. Cardiac rehabilitation (CR) is a medically supervised program designed to maintain or improve cardiovascular health of people living with HF, recommended by both American and European guidelines. A CR program consists of a multispecialty group including physicians, nurses, physiotherapists, trainers, nutritionists, and psychologists with the common purpose of improving functional capacity and quality of life of chronic HF patients. Physical activity, lifestyle, and psychological support are core components of a successful CR program. CR has been shown to be beneficial in all ejection fraction categories in HF and most patients, who are stable under medication, are capable of participating. An individualized exercise prescription should be developed on the basis of a baseline evaluation in all patients. The main modalities of exercise training are aerobic exercise and muscle strength training of different intensity and frequency. It is important to set the appropriate clinical outcomes from the beginning, in order to assess the effectiveness of a CR program. There are still significant limitations that prevent patients from participating in these programs and need to be solved. A significant limitation is the generally low quality of research in CR and the presence of negative trials, such as the rehabilitation after myocardial infarction trial, where comprehensive rehabilitation following myocardial infraction had no important effect on mortality, morbidity, risk factors, or health-related quality of life or activity. In the present editorial, we present all the updated knowledge and recommendations in CR programs.

[How has life expectancy without functional limitations developed in Germany? An analysis with data from the German Ageing Survey (DEAS)]. / Wie hat sich die Lebenserwartung ohne funktionelle Einschränkungen in Deutschland entwickelt? Eine Analyse mit Daten des Deutschen Alterssurveys (DEAS).

INTRODUCTION: The long-term increase in life expectancy raises the question of whether the increased life expectancy is accompanied by an extension of years without health limitations. The study analyzes how life expectancy without functional and mobility limitations from the ages of 46 and 65 and their proportions of remaining life expectancy have changed since 2008. METHODS: We analyze data from the German Ageing Survey of the 2008, 2014, and 2020/21 waves. Life expectancy without functional limitations (disability-free life expectancy-DFLE) was calculated using the Sullivan method. Severe functional limitations (using the Global Activity Limitation Indicator-GALI) and mobility limitations (climbing stairs, walking more than 1 km) were examined. RESULTS: Compression of morbidity in the GALI has been observed in 46- and 65-year-old men since 2014, but not in women of the same age. In terms of mobility, 46- and 65-year-old men show trends towards compression when climbing stairs and 46-year-old men when walking more than 1 km since 2014. The values for women have stagnated for the first two indicators mentioned, but not for 46-year-old women since 2014 when walking more than 1 km. DISCUSSION: Our analyses show different trends in DFLE depending on the indicator, age, and gender and do not allow a clear answer to the question of morbidity compression or expansion. We tend to see morbidity compression in men, whereas trends of stagnation or expansion tend to be seen in women. These results signal challenges in maintaining functional health, especially in women, and point to the need for targeted interventions to improve quality of life and healthy life expectancy.

Polyethylene microplastics alter root functionality and affect strawberry plant physiology and fruit quality traits.

Strawberry, a globally popular crop whose fruit are known for their taste and health benefits, were used to evaluate the effects of polyethylene microplastics (PE-MPs) on plant physiology and fruit quality. Plants were grown in 2-L pots with natural soil mixed with PE-MPs at two concentrations (0.2% and 0.02%; w/w) and sizes (⌀ 35 and 125 µm). Plant physiological responses, root histochemical and anatomical analyses as well as fruit biometric and quality features were conducted. Plants subjected to ⌀ 35 µm/0.2% PE-MPs exhibited the most severe effects in terms of CO2 assimilation due to stomatal limitations, along with the highest level of oxidative stress in roots. Though no differences were observed in plant biomass, the impact on fruit quality traits was severe in ⌀ 35 µm/0.2% MPs treatment resulting in a drop in fruit weight (-42%), soluble solid (-10%) and anthocyanin contents (-25%). The smallest sized PE-MPs, adsorbed on the root surface, impaired plant water status by damaging the radical apparatus, which finally resulted in alteration of plant physiology and fruit quality. Further research is required to determine if these alterations also occur with other MPs and to understand more deeply the MPs influence on fruit physio-chemistry.

Letter to editor : comparison of the surgical outcomes of the posterior approach, video­assisted thoracic surgery, and combined approach for thoracic dumbbell tumors based on a new classification: a retrospective study of published cases.

This critique evaluates a retrospective study comparing surgical outcomes for thoracic dumbbell tumors utilizing different approaches. The study provides comprehensive insights into the management of this complex condition, highlighting the strengths and weaknesses of its methodology and findings. While the study offers valuable information for guiding clinical practice, its retrospective design and inherent limitations warrant careful interpretation of the results. Addressing these limitations through prospective studies with randomized designs and larger patient populations could further enhance our understanding of the optimal surgical approach for thoracic dumbbell tumors.

Tools for assessing the methodological limitations of a QES-a short note.

The increasing prevalence and application of qualitative evidence syntheses (QES) in decision-making processes underscore the need for robust tools to assess the methodological limitations of a completed QES. This commentary discusses the limitations of three existing tools and presents the authors' efforts to address this gap. Through a simple comparative analysis, the three tools are examined in terms of their coverage of essential topic areas. The examination finds that existing assessment tools lack comprehensive coverage, clarity, and grounding in qualitative research principles. The authors advocate for the development of a new collaboratively developed evidence-based tool rooted in qualitative methodology and best practice methods. The conclusion emphasizes the necessity of a tool that can provide a comprehensive judgement on the methodological limitations of a QES, addressing the needs of end-users, and ultimately enhancing the trustworthiness of QES findings in decision-making processes.

Optimizing Care Delivery in Patients with Chronic Kidney Disease in the United States: Proceedings of a Multidisciplinary Roundtable Discussion and Literature Review.

BACKGROUND: Approximately 37 million individuals in the United States (US) have chronic kidney disease (CKD). Patients with CKD have a substantial morbidity and mortality, which contributes to a huge economic burden to the healthcare system. A limited number of clinical pathways or defined workflows exist for CKD care delivery in the US, primarily due to a lower prioritization of CKD care within health systems compared with other areas (e.g., cardiovascular disease [CVD], cancer screening). CKD is a public health crisis and by the year 2040, CKD will become the fifth leading cause of years of life lost. It is therefore critical to address these challenges to improve outcomes in patients with CKD. METHODS: The CKD Leaders Network conducted a virtual, 3 h, multidisciplinary roundtable discussion with eight subject-matter experts to better understand key factors impacting CKD care delivery and barriers across the US. A premeeting survey identified topics for discussion covering the screening, diagnosis, risk stratification, and management of CKD across the care continuum. Findings from this roundtable are summarized and presented herein. RESULTS: Universal challenges exist across health systems, including a lack of awareness amongst providers and patients, constrained care team bandwidth, inadequate financial incentives for early CKD identification, non-standardized diagnostic classification and triage processes, and non-centralized patient information. Proposed solutions include highlighting immediate and long-term financial implications linked with failure to identify and address at-risk individuals, identifying and managing early-stage CKD, enhancing efforts to support guideline-based education for providers and patients, and capitalizing on next-generation solutions. CONCLUSIONS: Payers and other industry stakeholders have opportunities to contribute to optimal CKD care delivery. Beyond addressing the inadequacies that currently exist, actionable tactics can be implemented into clinical practice to improve clinical outcomes in patients at risk for or diagnosed with CKD in the US.

A Comprehensive Review of Inhaled Nitric Oxide Therapy: Current Trends, Challenges, and Future Directions.

This comprehensive review explores the multifaceted landscape of inhaled nitric oxide (iNO) therapy, tracing its historical evolution, mechanisms of action, clinical applications, challenges, and future directions. The nitric oxide signaling pathway, characterized by vasodilatory effects and anti-inflammatory properties, forms the foundation of iNO's therapeutic efficacy. Clinical applications are found in neonatal respiratory distress syndrome, pulmonary hypertension, and acute respiratory distress syndrome, showcasing its versatility. However, challenges, including cost considerations, technical intricacies, safety concerns, and resistance, highlight the nuanced landscape surrounding iNO therapy. Implications for clinical practice underscore the need for a tailored and evidence-based approach, considering individual patient characteristics and indications. Recommendations for future research emphasize ongoing exploration, novel indications, and the development of targeted therapies. In conclusion, this review positions iNO as a dynamic and adaptable intervention, poised to reshape therapeutic strategies and enhance patient outcomes in critical care.

A landscape of recent advances in lipid nanoparticles and their translational potential for the treatment of solid tumors.

Lipid nanoparticles (LNPs) are biocompatible drug delivery systems that have found numerous applications in medicine. Their versatile nature enables the encapsulation and targeting of various types of medically relevant molecular cargo, including oligonucleotides, proteins, and small molecules for the treatment of diseases, such as cancer. Cancers that form solid tumors are particularly relevant for LNP-based therapeutics due to the enhanced permeation and retention effect that allows nanoparticles to accumulate within the tumor tissue. Additionally, LNPs can be formulated for both locoregional and systemic delivery depending on the tumor type and stage. To date, LNPs have been used extensively in the clinic to reduce systemic toxicity and improve outcomes in cancer patients by encapsulating chemotherapeutic drugs. Next-generation lipid nanoparticles are currently being developed to expand their use in gene therapy and immunotherapy, as well as to enable the co-encapsulation of multiple drugs in a single system. Other developments include the design of targeted LNPs to specific cells and tissues, and triggerable release systems to control cargo delivery at the tumor site. This review paper highlights recent developments in LNP drug delivery formulations and focuses on the treatment of solid tumors, while also discussing some of their current translational limitations and potential opportunities in the field.

Interactive boxing-cycling on frailty and activity limitations in frail and prefrail older adults: A randomized controlled trial.

BACKGROUND: Frailty is common among older adults, often associated with activity limitations during physical and walking tasks. The interactive boxing-cycling combination has the potential to be an innovative and efficient training method, and our hypothesis was that interactive boxing-cycling would be superior to stationary cycling in improving frailty and activity limitations in frail and prefrail older adults. OBJECTIVE: To examine the impact of interactive boxing-cycling on frailty and activity limitations in frail and prefrail older adults compared to stationary cycling. MATERIALS AND METHODS: A single-blinded randomized controlled trial. Forty-five participants who met at least one frailty phenotype criteria were randomly assigned to receive either interactive boxing-cycling (n = 23) or stationary-cycling (n = 22) for 36 sessions over 12 weeks. The interactive boxing-cycling was performed on a cycle boxer bike with an interactive boxing panel fixed in front of the bike. The primary outcomes were frailty status, including score and phenotypes. Secondary outcomes included activity limitations during physical and walking tasks. The pre- and post-intervention data of both groups were analyzed using a repeated measures two-way ANOVA. RESULTS: Both types of cycling significantly improved frailty scores (p<0.001). Interactive boxing-cycling was more effective than stationary cycling in reversing the frailty phenotype of muscle weakness (p = 0.03, odds ratio 9.19) and demonstrated greater improvements than stationary cycling in arm curl (p = 0.002, η2=0.20), functional reach (p = 0.001, η2=0.22), and grip strength (p = 0.02, η2=0.12) tests. Additionally, interactive boxing-cycling exhibited a greater effect on gait speed (p = 0.02, η2=0.13) and gait variability (p = 0.01, η2=0.14) during dual-task walking. CONCLUSION: In frail and prefrail older adults, interactive boxing-cycling effectively improves frailty but is not superior to stationary cycling. However, it is more effective at improving certain activity limitations. REGISTRATION NUMBER: TCTR20220328001.