Assessing the performance of AI chatbots in answering patients' common questions about low back pain.

OBJECTIVES: The aim of this study was to assess the accuracy and readability of the answers generated by large language model (LLM)-chatbots to common patient questions about low back pain (LBP). METHODS: This cross-sectional study analysed responses to 30 LBP-related questions, covering self-management, risk factors and treatment. The questions were developed by experienced clinicians and researchers and were piloted with a group of consumer representatives with lived experience of LBP. The inquiries were inputted in prompt form into ChatGPT 3.5, Bing, Bard (Gemini) and ChatGPT 4.0. Responses were evaluated in relation to their accuracy, readability and presence of disclaimers about health advice. The accuracy was assessed by comparing the recommendations generated with the main guidelines for LBP. The responses were analysed by two independent reviewers and classified as accurate, inaccurate or unclear. Readability was measured with the Flesch Reading Ease Score (FRES). RESULTS: Out of 120 responses yielding 1069 recommendations, 55.8% were accurate, 42.1% inaccurate and 1.9% unclear. Treatment and self-management domains showed the highest accuracy while risk factors had the most inaccuracies. Overall, LLM-chatbots provided answers that were 'reasonably difficult' to read, with a mean (SD) FRES score of 50.94 (3.06). Disclaimer about health advice was present around 70%-100% of the responses produced. CONCLUSIONS: The use of LLM-chatbots as tools for patient education and counselling in LBP shows promising but variable results. These chatbots generally provide moderately accurate recommendations. However, the accuracy may vary depending on the topic of each question. The reliability level of the answers was inadequate, potentially affecting the patient's ability to comprehend the information.

Organelle-Targeting Polymer Dots Exhibiting Thermally Activated Delayed Fluorescence for Subcellular Imaging.

Selective imaging of specific subcellular structures provides valuable information about the cellular microenvironment. Materials exhibiting thermally activated delayed fluorescence (TADF) are rapidly emerging as metal-free probes with long-lived emission for intracellular time-gated imaging applications. Polymers incorporating TADF emitters can self-assemble into luminescent nanoparticles, termed polymer dots (Pdots), and this strategy enables them to circumvent the limitations of commercial organelle trackers and small molecule TADF emitters. In this study, diblock copolymers comprised of a hydrophilic block containing organelle-targeting monomers and a hydrophobic TADF-active block were synthesized by ring-opening metathesis polymerization (ROMP). Oxanorbornene-based monomers incorporating morpholine and triphenylphosphonium groups for lysosome and mitochondria targeting, respectively, were also synthesized. ROMP by sequential addition yielded well-defined diblock copolymers with dispersities <1.28. To analyze the effect of tuning the hydrophilic corona on cellular viability and uptake, we prepared Pdots with poly(ethylene glycol) (PEG) and bis-guanidinium (BGN) coronas, resulting in limited and efficient cellular uptake, respectively. Red-emissive Pdots with BGN-based coronas and organelle-targeting functionality were obtained with quantum yields up to 12% in water under air. Colocalization analysis confirmed that lysosome and mitochondria labeling in live HeLa cells was accomplished within 2 h of incubation, affording Pearson's correlation coefficients of 0.37 and 0.70, respectively. The potential application of these Pdots for time-resolved imaging is highlighted by a proof of concept using time-gated spectroscopy, which effectively separates the delayed emission of the TADF Pdots from the background autofluorescence of biological serum.

Surgeon and Care Team Network Measures and Timely Breast Cancer Treatment.

Importance: Cancer treatment delay is a recognized marker of worse outcomes. Timely treatment may be associated with physician patient-sharing network characteristics, yet this remains understudied. Objective: To examine the associations of surgeon and care team patient-sharing network measures with breast cancer treatment delay. Design, Setting, and Participants: This cross-sectional study of Medicare claims in a US population-based setting was conducted from 2017 to 2020. Eligible participants included patients with breast cancer who received surgery and the subset who went on to receive adjuvant therapy. Patient-sharing networks were constructed for treating physicians. Data were analyzed from September 2023 to February 2024. Exposures: Surgeon linchpin score (a measure of local uniqueness or scarcity) and care density (a measure of physician team familiarity) were assessed. Surgeons were considered linchpins if their linchpin score was in the top 15%. The care density of a patient's physician team was calculated on preoperative teams for surgically-treated patients and postoperative teams for adjuvant therapy-receiving patients. Main Outcomes and Measures: The primary outcomes were surgical and adjuvant delay, which were defined as greater than 60 days between biopsy and surgery and greater than 60 days between surgery and adjuvant therapy, respectively. Results: The study cohort included 56 433 patients (18 004 aged 70-74 years [31.9%]) who were mostly from urban areas (44 931 patients [79.6%]). Among these patients, 8009 (14.2%) experienced surgical delay. Linchpin surgeon status (locally unique surgeon) was not statistically associated with surgical delay; however, patients with high preoperative care density (ie, high team familiarity) had lower odds of surgical delay compared with those with low preoperative care density (odds ratio [OR], 0.58; 95% CI, 0.53-0.63). Of the 29 458 patients who received adjuvant therapy after surgery, 5700 (19.3%) experienced adjuvant delay. Patients with a linchpin surgeon had greater odds of adjuvant delay compared with those with a nonlinchpin surgeon (OR, 1.30; 95% CI, 1.13-1.49). Compared with those with low postoperative care density, there were lower odds of adjuvant delay for patients with high postoperative care density (OR, 0.77; 95% CI, 0.69-0.87) and medium postoperative care density (OR, 0.85; 95% CI, 0.77-0.94). Conclusions and Relevance: In this cross-sectional study of Medicare claims, network measures capturing physician scarcity and team familiarity were associated with timely treatment. These results may help guide system-level interventions to reduce cancer treatment delays.

Implementation of back to living well, a community-based program for the tertiary prevention of low back pain: a study protocol.

BACKGROUND: The current literature supports the effectiveness of exercise, education, and self-management interventions for the long-term management of persistent low back pain. However, there is significant uncertainty about the implementation of interventions related to barriers, facilitators, and patient's preferences. This study will evaluate the Back to Living Well program implementation from a participant and organizational perspective. More specifically we address the following objectives: 1) identify program barriers and facilitators from participants' perspectives, 2) identify factors related to program, personal and contextual factors that contribute to negative and positive outcomes, and outcome trajectories, 3) identify factors influencing participants' selection of an in-person or e-health program, and 4) evaluate program specific barriers and facilitators from the organization and care delivery perspectives. METHODS: This study will utilize a mixed-method convergent design including a longitudinal cohort strand and a longitudinal qualitative interview strand. The RE-AIM framework will be used to assess program implementation. Participants (n = 90, 1:1: in person or virtual) who choose to register in the program as well as staff (n = 10 to 15) involved in the delivery of the program will be invited to participate. Participants will participate in a 12-week physical activity, education, and self-management program. Implementation outcomes will be measured at 3-, 6-, 12-months, and six months after the end of the follow-ups. Interview scripts and directed content analysis will be constructed based on the Theoretical Domains Framework and the Neuromatrix Model of Pain, Theoretical Domains Framework. Staff interviews will be constructed and analyzed using the Consolidated Framework for Implementation Research. Participants will also complete pain, disability, quality of life and psychological questionnaires, wear an activity tracker at all time points, and complete weekly pain and activity limitation questions using a mobile application. DISCUSSION: The study results will provide evidence to inform potential future implementation of the program. An effective, appropriately targeted, and well implemented exercise program for the long-term management (i.e., tertiary prevention) of LBP could minimize the burden of the condition on patients, the health care system and society. TRIAL REGISTRATION: ClinicalTrials.gov NCT05929846. This (Registration Date: July 3 2023) study has been approved by the Hamilton Integrated Research Ethics Board Project ID#15,354.

Chitosan Coating as a Strategy to Increase Postemergent Herbicidal Efficiency and Alter the Interaction of Nanoatrazine with Bidens pilosa Plants.

The atrazine nanodelivery system, composed of poly(ε-caprolactone) (PCL+ATZ) nanocapsules (NCs), has demonstrated efficient delivery of the active ingredient to target plants in previous studies, leading to greater herbicide effectiveness than conventional formulations. Established nanosystems can be enhanced or modified to generate new biological activity patterns. Therefore, this study aimed to evaluate the effect of chitosan coating of PCL+ATZ NCs on herbicidal activity and interaction mechanisms with Bidens pilosa plants. Chitosan-coated NCs (PCL/CS+ATZ) were synthesized and characterized for size, zeta potential, polydispersity, and encapsulation efficiency. Herbicidal efficiency was assessed in postemergence greenhouse trials, comparing the effects of PCL/CS+ATZ NCs (coated), PCL+ATZ NCs (uncoated), and conventional atrazine (ATZ) on photosystem II (PSII) activity and weed control. Using a hydroponic system, we evaluated the root absorption and shoot translocation of fluorescently labeled NCs. PCL/CS+ATZ presented a positive zeta potential (25 mV), a size of 200 nm, and an efficiency of atrazine encapsulation higher than 90%. The postemergent herbicidal activity assay showed an efficiency gain of PSII activity inhibition of up to 58% compared to ATZ and PCL+ATZ at 96 h postapplication. The evaluation of weed control 14 days after application ratified the positive effect of chitosan coating on herbicidal activity, as the application of PCL/CS+ATZ at 1000 g of a.i. ha-1 resulted in better control than ATZ at 2000 g of a.i. ha-1 and PCL+ATZ at 1000 g of a.i. ha-1. In the hydroponic experiment, chitosan-coated NCs labeled with a fluorescent probe accumulated in the root cortex, with a small quantity reaching the vascular cylinder and leaves up to 72 h after exposure. This behavior resulted in lower leaf atrazine levels and PSII inhibition than ATZ. In summary, chitosan coating of nanoatrazine improved the herbicidal activity against B. pilosa plants when applied to the leaves but negatively affected the root-to-shoot translocation of the herbicide. This study opens avenues for further investigations to improve and modify established nanosystems, paving the way for developing novel biological activity patterns.

Exercises for the prevention of non-specific low back pain.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effects of exercise alone or exercise plus education compared with inactive control or education alone to prevent non-specific LBP.

Alcohol withdrawal and amphetamine co-use in an animal model for attention deficit hyperactivity disorder.

Background: Non-medical use of amphetamine and other stimulants prescribed for treatment of attention deficit/hyperactivity disorder (ADHD) is of special concern when combined with alcohol consumption. In a previous study, we modeled chronic ethanol-amphetamine co-use in adolescent Long-Evans (LE) rats and provided evidence that amphetamine attenuates alcohol withdrawal symptoms.Objectives: This project modeled co-use of amphetamine with alcohol in adolescents with ADHD-like symptoms by examining ethanol-amphetamine administration in adolescent Spontaneously Hypertensive Rats (SHR), an experimental model for the study of ADHD. Withdrawal symptoms were compared among SHR and two control rat strains, LE and Wistar Kyoto (WKY).Methods: At postnatal day 32, parallel groups of 12-24 male SHR, WKY and LE rats were administered a liquid diet containing ethanol (3.6%) and/or amphetamine (20 mg/L). Following administration periods up to 26 days, rats were withdrawn from their treatment and tested for overall severity of alcohol withdrawal symptoms, general locomotor activity, and anxiety-like behavior.Results: Overall withdrawal severity was lower for SHR than for LE (p < .001) or WKY (p = .027). Co-consumption of amphetamine decreased withdrawal severity for LE (p = .033) and WKY (p = .011) but not SHR (p = .600). Only WKY showed increased anxiety-like behavior during withdrawal (p = .031), but not after amphetamine co-administration (p = .832).Conclusion: Alcohol withdrawal severity may be attenuated when co-used with amphetamine. However, as a model for ADHD, SHR adolescents appeared resistant to developing significant signs of alcohol withdrawal following alcohol consumption. Whether alcohol withdrawal symptoms are attenuated or absent, potential consequences could include a decreased awareness of an emerging problem with alcohol use.

The Association Between Oncology Outreach and Timely Treatment for Rural Patients with Breast Cancer: A Claims-Based Approach.

BACKGROUND: Oncology outreach is a common strategy for increasing rural access to cancer care, where traveling oncologists commute across healthcare settings to extend specialized care. Examining the extent to which physician outreach is associated with timely treatment for rural patients is critical for informing outreach strategies. METHODS: We identified a 100% fee-for-service sample of incident breast cancer patients from 2015 to 2020 Medicare claims and apportioned them into surgery and adjuvant therapy cohorts based on treatment history. We defined an outreach visit as the provision of care by a traveling oncologist at a clinic outside of their primary hospital service area. We used hierarchical logistic regression to examine the associations between patient receipt of preoperative care at an outreach visit (preoperative outreach) and > 60-day surgical delay, and patient receipt of postoperative care at an outreach visit (postoperative outreach) and > 60-day adjuvant delay. RESULTS: We identified 30,337 rural-residing patients who received breast cancer surgery, of whom 4071 (13.4%) experienced surgical delay. Among surgical patients, 14,501 received adjuvant therapy, of whom 2943 (20.3%) experienced adjuvant delay. In adjusted analysis, we found that patient receipt of preoperative outreach was associated with reduced odds of surgical delay (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.61-0.91); however, we found no association between patient receipt of postoperative outreach and adjuvant delay (OR 1.04, 95% CI 0.85-1.25). CONCLUSIONS: Our findings indicate that preoperative outreach is protective against surgical delay. The traveling oncologists who enable such outreach may play an integral role in catalyzing the coordination and timeliness of patient-centered care.

Polymer Dots with Delayed Fluorescence and Tunable Cellular Uptake for Photodynamic Therapy and Time-Gated Imaging.

By combining bioimaging and photodynamic therapy (PDT), it is possible to treat cancer through a theranostic approach with targeted action for minimum invasiveness and side effects. Thermally activated delayed fluorescence (TADF) probes have gained recent interest in theranostics due to their ability to generate singlet oxygen (1O2) while providing delayed emission that can be used in time-gated imaging. However, it is still challenging to design systems that simultaneously show (1) high contrast for imaging, (2) low dark toxicity but high phototoxicity and (3) tunable biological uptake. Here, we circumvent shortcomings of TADF systems by designing block copolymers and their corresponding semiconducting polymer dots (Pdots) that encapsulate a TADF dye in the core and expose an additional boron-dipyrromethene (BODIPY) oxygen sensitizer in the corona. This architecture provides orange-red luminescent particles (ΦPL up to 18 %) that can efficiently promote PDT (1O2 QY=42 %) of HeLa cells with very low photosensitizer loading (IC50 ~0.05-0.13 µg/mL after 30 min). Additionally, we design Pdots with tunable cellular uptake but similar PDT efficiencies using either polyethylene glycol or guanidinium-based coronas. Finally, we demonstrate that these Pdots can be used for time-gated imaging to effectively filter out background fluorescence from biological samples and improve image contrast.

Characterizing the Traveling Oncology Workforce and Its Influence on Patient Travel Burden: A Claims-Based Approach.

PURPOSE: Oncology outreach is a common strategy for extending cancer care to rural patients. However, a nationwide characterization of the traveling workforce that enables this outreach is lacking, and the extent to which outreach reduces travel burden for rural patients is unknown. METHODS: This cross-sectional study analyzed a rural (nonurban) subset of a 100% fee-for-service sample of 355,139 Medicare beneficiaries with incident breast, colorectal, and lung cancers. Surgical, medical, and radiation oncologists were linked to patients using Part B claims, and traveling oncologists were identified by observing hospital service area (HSA) transition patterns. We defined oncology outreach as the provision of cancer care by a traveling oncologist outside of their primary HSA. We used hierarchical gamma regression models to examine the separate associations between patient receipt of oncology outreach and one-way patient travel times to chemotherapy, radiotherapy, and surgery. RESULTS: On average, 9,935 of 39,960 oncologists conducted annual outreach, where 57.8% traveled with low frequency (0-1 outreach visits/mo), 21.1% with medium frequency (1-3 outreach visits/mo), and 21.1% with high frequency (>3 outreach visits/mo). Oncologists provided surgery, radiotherapy, and chemotherapy to 51,715, 27,120, and 5,874 rural beneficiaries, respectively, of whom 2.5%, 6.9%, and 3.6% received oncology outreach. Rural patients who received oncology outreach traveled 16% (95% CI, 11 to 21) and 11% (95% CI, 9 to 13) less minutes to chemotherapy and radiotherapy than those who did not receive oncology outreach, corresponding to expected one-way savings of 15.9 (95% CI, 15.5 to 16.4) and 11.9 (95% CI, 11.7 to 12.2) minutes, respectively. CONCLUSION: Our study introduces a novel claims-based approach for tracking the nationwide traveling oncology workforce and supports oncology outreach as an effective means for improving rural access to cancer care.

Evaluation of methodological and reporting quality of systematic reviews on conservative non-pharmacological musculoskeletal pain management in children and adolescents: A methodological analysis.

BACKGROUND: There are no studies investigating the methodological and report quality of systematic reviews of non-pharmacological interventions for musculoskeletal pain management among children and adolescents. OBJECTIVE: To evaluate the methodological and reporting quality of systematic reviews on conservative non-pharmacological pain management in children and adolescents with musculoskeletal pain. METHODS: Searches were conducted on the Cochrane Database of Systematic Reviews, Medline, Embase, and three other databases. Two pairs of reviewers independently assessed each article according to the predetermined selection criteria. We assessed the methodological quality of systematic reviews, using the AMSTAR 2 checklist and the quality of reporting, using PRISMA checklist. Descriptive analysis was used to summarise the characteristics of all included systematic reviews. The percentage of systematic reviews achieving each item from the AMSTAR 2, PRISMA checklist and the overall confidence in the results were described. RESULTS: We included 17 systematic reviews of conservative non-pharmacological pain management for musculoskeletal pain in children and adolescents. Of the 17 systematic reviews included, nine (53%) were rated as "critically low", seven (41%) were rated as "low", and one (6%) was rated as "high" methodological quality by AMSTAR-2. The reporting quality by items from PRISMA range from 17.6% (95% CI 6.2 to 41) to 100% (95% CI 81.6 to 100). CONCLUSION: This systematic review of physical interventions in children and adolescents showed overall 'very low' to 'high' methodological quality and usually poor reporting quality.

One step at a time. Shaping consensus on research priorities and terminology in telehealth in musculoskeletal pain: an international modified e-Delphi study.

BACKGROUND: Telehealth has emerged as an alternative model for treatment delivery and has become an important component of health service delivery. However, there is inconsistency in the use of terminologies and a lack of research priorities in telehealth in musculoskeletal pain. The purpose of this international, multidisciplinary expert panel assembled in a modified three-round e-Delphi survey is to achieve a consensus on research priorities and for the standard terminology for musculoskeletal pain telehealth practice. METHODS: In this international modified e-Delphi survey, we invited an expert panel consisting of researchers, clinicians, consumer representatives, industry partners, healthcare managers, and policymakers to participate in a three-round e-Delphi. Expert panels were identified through the Expertscape website, PubMed database, social media, and a snowball approach. In Round 1, potential research priorities and terminologies were presented to panel members. Panel members rated the agreement of each research priority on a 5-point Likert scale and an 11-point numerical scale, and each terminology on a 5-point Likert scale for the "telehealth in musculoskeletal pain " field over rounds. At least 80% of the panel members were required to agree to be deemed a consensus. We analyzed the data descriptively and assessed the stability of the results using the Wilcoxon matched-pairs signed rank test. RESULTS: We performed an international e-Delphi survey from February to August 2022. Of 694 invited people, 160 panel members participated in the first round, 133 in the second round (83% retention), and 134 in the third round (84% retention). Most of the panel members were researchers 76 (47%), clinicians 57 (36%), and consumer representatives 9 (6%) of both genders especially from Brazil 31 (19%), India 22 (14%), and Australia 19 (12%) in the first round. The panel identified fourteen telehealth research priorities spanned topics including the development of strategies using information and communication technology, telehealth implementation services, the effectiveness and cost-effectiveness of telehealth interventions, equity of telehealth interventions, qualitative research and eHealth literacy in musculoskeletal pain conditions from an initial list of 20 research priorities. The consensus was reached for "digital health" and "telehealth" as standard terminologies from an initial list of 37 terminologies. CONCLUSION: An international, multidisciplinary expert consensus recommends that future research should consider the 14 research priorities for telehealth musculoskeletal pain reached. Additionally, the terms digital health and telehealth as the most appropriate terminologies to be used in musculoskeletal telehealth research. REGISTER: Open Science Framework ( https://osf.io/tqmz2/ ).

Monitoring Training Loads in Judo Athletes: Different Time Courses of Physiological, Neuromuscular, and Perceptual Responses.

This study aims to elucidate the internal load, performance, physiological, and perceptual recovery responses during four weeks of traditional judo training. Ten cadet and junior judo athletes were evaluated daily for four weeks, in which their perception of recovery, heart rate variability, handgrip strength, and countermovement jump performance were assessed. A one-way repeated-measures ANOVA was performed to analyze the variables across the weeks. A significant time effect in internal load (F = 6.51; p = 0.001) has been observed. Handgrip test performance showed significantly higher values in the 3rd and 4th weeks (p <0.001), while countermovement jump performance was significantly higher in the 4th week (p =0.0007). The heart rate variability's coefficient of variation was lower in both the 3rd and 4th weeks (p =0.02). Regarding perceptual aspects, the Hooper Index showed a significant time effect (p =0.04), but pairwise comparison did not reveal differences between weeks. The present study indicates that neuromuscular, physiological, and perceptual responses to training load alterations present different time courses. This must be considered for the adequate monitoring of training programs.

Using machine learning to forecast symptom changes among subclinical depression patients receiving stepped care or usual care.

BACKGROUND: Subclinical depression (SD) is a mental health disorder characterized by minor depressive symptoms. Most SD patients are treated in the primary practice, but many respond poorly to treatment at the expense of provider resources. Stepped care approaches are appealing for tiering SD care to efficiently allocate scarce resources while jointly optimizing patient outcomes. However, stepped care can be time inefficient, as some persons may respond poorly and be forced to suffer with their symptoms for prolonged periods. Machine learning can offer insight into optimal treatment paths and inform clinical recommendations for incident patients. METHODS: As part of the Step-Dep trial, participants with SD were randomized to receive stepped care (N=96) or usual care (N=140). Machine learning was used to predict changes in depressive symptoms every three months over a year for each treatment group. RESULTS: Tree-based models were effective in predicting PHQ-9 changes among patients who received stepped care (r=0.35-0.46, MAE=0.14-0.17) and usual care (r=0.34-0.49, MAE=0.15-0.18). Patients who received stepped care were more likely to reduce PHQ-9 scores if they had high PHQ-9 but low HADS-A scores at baseline, a low number of chronic illnesses, and an internal locus of control. LIMITATIONS: Models may suffer from potential overfitting due to sample size limitations. CONCLUSION: Our findings demonstrate the promise of machine learning for predicting changes in depressive symptoms for SD patients receiving different treatments. Trained models can intake incident patient information and predict outcomes to inform personalized care.

Attitudes and beliefs of Brazilian physical therapists about chronic nonspecific low back pain and its impact on clinical decision-making: An Online Survey Study.

INTRODUCTION: Recent clinical practice guidelines recognize the importance of the biopsychosocial model in the management of patients with chronic nonspecific low back pain, and the attitudes and beliefs of physical therapists are believed to directly influence clinical decision-making. OBJECTIVE: To investigate factors associated to biomedical and biopsychosocial approaches and its impact on attitudes and beliefs to treat patients with chronic nonspecific low back pain. METHOD: This was a cross-sectional study conducted online with 302 Brazilian physiotherapists who treat patients with nonspecific chronic low back pain. The HC-PAIRS and PABS-PT were used to investigate attitudes and beliefs low back pain. Descriptive statistics and bivariate analyses were performed for association tests, comparing the scores on the scales between groups. In addition, multiple linear regression analyses were also used. RESULTS: The overall mean score of HC-PAIRS was 54.0 (9.0), and the biomedical and biopsychosocial factors of PABS-PT were 29.7 (9.0) and 36.2 (5.3), respectively. Significant associations were identified between gender (p = 0.04) and level of academic training (p < 0.00) and both scales, HC-PAIRS and PABSPT, respectively. CONCLUSION: Sociodemographic characteristics were associated with the beliefs of physical therapists; a higher score for treatment options for chronic low back pain based on the biomedical mode, was observed in female physiotherapist and in physios with higher education level. Variables such as age and length of professional experience indicated that the lower the age and/or length of professional experience of Brazilian physical therapists, the stronger the belief in the relationship between low back pain and tissue damage.

PRMT5 links lipid metabolism to contractile function of skeletal muscles.

Skeletal muscle plays a key role in systemic energy homeostasis besides its contractile function, but what links these functions is poorly defined. Protein Arginine Methyl Transferase 5 (PRMT5) is a well-known oncoprotein but also expressed in healthy tissues with unclear physiological functions. As adult muscles express high levels of Prmt5, we generated skeletal muscle-specific Prmt5 knockout (Prmt5MKO ) mice. We observe reduced muscle mass, oxidative capacity, force production, and exercise performance in Prmt5MKO mice. The motor deficiency is associated with scarce lipid droplets in myofibers due to defects in lipid biosynthesis and accelerated degradation. Specifically, PRMT5 deletion reduces dimethylation and stability of Sterol Regulatory Element-Binding Transcription Factor 1a (SREBP1a), a master regulator of de novo lipogenesis. Moreover, Prmt5MKO impairs the repressive H4R3 symmetric dimethylation at the Pnpla2 promoter, elevating the level of its encoded protein ATGL, the rate-limiting enzyme catalyzing lipolysis. Accordingly, skeletal muscle-specific double knockout of Pnpla2 and Prmt5 normalizes muscle mass and function. Together, our findings delineate a physiological function of PRMT5 in linking lipid metabolism to contractile function of myofibers.

Titanium biogenic nanoparticles to help the growth of Trichoderma harzianum to be used in biological control.

BACKGROUND: The biogenic synthesis of metallic nanoparticles is a green alternative that reduces the toxicity of this nanomaterials and may enable a synergy between the metallic core and the biomolecules employed in the process enhancing biological activity. The aim of this study was to synthesize biogenic titanium nanoparticles using the filtrate of the fungus Trichoderma harzianum as a stabilizing agent, to obtain a potential biological activity against phytopathogens and mainly stimulate the growth of T. harzianum, enhancing its efficacy for biological control. RESULTS: The synthesis was successful and reproductive structures remained in the suspension, showing faster and larger mycelial growth compared to commercial T. harzianum and filtrate. The nanoparticles with residual T. harzianum growth showed inhibitory potential against Sclerotinia sclerotiorum mycelial growth and the formation of new resistant structures. A great chitinolytic activity of the nanoparticles was observed in comparison with T. harzianum. In regard to toxicity evaluation, an absence of cytotoxicity and a protective effect of the nanoparticles was observed through MTT and Trypan blue assay. No genotoxicity was observed on V79-4 and 3T3 cell lines while HaCat showed higher sensitivity. Microorganisms of agricultural importance were not affected by the exposure to the nanoparticles, however a decrease in the number of nitrogen cycling bacteria was observed. In regard to phytotoxicity, the nanoparticles did not cause morphological and biochemical changes on soybean plants. CONCLUSION: The production of biogenic nanoparticles was an essential factor in stimulating or maintaining structures that are important for biological control, showing that this may be an essential strategy to stimulate the growth of biocontrol organisms to promote more sustainable agriculture.

Implementation of an online pain science education for chronic musculoskeletal pain in Brazilian public health system: protocol for a hybrid type III randomised controlled trial with economic evaluation.

BACKGROUND: Although clinical practice guidelines recommend pain education as the first-line option for the management of chronic musculoskeletal pain, there is a lack of pain education programmes in healthcare. Thus, digital health programmes can be an effective tool for implementing pain education strategies for public health. This trial will aim to analyse the implementation and effectiveness outcomes of three online pain science education strategies in the Brazilian public health system (SUS) for individuals with chronic musculoskeletal pain. METHODS: We will conduct a hybrid type III effectiveness-implementation randomised controlled trial with economic evaluation. We will include adult individuals with chronic musculoskeletal pain, recruited from primary healthcare in the city of Guarapuava, Brazil. Individuals will be randomised to three implementation groups receiving a pain science education intervention (EducaDor) but delivered in different modalities: group 1) synchronous online; group 2) asynchronous videos; and group 3) interactive e-book only. Implementation outcomes will include acceptability, appropriateness, feasibility, adoption, fidelity, penetration, sustainability, and costs. We will also assess effectiveness outcomes, such as pain, function, quality of life, sleep, self-efficacy, and adverse effects. Cost-effectiveness and cost-utility analyses will be conducted from the SUS and societal perspectives. The evaluations will be done at baseline, post-intervention (10 weeks), and 6 months. DISCUSSION: This study will develop and implement a collaborative intervention model involving primary healthcare professionals, secondary-level healthcare providers, and patients to enhance self-management of chronic pain. In addition to promoting better pain management, this study will also contribute to the field of implementation science in public health by generating important insights and recommendations for future interventions. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05302180; 03/29/2022).