Comparing Digital to Conventional Physical Therapy for Chronic Shoulder Pain: Randomized Controlled Trial.

BACKGROUND: Chronic shoulder pain (CSP) is a common condition with various etiologies, including rotator cuff disorders, adhesive capsulitis, shoulder instability, and shoulder arthritis. It is associated with substantial disability and psychological distress, resulting in poor productivity and quality of life. Physical therapy constitutes the mainstay treatment for CSP, but several barriers exist in accessing care. In recent years, telerehabilitation has gained momentum as a potential solution to overcome such barriers. It has shown numerous benefits, including improving access and convenience, promoting patient adherence, and reducing costs. However, to date, no previous randomized controlled trial has compared fully remote digital physical therapy to in-person rehabilitation for nonoperative CSP. OBJECTIVE: The aim of this study is to compare clinical outcomes between digital physical therapy and conventional in-person physical therapy in patients with CSP. METHODS: We conducted a single-center, parallel-group, randomized controlled trial involving 82 patients with CSP referred for outpatient physical therapy. Participants were randomized into digital or conventional physical therapy (8-week interventions). The digital intervention consisted of home exercise, education, and cognitive behavioral therapy (CBT), using a device with movement digitalization for biofeedback and asynchronous physical therapist monitoring through a cloud-based portal. The conventional group received in-person physical therapy, including exercises, manual therapy, education, and CBT. The primary outcome was the change (baseline to 8 weeks) in function and symptoms using the short-form of Disabilities of the Arm, Shoulder, and Hand questionnaire. Secondary outcome measures included self-reported pain, surgery intent, analgesic intake, mental health, engagement, and satisfaction. All questionnaires were delivered electronically. RESULTS: A total of 90 participants were randomized into digital or conventional physical therapy, with 82 receiving the allocated intervention. Both groups experienced significant improvements in function measured by the short-form of the Disabilities of the Arm, Shoulder, and Hand questionnaire, with no differences between groups (-1.8, 95% CI -13.5 to 9.8; P=.75). For secondary outcomes, no differences were observed in surgery intent, analgesic intake, and mental health or worst pain. Higher reductions were observed in average and least pain in the conventional group, which, given the small effect sizes (least pain 0.15 and average pain 0.16), are unlikely to be clinically meaningful. High adherence and satisfaction were observed in both groups, with no adverse events. CONCLUSIONS: This study shows that fully remote digital programs can be viable care delivery models for CSP given their scalability and effectiveness, assessed through comparison with high-dosage in-person rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04636528); https://clinicaltrials.gov/study/NCT04636528.

Racial and Ethnic Differences in Outcomes of a 12-Week Digital Rehabilitation Program for Musculoskeletal Pain: Prospective Longitudinal Cohort Study.

BACKGROUND: Musculoskeletal (MSK) pain disproportionately affects people from different ethnic backgrounds through higher burden and less access to care. Digital care programs (DCPs) can improve access and help reduce inequities. However, the outcomes of such programs based on race and ethnicity have yet to be studied. OBJECTIVE: We aimed to assess the impact of race and ethnicity on engagement and outcomes in a multimodal DCP for MSK pain. METHODS: This was an ad hoc analysis of an ongoing decentralized single-arm investigation into engagement and clinical-related outcomes after a multimodal DCP in patients with MSK conditions. Patients were stratified by self-reported racial and ethnic group, and their engagement and outcome changes between baseline and 12 weeks were compared using latent growth curve analysis. Outcomes included program engagement (number of sessions), self-reported pain scores, likelihood of surgery, Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire 9-item, and Work Productivity and Activity Impairment. A minimum clinically important difference (MCID) of 30% was calculated for pain, and multivariable logistic regression was performed to evaluate race as an independent predictor of meeting the MCID. RESULTS: A total of 6949 patients completed the program: 65.5% (4554/6949) of them were non-Hispanic White, 10.8% (749/6949) were Black, 9.7% (673/6949) were Asian, 9.2% (636/6949) were Hispanic, and 4.8% (337/6949) were of other racial or ethnic backgrounds. The population studied was diverse and followed the proportions of the US population. All groups reported high engagement and satisfaction, with Hispanic and Black patients ranking first among satisfaction despite lower engagement. Black patients had a higher likelihood to drop out (odds ratio [OR] 1.19, 95% CI 1.01-1.40, P=.04) than non-Hispanic White patients. Hispanic and Black patients reported the highest level of pain, surgical intent, work productivity, and impairment in activities of daily living at baseline. All race groups showed a significant improvement in all outcomes, with Black and Hispanic patients reporting the greatest improvements in clinical outcomes. Hispanic patients also had the highest response rate for pain (75.8%) and a higher OR of meeting the pain MCID (OR 1.74, 95% CI 1.24-2.45, P=.001), when compared with non-Hispanic White patients, independent of age, BMI, sex, therapy type, education level, and employment status. No differences in mental health outcomes were found between race and ethnic groups. CONCLUSIONS: This study advocates for the utility of a DCP in improving access to MSK care and promoting health equity. Engagement and satisfaction rates were high in all the groups. Black and Hispanic patients had higher MSK burden at baseline and lower engagement but also reported higher improvements, with Hispanic patients presenting a higher likelihood of pain improvement.

Digital Care Program for Urinary Incontinence in Females: A Large-Scale, Prospective, Cohort Study.

Female urinary incontinence (UI) is highly prevalent in the US (>60%). Pelvic floor muscle training (PFMT) represents first-line care for UI; however, access and adherence challenges urge new care delivery models. This prospective cohort study investigates the feasibility and safety of a remote digital care program (DCP) combining education and PFMT with real-time biofeedback with an average duration of 10 weeks. The primary outcome was the change in the Urinary Impact Questionnaire-short form (UIQ-7) from baseline to program-end, calculated through latent growth curve analysis (LGCA). Secondary outcomes included the impact of pelvic conditions (PFIQ-7), depression (PHQ-9), anxiety (GAD-7), productivity impairment (WPAI), intention to seek additional healthcare, engagement, and satisfaction. Of the 326 participants who started the program, 264 (81.0%) completed the intervention. Significant improvement on UIQ-7 (8.8, 95%CI 4.7; 12.9, p < 0.001) was observed, corresponding to a response rate of 57.3%, together with improvements in all other outcomes and high satisfaction (8.9/10, SD 1.8). This study shows the feasibility and safety of a completely remote DCP with biofeedback managed asynchronously by a physical therapist to reduce UI-related symptoms in a real-world setting. Together, these findings may advocate for the exploration of this care delivery option to escalate access to proper and timely UI care.

Engagement and Utilization of a Complete Remote Digital Care Program for Musculoskeletal Pain Management in Urban and Rural Areas Across the United States: Longitudinal Cohort Study.

BACKGROUND: Musculoskeletal (MSK) conditions are the number one cause of disability worldwide. Digital care programs (DCPs) for MSK pain management have arisen as alternative care delivery models to circumvent challenges in accessibility of conventional therapy. Despite the potential of DCPs to reduce inequities in accessing care, the outcomes of such interventions in rural and urban populations have yet to be studied. OBJECTIVE: The aim of this study was to assess the impact of urban or rural residency on engagement and clinical outcomes after a multimodal DCP for MSK pain. METHODS: This study consists of an ad hoc analysis of a decentralized single-arm investigation into engagement and clinical-related outcomes after a multimodal DCP in patients with MSK conditions. Patients were coded according to their zip codes to a specific rural-urban commuting area code and grouped into rural and urban cohorts. Changes in their engagement and clinical outcomes from baseline to program end were assessed. Latent growth curve analysis was performed to estimate change trajectories adjusting for the following covariates: age, gender, BMI, employment status, and pain acuity. Outcomes included engagement, self-reported pain, and the results of the Generalized Anxiety Disorder 7-item, Patient Health Questionnaire 9-item, and Work Productivity and Activity Impairment scales. A minimum clinically important difference (MCID) of 30% was considered for pain. RESULTS: Patients with urban and rural residency across the United States participated in the program (n=9992). A 73.8% (7378/9992) completion rate was observed. Both groups reported high satisfaction scores and similar engagement with exercise sessions, with rural residents showing higher engagement with educational content (P<.001) and higher program completion rates (P=.02). All groups showed a significant improvement in all clinical outcomes, including pain, mental health, and work productivity, without statistically significant intergroup differences. The percentage of patients meeting the MCID was similar in both groups (urban: 67.1%, rural: 68.3%; P=.30). CONCLUSIONS: This study advocates for the utility of a DCP in improving access to MSK care in urban and rural areas alike, showcasing its potential to promote health equity. High engagement, satisfaction, and completion rates were noted in both groups, as well as significant improvements in clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04092946; https://clinicaltrials.gov/ct2/show/NCT04092946.

Sleep Disturbance in Musculoskeletal Conditions: Impact of a Digital Care Program.

Background: Musculoskeletal (MSK) pain is highly prevalent worldwide, resulting in significant disability, and comorbid sleep disturbances. Digital therapy for MSK pain can provide significant improvements in care access, alongside pain and disability reductions. However, studies on the effect of such programs on sleep are lacking. Purpose: To evaluate the impact on pain-related sleep impairment after a 12-week remote multimodal digital care program (DCP) for MSK conditions. Patients and Methods: This is an ad-hoc analysis of a decentralized single-arm study into engagement and clinical outcomes after a DCP for MSK rehabilitation. Patients were stratified by baseline sleep disturbance, based on sleep questions in the questionnaires: Oswestry Disability Index, Neck Disability Index, and the Quick Disabilities of the Arm, Shoulder and Hand questionnaire. Additional outcomes were pain, Generalized Anxiety Disorder 7-item scale, Patient Health 9-item questionnaire, Work Productivity, and Activity Impairment, and program engagement. Results: At baseline, 5749 patients reported sleep disturbance (78.0% of eligible patients). These reported significantly worse clinical outcomes at baseline than patients without sleep disturbance (all p<0.001). Patients with comorbid sleep disturbance showed improvements in sleep, with a significant proportion reporting full recovery at program completion: 56% of patients with upper limb conditions (including 10% of patients with severe sleep disturbance at baseline), and 24% with spine conditions. These patients also reported significant improvements in all clinical outcomes at program completion. Engagement and satisfaction were high, and also higher than in patients without sleep impairment. Conclusion: This is the first study of its kind investigating the effect of a completely remote DCP for MSK pain on sleep. Patients reporting comorbid sleep disturbance had significant improvement in sleep, alongside pain, mental health and work productivity at program completion. The results suggest that a DCP for MSK pain can improve sleep disturbances in patients with upper limb and spine conditions.

Current and Emerging Techniques for Diagnosis and MRD Detection in AML: A Comprehensive Narrative Review.

Acute myeloid leukemia (AML) comprises a group of hematologic neoplasms characterized by abnormal differentiation and proliferation of myeloid progenitor cells. AML is associated with poor outcome due to the lack of efficient therapies and early diagnostic tools. The current gold standard diagnostic tools are based on bone marrow biopsy. These biopsies, apart from being very invasive, painful, and costly, have low sensitivity. Despite the progress uncovering the molecular pathogenesis of AML, the development of novel detection strategies is still poorly explored. This is particularly important for patients that check the criteria for complete remission after treatment, since they can relapse through the persistence of some leukemic stem cells. This condition, recently named as measurable residual disease (MRD), has severe consequences for disease progression. Hence, an early and accurate diagnosis of MRD would allow an appropriate therapy to be tailored, improving a patient's prognosis. Many novel techniques with high potential in disease prevention and early detection are being explored. Among them, microfluidics has flourished in recent years due to its ability at processing complex samples as well as its demonstrated capacity to isolate rare cells from biological fluids. In parallel, surface-enhanced Raman scattering (SERS) spectroscopy has shown outstanding sensitivity and capability for multiplex quantitative detection of disease biomarkers. Together, these technologies can allow early and cost-effective disease detection as well as contribute to monitoring the efficiency of treatments. In this review, we aim to provide a comprehensive overview of AML disease, the conventional techniques currently used for its diagnosis, classification (recently updated in September 2022), and treatment selection, and we also aim to present how novel technologies can be applied to improve the detection and monitoring of MRD.

Managing Musculoskeletal Pain in Older Adults Through a Digital Care Solution: Secondary Analysis of a Prospective Clinical Study.

BACKGROUND: Aging is closely associated with an increased prevalence of musculoskeletal conditions. Digital musculoskeletal care interventions emerged to deliver timely and proper rehabilitation; however, older adults frequently face specific barriers and concerns with digital care programs (DCPs). OBJECTIVE: This study aims to investigate whether known barriers and concerns of older adults impacted their participation in or engagement with a DCP or the observed clinical outcomes in comparison with younger individuals. METHODS: We conducted a secondary analysis of a single-arm investigation assessing the recovery of patients with musculoskeletal conditions following a DCP for up to 12 weeks. Patients were categorized according to age: ≤44 years old (young adults), 45-64 years old (middle-aged adults), and ≥65 years old (older adults). DCP access and engagement were evaluated by assessing starting proportions, completion rates, ability to perform exercises autonomously, assistance requests, communication with their physical therapist, and program satisfaction. Clinical outcomes included change between baseline and program end for pain (including response rate to a minimal clinically important difference of 30%), analgesic usage, mental health, work productivity, and non-work-related activity impairment. RESULTS: Of 16,229 patients, 12,082 started the program: 38.3% (n=4629) were young adults, 55.7% (n=6726) were middle-aged adults, and 6% (n=727) were older adults. Older patients were more likely to start the intervention and to complete the program compared to young adults (odds ratio [OR] 1.72, 95% CI 1.45-2.06; P<.001 and OR 2.40, 95% CI 1.97-2.92; P<.001, respectively) and middle-aged adults (OR 1.22, 95% CI 1.03-1.45; P=.03 and OR 1.38, 95% CI 1.14-1.68; P=.001, respectively). Whereas older patients requested more technical assistance and exhibited a slower learning curve in exercise performance, their engagement was higher, as reflected by higher adherence to both exercise and education pieces. Older patients interacted more with the physical therapist (mean 12.6, SD 18.4 vs mean 10.7, SD 14.7 of young adults) and showed higher satisfaction scores (mean 8.7, SD 1.9). Significant improvements were observed in all clinical outcomes and were similar between groups, including pain response rates (young adults: 949/1516, 62.6%; middle-aged adults: 1848/2834, 65.2%; and older adults: 241/387, 62.3%; P=.17). CONCLUSIONS: Older adults showed high adherence, engagement, and satisfaction with the DCP, which were greater than in their younger counterparts, together with significant clinical improvements in all studied outcomes. This suggests DCPs can successfully address and overcome some of the barriers surrounding the participation and adequacy of digital models in the older adult population.

Randomized-controlled trial assessing a digital care program versus conventional physiotherapy for chronic low back pain.

Low back pain (LBP) is the world's leading cause of years lived with disability. Digital exercise-based interventions have shown great potential in the management of musculoskeletal conditions, promoting access and easing the economic burden. However, evidence of their effectiveness for chronic LBP (CLBP) management compared to in-person physiotherapy has yet to be unequivocally established. This randomized controlled trial (RCT) aims to compare the clinical outcomes of patients with CLBP following a digital intervention versus evidence-based in-person physiotherapy. Our results demonstrate that patient satisfaction and adherence were high and similar between groups, although a significantly lower dropout rate is observed in the digital group (11/70, 15.7% versus 24/70, 34.3% in the conventional group; P = 0.019). Both groups experience significant improvements in disability (primary outcome), with no differences between groups in change from baseline (median difference: -0.55, 95% CI: -2.42 to 5.81, P = 0.412) or program-end scores (-1.05, 95% CI: -4.14 to 6.37; P = 0.671). Likewise, no significant differences between groups are found for secondary outcomes (namely pain, anxiety, depression, and overall productivity impairment). This RCT demonstrates that a remote digital intervention for CLBP can promote the same levels of recovery as evidence-based in-person physiotherapy, being a potential avenue to ease the burden of CLBP.

Impact on productivity impairment of a digital care program for chronic low back pain: A prospective longitudinal cohort study.

BACKGROUND: Low back pain (LBP) is the leading cause of disability in the United States and the main reason for absenteeism. Successful management of chronic LBP (CLBP) is dependent on multimodal evidence-based interventions. Digital interventions (DI) may ease accessibility to such treatments, increasing adherence, while reducing healthcare-related costs. OBJECTIVES: Assess the impact of a completely remote multimodal DI on productivity impairment in a real-work context cohort of patients with CLBP. DESIGN: Longitudinal study. METHODS: Ad-hoc analysis of an interventional, single-arm study of individuals with CLBP undergoing a DI for 12 weeks. Outcomes included the mean change in work productivity and activity impairment (including overall and non-work related activities), pain, depression, anxiety, fear-avoidance beliefs, analgesic usage, and engagement. Minimal clinically important change (MCIC) was calculated for productivity using anchor- and distribution-based methods. RESULTS: From 560 patients at program start, 78.4% completed the DI. A significant improvement in overall productivity (20.21, 95%CI: 16.48-23.94) and in non-work related activities (21.36, 95%CI: 17.49-25.22) was observed, corresponding to a responder rate of 57.1-83.3% and 60.5-79.8%, respectively, and depending on the MCIC method. Significant improvements were reported for pain (2.32 points, 95%CI: 2.02-2.61), anxiety (5.24, 95%CI: 4.18-6.29), depression (6.38, 95%CI: 4.78-7.98) and fear-avoidance beliefs (8.11, 95%CI: 6.20-10.02). Both engagement (sessions per week) and patient satisfaction scores were high, 2.9 (SD 1.0) and 8.8/10 (SD 1.6), respectively. CONCLUSIONS: This study demonstrated the utility of a multimodal DI to address productivity impairment. DIs have great potential to ease the burden of CLBP, providing an accessible and cost-effective modality of care. TRIAL REGISTRATION: The study was approved by the New England IRB (protocol number 120190313) and prospectively registered in ClinicalTrials.gov, NCT04092946, on September 17th, 2019.

Effectiveness of biofeedback-assisted asynchronous telerehabilitation in musculoskeletal care: A systematic review.

Background: Musculoskeletal conditions are the leading cause of disability worldwide. Telerehabilitation may be a viable option in the management of these conditions, facilitating access and patient adherence. Nevertheless, the impact of biofeedback-assisted asynchronous telerehabilitation remains unknown. Objective: To systematically review and assess the effectiveness of exercise-based asynchronous biofeedback-assisted telerehabilitation on pain and function in individuals with musculoskeletal conditions. Methods: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The search was conducted using three databases: PubMed, Scopus, and PEDro. Study criteria included articles written in English and published from January 2017 to August 2022, reporting interventional trials evaluating exercise-based asynchronous telerehabilitation using biofeedback in adults with musculoskeletal disorders. The risks of bias and certainty of evidence were appraised using the Cochrane tool and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE), respectively. The results are narratively summarized, and the effect sizes of the main outcomes were calculated. Results: Fourteen trials were included: 10 using motion tracker technology (N = 1284) and four with camera-based biofeedback (N = 467). Telerehabilitation with motion trackers yields at least similar improvements in pain and function in people with musculoskeletal conditions (effect sizes: 0.19-1.45; low certainty of evidence). Uncertain evidence exists for the effectiveness of camera-based telerehabilitation (effect sizes: 0.11-0.13; very low evidence). No study found superior results in a control group. Conclusions: Asynchronous telerehabilitation may be an option in the management of musculoskeletal conditions. Considering its potential for scalability and access democratization, additional high-quality research is needed to address long-term outcomes, comparativeness, and cost-effectiveness and identify treatment responders.

The potential of a multimodal digital care program in addressing healthcare inequities in musculoskeletal pain management.

Digital interventions have emerged as a solution for time and geographical barriers, however, their potential to target other social determinants of health is largely unexplored. In this post-hoc analysis, we report the impact of social deprivation on engagement and clinical outcomes after a completely remote multimodal musculoskeletal (MSK) digital care program managed by a culturally-sensitive clinical team. Patients were stratified in five categories according to their social deprivation index, and cross-referenced with their race/ethnicity, rurality and distance to healthcare facilities. From a total of 12,062 patients from all U.S. states, 8569 completed the program. Higher social deprivation was associated with greater baseline disease burden. We observed that all categories reported pain improvements (ranging from -2.0 95%CI -2.1, -1.9 to -2.1 95%CI -2.3, -1.9, p < 0.001) without intergroup differences in mean changes or responder rates (from 59.9% (420/701) to 66.6% (780/1172), p = 0.067), alongside reduction in analgesic consumption. We observed significant improvements in mental health and productivity across all categories, with productivity and non-work-related functional recovery being greater within the most deprived group. Engagement was high but varied slightly across categories. Together these findings highlight the importance of a patient-centered digital care program as a tool to address health inequities in musculoskeletal pain management. The idea of investigating social deprivation within a digital program provides a foundation for future work in this field to identify areas of improvement.

Digital Care Programs for Chronic Hip Pain: A Prospective Longitudinal Cohort Study.

Chronic hip pain is a cause of disability worldwide. Digital interventions (DI) may promote access while providing proper management. This single-arm interventional study assesses the clinical outcomes and engagement of a completely remote multimodal DI in patients with chronic hip pain. This home-based DI consisted of exercise (with real-time biofeedback), education, and cognitive-behavioral therapy. Outcomes were calculated between baseline and program end, using latent growth curve analysis. Primary outcome was the Hip Disability and Osteoarthritis Outcome Score (HOOS). Secondary outcomes were pain, intent to undergo surgery, mental health, productivity, patient engagement (exercise sessions frequency), and satisfaction. Treatment response was assessed using a 30% pain change cut-off. A completion rate of 74.2% (396/534), alongside high patient engagement (2.9 exercise sessions/week, SD 1.1) and satisfaction (8.7/10, SD 1.6) were observed. Significant improvements were observed across all HOOS sub-scales (14.7−26.8%, p < 0.05), with 66.8% treatment responders considering pain. Marked improvements were observed in surgery intent (70.1%), mental health (54%), and productivity impairment (60.5%) (all p < 0.001). The high engagement and satisfaction reported after this DI, alongside the clinical outcome improvement, support the potential of remote care in the management of chronic hip conditions.

Long-Term Clinical Outcomes of a Remote Digital Musculoskeletal Program: An Ad Hoc Analysis from a Longitudinal Study with a Non-Participant Comparison Group.

Digital solutions have emerged as an alternative to conventional physiotherapy, particularly for chronic musculoskeletal pain (CMP) management; however, its long-term effects remain largely unexplored. This study focuses on patients reporting CMP, assessing 1-year clinical outcomes after a multimodal digital care program (DCP) versus non-participants, who enrolled in the program but never engaged in a single exercise session or partook of the educational content made available to them. In this longitudinal study ad-hoc analysis, pain and functionality outcomes at 1-year reassessment were studied, focusing on the odds of reaching minimal clinically important difference (MCID) and, overall average reduction in both outcomes. Healthcare utilization was additionally studied within the same period. From 867 individuals allocated to the study, 460 completed the 1-year reassessment (intervention group: 310; comparison group: 150). The intervention group presented sustained and greater pain reduction until 1-year reassessment than the comparison group, reflecting greater odds ratio of achieving the MCID both in pain and functionality (1.90 95% CI: 1.27-2.86, p = 0.002 and 2.02 95% CI: 1.31-3.12, p = 0.001, respectively). A lower healthcare utilization during the 1-year follow-up was observed in the intervention group than in the comparison group. This study suggests that a digital CMP program may have a lasting impact on improved pain and functionality in patients with CMP.

Innovative, integrative, and interactive in-class activity on metabolic regulation: Evaluating educational impacts.

Medical students tend to have difficulties in developing a holistic view of metabolic pathway and hormone regulation. To address this issue, an interactive activity was implemented for first-year medical students at the School of Medicine, University of Minho, Portugal. Students' previous knowledge on metabolic pathways was evaluated by a pre-test followed by an interactive activity. In the supervised activity, students were challenged to elaborate a diagrammatic representation regarding enzymes, co-factors, and hormonal metabolic regulation in early fasting during the night, as well as in well-fed conditions. The activity was concluded with a post-test to determine the students' learning gains and a few days later students were evaluated by a final exam. Afterwards, students evaluated the activity by filling a questionnaire. Results from four different cohorts showed that the activity resulted in significant learning gains, particularly favoring students who have less prior knowledge. The comparison between the pre-test and the final exam also revealed significant learning gains for low achievers students. On the questionnaires, the majority of the students rated the activity as good or very good. Students agreed that this activity promotes: (a) reactivation of previous knowledge; (b) a better understanding of the interconnections between the metabolic pathways; (c) the application of learned concepts in real scenarios; and (d) sharing knowledge with peers. This study describes an active, unpretentious, and easily implemented activity available for early medical and biochemical curricula.

Functional Genetic Variants in ATG10 Are Associated with Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common acute leukemia, characterized by a heterogeneous genetic landscape contributing, among others, to the occurrence of metabolic reprogramming. Autophagy, a key player on metabolism, plays an essential role in AML. Here, we examined the association of three potentially functional genetic polymorphisms in the ATG10 gene, central for the autophagosome formation. We screened a multicenter cohort involving 309 AML patients and 356 healthy subjects for three ATG10 SNPs: rs1864182T>G, rs1864183C>T and rs3734114T>C. The functional consequences of the ATG10 SNPs in its canonical function were investigated in vitro using peripheral blood mononuclear cells from a cohort of 46 healthy individuals. Logistic regression analysis adjusted for age and gender revealed that patients carrying the ATG10rs1864182G allele showed a significantly decreased risk of developing AML (OR [odds ratio] = 0.58, p = 0.001), whereas patients carrying the homozygous ATG10rs3734114C allele had a significantly increased risk of developing AML (OR = 2.70, p = 0.004). Functional analysis showed that individuals carrying the ATG10rs1864182G allele had decreased autophagy when compared to homozygous major allele carriers. Our results uncover the potential of screening for ATG10 genetic variants in AML prevention strategies, in particular for subjects carrying other AML risk factors such as elderly individuals with clonal hematopoiesis of indeterminate potential.

Surface roughness dependent osteoblast and fibroblast response on poly(L-lactide) films and electrospun membranes.

Poly(l-lactide) electrospun mats with random and aligned fiber orientation and films have been produced with degrees of crystallinity ranging from 0 up to nearly 50%. The overall surface roughness is practically constant irrespective of the sampling areas (1 × 1 µm to 20 × 20 µm) for degrees of crystallinity below 30%, increasing for higher degrees of crystallinity for the larger sampling areas. Further, due to fiber confinement, surface roughness variations are smaller in electrospun mats. Samples with 50% of crystallinity show the lowest osteoblast and the highest fibroblast proliferation. Therefore, it is verified that higher roughness promotes lower osteoblast but higher fibroblast proliferation. The overall results indicate the relevant role of the sub-microenvironment variations associated to the microscale roughness in determining the different cell responses.