-
Journal of Neurology Aug 2023Duchenne muscular dystrophy (DMD) is a severe, progressive, muscle-wasting disease, characterized by progressive deterioration of skeletal muscle that causes rapid loss... (Review)
Review
Duchenne muscular dystrophy (DMD) is a severe, progressive, muscle-wasting disease, characterized by progressive deterioration of skeletal muscle that causes rapid loss of mobility. The failure in respiratory and cardiac muscles is the underlying cause of premature death in most patients with DMD. Mutations in the gene encoding dystrophin result in dystrophin deficiency, which is the underlying pathogenesis of DMD. Dystrophin-deficient myocytes are dysfunctional and vulnerable to injury, triggering a series of subsequent pathological changes. In this review, we detail the molecular mechanism of DMD, dystrophin deficiency-induced muscle cell damage (oxidative stress injury, dysregulated calcium homeostasis, and sarcolemma instability) and other cell damage and dysfunction (neuromuscular junction impairment and abnormal differentiation of muscle satellite). We also describe aberrant function of other cells and impaired muscle regeneration due to deterioration of the muscle microenvironment, and dystrophin deficiency-induced multiple organ dysfunction, while summarizing the recent advances in the treatment of DMD.
Topics: Humans; Muscular Dystrophy, Duchenne; Dystrophin; Muscle, Skeletal; Mutation; Neuromuscular Junction
PubMed: 37258941
DOI: 10.1007/s00415-023-11796-x -
Journal of the American College of... Sep 2023Centers specializing in coronary function testing are critical to ensure a systematic approach to the diagnosis and treatment of angina with nonobstructive coronary... (Review)
Review
Centers specializing in coronary function testing are critical to ensure a systematic approach to the diagnosis and treatment of angina with nonobstructive coronary arteries (ANOCA). Management leveraging lifestyle, pharmacology, and device-based therapeutic options for ANOCA can improve angina burden and quality of life in affected patients. Multidisciplinary care teams that can tailor and titrate therapies based on individual patient needs are critical to the success of comprehensive programs. As coronary function testing for ANOCA is more widely adopted, collaborative research initiatives will be fundamental to improve ANOCA care. These efforts will require standardized symptom assessments and data collection, which will propel future large-scale clinical trials.
Topics: Humans; Program Development; Quality of Life; Angina Pectoris; Coronary Vessels; Life Style
PubMed: 37704316
DOI: 10.1016/j.jacc.2023.06.044 -
Clinical Cancer Research : An Official... Aug 2023Tumor heterogeneity in head and neck squamous cell carcinoma (HNSCC) profoundly compromises patient stratification, personalized treatment planning, and prognostic...
PURPOSE
Tumor heterogeneity in head and neck squamous cell carcinoma (HNSCC) profoundly compromises patient stratification, personalized treatment planning, and prognostic prediction, which underscores the urgent need for more effective molecular subtyping for this malignancy. Here, we sought to define the intrinsic epithelial subtypes for HNSCC by integrative analyses of single-cell and bulk RNA sequencing datasets from multiple cohorts and assess their molecular features and clinical significance.
EXPERIMENTAL DESIGN
Malignant epithelial cells were identified from single-cell RNA sequencing (scRNA-seq) datasets and subtyped on the basis of differentially expressed genes. Subtype-specific genomic/epigenetic abnormalities, molecular signaling, genetic regulatory network, immune landscape, and patient survival were characterized. Therapeutic vulnerabilities were further predicted on the basis of drug sensitivity datasets from cell lines, patient-derived xenograft models, and real-world clinical outcomes. Novel signatures for prognostication and therapeutic prediction were developed by machine learning and independently validated.
RESULTS
Three intrinsic consensus molecular subtypes (iCMS1-3) for HNSCC were proposed from scRNA-seq analyses and recapitulated in 1,325 patients from independent cohorts using bulk-sequencing datasets. iCMS1 was characterized by EGFR amplification/activation, stromal-enriched environment, epithelial-to-mesenchymal transition, worst survival, and sensitivities to EGFR inhibitor. iCMS2 was featured by human papillomavirus-positive oropharyngeal predilection, immune-hot, susceptibilities to anti-PD-1, and best prognosis. Moreover, iCMS3 displayed immune-desert and sensitivities to 5-FU and MEK, STAT3 inhibitors. Three novel, robust signatures derived from iCMS subtype-specific transcriptomics features were developed by machine learning for patient prognostication and cetuximab and anti-PD-1 response predictions.
CONCLUSIONS
These findings reiterate molecular heterogeneity of HNSCC and advantages of scRNA-seq in pinpointing cellular diversities in complex cancer ecosystems. Our HNSCC iCMS regime might facilitate accurate patient stratification and individualized precise treatment.
PubMed: 37192003
DOI: 10.1158/1078-0432.CCR-22-3563 -
Pediatric Clinics of North America Dec 2023Community violence happens between unrelated individuals, who may or may not know each other, generally outside the home, and often results in assaultive injuries.... (Review)
Review
Community violence happens between unrelated individuals, who may or may not know each other, generally outside the home, and often results in assaultive injuries. Community violence interventions can prevent assaultive injuries and assist victims of community violence. Trauma-informed care is foundational to the success of community violence intervention. Place-based environmental interventions can decrease community violence on the population level, and further research and developments are needed in this area. Substance use is a significant barrier to intervention program involvement and greater research and program development is needed to support substance use treatment of those impacted by community violence.
Topics: Humans; Violence; Crime Victims; Substance-Related Disorders
PubMed: 37865433
DOI: 10.1016/j.pcl.2023.06.007 -
The Journal of School Nursing : the... Feb 2024Calzolari and colleagues invited others to have an "open…professional dialogue" on how Italy can introduce school nurses into their system. This editorial is a...
Calzolari and colleagues invited others to have an "open…professional dialogue" on how Italy can introduce school nurses into their system. This editorial is a response to that invitation. Although factors such as a broader nursing shortage and limited health resources definitely contribute to a global shortage of school nurses, three foundational reasons continue to challenge the demand for school nursing globally. The three reasons are traditional views and lack of understanding of the role of school nurses to address modern days challenges, inadequate system support and integration within education, and lack of data to illustrate value. These challenges must be addressed when discussing the inclusion of school nurses in education.
PubMed: 37981787
DOI: 10.1177/10598405231213929 -
Sensors (Basel, Switzerland) Aug 2023We present a novel closed-loop system designed to integrate biological and artificial neurons of the oscillatory type into a unified circuit. The system comprises an...
We present a novel closed-loop system designed to integrate biological and artificial neurons of the oscillatory type into a unified circuit. The system comprises an electronic circuit based on the FitzHugh-Nagumo model, which provides stimulation to living neurons in acute hippocampal mouse brain slices. The local field potentials generated by the living neurons trigger a transition in the FitzHugh-Nagumo circuit from an excitable state to an oscillatory mode, and in turn, the spikes produced by the electronic circuit synchronize with the living-neuron spikes. The key advantage of this hybrid electrobiological autogenerator lies in its capability to control biological neuron signals, which holds significant promise for diverse neuromorphic applications.
Topics: Animals; Mice; Electronics; Hippocampus; Neurons
PubMed: 37631552
DOI: 10.3390/s23167016 -
New Directions For Student Leadership Dec 2023
Topics: Humans; Leadership; Curriculum; Program Development
PubMed: 38329207
DOI: 10.1002/yd.20576 -
Australasian Journal on Ageing Sep 2023This study aimed to conduct a feasibility pilot of the Dementia Lifestyle Coach program; an individual coaching and counselling program for people recently diagnosed... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
This study aimed to conduct a feasibility pilot of the Dementia Lifestyle Coach program; an individual coaching and counselling program for people recently diagnosed with dementia, to help them to adjust to the diagnosis and live well.
METHODS
A randomised controlled pilot trial (n = 11) with wait-list control group was undertaken over 12 months. Intervention group participants received immediate personalised counselling from a registered psychologist and monthly support (face-to-face or by telephone) from a trained peer mentor living with dementia. The wait-listed control group commenced treatment 6 months after baseline.
RESULTS
Recruitment and delivery of the Dementia Lifestyle Coach program was highly feasible. The program was acceptable, with nine of the 11 participants describing benefits including informational and emotional support, improving their outlook and mood, and family relationships. The planned program was adapted to participants' individual needs.
CONCLUSIONS
This small pilot showed that it is feasible to recruit for and deliver a counselling and peer mentoring program for people recently diagnosed with dementia. A larger hybrid implementation randomised control trial should be conducted to evaluate efficacy and effectiveness.
Topics: Humans; Pilot Projects; Life Style; Program Development; Dementia
PubMed: 36546406
DOI: 10.1111/ajag.13169 -
The Journal of Continuing Education in... Oct 2023A majority of US medical schools have incorporated faculty coach-supported educational portfolios into the curriculum. Existing research describes coach professional...
INTRODUCTION
A majority of US medical schools have incorporated faculty coach-supported educational portfolios into the curriculum. Existing research describes coach professional development, competencies, and program perceptions. However, limited research exists on how programs address coach professional development needs. Our sequential objectives were to (1) explore faculty coach professional development experiences within medical student coaching programs and (2) develop a preliminary framework for medical faculty coach professional development.
METHODS
Faculty portfolio coaches who completed 4 years of a longitudinal coaching program were recruited to complete a semi-structured exit interview. Interviews were transcribed using detailed transcription. Two analysts inductively generated a codebook of parent and child codes to identify themes. They compared themes to the professional development model proposed by O'Sullivan and Irby.
RESULTS
Of the 25 eligible coaches, 15 completed the interview. Our team organized themes into two broad domains paralleling the established model: program-specific professional development and career-relevant professional development. Four program-specific professional development themes emerged: doing; modeling; relating; and hosting. Three career-relevant professional development themes emerged: advancement; meaning; and understanding. We then applied themes within each domain to propose strategies to optimize coach professional development and develop a framework modeled after O'Sullivan and Irby.
DISCUSSION
To our knowledge, we propose the first portfolio coach-informed framework for professional development. Our work builds on established standards, expert opinion, and research responsible for portfolio coach professional development and competencies. Allied health institutions with portfolio coaching programs can apply the framework for professional development innovation.
Topics: Humans; Clinical Competence; Curriculum; Faculty, Medical; Mentoring; Program Development
PubMed: 37053579
DOI: 10.1097/CEH.0000000000000502 -
Global Health Action Dec 2023Middle childhood, between six and twelve years, is a critical bridge between earlier childhood and adolescence with rapid physical and psychological transitions. Most of...
Middle childhood, between six and twelve years, is a critical bridge between earlier childhood and adolescence with rapid physical and psychological transitions. Most of the world's 2.6 billion young people, of which the middle childhood age group is a significant portion, live in low- and middle-income countries. Many live in environments that place them at high and growing risk for mental ill-health, injuries, and adoption of risky behaviours that often lead to non-communicable diseases in later years. Still, middle childhood, the 'missing middle,' is omitted from global health information systems, targeted policies, and strategies. The dearth of internationally comparable and standardised indicators on middle childhood in major international development agency databases hampers age-appropriate policy and programme development. Better understanding of the needs of this increasingly vulnerable population is critical. Middle childhood needs to be an explicit focus within child-focused research and implementation. Standardised, comprehensive, and relevant indicators are required to quantify the contribution of middle childhood to the global burden of disease and to facilitate interventions, monitoring, and evaluation, to ensure that all children flourish and thrive.
Topics: Child; Humans; Mental Health; Global Health; Child Health
PubMed: 37548519
DOI: 10.1080/16549716.2023.2242196