Reduced oxygen tension culturing conditionally alters toxicogenic response of differentiated H9c2 cardiomyoblasts to acrolein.

Acrolein is a reactive electrophilic aldehyde known to cause mitochondrial dysfunction, oxidative stress, and dysregulation of signaling transduction in vitro. Most in vitro systems employ standard cell culture maintenance conditions of 95% air/5% CO2, translating to a culture oxygen tension of approximately 20%, far above most physiological tissues. The purpose of this investigation was to examine whether low-serum, retinoic acid differentiated H9c2 cells were less sensitive to acrolein insult when cultured under reduced oxygen tension. H9c2 cells were maintained separately in 20% and 5% oxygen, differentiated for 5 d, and then exposed to acrolein for 30 min in media containing varying concentrations of tricarboxylic acid and glycolytic substrates, followed by fresh medium replacement. Cells were then assessed for MTT reduction at 2 h and 24 h after acrolein insult. We showed that pyruvate supplementation in combination with lowered oxygen culturing significantly attenuated acrolein-induced viability loss at 24 h. Poly(ADP-ribose) polymerase inhibition and EGTA preferentially provided partial rescue to low oxygen cultures, but not for standard cultures. Collectively, these results offer evidence supporting altered toxicogenic response of H9c2 during physiologically relevant oxygen tension culturing.

Acrolein measurement and degradation in Dulbecco's Modified Eagle Medium: an examination of in-vitro exposure metrics.

Acrolein is a reactive α,ß-unsaturated aldehyde known for its adduction to endogenous biomolecules, resulting in initiation or exacerbation of several disease pathways. In-vitro systems are routinely used to elucidate the cytotoxic or mechanistic role(s) of acrolein in pathogenesis. Nevertheless, the half-life of acrolein in biological or in-vitro systems, e.g. blood or culture media, has not been well characterized. Since in-vitro cytotoxic and mechanistic investigations routinely expose cultures to acrolein from 1 hour to 72 hours, we aimed to characterize the half-life of acrolein in culture medium to ascertain the plausible exposure window. Half-life determinations were conducted in low-serum DMEM at room temperature and 37 °C, both with and without H9c2 cells. For quantitative assessment, acrolein was derivatized to a fluorescent 7-hydroxyquinoline method validated in-house and assessed via fluorescent spectroscopy. In closed vessel experiments at room temperature, acrolein in DMEM was reduced by more than 40% at 24 hours, irrespective of the initial concentration. Expectedly, open vessel experiments demonstrated accelerated depletion over time at room temperature, and faster still at 37 °C. The presence of cells tended to further accelerate degradation by an additional 15-30%, depending on temperature. These results undermine described experimental exposure conditions stated in most in-vitro experiments. Recognition of this discrepancy between stated and actual exposure metrics warrant examination of novel alternative objective and representative exposure characterization for in-vitro studies to facilitate translation to in-vivo and in-silico methods.

Factors related to the psychosocial functioning of youth with neonatal brachial plexus injuries.

OBJECTIVE: Owing to the possible visible nature and functional impairments associated with neonatal brachial plexus injuries (NBPI), the current study investigated the relations of injury severity, social support, and coping strategies to social difficulties and self-concept in youth with NBPI. METHODS: 88 children (aged 10-17 years) with NBPI and their parent(s) were recruited from a national organization and two brachial plexus clinics. Participants completed a variety of questionnaires during their scheduled clinic visits. RESULTS: More social support from classmates was associated with better self-concept and fewer social difficulties. Less frequent use of negative coping strategies was associated with better self-concept and fewer social difficulties and was a significant moderator of the relation between injury severity and self-concept. CONCLUSIONS: Clinicians who work with children with NBPI should consider peer support and coping strategies when promoting the psychosocial functioning of these youth.

Pregnancy-adapted YEARS Algorithm: A Retrospective Analysis.

Introduction: Pulmonary embolism (PE) is an imperative diagnosis to make given its associated morbidity. There is no current consensus in the initial workup of pregnant patients suspected of a PE. Prospective studies have been conducted in Europe using a pregnancy-adapted YEARS algorithm, which showed safe reductions in computed tomography pulmonary angiography (CTPA) imaging in pregnant patients suspected of PE. Our objective in this study was 1) to measure the potential avoidance of CTPA use in pregnant patients if the pregnancy-adapted YEARS algorithm had been applied and 2) to serve as an external validation study of the use of this algorithm in the United States. Methods: This study was a single-system retrospective chart analysis. Criteria for inclusion in the cohort consisted of keywords: pregnant; older than 18; chief complaints of shortness of breath, chest pain, tachycardia, hemoptysis, deep vein thromboembolism (DVT), and D-dimer-from January 1, 2019- May 31,2022. We then analyzed this cohort retrospectively using the pregnancy-adapted YEARS algorithm, which includes clinical signs of a DVT, hemoptysis, and PE as the most likely diagnosis with a D-dimer assay. Patients within the cohort were then subdivided into two categories: aligned with the YEARS algorithm, or not aligned with the YEARS algorithm. Patients who did not receive a CTPA were analyzed for a subsequent diagnosis of a PE or DVT within 30 days. Results: A total of 74 pregnant patients were included in this study. There was a PE prevalence of 2.7% (two patients). Of the 36 patients who did not require imaging by the algorithm, seven CTPA were performed. Of the patients who did not receive an initial CTPA, zero were diagnosed with PE or DVT within a 30-day follow-up. In total, 85.1% of all the patients in this study were treated in concordance with the pregnancy-adapted YEARS algorithm. Conclusion: The use of the pregnancy-adapted YEARS algorithm could have resulted in decreased utilization of CTPA in the workup of PE in pregnant patients, and the algorithm showed similar reductions compared to prospective studies done in Europe. The pregnancy-adapted YEARS algorithm was also shown to be similar to the clinical rationale used by clinicians in the evaluation of pregnant patients, which indicates its potential for widespread acceptance into clinical practice.

Botulinum toxin type A outcomes in infants with refractory congenital muscular torticollis.

PURPOSE: The aim of this study was to determine the effectiveness of botulinum toxin type A (BoNT-A) injections in infants with congenital muscular torticollis (CMT) who were refractory to conservative management. METHODS: This was a retrospective study in which all subjects included were seen between 2004 and 2013 and were deemed appropriate for BoNT-A injections. A total of 291 patients were reviewed for inclusion in the study, and 134 patients met the inclusion criteria. Each child was injected with 15-30 units of BoNT-A into each of the following muscles: ipsilateral sternocleidomastoid, upper trapezius, and scalene muscles. The key outcome and variable measurements analyzed included age at time of diagnosis, age at time of initiation of physical therapy, age at time of injection, total number of injection series utilized, muscles injected, and degrees of active and passive cervical rotation and lateral flexion pre- and post-injection. A successful outcome was documented if a child could achieve 45° of active lateral flexion and 80° of active cervical rotation post-injection. Secondary variables including sex, age at time of injection, number of injection series utilized, surgery required, adverse effects of botulinum toxin, presence of plagiocephaly, side of torticollis, orthosis used, presence of hip dysplasia, skeletal anomalies, complications during pregnancy or birth, and any other pertinent information regarding the delivery were also measured. RESULTS: Based on this criteria, 82 children (61%) had successful outcomes. However, only four of the 134 patients required surgical correction. CONCLUSION: BoNT-A may be an effective and safe method for treatment in refractory cases of congenital muscular torticollis.

Bilingual randomized controlled trial design, of a telephone-based intervention to promote rehabilitation adherence; A study focus on recruitment of Hispanic children with traumatic brain injury.

BACKGROUND: While Hispanic children experience large long-term disparities in disability after traumatic Brain Injury (TBI), there is a gap in evidenced-based interventions to improve outcomes among this rapidly growing and at high-risk population. We developed and pilot tested a bilingual/bicultural intervention informed by Hispanic families consisting of Brain Injury Education and outpatient Navigation (1st BIEN). It integrates bilingual in-person education enriched by video content delivered through mobile phone devices, with outpatient navigation by bilingual and bicultural navigators during transitions of care and school return. METHODS: Randomized controlled trial to test the efficacy of 1st BIEN to maintain long-term adherence to rehabilitation and determine its effect on children's functional outcomes. The primary outcome is treatment adherence at 6 months post-discharge at centralized acute facilities and community providers. Secondary outcomes are functional status of the child using PROMIS parental report measures and parental health literacy, self-efficacy, and mental health; measured at baseline (pre-injury and discharge) 3-,6- and 12- months post discharge. Children's academic performance is assessed using school records the year before and the year after injury. DISCUSSION: Our study evaluates a novel, flexible and scalable approach using mobile phone devices to aid transitions of care, increase treatment adherence and improve TBI outcomes. It addresses the needs of an understudied population and builds upon their strengths. It is implemented by a bilingual and bicultural team with a deep understanding of the study population. It can serve as a model for TBI family centered interventions for at risk groups. TRIAL REGISTRATION: ClinicalTrials.govNCT05261477. Registered on March 2, 2022.

Telehealth in PM&R: Past, present, and future in clinical practice and opportunities for translational research.

Telehealth refers to the use of telecommunication devices and other forms of technology to provide services outside of the traditional in-person health care delivery system. Growth in the use of telehealth creates new challenges and opportunities for implementation in clinical practice. The American Academy of Physical Medicine and Rehabilitation (AAPM&R) assembled an expert group to develop a white paper to examine telehealth innovation in Physical Medicine and Rehabilitation (PM&R). The resultant white paper summarizes how telehealth is best used in the field of PM&R while highlighting current knowledge deficits and technological limitations. The report identifies new and transformative opportunities for PM&R to advance translational research related to telehealth and enhance patient care.

School reopening during COVID-19 pandemic: Considering students with disabilities.

Over 80% of the children in the world have had their education impacted by COVID-19. For children with disabilities who receive special education services, access to in-person education and other resources at school is particularly important. The American Academy of Pediatrics advocates for students to attend school in person, without specifics for how children with disabilities can safely return to school. To appropriately plan and accommodate children with disabilities we must prioritize safety, allow for adherence to the Individuals with Disabilities Education Act, and preserve essential school staff. The less cumbersome default of confining students with disabilities to home is not acceptable. We provide an outline describing why Individual Education Plans and 504 plans are important, how they are related to the COVID-19 pandemic, and recommendations for measures to help with safe return to school for children with disabilities.

Improvement in survival and muscle function in an mdx/utrn(-/-) double mutant mouse using a human retinal dystrophin transgene.

Duchenne muscular dystrophy is a progressive muscle disease characterized by increasing muscle weakness and death by the third decade. mdx mice exhibit the underlying muscle disease but appear physically normal with ordinary lifespans, possibly due to compensatory expression of utrophin. In contrast, double mutant mice (mdx/utrn(-/-)), deficient for both dystrophin and utrophin die by approximately 3 months and suffer from severe muscle weakness, growth retardation, and severe spinal curvature. The capacity of human retinal dystrophin (Dp260) to compensate for the missing 427 kDa muscle dystrophin was tested in mdx/utrn(-/-) mice. Functional outcomes were assessed by histology, EMG, MRI, mobility, weight and longevity. MCK-driven transgenic expression of Dp260 in mdx/utrn(-/-) mice converts their disease course from a severe, lethal muscular dystrophy to a viable, mild myopathic phenotype. This finding is relevant to the design of exon-skipping therapeutic strategies since Dp260 lacks dystrophin exons 1-29.

Inherited polyneuropathies.

The large degree of clinical heterogeneity within each of the major categories of inherited neuropathies can lead to difficulties in making correct diagnoses based on clinical findings alone. The observation of key clinical findings coupled with electrophysiological findings and understanding of inheritance patterns, should allow the clinician to make judicious use of genetic testing to confirm the clinical diagnosis. An understanding of the clinical and electrophysiological nature of these disorders, as well as an understanding of how to clinically distinguish the inherited conditions from acquired conditions, is imperative to this process.

Amoeba proteus displays a walking form of locomotion.

This report deals with observations on the directional locomotion of amoeba before and after fixation and scanning electron microscopy. The study was aimed at visualization of the stepwise events of directional movements. After the analysis of the data it is proposed that the amoeba undergoes a sequence of movement events that can be defined as a walking form of locomotion.