Extruded alginate tubes with myogenic potential.

BACKGROUND: There are currently no proven methods to reverse muscle loss in humans, which is caused by trauma (e.g., volumetric muscle loss, VML), genetic neuromuscular diseases (e.g., muscular dystrophies, MDs), and accelerated senescence (e.g., sarcopenia). Since muscle tissue is capable of regeneration through muscle satellite cells (MuSCs), the implantation of autologous (or other) donor MuSCs and MuSC-derived myoblasts into host muscles can promote donor-cell-derived myogenesis. Direct injection or implantation of MuSCs or MuSC-derived myoblasts into host muscles only promotes minimal donor-cell-derived myogenesis, whereas implantation of MuSCs/myoblasts along with associated muscle tissue (muscle fibers, extracellular matrix, neurovascular pathways, etc.) gives better results. METHODS: We aim to leverage the benefits of constraining donor myogenic cells within a template that resembles muscle tissue. In this paper, we present a workflow for basic and translational studies aimed at promoting donor-cell-derived myogenesis to increase functional muscle mass in mice. Our workflow involves preparing a slurry of 10% sodium alginate mixed with myogenic cells in cell culture media, extruding the cell-containing slurry into 10% calcium lactate to form tubes, and implanting the cellularized alginate tubes into host muscle. RESULTS: Our data suggest that, the extruded alginate tubes can tolerate a peak stress of 1892 ± 527 mN, that the elastic range is at ~75-125% strain beyond initial length, and that the Young's modulus (stiffness) is 14.17 ± 1.68 %/mm 2 . Importantly, these mechanical properties render the alginate tubes suitable for a published technique known as minimally-invasive muscle embedding (MIME) that was developed by us to implant myogenic material into host muscle. MIME involves threading donor myogenic tissue into a needle track created within a host muscle. Cellularized alginate tubes implanted into the tibialis anterior muscle of previously euthanized mice had numerous hematoxylin-stained structures similar to nuclear staining, supporting the idea that our alginate tubes can support cell seeding. Alginate tubes that were seeded with MuSCs, incubated in MuSC/myoblast growth (i.e., proliferation) media for two days, incubated in myotube differentiation media for six days, and then minced and reseeded in new dishes, were able to promote in vitro myoblast outgrowth over several days. DISCUSSION: This pilot study is limited in its translational scope because it was performed in vitro and with previously euthanized mice. Additional studies are needed to confirm that cellularized alginate tubes can promote the de novo development of donor-cell-derived muscle fibers, which can contribute to contractile force production. CONCLUSION: Alginate tubes with MuSC/myoblasts can be generated by a simple extrusion method. The alginate tubes have sufficient mechanical strength to tolerate insertion into a host muscle, in a minimally-invasive manner, through a needle track. The cellularized alginate tubes demonstrate myogenic potential since they are capable of being maintained in culture conditions for several days, after which they can still facilitate myoblast outgrowth in a dish.

Case Report: Pediatric Thyroid Storm Presenting to the Emergency Department with Afebrile Seizure.

Introduction: Seizures are a common presenting complaint and account for approximately 1% of total emergency department (ED) visits. Seizures are especially common in children less than five years old as they have a lower seizure threshold as compared to adults. One potentially dangerous etiology that is far less common, especially in children, is thyroid storm, the extreme manifestation of hyperthyroidism. Case Report: We describe the case of a 3-year-old girl who presented to the ED with an afebrile seizure but was found to be in thyroid storm. This case should serve as a reminder for emergency physicians to consider thyroid disease when evaluating patients presenting with seizures. Conclusion: Although most pediatric seizures are self-limited and frequently benign, it is imperative that the emergency physician evaluate for and rule out any potentially associated dangerous conditions such as thyroid storm.

Advances in pediatric emergency from 2023.

Most children receive emergency care by general emergency physicians and not in designated children's hospitals. There are unique considerations in the care of children that differ from the care of adults. Many management principles can be extrapolated from adult studies, but the unique pathophysiology of pediatric disease requires specialized attention and management updates. This article highlights ten impactful articles from the year 2023 whose findings can improve the care of children in the Emergency Department (ED). These studies address pediatric resuscitation, traumatic arrest, septic shock, airway management, nailbed injuries, bronchiolitis, infant fever, cervical spine injuries, and cancer risk from radiation (Table 1). The findings in these articles have the potential to impact the evaluation and management of children (Table 2).

Acute opioid overdose in pediatric patients.

Recent increases in pediatric and adolescent opioid fatalities mandate an urgent need for early consideration of possible opioid exposure and specific diagnostic and management strategies and interventions tailored to these unique populations. In contrast to adults, pediatric methods of exposure include accidental ingestions, prescription misuse, and household exposure. Early recognition, appropriate diagnostic evaluation, along with specialized treatment for opioid toxicity in this demographic are discussed. A key focus is on Naloxone, an essential medication for opioid intoxication, addressing its unique challenges in pediatric use. Unique pediatric considerations include recognition of accidental ingestions in our youngest population, critical social aspects including home safety and intentional exposure, and harm reduction strategies, mainly through Naloxone distribution and education on safe medication practices. It calls for a multifaceted approach, including creating pediatric-specific guidelines, to combat the opioid crisis among children and to work to lower morbidity and mortality from opioid overdoses.

Review of pediatric emergency care and the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic posed new challenges in health care delivery for patients of all ages. These included inadequate personal protective equipment, workforce shortages, and unknowns related to a novel virus. Children have been uniquely impacted by COVID-19, both from the system of care and socially. In the initial surges of COVID-19, a decrease in pediatric emergency department (ED) volume and a concomitant increase in critically ill adult patients resulted in re-deployment of pediatric workforce to care for adult patients. Later in the pandemic, a surge in the number of critically ill children was attributed to multisystem inflammatory syndrome in children. This was an unexpected complication of COVID-19 and further challenged the health care system. This article reviews the impact of COVID-19 on the entire pediatric emergency care continuum, factors affecting ED care of children with COVID-19 infection, including availability of vaccines and therapeutics approved for children, and pediatric emergency medicine workforce innovations and/or strategies. Furthermore, it provides guidance to emergency preparedness for optimal delivery of care in future health-related crises.

Industry 5 and the Human in Human-Centric Manufacturing.

Industry 4 (I4) was a revolutionary new stage for technological progress in manufacturing which promised a new level of interconnectedness between a diverse range of technologies. Sensors, as a point technology, play an important role in these developments, facilitating human-machine interaction and enabling data collection for system-level technologies. Concerns for human labour working in I4 environments (e.g., health and safety, data generation and extraction) are acknowledged by Industry 5 (I5), an update of I4 which promises greater attention to human-machine relations through a values-driven approach to collaboration and co-design. This article explores how engineering experts integrate values promoted by policy-makers into both their thinking about the human in their work and in their writing. This paper demonstrates a novel interdisciplinary approach in which an awareness of different disciplinary epistemic values associated with humans and work guides a systematic literature review and interpretive coding of practice-focussed engineering papers. Findings demonstrate evidence of an I5 human-centric approach: a high value for employees as "end-users" of innovative systems in manufacturing; and an increase in output addressing human activity in modelling and the technologies available to address this concern. However, epistemic publishing practices show that efforts to increase the effectiveness of manufacturing systems often neglect worker voice.

Pediatric and Adolescent Gynecologic Emergencies.

Pediatric gynecology encompasses a wide range of topics from the maternal estrogen impact on the neonate, to the unique pathophysiology of the lack of estrogen on prepubescent females, and the independence and sexual maturation that occurs with adolescence. This article will review the impact of normal hormonal variations in children, unique pathophysiology of certain conditions in the prepubescent period, as well as common injuries and infections of the genitourinary system in children.

Nocturnal surveys of lined seahorses reveal increased densities and seasonal recruitment patterns.

Although the nighttime ecology of organisms remains understudied, nocturnal surveys play an integral part in assessing fish assemblages and the selective forces shaping them. Eleuthera (Bahamas) contains an unusual population of lined seahorses (Hippocampus erectus) in an anchialine lake, possessing morphological characteristics distinct from those found in the ocean. Population surveys for seahorses and their potential predators were conducted at midnight and midday during wet and dry seasons, with belt transects perpendicular to the shoreline that increased in depth away from shore. Nocturnal surveys uncovered seahorse densities 259% higher than daytime transects on average. Sex ratios were consistently male-biased, and the frequency of animals from different reproductive categories varied significantly by time of day, with gravid males observed around the clock but females and nongravid males observed more often at night. Spatial and seasonal recruitment was detected for the first time in this species, with an increase in juveniles detected in the shallow ends of transects during dry season surveys. Juvenile recruitment is poorly understood across syngnathid fishes, so the detection of early recruits at night has broad implications for this fish family. Seahorses from all reproductive categories were perched significantly higher in the water column during the night regardless of their depth or season. Predator densities followed a similar pattern with higher densities observed at night, indicating that elevated nocturnal perch height may be a response to predator presence. However, the selective agents driving these nocturnal behaviors have yet to be identified. Considering H. erectus is listed on the IUCN Red List as "Vulnerable," the increase in nocturnal population size and the detection of juveniles has crucial implications for understanding their ecology, recruitment, and conservation.

Evaluation of the Delivery of a Live Attenuated Porcine Reproductive and Respiratory Syndrome Virus as a Unit Solid Dose Injectable Vaccine.

Solid dose vaccine formulation and delivery systems offer potential advantages over traditional liquid vaccine formulations. In addition to enhanced thermostability, needle-free delivery of unit solid dose injectable (USDI) vaccines offers safe, rapid, and error-free administration, with applicability to both human and animal health. Solid dose formulation technologies can be adapted for delivery of different vaccine formats including live attenuated vaccines, which remain the 'gold standard' for many disease targets. Porcine reproductive and respiratory syndrome viruses (PRRSV) cause one of the most economically important diseases affecting the global pig industry. Despite several shortcomings, live attenuated vaccines are widely used to control PRRSV. We optimised a freeze-dried USDI formulation of live attenuated PRRSV-1, which fully retained infectious titre, and evaluated its immunogenicity in comparison to virus delivered in liquid suspension via intramuscular and subcutaneous needle inoculation. Pigs vaccinated with the USDI formulation displayed vaccine viraemia, and PRRSV-specific antibody and T cell responses comparable to animals immunised with the liquid vaccine. The USDI vaccine formulation was stable for at least 6 months when stored refrigerated. These data demonstrate the potential for a solid dose vaccine delivery system as an alternative to conventional needle-syringe delivery of live attenuated PRRSV vaccines.

Seroconversion among rituximab-treated patients following SARS-CoV-2 vaccine supplemental dose.

Rituximab (RTX) is a very effective treatment for autoimmune rheumatic diseases (AIRD), but it increases infection risk and impairs vaccine responses. Herein we evaluated the antibody response of RTX-treated patients to the supplemental COVID-19 vaccine. After the supplemental dose, 53.1% of patients had detectable antibody titers. Only 36% of patients who did not mount an antibody response after the original vaccine series did have detectable antibodies after the supplemental dose (seroconversion). Patients with undetectable CD20+ cell levels did not seroconvert while hypogammaglobulinemia was associated with a 15-times decrease in the likelihood of seroconversion. Although we noted 11 COVID-19 infections after the supplemental dose, no patients who received monoclonal antibodies pre-exposure prophylaxis had COVID-19 afterwards. We propose that patients receiving RTX should continue to be prioritized for prophylaxis measures and that vaccination should be timed after B cell recovery wherever possible.

Marijuana use in children: An update focusing on pediatric tetrahydrocannabinol and cannabidiol use.

Cannabis is the most used recreational drug in the United States, and its use is increasing among children and adolescents.  With the increase in legalized use, there have been increases in intentional and accidental cannabis exposure in the pediatric population. There is also minimized perceived risk.  We review the current use of cannabis and its derivatives, the drug effects and clinical presentation, common misconceptions, pharmacology, and epidemiology. Finally, we review some long-term consequences of cannabis use.

The evolution of the testis transcriptome in pregnant male pipefishes and seahorses.

In many animals, sperm competition and sexual conflict are thought to drive the rapid evolution of male-specific genes, especially those expressed in the testes. A potential exception occurs in the male pregnant pipefishes, where females transfer eggs to the males, eliminating testes from participating in these processes. Here, we show that testis-related genes differ dramatically in their rates of molecular evolution and expression patterns in pipefishes and seahorses (Syngnathidae) compared to other fish. Genes involved in testis or sperm function within syngnathids experience weaker selection in comparison to their orthologs in spawning and livebearing fishes. An assessment of gene turnover and expression in the testis transcriptome suggests that syngnathids have lost (or significantly reduced expression of) important classes of genes from their testis transcriptomes compared to other fish. Our results indicate that more than 50 million years of male pregnancy have removed syngnathid testes from the molecular arms race that drives the rapid evolution of male reproductive genes in other taxa.

Managing acute pain in children presenting to the emergency department without opioids.

Pediatric pain is challenging to assess and manage. Frequently underestimated in children, untreated pain may have consequences including increased fear, anxiety, and psychological issues. With the current opioid crisis, emergency physicians must be knowledgeable in both pharmacologic and non-pharmacologic approaches to address pain and anxiety in children that lead to enhanced patient cooperation and family satisfaction. This document focuses pain management and distress mitigation strategies for the brief diagnostic and therapeutic procedures commonly performed.

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies: incidence using different testing criteria, and case series.

OBJECTIVES: To estimate the incidence of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies utilising different testing criteria, and review the clinical details of a series of patients with associated autoimmune myopathy. METHODS: The incidence of anti-HMGCR antibodies in 2019 from 3 groups, South West London, Berkshire/Surrey and Southampton, were compared in the adult population. Anti-HMGCR antibodies were measured by commercial chemiluminescent and immunodot assays. The case notes of patients with anti-HMGCR antibodies were reviewed for the case series. RESULTS: The estimated incidence of anti-HMGCR antibodies in the first 2 groups was 1.94 per million adults per year, and in the third group 10.3 per million adults per year. In the first 2 groups the test criteria restricted analysis to specific clinician request for anti-HMGCR. In the third group test criteria included cases with less specific clinical features or a cytoplasmic indirect immunofluorescence anti-nuclear antibody pattern. The latter strategy had a positive predictive value of 66.1% for anti-HMGCR associated myopathy. A case series of 27 patients with anti-HMGCR antibodies revealed 19 with myopathy, oesophageal involvement in 26% and median peak CK 8000 IU/L. Response to treatment, including intravenous immunoglobulin, was good with CK normalising after median 5.5 months. In 8 cases there was no evidence of autoimmune muscle disease, 7 not statin exposed. CONCLUSIONS: Varying criteria result in a 5-fold difference in estimated incidence of anti-HMGCR antibodies, revealing positive cases without evidence of myopathy. Patients with anti-HMGCR myopathy respond well to immune suppression, supporting wider testing for these antibodies amongst patients with myopathy.

Use of 18F-fluorodeoxyglucose positron emission tomography to standardize clinical trial recruitment in Takayasu's arteritis.

OBJECTIVES: To assess whether data from 18F-fluorodeoxyglucose (FDG) PET should be incorporated into eligibility criteria for clinical trials in Takayasu's arteritis (TAK). METHODS: The study was conducted in two parts. Part one was an international online survey among physicians with experience managing TAK to determine, using clinical vignettes, whether FDG-PET data influence decisions about enrolment in trials. Part two used patient data from an observational cohort study in TAK to assess agreement regarding decisions about enrolment into trials, based on clinical assessment with and without incorporation of FDG-PET data. RESULTS: In part one, 68 physicians responded to the survey. Most physicians had used FDG-PET to diagnose TAK (82%) or monitor disease activity (66%). In vignettes representing active clinical disease, FDG-PET findings increased physician confidence in disease assessment and reduced outlier assessments. The greatest variability in decisions regarding enrolment into trials was observed in vignettes representing constitutional symptoms alone and elevated acute-phase reactants. In these cases, FDG-PET findings influenced decisions about enrolment and improved physician confidence. In multivariable models, FDG-PET findings were 1.29 times more strongly associated with enrolment decisions compared with levels of acute-phase reactants. In part two, incorporation of FDG-PET data significantly improved agreement about enrolment decisions between raters [inter-rater reliability (IRR) = 0.68 (95% CI 0.67, 0.69) to IRR = 0.88 (95% CI 0.87, 0.89); P < 0.01]. CONCLUSIONS: Incorporation of FDG-PET data into assessment of TAK influences decisions about enrolment of patients into trials, improves physician confidence about clinical assessment and could help reduce variability in study populations. Future trials in TAK should consider incorporating FDG-PET data into eligibility criteria.

A prospective observational cohort study and systematic review of 40 patients with mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome.

OBJECTIVE: Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is characterized by overlapping features of relapsing polychondritis (RP) and Behcet's disease (BD). To date, no studies have defined the clinical spectrum of disease in a cohort of patients with MAGIC syndrome. METHODS: Adult patients within an ongoing prospective, observational cohort study in RP were clinically assessed for MAGIC syndrome. A systematic review was conducted to identify additional cases of MAGIC syndrome by searching four databases: PubMed (US National Library of Medicine), Embase (Elsevier), Scopus (Elsevier) and Web of Science: Core Collection (Clarivate Analytics). The inclusion criteria used were: [1] patients of any age or gender who were diagnosed with MAGIC syndrome, or both RP and BD; [2] case report or case series study; [3] published from 1985 - July 2020; and [4] in English language. Risk of bias was assessed using a checklist developed by the authors and based on the Consensus-based Clinical Case Reporting (CARE) Guidelines. Search results screening, article inclusion, data extraction and risk of bais assessment was performed independently by two investigators. Clinical characteristics, particularly BD-related features, were compared between patients with MAGIC syndrome and cases of non-MAGIC RP. The performance characteristics of different criteria to classify MAGIC syndrome were also evaluated. RESULTS: Out of 96 patients with RP, 13 (14%) patients were diagnosed with MAGIC syndrome. For the systematic review, 380 articles were retrieved of which 90 were screened at title and abstract levels. Of these screened, 60 were excluded and 30 proceeded to full text review where an additional 8 were excluded. Twenty-two articles were included in our review and from which 27 additional cases of MAGIC syndrome were identified. Pooling all 40 cases together and comparing them with non-MAGIC RP, there was a significantly higher prevalence of ocular involvement (28% vs 4%, p<0.01), cutaneous involvement (35% vs 1%, p<0.01), GI involvement (23% vs 4%, p<0.01), and CNS involvement (8% vs 0, p = 0.04) in MAGIC syndrome. A higher prevalence of aortitis (23% vs 1%, p<0.01), Raynaud's phenomenon (54% vs 11%, p<0.01), and elevated anti-collagen II antibodies (50% vs 9%, p = 0.04) were observed in MAGIC syndrome. Fulfillment of either McAdam's or Damiani's Criteria for RP plus the International Criteria for Behçet's Disease had excellent sensitivity (98%) to classify cases of MAGIC syndrome. CONCLUSION: A substantial proportion of patients with RP can be clinically diagnosed with MAGIC syndrome. These patients have features of RP, BD, and other unique features including aortitis, Raynaud's phenomenon and elevated anti-collagen II antibodies.

Addressing Advance Care Planning in Patients With COPD.

COPD is a progressive debilitating disease with diminished quality of life after hospital admissions. Because of the nature of the disease, it is important to address patients' goals of care, preferably prior to the development of refractory COPD. Advance Care Planning (ACP) is an all-encompassing term that involves discussing goals with patients. Various review articles on ACP and COPD focus on the definition of ACP, identification of barriers to addressing ACP, and the use of interventions to incorporate ACP in practice. There is evidence that ACP improves quality of communication, reduces admissions, and increases quality of life, but often the focus of that research has been on patients with cancer. Many of the articles have suggestions for how to apply ACP to chronic lung disease; however, without further research and definitive guidance, obtaining funding for programs dedicated to ACP may be difficult. There are currently no guidelines for addressing ACP in patients with COPD. Research addresses the reason that advance care planning is important, yet there are barriers that patients, families, and health care providers encounter that prevent meaningful discussions. Research has also found that the use of multidisciplinary teams improves care and quality of life; however, research should be dedicated to the investigation of the effects of advance care planning initiatives on outcomes in patients with COPD, particularly in the reduction of hospital admissions and improvement of quality of life. This review seeks to educate providers about end-stage COPD and advance care planning, the evidence that shows the importance of advance care planning, and the current and future state of research.

Physician Global Assessment as a Disease Activity Measure for Relapsing Polychondritis.

OBJECTIVE: Relapsing polychondritis (RP) is a systemic inflammatory disorder of cartilage that lacks validated disease activity measures. Our objective was to test physician global assessment (PhGA), a measure of disease activity commonly used in rheumatic diseases, in a cohort of patients with RP, which has not been done before. METHODS: Adult patients in an observational cohort of RP underwent standardized, comprehensive evaluation at approximately 6-month intervals. PhGA was scored by 3 physicians from the evaluating institution on a scale of 0-10 for each visit. A random subset of 20 visits was scored by 3 independent physicians not affiliated with the evaluating institution. Treatment change between consecutive visits was categorized as increased, decreased, or unchanged. RESULTS: In total, 78 patients were evaluated over 164 visits. The intraclass correlation coefficient (ICC2,1 ) for the 3 raters from the evaluating institution was excellent (0.79 [95% confidence interval (95% CI) 0.73, 0.84]) but was poor in the subset of cases scored by the additional raters (ICC2,1 0.27 [95% CI -0.01, 0.53]). Median PhGA was 3 (range 0-7). PhGA weakly correlated with C-reactive protein level (rs = 0.30, P < 0.01). In response to increased treatment, median PhGA decreased from 3 (interquartile range [IQR] 2, 4) to 2 (IQR 2, 3) (P < 0.01) but rarely went to 0. CONCLUSION: Within a single center, PhGA can be used to quantify disease activity and monitor disease response in RP. Persistent disease activity despite treatment, rather than a relapsing-remitting pattern, is observed for most patients with RP. Reliability of PhGA may not generalize across different institutions. A validated disease-specific activity index is needed in RP.

Discordance in patient and physician global assessment in relapsing polychondritis.

OBJECTIVES: Relapsing polychondritis (RP) is a rare, heterogeneous, systemic inflammatory disease that targets cartilage. Patient-reported outcome measures may differ from physician assessment. This study compared patient global assessment (PtGA) and physician global assessment (PhGA) scores in a prospective cohort of patients with RP. METHODS: Adult patients with RP underwent a standardized comprehensive evaluation at ∼6 month intervals. At each visit, three physicians scored PhGA by consensus. The patient independently completed four patient-reported outcomes: PtGA, 36-item Short Form Health Survey (SF-36), Brief Illness Perception Questionnaire (BIPQ) and Multidimensional Fatigue Inventory (MFI). Patient-physician discordance was defined as a difference between PtGA and PhGA of ≥3 on a 0-10 scale. RESULTS: A total of 76 patients were evaluated over 154 visits. The median PhGA was 3 [interquartile range (IQR) 2-3] and the median PtGA was 5 (IQR 4-7). PtGA and PhGA were concordant in 66 visits (42.9%) and patients scored disease severity ≥3 points higher than physicians scored disease activity (positive discordance) in 84 visits (54.5%). Compared with visits with concordance, visits with positive discordance were associated with significantly worse scores on the MFI, BIPQ, SF-36 physical component score and SF-36 mental component score. CONCLUSION: Patients with RP typically self-report high PtGA that does not align with PhGA. Discordance is likely driven by the high physical and psychological burden of illness experienced by patients. Multifaceted treatment approaches that address the burden of disease in RP from the patient perspective are needed.