An Ergonomics Analysis of Archers through Motion Tracking to Prevent Injuries and Improve Performance.

Archery ranks among the sports with a high incidence of upper extremity injuries, particularly affecting the drawing shoulder and elbow, as well as inducing stress on the lower back. This study seeks to bridge the gap by integrating real-time human motion with biomechanical software to enhance the ergonomics of archers. Thirteen participants were involved in four tasks, using different bows with varied draw weights and shooting distances. Through the application of advanced integrative technology, this study highlights the distinct postures adopted by both males and females, which indicate the biomechanical differences between genders. Additionally, an analysis of the correlation between exposed spinal forces and these adopted postures provides insights into injury risk assessment during the key archery movements. The findings of this study have the potential to significantly enhance the application of training methodologies and the design of assistive devices. These improvements are geared towards mitigating injury risks and enhancing the overall performance of archers.

Additive Manufacturing: A Comprehensive Review.

Additive manufacturing has revolutionized manufacturing across a spectrum of industries by enabling the production of complex geometries with unparalleled customization and reduced waste. Beginning as a rapid prototyping tool, additive manufacturing has matured into a comprehensive manufacturing solution, embracing a wide range of materials, such as polymers, metals, ceramics, and composites. This paper delves into the workflow of additive manufacturing, encompassing design, modeling, slicing, printing, and post-processing. Various additive manufacturing technologies are explored, including material extrusion, VAT polymerization, material jetting, binder jetting, selective laser sintering, selective laser melting, direct metal laser sintering, electron beam melting, multi-jet fusion, direct energy deposition, carbon fiber reinforced, laminated object manufacturing, and more, discussing their principles, advantages, disadvantages, material compatibilities, applications, and developing trends. Additionally, the future of additive manufacturing is projected, highlighting potential advancements in 3D bioprinting, 3D food printing, large-scale 3D printing, 4D printing, and AI-based additive manufacturing. This comprehensive survey aims to underscore the transformative impact of additive manufacturing on global manufacturing, emphasizing ongoing challenges and the promising horizon of innovations that could further elevate its role in the manufacturing revolution.

Definition and Clinical Evaluation for Trimethoprim-Sulfamethoxazole Severe Acute Respiratory Failure.

OBJECTIVES: Trimethoprim-sulfamethoxazole (TMP-SMX)-associated severe acute respiratory distress syndrome (ARDS) has gone underrecognized. We propose the first disease definition and clinical evaluation for a novel adverse drug reaction (ADR) based on a series of recently identified rare cases of life-threatening ADRs. DESIGN: A retrospective study was conducted. All medical records were evaluated. Available pathology samples were sent to Massachusetts General for clinical consultation. Blood samples from surviving patients were obtained and human leukocyte antigen (HLA) analysis was performed by the Children's Mercy Hospital Genomic Center and Vanderbilt University Medical Center. SETTING: U.S. ICUs, 1996-2021. PATIENTS: Nineteen young patients (10-37) were identified. Patients were previously healthy, with no preexisting pulmonary disease, no other cause for respiratory failure, and no chronic history of smoking/vaping. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Through our retrospective analysis, we analyzed clinical characteristics associated with TMP-SMX. Pathology samples were reviewed, and HLA analysis was performed on available samples by the study team or as standard of care at treatment hospitals in some cases. In 19 critically ill patients, we identified a pattern of severe respiratory failure requiring ICU admission, mechanical ventilation, and frequent extracorporeal membrane oxygenation use. We describe the first three-part clinical diagnosis and evaluation strategy: 1) Clinical definition: Unexplained severe respiratory failure in a patient receiving greater than or equal to 6 days of TMP-SMX at treatment dose (not prophylaxis). TMP-SMX ARDS is a diagnosis of exclusion. 2) Genetic association: One hundred percent of currently available TMP-SMX respiratory failure patient genomic data, ( n = 11) have been carriers of both HLA-B*07:02 and HLA-C*07:02 alleles. HLA allele evaluation could be considered in patients with suspected TMP-SMX respiratory failure. 3) Lung pathology: A unique pulmonary pathologic pattern of lung injury termed diffuse alveolar injury with delayed epithelialization has been observed in these cases. In suspected cases, surgical lung biopsy early in the clinical course could be considered. CONCLUSIONS: TMP-SMX is a commonly prescribed antibiotic. However, we find it imperative to share this relatively rare but life-threatening condition with clinicians as the mortality rate approaches 40%.

Nitrogen Heterocycle Synthesis through Hydride Abstraction of Acyclic Carbamates and Related Species: Scope, Mechanism, Stereoselectivity, and Product Conformation Studies.

Acyliminium ions and related species are potent electrophiles that can be quite valuable in the synthesis of nitrogen-containing molecules. This manuscript describes a protocol to form these intermediates through hydride abstractions of easily accessible allylic carbamates, amides, and sulfonamides that avoids the reversibility that is possible in classical condensation-based routes. These intermediates are used in the preparation of a range of nitrogen-containing heterocycles, and in many cases high levels of stereocontrol are observed. Specifically areas of investigation include the impact of chemical structure on oxidation efficiency, the geometry of the intermediate iminium ions, the impact of a substrate stereocenter on stereocontrol, and an examination of transition state geometry.

Computed Tomography Coronary Angiography on a Detector-Based Spectral Computed Tomography Platform: Evaluation of Patients With Coronary Artery Disease Reporting and Data System Score of 3 and Higher.

PURPOSE: Computed tomography (CT) coronary angiography performed on a detector-based spectral scanner helps more closely approximate severity of stenosis with nuclear medicine and cardiac catheterization tests compared with single-energy CT (SECT) in patients with an original CAD-RADS score of 3 and higher. METHODS: This retrospective trial was conducted between January 2017 and December 2019 and included 52 patients with a CAD-RADS score of 3 and higher. Two reading sessions were performed 6 weeks apart. The first reading session was performed using only conventional images and the second reading session was performed using spectral results. Detector-based spectral CT CAD-RADS scores were compared with cardiac stress test and/or cardiac catheterization results for final characterization of stenosis in 41 segments from 32 patients. The mean CAD-RADS score was calculated for both the conventional images and spectral images. RESULTS: The CAD-RADS score for SECT and the score for spectral CT for the 41 segments were compared. Available associated stress test and/or cardiac catheterization results were also compared with CAD-RADS scores. In 51% (21/41), a diagnosis concordant with best practices results was achieved with the help of spectral CT results. A mean CAD-RADS score of 3.56 was obtained using spectral results, compared with 3.93 using conventional images. A 2-tailed paired t test determined the difference to be significant with a P value of 0.007. CONCLUSIONS: Computed tomography coronary angiography is feasible on a detector-based spectral CT scanner and can improve diagnostic confidence over SECT angiography in patients with an original CAD-RADS score of 3 and higher.

Synthetic applications of hydride abstraction reactions by organic oxidants.

Carbon-hydrogen bond functionalizations provide an attractive method for streamlining organic synthesis, and many strategies have been developed for conducting these transformations. Hydride-abstracting reactions have emerged as extremely effective methods for oxidative bond-forming processes due to their mild reaction conditions and high chemoselectivity. This review will predominantly focus on the mechanism, reaction development, natural product synthesis applications, approaches to catalysis, and use in enantioselective processes for hydride abstractions by quinone, oxoammonium ion, and carbocation oxidants. These are the most commonly employed hydride-abstracting agents, but recent efforts illustrate the potential for weaker ketone and triaryl borane oxidants, which will be covered at the end of the review.

HLA-B*07:02 and HLA-C*07:02 are associated with trimethoprim-sulfamethoxazole respiratory failure.

We have identified an underrecognized severe adverse drug reaction (ADR) of trimethoprim-sulfamethoxazole (TMP-SMX) associated respiratory failure in previously healthy children and young adults. We investigated potential genetic risk factors associated with TMP-SMX induced respiratory failure in a cohort of seven patients. We explored whole genome sequence among seven patients representing nearly half of all reported cases worldwide and 63 unrelated control individuals in two stages: (1) human leukocyte antigen (HLA) locus variation as several other ADRs have been associated HLA genetic variants and (2) coding variation to catalog and explore potential rare variants contributing to this devastating reaction. All cases were either heterozygous (carriers) or homozygous for the common HLA-B*07:02-HLA-C*07:02 haplotype. Despite the small sample size, this observation is statistically significant both in conservative comparison to maximum reported population frequencies (binomial P = 0.00017 for HLA-B and P = 0.00028 for HLA-C) and to our control population assessed by same HLA genotyping approach (binomial P = 0.000001 for HLA-B and P = 0.000018 for HLA-C). No gene elsewhere in the genome harnessed shared rare case enriched coding variation. Our results suggests that HLA-B*07:02 and HLA-C*07:02 are necessary for a patient to develop respiratory failure due to TMP-SMX.

Mechanism-Based Approach to Reagent Selection for Oxidative Carbon-Hydrogen Bond Cleavage Reactions.

Numerous hydride-abstracting agents generate the same cationic intermediate, but substrate features such as intermediate cation stability, oxidation potential, and steric environment can influence reaction rates in an oxidant-dependent manner. This manuscript provides experimental data to illustrate the role that structural features play in the kinetics of hydride abstraction reactions with commonly used quinone-, oxoammonium ion-, and carbocation- based oxidants. Computational studies of the transition state structures and energies explain these results and energy decomposition analysis calculations reveal unique sensitivities to electrostatic attraction and steric repulsions. Rigorous rate studies of select reactions validated the capacity of the calculations to predict reactivity trends. Additionally, kinetics studies demonstrate the potential for product inhibition in DDQ-mediated reactions. These studies provide a clear guide to select the optimal oxidant for structurally disparate substrates and lead to predictions of reactivity that were validated experimentally.

Pharmacogenomics of Pain Management: The Impact of Specific Biological Polymorphisms on Drugs and Metabolism.

PURPOSE OF REVIEW: Pain is multifactorial and complex, often with a genetic component. Pharmacogenomics is a relative new field, which allows for the development of a truly unique and personalized therapeutic approach in the treatment of pain. RECENT FINDINGS: Until recently, drug mechanisms in humans were determined by testing that drug in a population and calculating response averages. However, some patients will inevitably fall outside of those averages, and it is nearly impossible to predict who those outliers might be. Pharmacogenetics considers a patient's unique genetic information and allows for anticipation of that individual's response to medication. Pharmacogenomic testing is steadily making progress in the management of pain by being able to identify individual differences in the perception of pain and susceptibility and sensitivity to drugs based on genetic markers. This has a huge potential to increase efficacy and reduce the incidence of iatrogenic drug dependence and addiction. The streamlining of relevant polymorphisms of genes encoding receptors, transporters, and drug-metabolizing enzymes influencing the pain phenotype can be an important guide to develop safe new strategies and approaches to personalized pain management. Additionally, some challenges still prevail and preclude adoption of pharmacogenomic testing universally. These include lack of knowledge about pharmacogenomic testing, inadequate standardization of the process of data handling, questionable benefits about the clinical and financial aspects of pharmacogenomic testing-guided therapy, discrepancies in clinical evidence supporting these tests, and doubtful reimbursement of the tests by health insurance agencies.

Continuing Medical Education for Air Medical Providers: The Successes and Challenges.

OBJECTIVE: Research has shown that patients transported by nonpediatric teams have higher rates of morbidity and mortality. There is currently a paucity of pediatric standardized ongoing medical education for emergency medical service providers, thus we aimed to develop a model curriculum to increase their knowledge regarding pediatric respiratory distress and failure. METHODS: The curriculum was based on the Kolb Learning Cycle to optimize learning. Target learners were flight nurses (registered nurse) and emergency medical technicians of a private helicopter emergency transport team. The topics included were pediatric stridor, wheezing, and respiratory failure. Online modules were developed for continued spaced education. Knowledge gained from the interventions was measured by precurricular and postcurricular testing and compared with paired t tests. A linear mixed regression model was used to investigate covariates of interest. RESULTS: Sixty-two learners attended the workshop. Fifty-nine learners completed both precurricular and postcurricular testing. The mean increase between pretest and posttest scores was 12.1% (95% confidence interval, 9.4, 14.8; P < 0.001). Type of licensure (private emergency medical technician vs registered nurse) and number of years experience had no association with the level of knowledge gained. Learners who had greater than 1 year of pediatric transport experience scored higher on their pretests. There was no significant retention shown by those who participated in spaced education. CONCLUSIONS: The curriculum was associated with a short term increased knowledge regarding pediatric respiratory distress and failure for emergency helicopter transport providers and could be used as an alternative model to develop standardized ongoing medical education in pediatrics. Further work is needed to achieve knowledge retention in this learner population.

Improving Nurse-Physician Teamwork: A Multidisciplinary Collaboration.

Nurses surveyed on an inpatient gynecology surgical unit suggested communication and teamwork between nurses and physicians could be improved. To enhance teamwork, a multidisciplinary collaboration committee of nurses and physicians was created.

Nurses as Champions for Patient Safety and Interdisciplinary Problem Solving.

Nurses on an inpatient surgical unit were apprehensive in activating the Rapid Response Team (RRT). Nurse-led interdisciplinary solutions addressed perceived barriers and led to open communication and issue resolution with physician colleagues.

New Right Ventricular Dysfunction in Pediatric Acute Respiratory Distress Syndrome on Venovenous Extracorporeal Membrane Oxygenation.

The development of new right ventricular (RV) dysfunction after cannulation to venovenous (VV) extracorporeal membrane oxygenation (ECMO) and its association with worse outcomes is increasingly recognized in adult patients, however, no studies have evaluated this phenomenon in pediatric patients. We report results of a single-center retrospective cohort study at a large academic children's hospital. New RV systolic dysfunction was present in 48% (12/25) of pediatric patients on VV ECMO for acute respiratory distress syndrome (ARDS). There was no statistically significant difference in survival, duration of mechanical ventilation, or hospital length of stay between those with and without RV dysfunction. Over half (5/9, 56%) of survivors with RV dysfunction on ECMO had RV dilation or RV hypertrophy on post-ECMO echocardiograms, and in two patients the RV dysfunction persisted for months following decannulation. Cardiac catheterization and autopsy reports suggested that echocardiographic assessment of RV systolic function alone may not be sufficient to diagnose clinically relevant RV injury. This is the first study to report the prevalence of RV dysfunction on VV ECMO for pediatric ARDS. Future multicenter collaboration is needed to create a clinically relevant definition of pediatric "RV injury" and to further evaluate risk factors and outcomes of RV dysfunction.

Recurrent diffuse alveolar hemorrhage and extracorporeal membrane oxygenation utilization in a hematopoietic stem cell transplant patient with Hunter's syndrome.

We describe the natural history of a three-month-old patient with Hunter Syndrome with hematopoietic stem cell transplant (HSCT) who developed recurrent diffuse alveolar hemorrhage (DAH) requiring extracorporeal membrane oxygenation (ECMO). The patient underwent HSCT with several complications, including veno-occlusive disease and DAH. He was managed with ECMO. Unfortunately, despite initial success he developed recurrent DAH and ultimately died. This is a novel report of this severe adverse event requiring ECMO following the use of HSCT in this rare patient population. We share the clinical strategies employed to address the complications associated with HSCT and the progression of his disease over his hospitalization.

Cell-Based Covalent-Capture Deubiquitinase Assay for Inhibitor Discovery.

Ubiquitination is a post-translational modification that elicits a variety of cellular responses. Deubiquitinases (DUBs) remove ubiquitin moieties from proteins and modulate cellular processes by counteracting the ubiquitin ligase activities. Ubiquitination and deubiquitination processes are tightly regulated by different mechanisms and their dysregulation is associated with many diseases. Discovery of DUB inhibitors could not only lead to therapeutics but also facilitate the understanding of ubiquitination/deubiquitination processes and their regulatory mechanisms. To enable the inhibitor discovery against DUBs, we developed a cell-based DUB assay that utilizes a cell-permeable ubiquitin probe, Biotin-cR10-Ub-PA, to covalently label DUBs in their native cellular environment. Amplified luminescent proximity homogeneous assay (Alpha, specifically AlphaLISA) is utilized to quantitatively assess the capture of the target DUB by the Biotin-cR10-Ub-PA probe. We demonstrated that this new cell-based DUB assay is robust and amenable to high-throughput screening. Human USP15 was selected as a DUB of interest and screened against a library of protease inhibitors as a proof of concept. In addition to the widely adopted pan-DUB inhibitor PR-619, several other DUB inhibitors from the library were also identified as hits. This new DUB assay can be readily adapted for inhibitor discovery against many other human DUBs to identify potent and cell-permeable inhibitors.

Aneuploidy rates and likelihood of obtaining a usable embryo for transfer among in vitro fertilization cycles using preimplantation genetic testing for monogenic disorders and aneuploidy compared with in vitro fertilization cycles using preimplantation genetic testing for aneuploidy alone.

OBJECTIVE: To compare aneuploidy rates among in vitro fertilization (IVF) cycles using preimplantation genetic testing for monogenic disorders (PGT-M) and aneuploidy (PGT-A) compared with IVF cycles using PGT-A alone, and to determine the likelihood of obtaining at least one usable embryo in cycles using PGT-M+PGT-A compared with cycles using PGT-A alone. DESIGN: Retrospective cohort study. SETTING: Single genetics laboratory. PATIENT(S): All IVF cycles for patients aged 18-45 undergoing PGT-A with or without concurrent PGT-M at a single genetics laboratory from November 2019 to March 2023. INTERVENTION(S): Use of PGT-M+PGT-A vs. use of PGT-A alone. MAIN OUTCOME MEASURE(S): Per cycle aneuploidy rate stratified by age, and per cycle likelihood of obtaining at least one usable embryo stratified by age and inheritance pattern of monogenic disease. RESULT(S): A total of 72,522 IVF cycles were included; 4,255 cycles (5.9%) using PGT-M+PGT-A and 68,267 cycles (94.1%) using PGT-A alone. The PGT-M+PGT-A group was younger than the PGT-A alone group (<35 years old: 56.1% vs. 30.5%). The majority of PGT-M cycles were performed for autosomal dominant pathogenic variants (42.4%), followed by autosomal recessive (36.5%), X-linked dominant (13.3%), and X-linked recessive (7.5%). The median number of embryos biopsied was higher in PGT-A alone compared with PGT-M+PGT-A cycles for patients aged <35, but it was equivalent in all other age groups. Age stratified aneuploidy rates did not significantly differ between PGT-M+PGT-A compared with PGT-A alone cycles. The probability of having a usable embryo declined with increasing age across all inheritance patterns. Compared with PGT-A alone, PGT-M+PGT-A cycles for patients aged ≤40 across all inheritance patterns were significantly less likely to yield a usable embryo, except in cycles for autosomal recessive diseases in the 38-40 age group and X-linked recessive diseases in the 35-37 age group. There were no consistent differences seen between groups in patients over 40. Cycles for patients with autosomal dominant diseases had the lowest likelihood of yielding a usable embryo for patients aged <43. CONCLUSION(S): In vitro fertilization cycles using PGT-M+PGT-A have similar age-specific aneuploidy rates to those using PGT-A alone. Cycles for patients ≤40 using PGT-M+PGT-A are significantly less likely to yield a usable embryo compared with those using PGT-A alone.

The nature of embryonic mosaicism across female age spectrum: an analysis of 21,345 preimplantation genetic testing for aneuploidy cycles.

Objective: To understand how mosaicism varies across patient-specific variables and clinics. Design: Cross-sectional cohort. Setting: Genetic testing laboratory. Patients: A total of 86,208 embryos from 17,366 patients underwent preimplantation genetic testing for aneuploidy using next-generation sequencing. Interventions: Mosaic embryos were classified as either low-level (20%-40%) or high-level (40%-80%) and by type of mosaic error: single segmental, complex segmental, single chromosome, or complex abnormal mosaic. The rate of mosaicism was stratified by the Society for Assisted Reproductive Technology age categories: <35 years, 35-37 years, 38-40 years, 41-42 years, and >42 years. Main Outcome Measures: Distribution of chromosomal findings and prevalence of mosaicism type by age. Probability of creating mosaic embryos in a subsequent cycle. Results: Among all embryos, 44% were euploid, 40.2% were aneuploid, and 15.8% were mosaic. Both low-level and high-level mosaicism were more prevalent among younger patients. Of all mosaic embryos, the youngest age cohort <35 years had the highest proportions of single and complex segmental mosaicism (37.9% and 6.8%, respectively), whereas those aged >42 years had the highest single whole chromosome and complex abnormal mosaicism (37.1% and 34.0%, respectively). Although there was variability in mosaic rates across clinics, the median mosaic rate over 3 years ranged from 14.48% to 17.72%. A diagnosis of a mosaic embryo in a previous cycle did not increase a patient's odds for having a mosaic embryo in a subsequent cycle. Conclusions: Mosaicism is overall higher in younger patients, but the complexity of mosaic errors increases with age. A history of mosaicism was not associated with mosaicism in subsequent cycles. Additional research is needed to understand the etiologies of the various subtypes of mosaic embryos and clinical outcomes associated with their transfer.

Simulation-Based System Analysis: Testing Preparedness for Extracorporeal Membrane Oxygenation Cannulation in Pediatric COVID-19 Patients.

INTRODUCTION: Coronavirus Disease-2019 presents risk to both patients and medical teams. Staff-intensive, complex procedures such as extracorporeal membrane oxygenation (ECMO) or extracorporeal cardiopulmonary resuscitation (eCPR) may increase chances of exposure and spread. This investigation aimed to rapidly deploy an in situ Simulation-based Clinical Systems Testing (SbCST) framework to identify Latent Safety Threats (LSTs) related to ECMO/eCPR initiation during a pandemic. METHODS: The adapted SbCST framework tested systems related to ECMO/eCPR initiation in the Neonatal and Pediatric Intensive Care Units. Systems were evaluated in six domains (Resources, Processes/Systems, Facilities, Clinical Performance, Infection Control, and Communication). We conducted three high-fidelity simulations with members from the Neonatal Intensive Care Unit General Surgery, Pediatric Intensive Care Unit Cardiovascular Surgery (CV), and Pediatric Intensive Care Unit General Surgery teams. Content experts evaluated systems issues during simulation, and LSTs were identified during debriefing. Data were analyzed for frequency of LSTs and trends in process gaps. RESULTS: Sixty-six LSTs were identified across three scenarios. Resource issues comprised the largest category (26%), followed by Process/System issues (24%), Infection Control issues (24%), Communication issues (17%), and Facility and Clinical Performance issues (5% each). LSTs informed new team strategies such as the use of a "door/PPE monitor" and "inside/outside" team configuration. CONCLUSIONS: The adapted SbCST framework identified multiple LSTs related to ECMO/eCPR cannulation and infection control guidelines in the setting of Coronavirus Disease-2019. Through SbCSTs, we developed guidelines to conserve PPE and develop optimal workflows to reduce patient/staff exposure in a high-risk procedure. This project may guide other hospitals to adapt SbCSTs strategies to test/adjust rapidly changing guidelines.

Pneumatosis intestinalis and intestinal perforation in a case of multisystem inflammatory syndrome in children.

This case demonstrates pneumatosis intestinalis and small bowel perforation in a paediatric patient with multisystem inflammatory syndrome in children (MIS-C). Our patient presented with fever, abdominal pain and shortness of breath. She progressed to haemodynamic failure and small bowel perforation approximately 1 week after admission. Patients with suspected or confirmed MIS-C should be monitored closely for abdominal catastrophe, especially when critically ill in the intensive care unit.