The Top 100 Most-Cited Publications in Clinical Craniofacial Research.

INTRODUCTION: Craniosynostosis is a birth defect defined as premature closure of sutures leading to possible neurological deficits and cosmetic deformities. Most of the current literature to date focuses on craniosynostosis etiology by analyzing genetics. This paper is a bibliometric analysis of the most influential works related to the clinical management of craniosynostosis to help guide clinicians in their decision-making. METHODS AND MATERIALS: Clarivate Web of Science database was used to identify the top 100 most-cited articles addressing the clinical management of craniosynostosis. A bibliometric review was performed to analyze publication metrics and track research trends. RESULTS: The 100 most-cited publications pertaining to craniosynostosis management were cited a cumulative 12,779 times. The highest cited article was Shillito and colleagues' "Craniosynostosis: A Review Of 519 Surgical Patients" with 352 citations. The oldest clinical craniosynostosis article dates back to 1948, and the most recent was published in 2016. The year with the most clinical-focused publications was 2011. The most prolific author was Renier, D. The United States produced 56 of the 100 articles. Most articles (n=52) were level 3 evidence. DISCUSSION: This bibliometric evaluation of craniosynostosis provides insight into the most impactful literature on this topic. The highest cited articles retrospectively analyze large sample sizes, outline proper evaluation, discuss intervention timelines, and highlight specific treatment plans for this birth defect. By filtering through existing literature, this analysis can guide clinicians on the management of craniosynostosis to maximize patient outcomes.

Influence of time-to-diagnosis on time-to-percutaneous coronary intervention for emergency department ST-elevation myocardial infarction patients: Time-to-electrocardiogram matters.

Objectives: Earlier electrocardiogram (ECG) acquisition for ST-elevation myocardial infarction (STEMI) is associated with earlier percutaneous coronary intervention (PCI) and better patient outcomes. However, the exact relationship between timely ECG and timely PCI is unclear. Methods: We quantified the influence of door-to-ECG (D2E) time on ECG-to-PCI balloon (E2B) intervention in this three-year retrospective cohort study, including patients from 10 geographically diverse emergency departments (EDs) co-located with a PCI center. The study included 576 STEMI patients excluding those with a screening ECG before ED arrival or non-diagnostic initial ED ECG. We used a linear mixed-effects model to evaluate D2E's influence on E2B with piecewise linear terms for D2E times associated with time intervals designated as ED intake (0-10 min), triage (11-30 min), and main ED (>30 min). We adjusted for demographic and visit characteristics, past medical history, and included ED location as a random effect. Results: The median E2B interval was longer (76 vs 68 min, p < 0.001) in patients with D2E >10 min than in those with timely D2E. The proportion of patients identified at the intake, triage, and main ED intervals was 65.8%, 24.9%, and 9.7%, respectively. The D2E and E2B association was statistically significant in the triage phase, where a 1-minute change in D2E was associated with a 1.24-minute change in E2B (95% confidence interval [CI]: 0.44-2.05, p = 0.003). Conclusion: Reducing D2E is associated with a shorter E2B. Targeting D2E reduction in patients currently diagnosed during triage (11-30 min) may be the greatest opportunity to improve D2B and could enable 24.9% more ED STEMI patients to achieve timely D2E.

Nasopharyngoscopic Evaluation of Velopharyngeal Closure During Speech.

Definitive oronasal separation through closure of the velopharyngeal (VP) sphincter is necessary for the development of normal speech and feeding. Individuals with velopharyngeal incompetence or insufficiency often exhibit hypernasal speech, poor speech intelligibility, and nasal regurgitation. Assessment of VP sphincter function using nasopharyngoscopy is a key element in identifying VP dysfunction. A foundational understanding of normal anatomy and physiology of the velopharyngeal mechanism is paramount to successful diagnosis. This includes recognition of 4 distinct VP sphincter closure patterns: coronal, sagittal, circular, and circular with Passavant's ridge. In this study, the authors showcase 2 patients with velopharyngeal competence who presented to an ear, nose, and throat clinic for nasopharyngoscopic evaluation. This study sought to demonstrate the use of nasopharyngoscopy to recognize velopharyngeal closure patterns and discuss how they may influence the surgical management of VP dysfunction.

The Excited-State Lifetime of Poly(NDI2OD-T2) Is Intrinsically Short.

Conjugated polymers composed of alternating electron donor and acceptor segments have come to dominate the materials being considered for organic photoelectrodes and solar cells, in large part because of their favorable near-infrared absorption. The prototypical electron-transporting push-pull polymer poly(NDI2OD-T2) (N2200) is one such material. While reasonably efficient organic solar cells can be fabricated with N2200 as the acceptor, it generally fails to contribute as much photocurrent from its absorption bands as the donor with which it is paired. Moreover, transient absorption studies have shown N2200 to have a consistently short excited-state lifetime (∼100 ps) that is dominated by a ground-state recovery. In this paper, we investigate whether these characteristics are intrinsic to the backbone structure of this polymer or if these are extrinsic effects from ubiquitous solution-phase and thin-film aggregates. We compare the solution-phase photophysics of N2200 with those of a pair of model compounds composed of alternating bithiophene (T2) donor and naphthalene diimide (NDI) acceptor units, NDI-T2-NDI and T2-NDI-T2, in a dilute solution. We find that the model compounds have even faster ground-state recovery dynamics (τ = 45, 27 ps) than the polymer (τ = 133 ps), despite remaining molecularly isolated in solution. In these molecules, as in the case of the N2200 polymer, the lowest excited state has a T2 to NDI charge-transfer (CT) character. Electronic-structure calculations indicate that the short lifetime of this state is due to fast nonradiative decay to the ground state (GS) promoted by strong CT-GS electronic coupling and strong electron-vibrational coupling with high-frequency (quantum) normal modes.

The impact of source and consumption of news on mental distress among inflammatory bowel disease patients during the COVID-19 pandemic.

Background: We sought to understand the trends in media use, and how consumption and source affected mental health of persons with inflammatory bowel disease during the early parts of the pandemic. Dissemination of news during the coronavirus disease 2019 (COVID-19) pandemic was integral to educating the public but also could be harmful if constantly consumed, leading to worsening anxiety. Methods: We performed a survey study in autumn 2020 during the second wave of COVID-19 in Manitoba. The survey included questions on consumption of COVID-19 news, along with validated measures of perceived stress, generalized anxiety, health anxiety, and depression. We used multivariable logistic regression analysis to assess trusted sources of news as a predictor of clinically significant mental health symptoms. Results: Of the 2940 participants in the registry, 1384 (47.1%) persons responded. The most trusted sources of news were television (64.2%), internet (46.1%), newspaper (27.6%), friends/family (21.7%), social media (16.9%), and radio (16.6%). Those who trusted social media had higher odds of depression (aOR 1.52, 95%CI 1.04-2.22), and perceived stress (aOR 2.56, 95%CI 1.09-2.21). Persons who reported extreme difficulty limiting their time-consuming news about COVID-19 and who spent more than 1 h daily consuming information on COVID-19 both had increased odds of any clinically significant mental health symptoms. Conclusions: It is unknown if consumption of COVID-19 news led to heightened mental health symptoms or if increasing anxieties and concerns led to consuming more news. Further research is needed to assess whether these elevated mental health symptoms led to worse disease outcomes.

Dysphagia is associated with increased mortality risk after hip fracture surgery.

PURPOSE: This study aims to explore the prevalence of dysphagia, as well as mortality associated with dysphagia in the elderly population receiving surgical treatment for a hip fracture. METHODS: A retrospective cohort study was completed at an academic level 1 tertiary care center. Patients older than or equal to 65 admitted with a hip fracture diagnosis from January 2015 to December 2020 (n = 617) were included. The main outcome was the prevalence of dysphagia and association with mortality. Secondary analysis included timing of dysphagia and contributions to mortality. RESULTS: Fifty-six percent of patients had dysphagia, and the mortality rates were higher in patients with dysphagia (8.9%) versus those without dysphagia (2.6%), chi-square p = 0.001, and odds ratio 3.69 (CI 1.6-8.5). Mortality rates in patients with acute dysphagia were also higher (12.4%) than those with chronic dysphagia (5%) and chi-squared p = 0.02. Mortality rates in patients with a perioperative dysphagic event (13.9%) were higher than those with non-perioperative dysphagia (4%) and chi-squared p = 0.001. Mortality rates in patients who had acute perioperative dysphagia (21.2%) were higher than those with chronic dysphagia that presented perioperatively (6.8%) and chi-squared p = 0.006. CONCLUSIONS: This study demonstrates high rates of dysphagia in the elderly hip fracture population and a significant association between dysphagia and mortality. Timing and chronicity of dysphagia were relevant, as patients with acute perioperative dysphagia had the highest mortality rate. Unlike other identified risk factors, dysphagia may be at least partially modifiable. More research is needed to determine whether formal evaluation and treatment of dysphagia lowers mortality risk.

Polyphosphazene-Based Anion-Anchored Polymer Electrolytes For All-Solid-State Lithium Metal Batteries.

Safety concerns of traditional liquid electrolytes, especially when paired with lithium (Li) metal anodes, have stimulated research of solid polymer electrolytes (SPEs) to exploit the superior thermal and mechanical properties of polymers. Polyphosphazenes are primarily known for their use as flame retardant materials and have demonstrated high Li-ion conductivity owing to their highly flexible P = N backbone which promotes Li-ion conduction via inter- and intrachain hopping along the polymer backbone. While polyphosphazenes are largely unexplored as SPEs in the literature, a few existing examples showed promising ionic conductivity. By anchoring the anion to the polymer backbone, one may primarily allow the movement of Li ions, alleviating the detrimental effects of polarization that are common in conventional dual-ion conducting SPEs. Anion-anchored SPEs, known as single Li-ion conducting solid polymer electrolytes (SLiC-SPEs), exhibit high Li-ion transference numbers (tLi+), which limits Li dendrite growth, thus further increasing the safety of SPEs. However, previously reported SLiC-SPEs suffer from inadequate ionic conductivity, small electrochemical stability windows (ESWs), and limited cycling stability. Herein, we report three polyphosphazene-based SLiC-SPEs comprising lithiated polyphosphazenes. The SLiC polyphosphazenes were prepared through a facile synthesis route, opening the door for enhanced tunability of polymer properties via facile macromolecular nucleophilic substitution and subsequent lithiation. State-of-the-art characterization techniques, such as differential scanning calorimetry (DSC), electrochemical impedance spectroscopy (EIS), and solid-state nuclear magnetic resonance spectroscopy (ssNMR) were employed to probe the effect of the polymer structure on Li-ion dynamics and other electrochemical properties. Produced SPEs showed thermal stability up to ∼208 °C with ionic conductivities comparable to that of the best-reported SLiC-SPEs that definitively comprise no solvents or plasticizers. Among the three lithiated polyphosphazenes, the SPE containing dilithium poly[bis(trifluoroethylamino)phosphazene] (pTFAP2Li) exhibited the most promising electrochemical characteristics with tLi+ of 0.76 and compatibility with both Li metal anodes and LiFePO4 (LFP) cathodes; through 40 cycles at 100 °C, the PEO-pTFAP2Li blend showed 81.2% capacity utilization and 86.8% capacity retention. This work constitutes one of the first successful demonstrations of the cycling performance of a true all-solid-state Li-metal battery using SLiC polyphosphazene SPEs.

Management of Maxillofacial Trauma in Pregnant Women.

INTRODUCTION: Trauma during pregnancy deserves special attention as management must be directed towards both the mother and the fetus. Management of maxillofacial fractures in pregnancy can adversely affect the well-being of the fetus by impinging on normal functions such as respiration, mastication, and nutrition. Pregnancy complicates the management of facial injury due to the maintenance of the patent airway, anesthesia considerations, and imaging restraints. The purpose of this study is to use three illustrative from our own institution to further elucidate education on the management of mandible fracture in pregnancy with a focus on multidisciplinary treatment and outcomes. METHODS: A retrospective chart review was performed for all cases of facial fractures admitted to Ryder Trauma Center from 2012 to 2022. During this time, 4,910 patients presented with facial fractures 1319 patients were female. Three of the patients were pregnant at the time of admission. Demographics, mechanism of injury, associated injuries, and management information were collected. RESULTS: Patient 1 was a 20-year-old female presented to Ryder Trauma Center following a motor vehicle collision. She was 17 weeks pregnant at the time of admission and was found to have a left mandibular angle fracture. Patient 2 was a 14-year-old female who presented to Ryder Trauma Center status post gunshot wound to the mandible after she and her brother were unknowingly playing with a loaded gun. She was 18 weeks pregnant at the time of admission, with a past medical history of domestic violence, suicidal ideation, and major depressive disorder. Patient 3 was a 20-year-old female 36 weeks pregnant at the time of admission. She presented with a right paraymphyseal fracture and left mandibular angle fracture as a result of falling on the stairs. Patients all underwent surgical repair of fractures.

Yard Work and Gardening: A Pastime with Potential for Craniofacial Injury.

INTRODUCTION: Yard and garden tools are increasingly used by Americans. Despite the growing popularity of gardening as a leisure activity, the rate of injury associated with these tools remains remarkedly high. Previous research has highlighted the risks associated with improper handling of tools and associated potential long-term consequences. This retrospective study aims to provide a comprehensive analysis of the craniofacial injuries caused by yard and garden equipment. The investigation will emphasize the need for improved safety measures and regulations. METHODS AND MATERIALS: Publicly available data from the National Electronic Injury Surveillance System (NEISS) database were utilized to identify craniofacial injuries related to yard and garden tool handling during a 10-year period (2013-2022). Study population included patients aged 1 to 85+ years who visited emergency departments secondary to these injuries. Data analysis involved queries for specific products and diagnostic codes related to craniofacial injuries. RESULTS: Over the study period, a total of 588,384 craniofacial injuries associated with yard and garden tools were recorded, averaging 58,838 injuries annually. Men accounted for a significantly higher proportion of injuries (69.2%) compared to women (30.8%). Elderly population, particularly those aged 60 to 64 years, experienced the highest incidence of craniofacial injuries. Cranium was the most commonly affected anatomical location, comprising 34% of all injuries. Lacerations and contusions were the most frequent injury diagnoses. Greenhouse or gardening supplies and lawnmowers are the most common causative agents, respectively. DISCUSSION: Our study highlights the persistent incidence of craniofacial injuries associated with yard and garden tool handling emphasizing the need for standardized safety regulations and guidelines. Sociological and demographic factors, such as differences in gardening habits and behavioral patterns between genders, contribute to the observed disparities in injury rates. Understanding the underlying factors contributing to these craniofacial injuries is crucial to promoting safer practices and reducing the overall burden associated with yard and garden tools.

Clinical Practice Guideline: Age-Related Hearing Loss.

OBJECTIVE: Age-related hearing loss (ARHL) is a prevalent but often underdiagnosed and undertreated condition among individuals aged 50 and above. It is associated with various sociodemographic factors and health risks including dementia, depression, cardiovascular disease, and falls. While the causes of ARHL and its downstream effects are well defined, there is a lack of priority placed by clinicians as well as guidance regarding the identification, education, and management of this condition. PURPOSE: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the identification and management of ARHL. These opportunities are communicated through clear actionable statements with explanation of the support in the literature, evaluation of the quality of the evidence, and recommendations on implementation. The target patients for the guideline are any individuals aged 50 years and older. The target audience is all clinicians in all care settings. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of ARHL. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The GDG made strong recommendations for the following key action statements (KASs): (KAS 4) If screening suggests hearing loss, clinicians should obtain or refer to a clinician who can obtain an audiogram. (KAS 8) Clinicians should offer, or refer to a clinician who can offer, appropriately fit amplification to patients with ARHL. (KAS 9) Clinicians should refer patients for an evaluation of cochlear implantation candidacy when patients have appropriately fit amplification and persistent hearing difficulty with poor speech understanding. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should screen patients aged 50 years and older for hearing loss at the time of a health care encounter. (KAS 2) If screening suggests hearing loss, clinicians should examine the ear canal and tympanic membrane with otoscopy or refer to a clinician who can examine the ears for cerumen impaction, infection, or other abnormalities. (KAS 3) If screening suggests hearing loss, clinicians should identify sociodemographic factors and patient preferences that influence access to and utilization of hearing health care. (KAS 5) Clinicians should evaluate and treat or refer to a clinician who can evaluate and treat patients with significant asymmetric hearing loss, conductive or mixed hearing loss, or poor word recognition on diagnostic testing. (KAS 6) Clinicians should educate and counsel patients with hearing loss and their family/care partner(s) about the impact of hearing loss on their communication, safety, function, cognition, and quality of life (QOL). (KAS 7) Clinicians should counsel patients with hearing loss on communication strategies and assistive listening devices. (KAS 10) For patients with hearing loss, clinicians should assess if communication goals have been met and if there has been improvement in hearing-related QOL at a subsequent health care encounter or within 1 year. The GDG offered the following KAS as an option: (KAS 11) Clinicians should assess hearing at least every 3 years in patients with known hearing loss or with reported concern for changes in hearing.

Clinical Practice Guideline: Age-Related Hearing Loss Executive Summary.

OBJECTIVE: Age-related hearing loss (ARHL) is a prevalent but often underdiagnosed and undertreated condition among individuals aged 50 and above. It is associated with various sociodemographic factors and health risks including dementia, depression, cardiovascular disease, and falls. While the causes of ARHL and its downstream effects are well defined, there is a lack of priority placed by clinicians as well as guidance regarding the identification, education, and management of this condition. PURPOSE: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the identification and management of ARHL. These opportunities are communicated through clear actionable statements with an explanation of the support in the literature, the evaluation of the quality of the evidence, and recommendations on implementation. The target patients for the guideline are any individuals aged 50 years and older. The target audience is all clinicians in all care settings. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the Guideline Development Group (GDG). It is not intended to be a comprehensive, general guide regarding the management of ARHL. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The GDG made strong recommendations for the following key action statements (KASs): (KAS 4) If screening suggests hearing loss, clinicians should obtain or refer to a clinician who can obtain an audiogram. (KAS 8) Clinicians should offer, or refer to a clinician who can offer, appropriately fit amplification to patients with ARHL. (KAS 9) Clinicians should refer patients for an evaluation of cochlear implantation candidacy when patients have appropriately fit amplification and persistent hearing difficulty with poor speech understanding. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should screen patients aged 50 years and older for hearing loss at the time of a health care encounter. (KAS 2) If screening suggests hearing loss, clinicians should examine the ear canal and tympanic membrane with otoscopy or refer to a clinician who can examine the ears for cerumen impaction, infection, or other abnormalities. (KAS 3) If screening suggests hearing loss, clinicians should identify sociodemographic factors and patient preferences that influence access to and utilization of hearing health care. (KAS 5) Clinicians should evaluate and treat or refer to a clinician who can evaluate and treat patients with significant asymmetric hearing loss, conductive or mixed hearing loss, or poor word recognition on diagnostic testing. (KAS 6) Clinicians should educate and counsel patients with hearing loss and their family/care partner(s) about the impact of hearing loss on their communication, safety, function, cognition, and quality of life. (KAS 7) Clinicians should counsel patients with hearing loss on communication strategies and assistive listening devices. (KAS 10) For patients with hearing loss, clinicians should assess if communication goals have been met and if there has been improvement in hearing-related quality of life at a subsequent health care encounter or within 1 year. The GDG offered the following KAS as an option: (KAS 11) Clinicians should assess hearing at least every 3 years in patients with known hearing loss or with reported concern for changes in hearing.

Dynamic Prediction of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD. METHODS: We pooled data from 6 existing cohort studies from Canada, The Netherlands, the United Kingdom, and the United States. Patients with IBD and an indication for CRC surveillance were included if they underwent at least 1 follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on the literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modeling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation. RESULTS: The surveillance cohorts comprised 3731 patients, enrolled and followed-up in the time period from 1973 to 2021, with a median follow-up period of 5.7 years (26,336 patient-years of follow-up evaluation); 146 individuals were diagnosed with aCRN. The model contained 8 predictors, with a cross-validation median concordance statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration. CONCLUSIONS: The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals before clinical application.

Use of Intravenous Albumin: A Guideline From the International Collaboration for Transfusion Medicine Guidelines.

BACKGROUND: Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis. METHODS: Cochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development and Evaluation methodology. The guidelines were revised after public consultation. RESULTS: The panel made 14 recommendations on albumin use in adult critical care (three recommendations), pediatric critical care (one recommendation), neonatal critical care (two recommendations), cardiovascular surgery (two recommendations), kidney replacement therapy (one recommendation), and complications of cirrhosis (five recommendations). Of the 14 recommendations, two recommendations had moderate certainty of evidence, five recommendations had low certainty of evidence, and seven recommendations had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large-volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin commonly is transfused. CONCLUSIONS: Currently, few evidence-based indications support the routine use of albumin in clinical practice to improve patient outcomes. These guidelines provide clinicians with actionable recommendations on the use of albumin.

Rapid unleashing of macrophage efferocytic capacity via transcriptional pause release.

During development, inflammation or tissue injury, macrophages may successively engulf and process multiple apoptotic corpses via efferocytosis to achieve tissue homeostasis1. How macrophages may rapidly adapt their transcription to achieve continuous corpse uptake is incompletely understood. Transcriptional pause/release is an evolutionarily conserved mechanism, in which RNA polymerase (Pol) II initiates transcription for 20-60 nucleotides, is paused for minutes to hours and is then released to make full-length mRNA2. Here we show that macrophages, within minutes of corpse encounter, use transcriptional pause/release to unleash a rapid transcriptional response. For human and mouse macrophages, the Pol II pause/release was required for continuous efferocytosis in vitro and in vivo. Interestingly, blocking Pol II pause/release did not impede Fc receptor-mediated phagocytosis, yeast uptake or bacterial phagocytosis. Integration of data from three genomic approaches-precision nuclear run-on sequencing, RNA sequencing, and assay for transposase-accessible chromatin using sequencing (ATAC-seq)-on efferocytic macrophages at different time points revealed that Pol II pause/release controls expression of select transcription factors and downstream target genes. Mechanistic studies on transcription factor EGR3, prominently regulated by pause/release, uncovered EGR3-related reprogramming of other macrophage genes involved in cytoskeleton and corpse processing. Using lysosomal probes and a new genetic fluorescent reporter, we identify a role for pause/release in phagosome acidification during efferocytosis. Furthermore, microglia from egr3-deficient zebrafish embryos displayed reduced phagocytosis of apoptotic neurons and fewer maturing phagosomes, supporting defective corpse processing. Collectively, these data indicate that macrophages use Pol II pause/release as a mechanism to rapidly alter their transcriptional programs for efficient processing of the ingested apoptotic corpses and for successive efferocytosis.

The mechanism of cytoplasmic incompatibility is conserved in Wolbachia-infected Aedes aegypti mosquitoes deployed for arbovirus control.

The rising interest and success in deploying inherited microorganisms and cytoplasmic incompatibility (CI) for vector control strategies necessitate an explanation of the CI mechanism. Wolbachia-induced CI manifests in the form of embryonic lethality when sperm from Wolbachia-bearing testes fertilize eggs from uninfected females. Embryos from infected females however survive to sustain the maternally inherited symbiont. Previously in Drosophila melanogaster flies, we demonstrated that CI modifies chromatin integrity in developing sperm to bestow the embryonic lethality. Here, we validate these findings using wMel-transinfected Aedes aegypti mosquitoes released to control vector-borne diseases. Once again, the prophage WO CI proteins, CifA and CifB, target male gametic nuclei to modify chromatin integrity via an aberrant histone-to-protamine transition. Cifs are not detected in the embryo, and thus elicit CI via the nucleoprotein modifications established pre-fertilization. The rescue protein CifA in oogenesis localizes to stem cell, nurse cell, and oocyte nuclei, as well as embryonic DNA during embryogenesis. Discovery of the nuclear targeting Cifs and altered histone-to-protamine transition in both Aedes aegypti mosquitoes and D. melanogaster flies affirm the Host Modification Model of CI is conserved across these host species. The study also newly uncovers the cell biology of Cif proteins in the ovaries, CifA localization in the embryos, and an impaired histone-to-protamine transition during spermiogenesis of any mosquito species. Overall, these sperm modification findings may enable future optimization of CI efficacy in vectors or pests that are refractory to Wolbachia transinfections.

Sanitation in urban areas may limit the spread of antimicrobial resistance via flies.

Synanthropic filth flies are common where sanitation is poor and fecal wastes are accessible to them. These flies have been proposed as mechanical vectors for the localized transport of fecal microbes including antimicrobial resistant (AMR) organisms and associated antimicrobial resistance genes (ARGs), increasing exposure risks. We evaluated whether an onsite sanitation intervention in Maputo, Mozambique reduced the concentration of enteric bacteria and the frequency of detection of ARGs carried by flies collected in household compounds of low-income neighborhoods. Additionally, we assessed the phenotypic resistance profile of Enterobacteriaceae isolates recovered from flies during the pre-intervention phase. After fly enumeration at study compounds, quantitative polymerase chain reaction was used to quantify an enteric 16S rRNA gene (i.e., specific to a cluster of phylotypes corresponding to 5% of the human fecal microflora), 28 ARGs, and Kirby Bauer Disk Diffusion of Enterobacteriaceae isolates was utilized to assess resistance to eleven clinically relevant antibiotics. The intervention was associated with a 1.5 log10 reduction (95% confidence interval: -0.73, -2.3) in the concentration of the enteric 16S gene and a 31% reduction (adjusted prevalence ratio = 0.69, [0.52, 0.92]) in the mean number of ARGs per fly compared to a control group with poor sanitation. This protective effect was consistent across the six ARG classes that we detected. Enterobacteriaceae isolates-only from the pre-intervention phase-were resistant to a mean of 3.4 antibiotics out of the eleven assessed. Improving onsite sanitation infrastructure in low-income informal settlements may help reduce fly-mediated transmission of enteric bacteria and the ARGs carried by them.

Epidemiology of Craniofacial Injuries from Exercise and Weightlifting: A 10-Year Analysis.

INTRODUCTION: Exercise is the cornerstone of a healthy lifestyle. It is recognized for enhancing cardiovascular health and bolstering mental well-being. While the fitness industry grows, the incidence of exercise-related injuries continues to rise. This study examines craniofacial injuries resulting from exercise and weightlifting over the past decade. The goal is to uncover trends, demographics, diagnoses, and patient dispositions. METHODS AND MATERIALS: A retrospective review was conducted using the National Electronic Injury Surveillance System database. Emergency department visits for craniofacial injuries associated with exercise and weightlifting between 2013 and 2022 were analyzed. One-sample t-tests and the Mann-Kendall test were used to evaluate injury prevalence and significant trends. RESULTS: Over the past decade, 582,972 craniofacial injuries related to exercise and weightlifting were documented. Men accounted for 55.7% of cases. Annual incidence increased by 32.7% between 2013 and 2022. It was statistically significant. Adolescents aged 15 to 19 displayed the highest injury rate. Head injuries were most common (45%), followed by face (26%), neck (21%), mouth (4%), eye (3%), and ear (1%). Diagnoses included internal injury (25.2%), laceration (24.8%), contusions/abrasions (12.9%), and strain/sprain (11.9%). Hospitalization was required for only 8.5% of patients. DISCUSSION: This study elucidates the need for injury prevention strategies. Vulnerable subgroups such as males, adolescents, and the elderly demand targeted prevention efforts. Future research should explore specific mechanisms of injury to identify high-risk exercise. This study promotes the need for safe exercise practices and increases awareness of craniofacial injury risks associated with physical activity.

Prophage proteins alter long noncoding RNA and DNA of developing sperm to induce a paternal-effect lethality.

The extent to which prophage proteins interact with eukaryotic macromolecules is largely unknown. In this work, we show that cytoplasmic incompatibility factor A (CifA) and B (CifB) proteins, encoded by prophage WO of the endosymbiont Wolbachia, alter long noncoding RNA (lncRNA) and DNA during Drosophila sperm development to establish a paternal-effect embryonic lethality known as cytoplasmic incompatibility (CI). CifA is a ribonuclease (RNase) that depletes a spermatocyte lncRNA important for the histone-to-protamine transition of spermiogenesis. Both CifA and CifB are deoxyribonucleases (DNases) that elevate DNA damage in late spermiogenesis. lncRNA knockdown enhances CI, and mutagenesis links lncRNA depletion and subsequent sperm chromatin integrity changes to embryonic DNA damage and CI. Hence, prophage proteins interact with eukaryotic macromolecules during gametogenesis to create a symbiosis that is fundamental to insect evolution and vector control.

Dissociable Contributions of the Medial Parietal Cortex to Recognition Memory.

Human neuroimaging studies of episodic memory retrieval routinely observe the engagement of specific cortical regions beyond the medial temporal lobe. Of these, medial parietal cortex (MPC) is of particular interest given its distinct functional characteristics during different retrieval tasks. Specifically, while recognition and autobiographical recall tasks are both used to probe episodic retrieval, these paradigms consistently drive distinct spatial patterns of response within MPC. However, other studies have emphasized alternate MPC functional dissociations in terms of brain network connectivity profiles or stimulus category selectivity. As the unique contributions of MPC to episodic memory remain unclear, adjudicating between these different accounts can provide better consensus regarding MPC function. Therefore, we used a precision-neuroimaging dataset (7T functional magnetic resonance imaging) to examine how MPC regions are differentially engaged during recognition memory and how these task-related dissociations may also reflect distinct connectivity and stimulus category functional profiles. We observed interleaved, though spatially distinct, subregions of MPC where responses were sensitive to either recognition decisions or the semantic representation of stimuli. In addition, this dissociation was further accentuated by functional subregions displaying distinct profiles of connectivity with the hippocampus during task and rest. Finally, we show that recent observations of dissociable person and place selectivity within the MPC reflect category-specific responses from within identified semantic regions that are sensitive to mnemonic demands. Together, by examining precision functional mapping within individuals, these data suggest that previously distinct observations of functional dissociation within MPC conform to a common principle of organization throughout hippocampal-neocortical memory systems.