Utilizing the Fujimori Gate Flap for the Reconstruction of Squamous Cell Carcinoma: A Case Report.

The surgical treatment of oral squamous cell carcinoma (SCC) results in tissue defects caused by the removal of the cancerous tissue. There are various reconstruction options available for lip construction. Harvesting the flap to reconstruct these defects undoubtedly results in substantial morbidity. Lip reconstruction can be performed more efficiently and with reduced side effects by utilizing flaps, which can minimize donor site morbidity and shorten surgical harvesting time. We are reporting a case involving a 52-year-old male with SCC of the lip who presented without any comorbidity. This case report describes the careful lip reconstruction using the Fujimori gate flap technique following complete surgical excision of the lesion.

A review of climate change and cardiovascular diseases in the Indian policy context.

There is growing evidence that climate change adversely affects human health. Multiple diseases are sensitive to climate change, including cardiovascular diseases (CVDs), which are also the leading cause of death globally. Countries such as India face a compounded challenge, with a growing burden of CVDs and a high vulnerability to climate change, requiring a co-ordinated, multi-sectoral response. In this framework synthesis, we analysed whether and how CVDs are addressed with respect to climate change in the Indian policy space. We identified 10 relevant national-level policies, which were analysed using the framework method. Our analytical framework consisted of four themes: (i) political commitment; (ii) health information systems; (iii) capacity building; and (iv) cross-sectoral actions. Additionally, we analysed a subset of these policies and 29 state-level climate change and health action plans using content analysis to identify health priorities. Our analyses revealed a political commitment in addressing the health impacts of climate change; however, CVDs were poorly contextualized with most of the efforts focusing on vector-borne and other communicable diseases, despite their recognized burden. Heat-related illnesses and cardiopulmonary diseases were also focused on but failed to encompass the most climate-sensitive aspects. CVDs are insufficiently addressed in the existing surveillance systems, despite being mentioned in several policies and interventions, including emergency preparedness in hospitals and cross-sectoral actions. CVDs are mentioned as a separate section in only a small number of state-level plans, several of which need an impetus to complete and include CVD-specific sections. We also found several climate-health policies for specific diseases, albeit not for CVDs. This study identified important gaps in India's disease-specific climate change response and might aid policy makers in strengthening future versions of these policies and boost research and context-specific interventions on climate change and CVDs.

Medial amygdalar tau is associated with mood symptoms in preclinical Alzheimer's disease.

BACKGROUND: While the amygdala receives early tau deposition in Alzheimer's disease (AD) and is involved in social and emotional processing, the relationship between amygdalar tau and early neuropsychiatric symptoms in AD is unknown. We sought to determine whether focal tau binding in the amygdala and abnormal amygdalar connectivity were detectable in a preclinical AD cohort and identify relationships between these and self-reported mood symptoms. METHODS: We examined n=598 individuals (n=347 amyloid-positive (58% female), n=251 amyloid-negative (62% female); subset into tau PET and fMRI cohorts) from the A4 Study. In the tau PET cohort, we used amygdalar segmentations to examine representative nuclei from three functional divisions of the amygdala. We analyzed between-group differences in division-specific tau binding in the amygdala in preclinical AD. We conducted seed-based functional connectivity analyses from each division in the fMRI cohort. Finally, we conducted exploratory post-hoc correlation analyses between neuroimaging biomarkers of interest and anxiety and depression scores. RESULTS: Amyloid-positive individuals demonstrated increased tau binding in medial and lateral amygdala, and tau binding in these regions was associated with mood symptoms. Across amygdalar divisions, amyloid-positive individuals had relatively higher regional connectivity from amygdala to other temporal regions, insula, and orbitofrontal cortex, but medial amygdala to retrosplenial cortex was lower. Medial amygdala to retrosplenial connectivity was negatively associated with anxiety symptoms, as was retrosplenial tau. CONCLUSIONS: Our findings suggest that preclinical tau deposition in the amygdala and associated changes in functional connectivity may relate to early mood symptoms in AD.

Tumor biomechanics as a novel imaging biomarker to assess response to immunotherapy in a murine glioma model.

Glioblastoma is the most common and aggressive primary malignant brain tumor with poor prognosis. Novel immunotherapeutic approaches are currently under investigation. Even though magnetic resonance imaging (MRI) is the most important imaging tool for treatment monitoring, response assessment is often hampered by therapy-related tissue changes. As tumor and therapy-associated tissue reactions differ structurally, we hypothesize that biomechanics could be a pertinent imaging proxy for differentiation. Longitudinal MRI and magnetic resonance elastography (MRE) were performed to monitor response to immunotherapy with a toll-like receptor 7/8 agonist in orthotopic syngeneic experimental glioma. Imaging results were correlated to histology and light sheet microscopy data. Here, we identify MRE as a promising non-invasive imaging method for immunotherapy-monitoring by quantifying changes in response-related tumor mechanics. Specifically, we show that a relative softening of treated compared to untreated tumors is linked to the inflammatory processes following therapy-induced re-education of tumor-associated myeloid cells. Mechanistically, combined effects of myeloid influx and inflammation including extracellular matrix degradation following immunotherapy form the basis of treated tumors being softer than untreated glioma. This is a very early indicator of therapy response outperforming established imaging metrics such as tumor volume. The overall anti-tumor inflammatory processes likely have similar effects on human brain tissue biomechanics, making MRE a promising tool for gauging response to immunotherapy in glioma patients early, thereby strongly impacting patient pathway.

A Case of Advanced Oral Submucous Fibrosis Management: Beyond Conventional Approach.

A chronic, persistent, possibly cancerous condition that mostly affects the oral cavity is called oral submucous fibrosis (OSMF) and causes severe functional impairment. Due to its complex nature, OSMF requires a comprehensive strategy that includes both surgical and medication therapies. Multidisciplinary treatment was started, which included a complete stoppage of habit, dental hygiene precautions, dietary counselling, surgical intervention, supportive medicinal therapy, and physiotherapy. Following surgery and adjunct therapy, the patient's mouth opening and functional results were improved. The patient is kept for regular follow-up to assess the recurrence of fibrosis or any incidence of malignant transformation. This case emphasizes the difficulties in treating advanced OSMF and emphasizes how crucial it is to improve patient outcomes by early detection, stopping betel nut chewing, and thorough multidisciplinary care.

Understanding uptake of information about innovations among emergency department clinicians during the COVID-19 pandemic.

Objectives: Early in the COVID-19 pandemic, little was known about managing sick patients, but emergency department (ED) clinicians had to decide which treatments and care processes to adopt. Our objective was to describe how ED clinicians learned about innovations and how they assessed them for credibility during the pandemic. Methods: We purposively sampled clinicians from hospital-based EDs to conduct focus groups with ED clinicians and staff. We used both inductive and deductive approaches to conduct thematic analysis of transcripts. Results: We conducted focus groups with clinicians from eight EDs across the United States. We found that ED clinicians in our sample relied on friends and colleagues or departmental and institutional leadership for information on innovations. They used social media sources when they came from credible accounts but did not directly seek information from professional societies. Clinicians reported a range of challenges to obtain credible information during the pandemic, including a fractured and changing information environment, policies misaligned across clinical sites or that conflicted with clinical knowledge, high patient volume, fear of harming patients, and untimely information. Facilitators included access to experienced and trusted colleagues and leaders and practicing at multiple EDs. Conclusion: Participants cited anecdotal evidence, institutional practice, and word-of-mouth-rather than peer-reviewed evidence and professional society communications-as their primary sources of information about care innovations during the early phases of the pandemic. These results underscore the importance of developing trusted local mechanisms and wider networks to identify and vet information for frontline clinicians during rapidly emerging public health emergencies.

Misaligned Supports: Differences in Reported Health Care Worker Well-being Supports Provided and Needed During the COVID-19 Pandemic.

PURPOSE: To describe the well-being supports provided to health care workers (HCWs) during the COVID-19 pandemic in health centers and hospitals. DESIGN: Cross-sectional qualitative interviews before and after implementation of a peer-based support intervention. SETTING: Purposively sampled hospitals and health centers across the US. PARTICIPANTS: 28 site leaders and 56 HCWs sampled from 16 hospitals and 12 health centers. METHOD: Site leaders and HCWs were asked to describe supports available to HCWs during the COVID-19 pandemic. Thematic and content coding and analysis of interview responses were conducted using Dedoose. RESULTS: Both site leaders and HCWs identified a range of support resources available. Communication resources were the most frequently cited in both groups. Health care workers reported bi-directional communication, while one-way communication was emphasized by site leaders. Hospitals highlighted counseling support, particularly Employee Assistance Programs (EAP), while health centers prioritized community support. Wellness activities were more prevalent in hospital settings, while health centers offered specific workplace-provided training for HCWs. Health care workers encountered barriers when accessing support, including limited time, fear of stigma, and disruptions to their existing support networks attributable to the pandemic. CONCLUSION: While there are resources for HCWs, the available supports may not align with their needs and barriers to access may limit the effectiveness of these supports. Continued engagement between leaders and HCWs could help better align resources with needs.

Medial amygdalar tau is associated with anxiety symptoms in preclinical Alzheimer's disease.

BACKGROUND: While the amygdala receives early tau deposition in Alzheimer's disease (AD) and is involved in social and emotional processing, the relationship between amygdalar tau and early neuropsychiatric symptoms in AD is unknown. We sought to determine whether focal tau binding in the amygdala and abnormal amygdalar connectivity were detectable in a preclinical AD cohort and identify relationships between these and self-reported mood symptoms. METHODS: We examined n=598 individuals (n=347 amyloid-positive (58% female), n=251 amyloid-negative (62% female); subset into tau PET and fMRI cohorts) from the A4 Study. In our tau PET cohort, we used amygdalar segmentations to examine representative nuclei from three functional divisions of the amygdala. We analyzed between-group differences in division-specific tau binding in the amygdala in preclinical AD. We conducted seed-based functional connectivity analyses from each division in the fMRI cohort. Finally, we conducted exploratory post-hoc correlation analyses between neuroimaging biomarkers of interest and anxiety and depression scores. RESULTS: Amyloid-positive individuals demonstrated increased tau binding in medial and lateral amygdala (F(4,442)=14.61, p=0.00045; F(4,442)=5.83, p=0.024, respectively). Across amygdalar divisions, amyloid-positive individuals had relatively increased regional connectivity from amygdala to other temporal regions, insula, and orbitofrontal cortex. There was an interaction by amyloid group between tau binding in the medial and lateral amygdala and anxiety. Medial amygdala to retrosplenial connectivity negatively correlated with anxiety symptoms (rs=-0.103, p=0.015). CONCLUSIONS: Our findings suggest that preclinical tau deposition in the amygdala may result in meaningful changes in functional connectivity which may predispose patients to mood symptoms.

Assembly of the Tn7 targeting complex by a regulated stepwise process.

The Tn7 family of transposons is notable for its highly regulated integration mechanisms, including programmable RNA-guided transposition. The targeting pathways rely on dedicated target selection proteins from the TniQ family and the AAA+ adaptor TnsC to recruit and activate the transposase at specific target sites. Here, we report the cryoelectron microscopy (cryo-EM) structures of TnsC bound to the TniQ domain of TnsD from prototypical Tn7 and unveil key regulatory steps stemming from unique behaviors of ATP- versus ADP-bound TnsC. We show that TnsD recruits ADP-bound dimers of TnsC and acts as an exchange factor to release one protomer with exchange to ATP. This loading process explains how TnsC assembles a heptameric ring unidirectionally from the target site. This unique loading process results in functionally distinct TnsC protomers within the ring, providing a checkpoint for target immunity and explaining how insertions at programmed sites precisely occur in a specific orientation across Tn7 elements.

Molecular expression, purification and structural characterization of recombinant L-Glutaminase from Streptomyces roseolus.

The present research reports the anti-cancer potential of recombinant L-Glutaminase from Streptomyces roseolus. L-Glutaminase gene was synthesized by codon-optimization, cloned and successfully expressed in E. coli BL21 (DE3). Affinity purified recombinant L-Glutaminase revealed a molecular mass of 32 kDa. Purified recombinant L-Glutaminase revealed stability at pH 7.0-8.0 with optimum activity at 70 °C further indicating its thermostable nature based on thermodynamic characterization. Recombinant L-Glutaminase exhibited profound stability in the presence of several biochemical parameters and demonstrated its metalloenzyme nature and was also found to be highly specific towards favorable substrate (l-Glutamine) based on kinetics. It demonstrated antioxidant property and pronounced cytotoxic effect against breast cancer (MCF-7 cell lines) in a dose dependent behavior with IC50 of 40.68 µg/mL. Matrix-assisted laser desorption ionization-time of flight-mass spectroscopy (MALDI-TOF-MS) analysis of desired mass peaks ascertained the recombinant L-Glutaminase identity. N-terminal amino acid sequence characterization through Edman degradation revealed highest resemblance for L-glutaminase within the Streptomyces sp. family. The purified protein was characterized structurally and functionally by employing spectroscopic methods like Raman, circular dichroism and nuclear magnetic resonance. The thermostability was assessed by thermogravimetric analysis. The outcomes of the study, suggests the promising application of recombinant L-Glutaminase as targeted therapeutic candidate for breast cancer.

Mechanism, and treatment of anti-CV2/CRMP5 autoimmune pain.

Paraneoplastic neurological syndromes arise from autoimmune reactions against nervous system antigens due to a maladaptive immune response to a peripheral cancer. Patients with small cell lung carcinoma or malignant thymoma can develop an autoimmune response against the CV2/collapsin response mediator protein 5 (CRMP5) antigen. For reasons that are not understood, approximately 80% of patients experience painful neuropathies. Here, we investigated the mechanisms underlying anti-CV2/CRMP5 autoantibodies (CV2/CRMP5-Abs)-related pain. We found that patient-derived CV2/CRMP5-Abs can bind to their target in rodent dorsal root ganglia (DRG) and superficial laminae of the spinal cord. CV2/CRMP5-Abs induced DRG neuron hyperexcitability and mechanical hypersensitivity in rats that were abolished by preventing binding to their cognate autoantigen CRMP5. The effect of CV2/CRMP5-Abs on sensory neuron hyperexcitability and mechanical hypersensitivity observed in patients was recapitulated in rats using genetic immunization providing an approach to rapidly identify possible therapeutic choices for treating autoantibody-induced pain including the repurposing of a monoclonal anti-CD20 antibody that selectively deplete B-lymphocytes. These data reveal a previously unknown neuronal mechanism of neuropathic pain in patients with paraneoplastic neurological syndromes resulting directly from CV2/CRMP5-Abs-induced nociceptor excitability. CV2/CRMP5-Abs directly sensitize pain responses by increasing sensory neuron excitability and strategies aiming at either blocking or reducing CV2/CRMP5-Abs can treat pain as a comorbidity in patients with paraneoplastic neurological syndromes.

Biochemical characterization of immobilized recombinant subtilisin and synthesis and functional characterization of recombinant subtilisin capped silver and zinc oxide nanoparticles.

This pioneering research explores the transformative potential of recombinant subtilisin, emphasizing its strategic immobilization and nanoparticle synthesis to elevate both stability and therapeutic efficacy. Achieving an impressive 95.25 % immobilization yield with 3 % alginate composed of sodium along with 0.2 M CaCl2 indicates heightened pH levels and thermal resistance, with optimal action around pH 10 as well as 80 °C temperature. Notably, the Ca-alginate-immobilized subtilisin exhibits exceptional storage longevity and recyclability, affirming its practical viability. Comprehensive analyses of the recombinant subtilisin under diverse conditions underscore its adaptability, reflected in kinetic enhancements with increased Vmax (10.7 ± 15 × 103 U/mg) and decreased Km (0.19 ± 0.3 mM) values post-immobilization using N-Suc-F-A-A-F-pNA. UV-visible spectroscopy confirms the successful capping of nanoparticles made of Ag and ZnO by recombinant subtilisin, imparting profound antibacterial efficacy against diverse organisms and compelling antioxidant properties. Cytotoxicity was detected against the MCF-7 breast cancer line of cells, exhibiting IC50 concentrations at 8.87 as well as 14.52 µg/mL of AgNP as well as ZnONP, correspondingly, indicating promising anticancer potential. Rigorous characterization, including FTIR, SEM-EDS, TGA and AFM robustly validate the properties of the capped nanoparticles. Beyond therapeutic implications, the investigation explores industrial applications, revealing the versatility of recombinant subtilisin in dehairing, blood clot dissolution, biosurfactant activity, and blood stain removal. In summary, this research unfolds the exceptional promise of recombinant subtilisin and its nanoparticles, presenting compelling opportunities for diverse therapeutic applications in medicine. These findings contribute substantively to biotechnology and healthcare and stimulate avenues for further innovation and exploration.

Testing an Intervention to Improve Health Care Worker Well-Being During the COVID-19 Pandemic: A Cluster Randomized Clinical Trial.

Importance: Stress First Aid is an evidence-informed peer-to-peer support intervention to mitigate the effect of the COVID-19 pandemic on the well-being of health care workers (HCWs). Objective: To evaluate the effectiveness of a tailored peer-to-peer support intervention compared with usual care to support HCWs' well-being at hospitals and federally qualified health centers (FQHCs) during the COVID-19 pandemic. Design, Setting, and Participants: This cluster randomized clinical trial comprised 3 cohorts of HCWs who were enrolled from March 2021 through July 2022 at 28 hospitals and FQHCs in the US. Participating sites were matched as pairs by type, size, and COVID-19 burden and then randomized to the intervention arm or usual care arm (any programs already in place to support HCW well-being). The HCWs were surveyed before and after peer-to-peer support intervention implementation. Intention-to-treat (ITT) analysis was used to evaluate the intervention's effect on outcomes, including general psychological distress and posttraumatic stress disorder (PTSD). Intervention: The peer-to-peer support intervention was delivered to HCWs by site champions who received training and subsequently trained the HCWs at their site. Recipients of the intervention were taught to respond to their own and their peers' stress reactions. Main Outcomes and Measures: Primary outcomes were general psychological distress and PTSD. General psychological distress was measured with the Kessler 6 instrument, and PTSD was measured with the PTSD Checklist. Results: A total of 28 hospitals and FQHCs with 2077 HCWs participated. Both preintervention and postintervention surveys were completed by 2077 HCWs, for an overall response rate of 28% (41% at FQHCs and 26% at hospitals). A total of 862 individuals (696 females [80.7%]) were from sites that were randomly assigned to the intervention arm; the baseline mean (SD) psychological distress score was 5.86 (5.70) and the baseline mean (SD) PTSD score was 16.11 (16.07). A total of 1215 individuals (947 females [78.2%]) were from sites assigned to the usual care arm; the baseline mean (SD) psychological distress score was 5.98 (5.62) and the baseline mean (SD) PTSD score was 16.40 (16.43). Adherence to the intervention was 70% for FQHCs and 32% for hospitals. The ITT analyses revealed no overall treatment effect for psychological distress score (0.238 [95% CI, -0.310 to 0.785] points) or PTSD symptom score (0.189 [95% CI, -1.068 to 1.446] points). Post hoc analyses examined the heterogeneity of treatment effect by age group with consistent age effects observed across primary outcomes (psychological distress and PTSD). Among HCWs in FQHCs, there were significant and clinically meaningful treatment effects for HCWs 30 years or younger: a more than 4-point reduction for psychological distress (-4.552 [95% CI, -8.067 to -1.037]) and a nearly 7-point reduction for PTSD symptom scores (-6.771 [95% CI, -13.224 to -0.318]). Conclusions and Relevance: This trial found that this peer-to-peer support intervention did not improve well-being outcomes for HCWs overall but had a protective effect against general psychological distress and PTSD in HCWs aged 30 years or younger in FQHCs, which had higher intervention adherence. Incorporating this peer-to-peer support intervention into medical training, with ongoing support over time, may yield beneficial results in both standard care and during public health crises. Trial Registration: ClinicalTrials.gov Identifier: NCT04723576.

Microarchitecture of the penis bone (baculum) of a seal: A 3D morphometric examination using synchrotron and laboratory micro-computed tomography.

We examined the ultrastructure of the mammalian os penis at the high-resolution synchrotron level. Previously, bacular microanatomy had only been investigated histologically. We studied the baculum of the harp seal (Pagophilus groenlandicus), in which the baculum varies more in size and shape than does a mechanically constrained bone (humerus). We (1) investigated the microarchitecture of bacula and humeri from the same seal specimens, and (2) described changes in bone micro- and macro-morphology associated with age (n = 15, age range = 1-35 years) and bone type. We analyzed cross-sectional geometry non-destructively through laboratory micro-computed tomography. We suggest that the midshaft may resist axial compression while the proximal region may resist torsion, based on measurements of cross-sectional and cortical areas, perimeter, ratio of maximum and minimum moments of inertia, and polar moment of inertia. In addition, midshaft bacula may be less mechanosensitive than humeri, based on microstructural variables (e.g., volume, surface area, diameter associated with lacunae and cortical porosity) analyzed across age groupings. Our findings related to the microarchitecture of the pinniped baculum provide a basis for further studies on development, mechanical properties, functions, and adaptations in this and other pinniped species. Our use of a multi-modal imaging approach was minimally destructive for reproducible and accurate comparison of three-dimensional bone ultrastructure. Such methods, coupled with multidisciplinary analyses, enable diverse studies of bone biology, life history, and evolution using museum collections.

Longitudinal Analysis of Mpox Virus DNA Detectability From Multiple Specimen Types During Acute Illness: A Cohort Study.

Background: Longitudinal data on the detectability of monkeypox virus (MPXV) genetic material in different specimen types are scarce. Methods: We describe MPXV-specific polymerase chain reaction (PCR) results from adults with confirmed mpox infection from Toronto, Canada, including a cohort undergoing weekly collection of specimens from multiple anatomic sites until 1 week after skin lesions had fully healed. We quantified the time from symptom onset to resolution of detectable viral DNA (computed tomography [Ct] ≥ 35) by modeling exponential decay in Ct value as a function of illness day for each site, censoring at the time of tecovirimat initiation. Results: Among 64 men who have sex with men, the median (interquartile range [IQR]) age was 39 (32.75-45.25) years, and 49% had HIV. Twenty received tecovirimat. Viral DNA was detectable (Ct < 35) at baseline in 74% of genital/buttock/perianal skin swabs, 56% of other skin swabs, 44% of rectal swabs, 37% of throat swabs, 27% of urine, 26% of nasopharyngeal swabs, and 8% of semen samples. The median time to resolution of detectable DNA (IQR) was longest for genital/buttock/perianal skin and other skin swabs at 30.0 (23.0-47.9) and 22.4 (16.6-29.4) days, respectively, and shortest for nasopharyngeal swabs and semen at 0 (0-12.1) and 0 (0-0) days, respectively. We did not observe an effect of tecovirimat on the rate of decay in viral DNA detectability in any specimen type (all P > .05). Conclusions: MPXV DNA detectability varies by specimen type and persists for over 3-4 weeks in skin specimens. The rate of decay did not differ by tecovirimat use in this nonrandomized study.

Uptake of Cyclodextrin Nanoparticles by Macrophages is Dependent on Particle Size and Receptor-Mediated Interactions.

Physiochemical properties of nanoparticles, such as their size and chemical composition, dictate their interaction with professional phagocytes of the innate immune system. Macrophages, in particular, are key regulators of the immune microenvironment that heavily influence particle biodistribution as a result of their uptake. This attribute enables macrophage-targeted delivery, including for phenotypic modulation. Saccharide-based materials, including polyglucose polymers and nanoparticles, are efficient vehicles for macrophage-targeted delivery. Here, we investigate the influence of particle size on cyclodextrin nanoparticle (CDNP) uptake by macrophages and further examine the receptor-mediated interactions that drive macrophage-targeted delivery. We designed and synthesized CDNPs ranging in size from 25 nm to >100 nm in diameter. Increasing particle size was correlated with greater uptake by macrophages in vitro. Both scavenger receptor A1 and mannose receptor were critical mediators of macrophage-targeted delivery, inhibition of which reduced the extent of uptake. Finally, we investigated the cellular bioavailability of drug-loaded CDNPs using a model anti-inflammatory drug, celastrol, which demonstrated that drug bioactivity is improved by CDNP loading relative to free drug alone. This study thus elucidates the interactions between the polyglucose nanoparticles and macrophages, thereby facilitating their application in macrophage-targeted drug delivery that has applications in the context of tissue injury and repair.

Fetal Diagnosis of Supravalvular Aortic Stenosis and Pulmonary Stenosis in a Family with Non-Syndromic Elastin Mutation.

Supravalvular aortic stenosis (SVAS) has been well described in Williams-Beuren Syndrome and non-syndromic elastin (ELN) mutations. Non-syndromic ELN mutations are inherited in an autosomal dominant pattern with incomplete penetrance and variable expressivity. ELN haploinsufficiency leads to progressive arteriopathy, typically affecting the aortic sinotubular junction. Multi-level pulmonary stenosis has also been reported and biventricular obstruction may portend a worse prognosis. Fetal presentation of ELN mutation with SVAS has not been previously reported in the literature. We present a case of fetal diagnosis of SVAS and multi-level pulmonary stenosis in a family with a known pathogenic ELN mutation (Exon 6, c.278del [p.Pro93Leufs*29]). On the fetus' initial fetal echo, there was only mild flow acceleration through the aortic outflow tract, however, she went on to develop progressive bilateral obstruction. In the early post-natal period, the child was clinically asymptomatic and showed similar mild SVAS and mild valvar and supravalvular pulmonary stenosis. Our case highlights the need for serial monitoring of fetuses with suspected or confirmed ELN arteriopathy.

COVID-19 testing and vaccination uptake among youth and young adults: Disparities by age, race/ethnicity, sexual orientation, and gender identity.

BACKGROUND: The COVID-19 pandemic disproportionately impacts youth and young adults (YYA) and YYA with multiple marginalized identities, yet little is known about differences in uptake, testing access, and vaccine concerns among YYA by diverse demographic identities. METHODS: Between 2/2021 and 2/2022, we conducted a national, cross-sectional online survey focused on diverse YYA ages 14 to 24 (n = 983). We explored the prevalence of COVID-19 testing and vaccination among YYA by age, race/ethnicity, and sexual and gender identities. Bivariate and multivariable logistic regression models were developed to estimate associations between individual variables and COVID-19 testing and vaccination. RESULTS: The overall COVID-19 testing and vaccination rates in our sample were high (75.99% and 69.07%, respectively). No differences in testing by demographics were found. Compared to individuals aged 14 to 17 years, those aged 18 to 21 years and 22 to 24 years were over 2 times and 4 times as likely to report receiving a vaccine, respectively. All race/ethnicity groups except for Asian individuals were more likely to report being vaccinated compared to their white peers. CONCLUSIONS: Our findings showed critical disparities in COVID-19 vaccination among YYA with marginalized identities and emphasized the urgency for data collection and research on pandemic prevention for vulnerable YYA populations.

Prospective Evaluation of High Titer Autoantibodies and Fetal Home Monitoring in the Detection of Atrioventricular Block Among Anti-SSA/Ro Pregnancies.

OBJECTIVE: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB). METHODS: Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti-52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17-26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB. RESULTS: Anti-52-kD and/or 60-kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti-60-kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non-AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second-degree AVB, all <12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third-degree and two participants with third-degree AVB were diagnosed by urgent echocardiogram >17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal. CONCLUSION: High-titer antibodies are associated with an increased incidence of AVB. Anti-SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms.

Prenatal Diagnosis and Intervention in a Fetal Enterogenous Cyst.

The ultrasound diagnosis of a fetal intra-abdominal cyst is typically established during the second or third trimester in the majority of cases. They primarily arise from the gastrointestinal or genitourinary system during the development of intra-abdominal structure and if isolated may resolve spontaneously. Enteric or enterogenous or enteric duplication cysts, which are congenital developments from the intestine, are most common. This case of an enterogenous cyst is presented because of its extreme rarity, its large size, and the need for prenatal intervention. Early identification and definitive treatment are necessary for proper management of this condition.