Enantio- and Diastereoselective Variations on α-Iminonitriles: Harnessing Chiral Cyclopropenimine-Thiourea Organocatalysts.

Chiral 1-pyrrolines containing a nitrile motif serve as crucial structural scaffolds in biologically active molecules and exhibit diversity as building blocks owing to their valuable functional groups; however, the asymmetric synthesis of such compounds remains largely unexplored. Herein, we present an enantio- and diastereoselective method for the synthesis of α-chiral nitrile-containing 1-pyrroline derivatives bearing vicinal stereocenters through the design and introduction of chiral cyclopropenimine-based bifunctional catalysts featuring a thiourea moiety. This synthesis entails a highly stereoselective conjugate addition of α-iminonitriles to a wide array of enones, followed by cyclocondensation, thereby affording a series of cyanopyrroline derivatives, some of which contain all-carbon quaternary centers. Moreover, we demonstrate the synthetic utility of this strategy by performing a gram-scale reaction with 1% catalyst loading, along with a variety of chemoselective transformations of the product, including the synthesis of a vildagliptin analogue. Finally, we showcase the selective synthesis of all four stereoisomers of the cyanopyrroline products through trans-to-cis isomerization, highlighting the versatility of our approach.

Purification and characterisation of the platelet-activating GPVI/FcRγ complex in SMALPs.

The collagen/fibrin(ogen) receptor, glycoprotein VI (GPVI), is a platelet activating receptor and a promising anti-thrombotic drug target. However, while agonist-induced GPVI clustering on platelet membranes has been shown to be essential for its activation, it is unknown if GPVI dimerisation represents a unique conformation for ligand binding. Current GPVI structures all contain only the two immunoglobulin superfamily (IgSF) domains in the GPVI extracellular region, so lacking the mucin-like stalk, transmembrane, cytoplasmic tail of GPVI and its associated Fc receptor γ (FcRγ) homodimer signalling chain, and provide contradictory insights into the mechanisms of GPVI dimerisation. Here, we utilised styrene maleic-acid lipid particles (SMALPs) to extract GPVI in complex with its two associated FcRγ chains from transfected HEK-293T cells, together with the adjacent lipid bilayer, then purified and characterised the GPVI/FcRγ-containing SMALPs, to enable structural insights into the full-length GPVI/FcRγ complex. Using size exclusion chromatography followed by a native polyacrylamide gel electrophoresis (PAGE) method, SMA-PAGE, we revealed multiple sizes of the purified GPVI/FcRγ SMALPs, suggesting the potential existence of GPVI oligomers. Importantly, GPVI/FcRγ SMALPs were functional as they could bind collagen. Mono-dispersed GPVI/FcRγ SMALPs could be observed under negative stain electron microscopy. These results pave the way for the future investigation of GPVI stoichiometry and structure, while also validating SMALPs as a promising tool for the investigation of human membrane protein interactions, stoichiometry and structure.

Guideline concordant care for patients with locally advanced cervical cancer by disaggregated Asian American and Native Hawaiian/Pacific Islander groups: A National Cancer Database Analysis.

OBJECTIVE: Despite the within-group heterogeneity, Asian American (AA) and Native Hawaiian and Pacific Islander (NH/PI) patients are often grouped together. We compared the patterns of guideline-concordant care for locally advanced cervical cancer for disaggregated AA and NH/PI patients. METHODS: Patients with stage II-IVA cervical cancer between 2004 and 2020 were identified from the National Cancer Database. AA patients were disaggregated as East Asian (EA), South Asian (SA), and Southeast Asian (SEA). NH/PI patients were classified as a distinct racial subgroup. The primary outcome was the proportion undergoing guideline-concordant care, defined by radiation therapy with concurrent chemotherapy, brachytherapy, and completion of treatment within eight weeks. RESULTS: Of 48,116 patients, 2107 (4%) were AA and 171 (<1%) were NH/PI. Of the AA patients, 36% were SEA, 31% were EA, 12% were SA, and 21% could not be further disaggregated due to missing or unknown data. NH/PI patients were more likely to be diagnosed at an early age (53% NH/PI vs. 30% AA, p < 0.001) and have higher rates of comorbidities (18% NH/PI vs. 14% AA, p < 0.001). Within the AA subgroups, only 82% of SEA patients received concurrent chemotherapy compared to 91% of SA patients (p = 0.026). SA patients had the longest median OS (158 months) within the AA subgroups compared to SEA patients (113 months, p < 0.001). CONCLUSION: Disparities exist in the receipt of standard of care treatment for cervical cancer by racial and ethnic subgroups. It is imperative to disaggregate race and ethnicity data to understand potential differences in care and tailor interventions to achieve health equity.

Demographic reporting and language exclusion in gynecologic oncology clinical trials.

BACKGROUND: Participation in clinical trials may help mitigate disparate cancer outcomes. Thus, ensuring equitable access to clinical trials is a major priority for national cancer organizations. OBJECTIVE: This study aimed to examine clinical trial eligibility criteria that may adversely affect the enrollment of underrepresented groups and assess the availability of demographic information in published gynecologic oncology studies. STUDY DESIGN: ClinicalTrials.gov was searched for gynecologic oncology studies conducted between 1997 and 2021. Each study's inclusion and exclusion criteria were reviewed to determine whether demographic factors were used for enrollment screening. For published studies, demographic variables that were reported were identified. The expected clinical trial enrollment based on disease incidence and mortality was compared with the observed trial enrollment based on race. RESULTS: There were 1597 gynecologic oncology studies: 883 (55%) from ovarian cancer studies, 336 (21%) from cervical cancer studies, 262 (17%) from uterine cancer studies, and 116 (7%) from multisite gynecologic oncology studies. Of the 581 published studies, 554 (95%) reported age, 363 (63%) reported race, and 171 (29%) reported ethnicities. Cervical cancer studies were most likely to report demographic information, including race (P=.026) and ethnicity (P<.001). During the study period, 189 studies (12%) excluded patients based on the language spoken. Industry-sponsored trials (odds ratio, 0.07; 95% confidence interval, 0.02-0.30) and organization-sponsored trials (odds ratio, 0.40; 95% confidence interval, 0.22-0.73) were less likely to exclude patients because of language than investigator-initiated trials. A minority of patients (37%) in cervical cancer trials were of White race, compared with 85% of patients in uterine cancer trials and 82% of patients in ovarian cancer trials. CONCLUSION: Over the last 3 decades, 1 in 10 gynecologic oncology trials excluded patients because of language. Race and ethnicity were reported in more than half of the available studies. Initiatives to increase transparency in recruiting underrepresented patients and reporting demographic data are urgently needed.

Cases of Meningococcal Disease Associated with Travel to Saudi Arabia for Umrah Pilgrimage - United States, United Kingdom, and France, 2024.

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2).

Survival and neurological outcomes following management of intramedullary spinal metastasis patients: a case series with comprehensive review of the literature.

Intramedullary spinal cord metastasis (ISCM), though rare, represents a potentially debilitating manifestation of systemic cancer. With emerging advances in cancer care, ISCMs are increasingly being encountered in clinical practice. Herein, we describe one of the larger retrospective single institutional case series on ISCMs, analyze survival and treatment outcomes, and review the literature. All surgically evaluated ISCMs at our institution between 2005 and 2023 were retrospectively reviewed. Demographics, tumor features, treatment, and clinical outcome characteristics were collected. Neurological function was quantified via the Frankel grade and the McCormick score (MCS). The pre- and post-operative Karnofsky performance scores (KPS) were used to assess functional status. Descriptive statistics, univariate analysis, log-rank test, and the Kaplan-Meier survival analysis were performed. A total of 9 patients were included (median age 67 years (range, 26-71); 6 were male). Thoracic and cervical spinal segments were most affected (4 patients each). Six patients (75%) underwent surgical management (1 biopsy and 5 resections), and 3 cases underwent chemoradiation only. Post-operatively, 2 patients had an improvement in their neurological exam with one patient becoming ambulatory after surgery; three patients maintained their neurological exam, and 1 had a decline. There was no statistically significant difference in the pre- and post-operative MCS and median KPS scores in surgically treated patients. Median OS after ISCM diagnosis was 7 months. Absence of brain metastasis, tumor histology (renal and melanoma), cervical/thoracic location, and post-op KPS ≥ 70 showed a trend toward improved overall survival. The incidence of ISCM is increasing, and earlier diagnosis and treatment are considered key for the preservation of neurological function. When patient characteristics are favorable, surgical resection of ISCM can be considered in patients with rapidly progressive neurological deficits. Surgical treatment was not associated with an improvement in overall survival in patients with ISCMs.

Enterotoxigenic Staphylococcus aureus in Brazilian artisanal cheeses: Occurrence, counts, phenotypic and genotypic profiles.

The present study aimed to assess the occurrence and counts of Staphylococcus aureus in Brazilian artisanal cheeses (BAC) produced in five regions of Brazil: Coalho and Manteiga (Northeast region); Colonial and Serrano (South); Caipira (Central-West); Marajó (North); and Minas Artisanal cheeses, from Araxá, Campos das Vertentes, Cerrado, Serro and Canastra microregions (Southeast). The resistance to chlorine-based sanitizers, ability to attach to stainless steel surfaces, and antibiogram profile of a large set of S. aureus strains (n = 585) were assessed. Further, a total of 42 isolates were evaluated for the presence of enterotoxigenic genes (sea, seb, sec, sed, see, seg, sei, sej, and ser) and submitted to typing using pulsed-field gel electrophoresis (PFGE). BAC presented high counts of S. aureus (3.4-6.4 log CFU/g), varying from 25 to 62.5%. From the S. aureus strains (n = 585) assessed, 16% could resist 200 ppm of sodium hypochlorite, whereas 87.6% produced strong ability to attach to stainless steel surfaces, corroborating with S. aureus ability to persist and spread in the environment. Furthermore, the relatively high frequency (80.5%) of multidrug-resistant S. aureus and the presence of enterotoxin genes in 92.6% of the strains is of utmost attention. It reveals the lurking threat of SFP that can survive when conditions are favorable. The presence of enterotoxigenic and antimicrobial-resistant strains of S. aureus in cheese constitutes a potential risk to public health. This result calls for better control of cheese contamination sources, and taking hygienic measures is necessary for food safety. More attention should be paid to animal welfare and hygiene practices in some dairy farms during manufacturing to enhance the microbiological quality of traditional cheese products.

Sex-specific ornament evolution is a consistent feature of climatic adaptation across space and time in dragonflies.

Adaptation to different climates fuels the origins and maintenance of biodiversity. Detailing how organisms optimize fitness for their local climates is therefore an essential goal in biology. Although we increasingly understand how survival-related traits evolve as organisms adapt to climatic conditions, it is unclear whether organisms also optimize traits that coordinate mating between the sexes. Here, we show that dragonflies consistently adapt to warmer climates across space and time by evolving less male melanin ornamentation-a mating-related trait that also absorbs solar radiation and heats individuals above ambient temperatures. Continent-wide macroevolutionary analyses reveal that species inhabiting warmer climates evolve less male ornamentation. Community-science observations across 10 species indicate that populations adapt to warmer parts of species' ranges through microevolution of smaller male ornaments. Observations from 2005 to 2019 detail that contemporary selective pressures oppose male ornaments in warmer years; and our climate-warming projections predict further decreases by 2070. Conversely, our analyses show that female ornamentation responds idiosyncratically to temperature across space and time, indicating the sexes evolve in different ways to meet the demands of the local climate. Overall, these macro- and microevolutionary findings demonstrate that organisms predictably optimize their mating-related traits for the climate just as they do their survival-related traits.

Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.

BACKGROUND: Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. METHODS: Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. RESULTS: Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. CONCLUSIONS: In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.

Anti-inflammatory, Antioxidative, and Moisturizing Effects of Oxyceros horridus Lour. Ethanol Extract in Human Keratinocytes via the p38 Signaling Pathway.

Skin is the largest and outermost organ in the human body; it serves as a vital defense mechanism against various external threats. Therefore, it is crucial to maintain its health through protection against harmful substances and adequate moisture levels. This study investigates the anti-inflammatory, antioxidant, and moisturizing properties of Oxyceros horridus Lour. (Oh-EE) in human keratinocytes. Oh-EE demonstrates potent antioxidant activity and effectively protects against oxidative stress induced by external stimuli such as UVB radiation and H2O2. Additionally, it exhibits significant anti-inflammatory effects proven by its ability to downregulate the expression of pro-inflammatory cytokines, namely COX-2 and IL-6. The study also explores the involvement of the AP-1 pathway, highlighting the ability of Oh-EE to suppress the expression of p38 and its upstream regulator, MKK3/6, under UVB-induced conditions. Interestingly, Oh-EE can activate the AP-1 pathway in the absence of external triggers. Furthermore, Oh-EE enhances skin moisture by upregulating the expression of key genes involved in skin hydration, namely HAS3 and FLG. These findings underscore the potential of Oh-EE as a versatile ingredient in skincare formulations, providing a range of skin benefits. Further research is warranted to comprehensively understand the underlying mechanisms through which Oh-EE exerts its effects.

Thrombectomy in young adults with embolic stroke of undetermined source: Analysis of the Young ESUS study.

OBJECTIVES: Embolic Stroke of Undetermined Source (ESUS) is a distinct stroke entity that disproportionately affects young adults. We sought to describe characteristics, workup and outcomes of young adult ESUS patients who underwent thrombectomy, and compare outcomes to those reported in different age groups. MATERIALS AND METHODS: Young-ESUS is a multicenter longitudinal cohort study that enrolled consecutive patients aged 21-50 years at 41 stroke centers in 13 countries between 2017- 2019. Between-group comparisons were performed using Wilcoxon rank sum test for continuous variables or Fisher's exact test for binary variables. Distribution of functional outcomes after thrombectomy for our young adult cohort versus pediatric and older adult cohorts reported in the literature were described using the Kruskal-Wallis test. RESULTS: Of 535 patients enrolled in Young-ESUS, 65 (12.1%) were treated with endovascular thrombectomy. Patients who underwent thrombectomy were more likely to undergo in-depth cardiac testing than those who did not, but cardiac abnormalities were not detected more often in this group. Among thrombectomy patients, 35/63 (55.6%) had minimal to no functional disability at follow up. When adjusted for age, stroke severity and IV alteplase, the odds of achieving favorable outcome did not differ between treated versus untreated patients. CONCLUSIONS: Thrombectomy is not rare in young adults with ESUS. Despite extensive workup, cardiac abnormalities were not more prevalent in the thrombectomy group. More research to determine optimal workup, etiologic factors and favorable outcome of stroke across the lifespan is needed.

Reported Impact of COVID-19 Workload and Stressors on School Nurses' Provision of Care During the 2021-2022 School Year: A Secondary Analysis of U.S. School Nurse Survey Data.

Many school nurses experienced increased work burden and stress during the COVID-19 pandemic. This analysis examined data from a Centers for Disease Control and Prevention cross-sectional, nationwide survey of school nurses in March 2022 to examine associations between school nurses' ability to conduct their core responsibilities and selected nurse and school factors among school nurses during the 2021-2022 school year and COVID-19 pandemic. Perceived adequate staffing and financial compensation reduced the odds of reported difficulties across all core school nursing tasks. Nurses without a registered nurse license and with higher caseloads were more likely to report difficulty in implementing specific tasks. The impact of these factors varied, with inadequate financial compensation having the largest association with school nurses' difficulty implementing all the core responsibilities. The study results improve our understanding of school nurses' challenges in implementing core school nursing responsibilities during the COVID-19 pandemic in the 2021-2022 school year.

Consensus Recommendations for Standardized Data Elements, Scales, and Time Segmentations in Studies of Human Circadian/Diurnal Biology and Stroke.

Increasing evidence indicates that circadian and diurnal rhythms robustly influence stroke onset, mechanism, progression, recovery, and response to therapy in human patients. Pioneering initial investigations yielded important insights but were often single-center series, used basic imaging approaches, and used conflicting definitions of key data elements, including what constitutes daytime versus nighttime. Contemporary methodologic advances in human neurovascular investigation have the potential to substantially increase understanding, including the use of large multicenter and national data registries, detailed clinical trial data sets, analysis guided by individual patient chronotype, and multimodal computed tomographic and magnetic resonance imaging. To fully harness the power of these approaches to enhance pathophysiologic knowledge, an important foundational step is to develop standardized definitions and coding guides for data collection, permitting rapid aggregation of data acquired in different studies, and ensuring a common framework for analysis. To meet this need, the Leducq Consortium International pour la Recherche Circadienne sur l'AVC (CIRCA) convened a Consensus Statement Working Group of leading international researchers in cerebrovascular and circadian/diurnal biology. Using an iterative, mixed-methods process, the working group developed 79 data standards, including 48 common data elements (23 new and 25 modified/unmodified from existing common data elements), 14 intervals for time-anchored analyses of different granularity, and 7 formal, validated scales. This portfolio of standardized data structures is now available to assist researchers in the design, implementation, aggregation, and interpretation of clinical, imaging, and population research related to the influence of human circadian/diurnal biology upon ischemic and hemorrhagic stroke.

Copper-Catalyzed C-C Cross-Couplings of Tertiary Alkyl Halides with Anilines Enabled by Cyclopropenimine-Based Ligands.

Catalytic cross-couplings of tertiary alkyl electrophiles with carbon nucleophiles offer a powerful platform for constructing quaternary carbon centers, which are prevalent in bioactive molecules. However, these reactions remain underdeveloped primarily because of steric challenges that impede efficient bond formation. Herein, we describe the copper-catalyzed synthesis of such centers through the C(sp3)-C(sp2) bond-forming reaction between tertiary alkyl halides and arene rings of aniline derivatives, enabled by the strategic implementation of bidentate bis(cyclopropenimine) ligands. The copper catalyst bound by two imino-nitrogen atoms of these ligands, which have never been employed in metal catalysis previously, is highly effective in rapidly activating tertiary halides to generate alkyl radicals, allowing them to react with aryl nucleophiles under mild conditions with remarkably short reaction times (1-2 h). Various tertiary halides bearing carbonyl functional groups can be coupled with secondary or primary anilines, furnishing a range of quaternary carbon centers in good yields. Several mechanistic observations support the generation of copper(II) species and alkyl radicals which as a result elucidate the steps in the proposed catalytic cycle.

Disparities in Implementing COVID-19 Prevention Strategies in Public Schools, United States, 2021-22 School Year.

During the COVID-19 pandemic, US schools have been encouraged to take a layered approach to prevention, incorporating multiple strategies to curb transmission of SARS-CoV-2. Using survey data representative of US public K-12 schools (N = 437), we determined prevalence estimates of COVID-19 prevention strategies early in the 2021-22 school year and describe disparities in implementing strategies by school characteristics. Prevalence of prevention strategies ranged from 9.3% (offered COVID-19 screening testing to students and staff) to 95.1% (had a school-based system to report COVID-19 outcomes). Schools with a full-time school nurse or school-based health center had significantly higher odds of implementing several strategies, including those related to COVID-19 vaccination. We identified additional disparities in prevalence of strategies by locale, school level, and poverty. Advancing school health workforce and infrastructure, ensuring schools use available COVID-19 funding effectively, and promoting efforts in schools with the lowest prevalence of infection prevention strategies are needed for pandemic preparedness.

Beyond BRCA: Patterns of risk-reducing surgery for non-BRCA, homologous recombination repair pathway gene variant carriers.

OBJECTIVE: The real-world management of patients with non-BRCA, homologous recombination repair pathway variants with increased or uncertain risks of ovarian cancer is unknown. The objective was to determine the adoption of risk-reducing salpingo-oophorectomy (RRSO) for carriers of variants with increased or uncertain risks of ovarian cancer beyond BRCA. METHODS: This was a retrospective cohort study of patients at three hospitals with non-BRCA, homologous recombination repair pathway variants with increased risk (BRIP1, RAD51C, RAD51D) and uncertain risk (ATM, BARD1, NBN, PALB2) of ovarian cancer. Outcomes of interest were adoption of RRSO and factors associated with adoption of RRSO. Wilcoxon rank-sum, chi-square, and logistic regression were performed with p < 0.05. RESULTS: Of 318 patients, 76 (24%) had pathogenic variants with increased risks of ovarian cancer (BRIP1, 45; RAD51C, 20; RAD51D, 11), and 242 (76%) had variants with uncertain risks of ovarian cancer (ATM, 145; PALB2, 69; NBN, 23; BARD1, 5). Of 64 patients eligible for RRSO by National Comprehensive Cancer Network (NCCN) criteria or family history, 31 (48%) underwent RRSO. Among eligible patients who did not undergo RRSO, 24 (73%) were not referred for gynecologic oncology consultation. Older age at testing (adjusted odds ratio [aOR] 1.08, 95% confidence interval [CI] 1.03-1.13) and referral to gynecologic oncology (aOR 33.48, CI 8.10-138.39) were associated with increased adoption of RRSO when adjusting for personal and family history of breast and ovarian cancer. CONCLUSION: Half of RRSO-eligible patients by NCCN criteria beyond BRCA did not undergo RRSO. Opportunities exist for improving education to increase referrals to facilitate RRSO for these patients.

Missed opportunities in the real-world genetic testing in BRCA gene variant carriers with cancers meeting NCCN criteria.

OBJECTIVE: The objective of this study was to determine the proportion of patients meeting the National Comprehensive Cancer Network (NCCN)'s BRCA genetic testing criteria prior to a diagnosis of a BRCA-related cancer. METHODS: This was a cross-sectional study of patients with BRCA pathogenic variants and a diagnosis of a BRCA-related cancer. Patients were included if they had known dates of genetic testing and cancer diagnosis. NCCN criteria (version 2.2021) were applied to determine if patients met criteria for testing before a BRCA-related cancer diagnosis. The outcome of interest was the proportion of patients undergoing genetic testing following a diagnosis of a BRCA-related cancer who qualified for genetic testing based on NCCN criteria. Chi-square, Mann-Whitney U test, and logistic regression were performed with significance at p < 0.05. RESULTS: Of 270 patients with a BRCA-related cancer, 229 (85%) underwent genetic testing after a cancer diagnosis. Most patients (97%) met at least one NCCN criteria for BRCA testing; 166 (73%) of patients who were tested following a BRCA-related cancer diagnosis also met the criteria for testing by family history. Publicly insured or uninsured patients were three times more likely to undergo BRCA testing after a diagnosis of cancer (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.09-8.40). Patients with a family history of pathogenic variants were more likely to undergo testing before a cancer diagnosis (OR 0.10, 95% CI 0.05-0.23). CONCLUSION: Most patients with BRCA-associated cancers undergo genetic testing after their cancer diagnosis. Increased education on genetic testing criteria and novel methods to improve testing are desperately needed.

Concurrent uterine surgery and uptake of hormone therapy in patients undergoing bilateral salpingo-oophorectomy for risk-reducing or therapeutic indications.

OBJECTIVE: This study aimed to analyze factors associated with concurrent uterine surgery in patients undergoing bilateral salpingo-oophorectomy (BSO) for risk reducing or therapeutic purposes. Additionally, trends in surgical choice and uptake of post-operative hormone therapy (HT) were examined. METHODS: A 10-year retrospective study was conducted on patients who underwent risk-reducing or therapeutic BSO at one institution. Multinomial regression analysis of patient and case characteristics was performed evaluating associations with surgery type (BSO, BSO and hysterectomy, or BSO and endometrial sampling). Trends in surgery type and uptake of HT post operatively are described. RESULTS: Among the study sample of 643 patients, 140 (22%) patients underwent therapeutic BSO for a history of hormone receptor (HR) positive breast cancer, while the remainder underwent risk-reducing BSO due to a pathogenic variant and/or family history. Pathogenic variants included BRCA1 (141, 40%) BRCA2 (173, 49%), and Lynch syndrome genes (15, 4%). Regression analysis revealed significant associations between concurrent hysterectomy and Black race (RR = 3.55, CI = 1.51-8.38, p = 0.004), history of HR positive breast cancer (RR = 1.88, CI = 1.03-3.42, p = 0.04), and surgeon (Surgeon 1, RR = 2.43, CI = 1.36-4.35, p = 0.003). Among eligible patients under age 51, 36% initiated HT. Over the study period, concurrent hysterectomy rates declined while endometrial sampling increased. CONCLUSIONS: Rates of hysterectomy declined over the study period and slightly more than one-third of eligible patients utilized post-operative HT. Further research on concurrent uterine surgery is needed to establish standardized treatment recommendations in the risk-reducing and therapeutic BSO population. Additionally, education regarding the benefits of postoperative HT in eligible patients is warranted.

Seasonal Trends in Emergency Department Visits for Mental and Behavioral Health Conditions Among Children and Adolescents Aged 5-17 Years - United States, January 2018-June 2023.

Mental and behavioral health conditions among school-aged children, including substance use disorders and overall emotional well-being, are a public health concern in the United States. Timely data on seasonal patterns in child and adolescent conditions can guide optimal timing of prevention and intervention strategies. CDC examined emergency department (ED) visit data from the National Syndromic Surveillance Program for 25 distinct conditions during January 2018-June 2023 among U.S. children and adolescents aged 5-17 years, stratified by age group. Each year, during 2018-2023, among persons aged 10-14 and 15-17 years, the number and proportion of weekly ED visits for eight conditions increased in the fall school semester and remained elevated throughout the spring semester; ED visits were up to twice as high during school semesters compared with the summer period. Among children aged 5-9 years, the number and proportion of visits increased for five mental and behavioral health conditions. Seasonal increases in ED visits for some conditions among school-aged children warrant enhanced awareness about mental distress symptoms and the challenges and stressors in the school environment. Systemic changes that prioritize protective factors (e.g., physical activity; nutrition; sleep; social, community, or faith-based support; and inclusive school and community environments) and incorporate preparedness for increases in conditions during back-to-school planning might improve child and adolescent mental health.

Impact of edema formation on functional outcome in pediatric stroke patients.

BACKGROUND: Quantitative lesion net water uptake (NWU) has been described as an imaging biomarker reflecting vasogenic edema as an early indicator of infarct progression. We hypothesized that edema formation measured by NWU is higher in children compared to adults but despite this functional outcome may be better in children. METHODS: This study analyzed children enrolled in the Save ChildS Study who had baseline and follow-up computed tomography available and the data were compared to adult patients. RESULTS: Some 207 patients, of whom 13 were children and 194 were adults, were analyzed. Median NWU at baseline was 7.8% (IQR: 4.3-11.3), and there were no significant differences between children and adults (7.5% vs. 7.8%; p = 0.87). The early edema progression rate was 3.0%/h in children and 2.3%/h in adults. Median ΔNWU was 15.1% in children and 10.5% in adults. Children had significantly more often excellent (mRS 0-1; children 10/13 = 77% vs. adults 28/196 = 14%; p < 0.0001) and favorable clinical outcomes (mRS 0-2, 12/13 = 92% vs. 39/196 = 20%; p < 0.0001). CONCLUSIONS: In this study, clinical outcomes in children with large vessel occlusion strokes were better than in adults despite similar clinical and imaging characteristics and similar edema formation. This may be impacted by the generally better outcomes of children after strokes but may demonstrate that the degree of early ischemic changes using Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and edema progression rate may not be a reason for exclusion from endovascular thrombectomy.