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Background: India aims to eliminate rubella and congenital rubella syndrome (CRS) by 2023. We conducted serosurveys among pregnant women to monitor the trend of rubella immunity and estimate the CRS burden in India following a nationwide measles and rubella vaccination campaign., Methods: We surveyed pregnant women at 13 sentinel sites across India from Aug to Oct 2022 to estimate seroprevalence of rubella IgG antibodies. Using age-specific seroprevalence data from serosurveys conducted during 2017/2019 (prior to and during the vaccination campaign) and 2022 surveys (after the vaccination campaign), we developed force of infection (FOI) models and estimated incidence and burden of CRS., Results: In 2022, rubella seroprevalence was 85.2% (95% CI: 84.0, 86.2). Among 10 sites which participated in both rounds of serosurveys, the seroprevalence was not different between the two periods (pooled prevalence during 2017/2019: 83.5%, 95% CI: 82.1, 84.8; prevalence during 2022: 85.1%, 95% CI: 83.8, 86.3). The estimated annual incidence of CRS during 2017/2019 in India was 218.3 (95% CI: 209.7, 226.5) per 100, 000 livebirths, resulting in 47,120 (95% CI: 45,260, 48,875) cases of CRS every year. After measles-rubella (MR) vaccination campaign, the estimated incidence of CRS declined to 5.3 (95% CI: 0, 21.2) per 100,000 livebirths, resulting in 1141 (95% CI: 0, 4,569) cases of CRS during the post MR-vaccination campaign period., Conclusion: The incidence of CRS in India has substantially decreased following the nationwide MR vaccination campaign. About 15% of women in childbearing age in India lack immunity to rubella and hence susceptible to rubella infection. Since there are no routine rubella vaccination opportunities for this age group under the national immunization program, it is imperative to maintain high rates of rubella vaccination among children to prevent rubella virus exposure among women of childbearing age susceptible for rubella., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Although commonly considered the gold standard for measurement of non-rainfall water (NRW), providing reasonable reliable data for vegetated soils, microlysimeters (MLs) tend to grossly overestimate NRW (primarily in form of dew) on barren soil. In arid and semiarid regions, the reported values may be overestimated by hundreds and even 1000 %. This bias is attributed to (i) the effect of the structure and dimension of the ML (ii) the tacit assumption that the weight difference between morning and the previous midday/evening results from dew or (iii) the belief that the MLs will provide reliable values if the difference in weight would be calculated only from the evening or night. For instance, from the time during which the air temperature reaches the dewpoint temperature or from the time during which condensation takes place on an adjacent leaf-wetness sensor. Calculating dew by the weight difference of MLs led to the notions that the fine-textured soil will necessarily promote higher values of dew, and the notion that higher amounts of dew are expected following days with low relative humidity, both of which hamper our understanding regarding dew formation. The reasons for the apparent different performance of MLs in vegetated (wet) and barren (arid) regions are discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The solubilization of sodium diclofenac (Na-DFC) in a glycerol monooleate-based emulsion triggers series of structural changes. Incorporation of Na-DFC, leads to formation of a reverse hexagonal mesophase between 2 and 5 wt% Na-DFC. Between 6 and 9 wt% Na-DFC, the hexagonal symmetry gradually transitions to a disordered lamellar mesophase. These structural shifts impact the system's storage modulus, structuring enthalpy, and structural diffusivity. Despite these transitions, the driving force for Na-DFC release remains consistent, leading to hypothesize that the interfacial structure remains unchanged during Na-DFC release. The nano-structural modifications imposed by the Na-DFC load and release were assessed by small-angle X-ray diffraction (SAXD), spin-probe electron paramagnetic resonance (EPR), and nuclear quadrupole resonance (NQR). The selective solubilization of Na-DFC was demonstrated by SAXD peak fittings, revealing an increase of hexagonally oriented rods at the expense of non-oriented micelles, rather than gradual micellar elongation. Computation of the EPR spectra also showcased the selective solubilization of Na-DFC at an enhanced free energy interface (γ), evidenced by step-wise variations in polarity, microviscosity, and order parameters. Additionally, NQR analysis highlighted a higher anisotropy for sodium compared to deuterium, linking the selective solubilization of Na-DFC to heterogeneous structural transformations. These findings underscore the heterogeneous nature of solubilization-release processes, driven by locally increased micellar free energy. Consequently, the loaded Na-DFC interfaces maintain a constant γ, ensuring a consistent release driving force despite the structural transitions affecting the matrix. The ability to selectively solubilize guest molecules may herald a new era in the utilization of selective molecular interfacial loading., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Greenness-or vegetative presence-has been identified as a factor in chronic disease. The present study examines the longitudinal relationship between objective measures of greenness at the residential block level and incidence of 6 cardiovascular disease conditions., Methods and Results: Analyses examined the impact of consistently high versus consistently low "precision" greenness at the Census block level on the 5-year incidence of cardiovascular disease conditions, including acute myocardial infarction, atrial fibrillation, heart failure, ischemic heart disease, stroke/transient ischemic attack, and hypertension, among 229 034 US Medicare beneficiaries in Miami-Dade County, Florida, USA. Zero-inflated Poisson regression was used to model the odds of developing any new cardiovascular disease and number of new cardiovascular disease conditions based on greenness tertiles computed across 2011 and 2016 Normalized Difference Vegetation Index values, adjusting for individual age, sex, race, ethnicity, baseline cardiovascular disease conditions, neighborhood income, and walkability in 2011 and 2016. When compared with individuals consistently in the low greenness tertile in 2011 and 2016, those consistently in the high greenness tertile in 2011 and 2016 had a 9% lower odds of having any new cardiovascular conditions (odds ratio [OR], 0.91 [95% CI, 0.84-0.99]; P =0.021)., Conclusions: Over a 5-year period, consistently high greenness, when compared with consistently low greenness, was associated with lower odds of any new cardiovascular disease conditions. Identifying the role of greenness exposure in such a small geographic area, the Census block on which the older adult resides, allows for more precise, strategic decisions on where additional trees can be added-by selecting at-risk blocks rather than entire neighborhoods for tree-planting interventions.

Background: Long-acting injectable cabotegravir and rilpivirine is licensed for individualised treatment of HIV-1 infection in resource-rich settings. Additional evidence is required to support use in African treatment programmes where demographic factors, viral subtypes, previous treatment, and delivery and monitoring approaches differ. The aim of this study was to determine whether switching to long-acting therapy with injections every 8 weeks is non-inferior to daily oral therapy in Africa., Methods: CARES is a randomised, open-label, non-inferiority trial being conducted at eight sites in Uganda, Kenya, and South Africa. Participants with HIV viral load below 50 copies per mL on oral antiretroviral therapy and no history of virological failure were randomly assigned (1:1; web-based, permuted blocks) to receive cabotegravir (600 mg) and rilpivirine (900 mg) by intramuscular injection every 8 weeks, or to continue oral therapy. Viral load was monitored every 24 weeks. The primary outcome was week 48 viral load below 50 copies per mL, assessed with the Food and Drug Administration snapshot algorithm (non-inferiority margin 10 percentage points) in the intention-to-treat exposed population. This trial is registered with the Pan African Clinical Trials Registry (202104874490818) and is ongoing up to 96 weeks., Findings: Between Sept 1, 2021, and Aug 31, 2022, we enrolled 512 participants (295 [58%] female; 380 [74%] previous non-nucleoside reverse transcriptase inhibitor exposure). Week 48 viral load was below 50 copies per mL in 246 (96%) of 255 participants in the long-acting therapy group and 250 (97%) of 257 in the oral therapy group (difference -0·8 percentage points; 95% CI -3·7 to 2·3), demonstrating non-inferiority (confirmed in per-protocol analysis). Two participants had virological failure in the long-acting therapy group, both with drug resistance; none had virological failure in the oral therapy group. Adverse events of grade 3 or greater severity occurred in 24 (9%) participants on long-acting therapy and ten (4%) on oral therapy; one participant discontinued long-acting therapy (for injection-site reaction)., Interpretation: Long-acting therapy had non-inferior efficacy compared with oral therapy, with a good safety profile, and can be considered for African treatment programmes., Funding: Janssen., Competing Interests: Declaration of interests CK reports funding paid to institution and donation of drugs to institution from Janssen for the work reported in this manuscript. SS reports funding paid to institution and personal fees for speaking at symposia from Janssen and donation of drugs to institution from ViiV, all outside the work reported in this manuscript. FC reports funding paid to institution and donation of drugs to institution from Janssen and funding paid to institution from ViiV, Gilead, Wellcome Trust, and the National Institute of Health Research UK outside the work reported in this manuscript; and unpaid role as Chair of Steering Committee for an investigator-initiated long-acting implementation trial. KM reports personal fees for speaking at symposia from Janssen outside of the work reported in this manuscript. VVE is an employee of Johnson & Johnson and holds stock options in Johnson & Johnson; and a patent related to rilpivirine. PM was an employee of Janssen at the time of trial design, and then an employee of ViiV during the time of trial conduct, manuscript submission, and publication; and holds stock from GSK as an employee of ViiV. FAB is an employee of Johnson & Johnson and holds stock options of Johnson & Johnson. NIP reports grants paid to institution, donation of drugs to institution, and personal fees for speaking at symposia from Janssen outside the work reported in this manuscript; and is the Chief Investigator on a trial with funding paid to institution by the EU for testing anti-tuberculosis drug combinations based on the drug ganfeborole, owned by GSK. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

This study assesses whether the Democratic Party holds issue ownership over science in the United States. We analyze data from a national survey that asked 1041 adults questions specifically designed to measure perceptions of science ownership. While the results suggest that the Democratic Party does hold a significant advantage in ownership of science in an abstract sense, perceptions of ownership of specific types of science vary across the two parties. Those who identify as Independents drive much of the aggregate perceptions of ownership of science, whereas partisans' perceptions of issue ownership of science are mostly driven by in-party favoritism. Post hoc analyses suggest that news media use contributes to perceptions of science ownership and reinforces affinity-party preference.

Background: Congenital portosystemic shunts (CPSS) are rare congenital abnormalities causing abnormal blood flow between the portal vein and systemic circulation. This study reports on the peri-operative anticoagulation management of CPSS patients post closure, focusing on the incidence of thrombotic and bleeding complications., Methods: This is a single-center retrospective analysis of CPSS patients who underwent surgery or endovascular intervention between 2005 and 2021. The protocol included unfractionated heparin (UFH) during and immediately after surgery, followed by either warfarin or low molecular weight heparin (LMWH) postoperatively. Outcomes assessed included postoperative thrombotic and bleeding complications., Results: A total of 44 patients were included. Postoperatively, 89% received treatment-dose UFH, transitioning to warfarin or LMWH at discharge. Thrombotic complications occurred in 16% of patients, predominantly in the superior mesenteric vein. Surgical interventions and continuous infusion of tissue plasminogen activator (tPA) were used for clot resolution. Bleeding complications were observed in 64% of patients, primarily managed with transfusions and temporary UFH interruption. No deaths related to thrombotic, or bleeding events were reported., Conclusions: Our findings underscore the delicate balance required in anticoagulation management for CPSS patients, revealing an occurrence of both thrombotic and bleeding complications postoperatively., Levels of Evidence: Level II, retrospective study., Competing Interests: Conflicts of interest None of the authors have financial disclosures related to the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sovateltide (IRL-1620), an endothelin B receptor agonist, has previously demonstrated neuroprotective and neuroregenerative effects in animal models of acute ischemic stroke. Recently, clinical trials indicated that it could also be effective in humans with stroke. Here, we systematically investigate whether IRL-1620 may be used for the treatment of ischemia-induced brain injury., Methods: A systematic review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. MEDLINE (PubMed) and Scopus databases were searched for eligible studies up to December 2022. The databases ClinicalTrials.gov and Pharmazz Inc. were screened for unpublished or ongoing trials. Only studies in English were evaluated for eligibility. Meta-analysis of the included studies was also conducted., Results: Finally, seven studies were included in the review, all in animal rat models because of scarcity of clinical trials. Six studies, all in middle cerebral artery occlusion (MCAO) models, were selected for meta-analysis. In the two studies assessing mortality, no deaths were reported in the IRL-1620 group 24 h after MCAO, whereas the vehicle group had almost a five times higher mortality risk (risk ratio 5.3, 95% confidence interval 0.7-40.1, I 2  = 0%). In all five studies evaluating outcome on day 7 after MCAO, IRL-1620 was associated with statistically significantly lower neurological deficit and improved motor performance compared with the vehicle. Infract volume, differentiation potential of neuronal progenitor cells, and mitochondrial fate also improved with IRL-1620 administration., Conclusions: According to the above, in animal MCAO models, IRL-1620 enhanced neurogenesis and neuroprotection and improved outcome. Future studies are needed to expand our understanding of its effects in human study participants with acute ischemic stroke as well as in other common causes of cerebral ischemia including cardiac arrest., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Posttransplant diabetes mellitus (PTDM) is a prevalent complication of liver transplantation and is associated with cardiometabolic complications. We studied the consequences of genetic effects of liver donors and recipients on PTDM outcomes, focusing on the diverse genetic pathways related to insulin that play a role in the development of PTDM. One thousand one hundred fifteen liver transplant recipients without a pretransplant diagnosis of type 2 diabetes mellitus (T2D) and their paired donors recruited from 2 transplant centers had polygenic risk scores (PRS) for T2D, insulin secretion, and insulin sensitivity calculated. Among recipients in the highest T2D-PRS quintile, donor T2D-PRS did not contribute significantly to PTDM. However, in recipients with the lowest T2D genetic risk, donor livers with the highest T2D-PRS contributed to the development of PTDM (OR [95% CI] = 3.79 [1.10-13.1], P = .035). Recipient risk was linked to factors associated with insulin secretion (OR [95% CI] = 0.85 [0.74-0.98], P = .02), while donor livers contributed to PTDM via gene pathways involved in insulin sensitivity (OR [95% CI] = 0.86 [0.75-0.99], P = .03). Recipient and donor PRS independently and collectively serve as predictors of PTDM onset. The genetically influenced biological pathways in recipients primarily pertain to insulin secretion, whereas the genetic makeup of donors exerts an influence on insulin sensitivity., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the usefulness of the 'differential renal length index' (iDRL) before and after pyeloplasty, as the anteroposterior diameter is commonly used to quantify hydronephrosis but inaccuracies arise due to interobserver variability, hydration status and pure intra-renal dilatation., Patients and Methods: Prospectively collected data, from two centres, of all children undergoing pyeloplasty for isolated unilateral pelvi-ureteric junction obstruction (PUJO) (2015-2021) were analysed. Subgroup analysis was undertaken: Group A - differential renal function (DRF) ≥40%, Group B - subnormal DRF (20-39%), and Group C - symptomatic. Children with structural anomalies of upper and lower urinary tract, bilateral involvement, and subnormal DRF (<20%) were excluded. All the children had a pre- and postoperative ultrasound scan and Tc99 m mercapto-acetyltriglycine (MAG3) renograms. The iDRL was calculated as follows: iDRL = ([a - b]/b) × 100, where 'a' is the length of hydronephrotic kidney (cm) and 'b' is the length of contralateral normal kidney (cm). The mean difference and standard error of mean (SEM) between the pre- and postoperative iDRL was evaluated using the paired Student's t-test, with P < 0.05 considered statistically significant., Results: A total of 119 children with 1-year follow-up were included. For the entire cohort, the mean (SEM) preoperative iDRL was 27.7 (1.4) and postoperatively was 12.5 (1.1), with a mean (range) DRF improvement of 54% (44-66%) (P < 0.001). In Group A (n = 97), the mean (SEM) preoperative iDRL was 26.6 (1.5) and postoperatively was 13.1 (1.2), with a mean (range) DRF improvement of 50% (38-63%) (P < 0.001). In Group B (n = 22), the mean (SEM) preoperative iDRL was 32.6 (3.5) and postoperatively was 10.0 (2.8), with a mean (range) DRF improvement of 69% (49-89%) (P < 0.001). In Group C (n = 28), the mean (SEM) preoperative iDRL was 19.9 (2.3) and postoperatively was 7.7 (1.9), with a mean (range) DRF improvement of 61% (38-85%) (P < 0.001)., Conclusion: Our study identifies the iDRL as a useful measure of improvement following successful pyeloplasty. In the subgroup with DRF of >39% minimum improvement was >37%. Similar minimum DRF improvement was also noted (>37%) in hypo-functioning kidneys and symptomatic PUJO., (© 2024 BJU International.)

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic severely disrupted hospice care, yet there is little research regarding how widespread disruptions affected clinician and family decision-making. We aimed to understand how the pandemic affected structures, processes, and outcomes of end-of-life care., Research Design and Methods: Retrospective narrative chart review of electronic health records of 61 patients referred and admitted to hospice from 3 New York City geriatrics practices who died between March 1, 2020, and March 31, 2021. We linked longitudinal, unstructured medical, and hospice electronic health record notes to create a real-time, multiperspective trajectory of patients' interactions with providers using directed content analysis., Results: Most patients had dementia and were enrolled in hospice for 11 days. Care processes were shaped by structural factors (staffing, supplies, and governmental/institutional policies), and outcomes were prioritized by care teams and families (protecting safety, maintaining high-touch care, honoring patient values, and supporting patients emotionally and spiritually). Processes used to achieve these outcomes were decision-making, care delivery, supporting a "good death," and emotional and spiritual support., Discussion and Implications: Care processes were negotiated throughout the end of life, with clinicians and families making in-the-moment decisions. Some adaptations were effective but also placed extraordinary pressure on paid and family caregivers. Healthcare teams' and families' goals to meet patients' end-of-life priorities can be supported by ongoing assessment of patient goals and process changes needed to support them, stronger structural supports for paid and family caregivers, incentivizing relationships across primary care and hospice teams, and extending social work and spiritual care., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Eye emergencies constitute a significant portion of attendances to general Emergency Departments (EDs) in the UK, therefore it is important to assess the confidence of doctors who work in this setting in managing these potentially sight- and life-threatening presentations. This systematic review aims to assess the confidence of UK doctors working in general EDs in managing ophthalmic emergencies., Methods: MEDLINE (Ovid), EMBASE (Ovid), ProQuest Central and Web of Science databases and grey literature were searched from inception to 1 October 2022 for publications that (1) featured doctors working in UK general EDs, (2) assessed doctors' confidence in managing ophthalmic emergencies, (3) contained original data, (4) were full-text, and (5) written in English. Methodological quality was assessed using the AXIS tool., Results: 462 articles were screened, and 7 papers included for data extraction, which collectively assessed the confidence of 956 doctors working in EDs in managing ophthalmic emergencies. There was a widespread lack of confidence amongst foundation doctors, which has worsened over time. Most doctors lacked confidence in performing funduscopy and using the slit-lamp, and considered formal ophthalmology training received in EDs to be inadequate., Conclusions: Evidence suggests a lack of confidence amongst foundation doctors in managing ophthalmic emergencies. High-quality evidence investigating the confidence amongst more experienced Emergency Medicine (EM) physicians was lacking. It is important to assess why foundation doctors feel so ill-prepared to manage eye emergencies and develop further ophthalmic training for doctors working in EDs. Further investigation exploring the confidence of EM trainees and consultants is required., (© 2024. The Author(s).)

Ultrasound-assisted extraction (UAE) was evaluated as a green procedure to produce faba beans protein isolates from faba beans. Magnetic stirring was performed as conventional extraction. A three-level five-factor Box-Behnken Design (BBD) was applied to obtain the optimal UAE conditions to concurrently maximize extraction yield and protein content. The response surface methodology (RSM) showed a quadratic curvature for extraction yield and protein. The optimal extraction conditions were determined as: Power of 123 W, solute/solvent ratio of 0.06 (1:15 g/mL), sonication time of 41 min, and total volume of 623 mL with a desirability value of 0.82. Under these conditions, the extraction yield of 19. 75 ± 0.87 % (Protein yield of 67.84 %) and protein content of 92.87 ± 0.53 % were obtained for optimum ultrasound extraction. Control samples using magnetic stirring under similar conditions without ultrasound treatment showed an extraction yield of 16.41 ± 0.02 % (Protein yield of 54.65 %) and a protein content of 89. 88 ± 0.40 %. This shows that BBD can effectively be used to optimize the extraction of proteins from faba beans using optimal extraction conditions, resulting in a higher extraction yield and protein purity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging Omicron subvariants. Here, we characterized the RBD-specific memory B cell (Bmem) response following a fourth dose with a BA.1 or BA.5 bivalent vaccine, in direct comparison with a WH1 monovalent fourth dose. Healthcare workers previously immunized with mRNA or adenoviral vector monovalent vaccines were sampled before and one month after a fourth dose with a monovalent or a BA.1 or BA.5 bivalent vaccine. Serum neutralizing antibodies (NAb) were quantified, as well as RBD-specific Bmem with an in-depth spectral flow cytometry panel including recombinant RBD proteins of the WH1, BA.1, BA.5, BQ.1.1, and XBB.1.5 variants. Both bivalent vaccines elicited higher NAb titers against Omicron subvariants compared to the monovalent vaccine. Following either vaccine type, recipients had slightly increased WH1 RBD-specific Bmem numbers. Both bivalent vaccines significantly increased WH1 RBD-specific Bmem binding of all Omicron subvariants tested by flow cytometry, while recognition of Omicron subvariants was not enhanced following monovalent vaccination. IgG1 + Bmem dominated the response, with substantial IgG4 + Bmem only detected in recipients of an mRNA vaccine for their primary dose. Thus, Omicron-based bivalent vaccines can significantly boost NAb and Bmem specific for ancestral WH1 and Omicron variants and improve recognition of descendent subvariants by pre-existing, WH1-specific Bmem beyond that of a monovalent vaccine. This provides new insights into the capacity of variant-based mRNA booster vaccines to improve immune memory against emerging SARS-CoV-2 variants and potentially protect against severe disease. ONE-SENTENCE SUMMARY: Omicron BA.1 and BA.5 bivalent COVID-19 boosters, used as a fourth dose, increase RBD-specific Bmem cross-recognition of Omicron subvariants, both those encoded by the vaccines and antigenically distinct subvariants, further than a monovalent booster., Competing Interests: Declaration of Competing Interest MCvZ, REO’H and PMH are inventors on a patent application related to this work. All the other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Blood-brain barrier (BBB) integrity is presumed to be impaired in hypertension, resulting from cerebral endothelial dysfunction. Hypertension precedes various cerebrovascular diseases, such as cerebral small vessel disease, and is a risk factor for developing neurodegenerative diseases for which BBB disruption is a preceding pathophysiological process. In this cross-sectional study, we investigated the relation between hypertension, current blood pressure, and BBB leakage in human subjects., Methods: BBB leakage was determined in 22 patients with hypertension and 19 age- and sex-matched normotensive controls (median age [range], 65 [45-80] years; 19 men) using a sparsely time-sampled contrast-enhanced 7T magnetic resonance imaging protocol. Structural cerebral small vessel disease markers were visually rated. Multivariable regression analyses, adjusted for age, sex, cardiovascular risk factors, and cerebral small vessel disease markers, were performed to determine the relation between hypertension status, systolic and diastolic blood pressure, mean arterial pressure, drug treatment, and BBB leakage., Results: Both hypertensive and normotensive participants showed mild scores of cerebral small vessel disease. BBB leakage did not differ between hypertensive and normotensive participants; however, it was significantly higher for systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the cortex, and diastolic blood pressure and mean arterial pressure in the gray matter. Effectively treated patients showed less BBB leakage than those with current hypertension., Conclusions: BBB integrity in the total and cortical gray matter decreases with increasing blood pressure but is not related to hypertension status. These findings show that BBB disruption already occurs with increasing blood pressure, before the presence of overt cerebral tissue damage. Additionally, our results suggest that effective antihypertensive medication has a protective effect on the BBB., Registration: URL: https://trialsearch.who.int/; Unique identifier: NL7537., Competing Interests: None.

Purpose of Review: Cancer immunotherapy is one of the most emerging and rapidly growing fields.Ocular side effects associated with these therapies are common and can be present in up to 70% of patients.The cornea may be involved in different pathogenic mechanisms triggered by different immunotherapeutic agents, and corneal disease varies from mild symptoms to severe corneal ulceration and melting with visual loss.We aimed to review the incidence, mechanism, and management of ocular surface side effects in cancer patients receiving immunotherapy., Recent Findings: With the recent use of immunotherapeutic agents in cancer patients, in particular immune checkpoint inhibitors (ICIs) and epidermal growth factor receptor (EGFR) inhibitors, ocular surface and corneal involvement are common side effects.These patients can be at risk of sight threatening complications that warrant prompt diagnosis and careful monitoring and management., Summary: Immunotherapy- related corneal complications in cancer patients are associated with a decreased quality of life. Prompt recognition and an interdisciplinary approach between ophthalmologists and oncologists are crucial to handle immune related ocular adverse events in these patients, in order to maintain ocular surface integrity and avoid a vision threatening complication., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To derive and validate internally a novel risk assessment tool to identify young children at risk for all-cause mortality ≤60 days of discharge from hospitals in sub-Saharan Africa., Study Design: We performed a prospective observational cohort study of children aged 1-59 months discharged from Muhimbili National Hospital in Dar es Salaam, Tanzania and John F. Kennedy Medical Center in Monrovia, Liberia (2019-2022). Caregivers received telephone calls up to 60 days after discharge to ascertain participant vital status. We collected socioeconomic, demographic, clinical, and anthropometric data during hospitalization. Candidate variables with P < .20 in bivariate analyses were included in a multivariable logistic regression model with best subset selection to identify risk factors for the outcome. We internally validated our tool using bootstrapping with 500 repetitions., Results: There were 1933 young children enrolled in the study. The median (IQR) age was 11 (4, 23) months and 58.7% were males. In total, 67 (3.5%) died during follow-up. Ten variables contributed to our tool (total possible score 82). Cancer (aOR 10.6, 95% CI 2.58, 34.6), pedal edema (aOR 6.94, 95% CI 1.69, 22.6), and leaving against medical advice (aOR 6.46, 95% CI 2.46, 15.3) were most predictive of post-discharge mortality. Our risk assessment tool demonstrated good discriminatory value (optimism corrected area under the receiver operating characteristic curve 0.77), high precision, and sufficient calibration., Conclusions: After validation, this tool may be used to identify young children at risk for post-discharge mortality to direct resources for follow-up of high-risk children., Competing Interests: Declaration of Competing Interest C.P.D is a member of the Editorial Board of the Journal of Pediatrics but played no role in the handling of this manuscript. The other authors declare no conflicts of interest. This study was funded by the National Institutes of Health (K24 DK104676 and P30 DK040561 to CPD, K24 AT009893 to CRM, and K23HL173694 to CAR), the Boston Children's Hospital Global Health Program to CAR, the Palfrey Fund for Child Health Advocacy to CAR, and the Emory Pediatric Research Alliance Junior Faculty Focused Award to CAR. This work was presented, in part, as a platform presentation at the American Academy of Pediatrics National Conference & Exhibition in October 2023 in Washington DC., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sweet potatoes are rich in cardioprotective phytochemicals with potential anti-platelet aggregation activity, although this benefit may vary among cultivars/genotypes. The phenolic profile [HPLC-ESI (-) -qTOF-MS 2 ], cheminformatics (ADMET properties, affinity toward platelet proteins) and anti-PA activity of phenolic-rich hydroalcoholic extracts obtained from orange (OSP) and purple (PSP) sweet potato storage roots, was evaluated. The phenolic richness [Hydroxycinnamic acids> flavonoids> benzoic acids] was PSP > OSP. Their main chlorogenic acids could interact with platelet proteins (integrins/adhesins, kinases/metalloenzymes) but their bioavailability could be poor. Just OSP exhibited a dose-dependent anti-platelet aggregation activity [inductor (IC 50, mg.ml -1 ): thrombin receptor activator peptide-6 (0.55) > Adenosine-5'-diphosphate (1.02) > collagen (1.56)] and reduced P-selectin expression (0.75-1.0 mg.ml -1 ) but not glycoprotein IIb/IIIa secretion. The explored anti-PA activity of OSP/PSP seems to be inversely related to their phenolic richness. The poor first-pass bioavailability of its chlorogenic acids (documented in silico) may represent a further obstacle for their anti-PA in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Non-thermal plasma (NTP) has shown promising anti-cancer effects, but there is still limited knowledge about the underlying cell death mechanisms induced by NTP and inherent differences between NTP treatment modalities. This study aimed to investigate four major regulated cell death (RCD) pathways, namely apoptosis, pyroptosis, necroptosis, and ferroptosis, in melanoma cancer cells following NTP treatment, and to provide an overview of molecular mechanistic differences between direct and indirect NTP treatment modalities. To discriminate which cell death pathways were triggered after treatment, specific inhibitors of apoptosis, pyroptosis, necroptosis, and ferroptosis were evaluated. RCD-specific molecular pathways were further investigated to validate the findings with inhibitors. Both direct and indirect NTP treatment increased caspase 3/7 and annexin V expression, indicative of apoptosis, as well as lipid peroxidation, characteristic of ferroptosis. Pyroptosis, on the other hand, was only induced by direct NTP treatment, evidenced by increased caspase 1 activity, whereas necroptosis was stimulated in a cell line-dependent manner. These findings highlight the molecular differences and implications of direct and indirect NTP treatment for cancer therapy. Altogether, activation of multiple cell death pathways offers advantages in minimizing treatment resistance and enhancing therapeutic efficacy, particularly in a combination setting. Understanding the mechanisms underlying NTP-induced RCD will enable the development of strategic combination therapies targeting multiple pathways to achieve cancer lethality., (© 2024. The Author(s).)

Objective: To evaluate the outcomes of transcatheter edge-to-edge repair (TEER) with MitraClip™ (Abbott Vascular) in symptomatic high surgical risk Indian patients with significant mitral regurgitation (MR)., Methods: Patients with moderately severe or severe primary or secondary MR and deemed high surgical risk were treated with MitraClip™. The data were collected retrospectively from medical records. The primary outcome was technical success, and secondary outcomes were ≤ 2+ MR reduction and improvement in functional capacity at 30 days., Results: Between November 2018 and August 2023, 64 patients were treated with MitraClip. The mean age was 70.0 ±12.1 years and 64% were males. The mean EuroScore II and STS score predicted mortality for mitral valve repair were 5.8 ± 4.5% and 4.0 ± 3.8% respectively. MR etiology was primary in 56.3%, secondary in 40.6% and mixed in 3.1%. The device was implanted successfully in all but one patient with technical success rate of 98.4%. The average number of clips per patient was 1.5 ± 0.6 and 42.2% patients received more than one clip. The mean mitral valve gradient was 3.5 ± 1.6 mmHg. The MR severity of ≤ 2+ was achieved in 91.8% of the subjects and similar proportion were in New York Heart Association Functional Class I or II at 30 days., Conclusion: In high-risk Indian patients with symptomatic significant MR, TEER with MitraClip™ was achieved with a high technical success rate. It was associated with significant reduction in MR severity and improvement in functional capacity in > 90% of the subjects., Competing Interests: Declaration of Competing Interest COI disclosure enclosed, (Copyright © 2024. Published by Elsevier, a division of RELX India, Pvt. Ltd.)

Background: The karyotype is a major determinant of prognosis in myelodysplastic syndrome (MDS). Details of the cytogenetic profile of MDS in South Asia are limited because cytogenetic services are not widely available., Methods: We performed a retrospective analysis of the cytogenetic and clinicopathologic profile of adult primary MDS seen consecutively at a tertiary-care centre in South India between 2003 and 2017. Patients were re-categorised according to the 2022 World Health Organisation (WHO) and the International Consensus classifications (ICC)., Results: There were 936 patients aged 18-86 years (median age 53, 65% males), with MDS with del 5q, low blasts and increased blasts in 7.5%, 58.4% and 34.1% respectively. Clonal abnormalities were seen in 55% of patients, with solitary abnormalities in 29.8% and complex karyotypes (CK, ≥ 3 abnormalities) in 15%. The most frequent abnormalities were monosomy 7/deletion 7q (16.1%), deletion 5q (14.5%), trisomy 8 (11.5%), and deletion 20q (5.1%). Cytogenetic prognosis groups were distributed as follows: very good, 2%; good, 55.6%; intermediate, 16.2%; poor, 15%; very poor, 11.2%. Clinical (IPSS-R) risk stratification (842 patients) showed: very low-risk, 3.9%; low-risk, 30.9%; intermediate-risk, 24.2%; high-risk, 21%; very high-risk, 20%. Age-adjustment (IPSS-RA) raised the very low-risk group to 12.4%; the other groups decreased by 1-3% each., Conclusion: The most significant finding of this cytogenetic analysis of MDS in India is that abnormal karyotypes with poor prognosis markers including monosomy 7 and CK were more frequent than in most other reports, among patients who were overall younger. Trisomy 8, deletion 20q, the IPSS-R intermediate-risk and both high-risk groups were more common than in the West. Trisomy 8 was less common than in South-East Asia while CK and deletion 20q were comparable. Evaluation of such large cohorts highlights the unique features of MDS in different parts of the world. These findings suggest that there could be differences in predisposing factors, environmental or genetic, and emphasise the need for further exploration to better understand the varied nature of MDS., (© 2024. The Author(s).)

Background: Intraoperative hemorrhage in cardiac surgery increases risk of morbidity and mortality. Low pre-operative and perioperative levels of fibrinogen, a key clotting factor, are associated with severity of hemorrhage and increased transfusion of blood components. The ability to supplement fibrinogen during hemorrhagic resuscitation is delayed 45-60 min because cryoprecipitated antihemophilic factor (cryo AHF) is stored frozen, due to a short post-thaw shelf life. Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex, IFC) can be kept thawed, at room temperature, for up to 5 days, making it possible to be immediately available for hemorrhaging patients. This trial will investigate if earlier correction of acquired hypofibrinogenemia with IFC in hemorrhaging cardiac surgery patients reduces the total number of perioperatively transfused allogeneic blood products (red blood cells, plasma, and platelets) as compared to cryo AHF., Methods: This is a single center, prospective, cluster randomized trial with an adaptive design. Acquired hypofibrinogenemia will be assessed by rotational thromboelastometry (ROTEM) and the threshold for cryo AHF/IFC transfusion defined as FIBTEM A10 ≤ 10 mm in bleeding patients. IFC/cryo AHF will be randomized by 1-month blocks. Cardiac surgery patients will be enrolled in the study if they have an eligible procedure and at least one dose of a cryo AHF/IFC product (approximately 2 g fibrinogen) is transfused. Data from the electronic health record, including the blood bank and lab information systems, will be prospectively collected from the health system's data warehouse., Discussion: This trial aims to provide evidence of the clinical efficacy of utilizing readily available thawed IFC during acute bleeding in the cardiac surgery setting compared to traditional cryo AHF., Trial Registration: ClinicalTrials.gov NCT05711524. Feb 3, 2023., (© 2024. The Author(s).)

Objective: This study aimed to report changes in utilization and payment trends of low-back pain (LBP) interventions and the impact of nonsurgeon interventionalists on these changes., Methods: Medicare Part B national summary data files were used to gather annual utilization and Centers for Medicare and Medicaid Services (CMS) payment data for LBP interventions from 2000 to 2021. Healthcare Common Procedure Coding System (HCPCS) codes were grouped as decompression, spinal fusion, sacroiliac (SI) joint fusion, epidural steroid injections (ESIs), physical therapy (PT), and chiropractic manipulation (Chiro). The total allowed services and payments were collected for each HCPCS group. CMS provider-level files, available from 2013 to 2021, were used to collect neurosurgeon, orthopedic surgeon, and nonsurgeon interventionalist (interventional radiology and pain management) data for each surgical HCPCS code group (decompression, spinal fusion, and SI joint fusion). The United States Consumer Price Index was used to adjust for inflation., Results: From 2000 to 2021, there were 339,720,725 Medicare-approved interventions and payments of approximately $21 billion for LBP (percentage of cumulative payments: 41.8% Chiro, 16.5% ESI, 14.4% spinal fusion, 14.3% PT, 10.2% decompression, and 0.4% SI joint fusion). In a subgroup analysis, spinal fusions for Medicare patients were performed by orthopedic surgeons (59.2%), neurosurgeons (40.6%), and nonsurgeon interventionalists (< 1%) from 2013 to 2021. From 2013 to 2021, neurosurgeon and orthopedic surgeon fusion utilization each grew by < 3% and associated Medicare payments to each specialty declined by 1% each year. During the same period, nonsurgeon interventionalist utilization grew 26% each year and associated Medicare payments to nonsurgeon interventionalists for spine fusions grew 62% each year. In a subgroup analysis, SI joint fusions for Medicare patients were performed by orthopedic surgeons (50.7%), neurosurgeons (24.8%), and nonsurgeon interventionalists (24.5%) from 2018 to 2021. Neurosurgeon utilization of SI joint fusion declined by 1% each year and associated Medicare payments to this group grew 2% each year. Orthopedic surgeon utilization of SI joint fusion declined 1% and associated Medicare payments to this group grew 4% each year. Nonsurgeon interventionalist use of SI joint fusions grew 415% and payments grew 435% each year., Conclusions: The substantial growth in Medicare payments for surgical LBP interventions is disproportionally driven by nonsurgeon interventionalists. The exponential growth of nonsurgeon interventionalists performing spinal fusion surgeries, particularly SI joint fusions, largely accounts for the significant increase in Medicare expenditures.

Objective: During the advent of laparoscopy, surgeons directly explored the abdominal cavity with a telescope-like device through a small incision. Since then, numerous technological advances have transformed minimally invasive surgery (MIS). Yet, in our wireless world, various devices crowd the surgical field, with long wires and light sources posing fall and fire risks. The primary objective of this study was to analyze the first reported human use of a novel wireless laparoscopy system or WLS (ArthroFree™, Lazurite®, Cleveland, Ohio)., Methods: The utility and convenience of the WLS was assessed via two avenues: (1) by analyzing surgical outcomes from first human use and (2) by surveying healthcare professionals regarding its quality and utility., Results: Eighteen patients (mean age 44.2, 83.3% female, mean BMI 33.4) underwent operations with the WLS. Operations included gynecologic and general surgical procedures. There were no intraoperative or postoperative complications, and no conversions to traditional laparoscopy or laparotomy. Mean operating time was 71.94 ± 20.41 min, and estimated blood loss was minimal. Survey results revealed varied individual experiences. Strengths included adequate illumination, improved ergonomics, and simplicity of setup and ease of operation. One respondent criticized the image resolution. Feedback indicated an overall positive impact, and 67% of respondents supported inclusion of the device at their facility. Moreover, its deployment in resource-limited settings abroad has demonstrated its efficacy in global surgery, indicating its potential in various healthcare environments., Conclusions: This is the first reported human use of a novel WLS. Clinical results supported efficiency and safety of the technology. The successful deployment of the WLS in diverse surgical environments, including resource-limited settings, highlights its potential as a universally adaptable tool in global surgery. This report represents a strong first step toward a wireless operating room with the promise of redefining surgical standards as well as bridging gaps in surgical care worldwide., (© 2024. The Author(s).)

Background: Development of a non-sputum test using readily-obtainable biospecimens remains a global priority for tuberculosis (TB) control. We quantified lipoarabinomannan (LAM) concentrations, a pathogen biomarker for Mycobacterium tuberculosis, in urine, plasma and serum for real-world diagnostic accuracy of pulmonary TB among people living with and without HIV., Methods: We conducted a prospective diagnostic study among adults with TB symptoms in South Africa. We measured LAM concentrations in time-matched urine, plasma and serum with an electrochemiluminescence immunoassay using two capture antibodies (FIND 28 and S4-20). From the completed cohort, we randomly selected 210 participants (2 cases: 1 control) based on sensitivity estimates, and we compared diagnostic accuracy of LAM measurements against the microbiological reference standard., Findings: Urine and blood specimens from 210 of 684 adults enrolled were tested for LAM. Among 138 TB-positive adults (41% female), median urine LAM was 137 pg/mL and 52 pg/mL by FIND 28 and S4-20, respectively. Average LAM concentrations were highest in HIV-positive participants with CD4+ T cells <200 cells/mm 3 . Urine LAM by S4-20 achieved diagnostic sensitivity of 62% (95% CI: 53%-70%) and specificity of 99% (95% CI: 96%-100%). Plasma and serum LAM by FIND 28 showed similar sensitivity (70%, 95% CI: 62%-78%) and comparable specificities (90%, 95% CI: 82%-97%; 94%, 95% CI: 88%-99%). Diagnostic sensitivity of urine LAM by S4-20 was higher among participants without HIV (41%, 95% CI: 24%-61%) compared to HIV-positive participants with CD4 ≥200 cells/mm 3 (20%, 95% CI: 8%-39%)., Interpretation: Detection of LAM was achievable in non-sputum specimens for pulmonary TB, but additional analyte concentration or signal amplification may be required to achieve diagnostic accuracy targets., Funding: Bill and Melinda Gates Foundation., Competing Interests: Declaration of interests PKD and DW declare receiving grant funding, paid to the institution, from the Bill and Melinda Gates Foundation. PKD reports receiving consulting fees from ThermoFischer, InBios Internation, and Abbott Diagnostics, and advisory board fees from Abbvie and Cepheid. Rutgers University (AP) has a patent on the use of the A194-01 antibody for diagnosis of TB infections., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The phase 3 VISION trial demonstrated that [ 177 Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]-positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor-signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [ 177 Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [ 177 Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using t testing of proportions and survival analyses. Results: In total, 117 patients with mCRPC who received [ 177 Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA RRs (42% vs. 46%; P = 0.50) and OS (median: 15.1 vs. 15.3 mo; P > 0.05). Conclusion: Patients with PSMA-positive mCRPC who received [ 177 Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Despite growing recognition, neuropsychiatric diseases associated with infections are a major unsolved problem worldwide. Group A streptococcal (GAS) infections can cause autoimmune sequelae characterized by movement disorders, such as Sydenham chorea (SC), and neuropsychiatric disorders. The molecular mechanisms underlying these diseases are not fully understood. Our previous work demonstrates that autoantibodies (AAbs) can target dopaminergic neurons and increase dopamine receptor D2 (D2R) signaling. However, AAb influence on dopamine receptor D1 (D1R) activity is underexplored. We found evidence that suggests GAS-induced cross-reactive AAbs promote autoimmune encephalitis of the basal ganglia (BGE), a region of high dopamine receptor density. Here, we report a new mechanism whereby neuropsychiatric syndromes are distinguished from movement disorders by differences in D1R and D2R AAb titers, signaling, receiver operating characteristic (ROC) curves, and immunoreactivity with D1R and D2R autoreactive epitopes. D1R AAb signaling was observed through patient serum AAbs and novel patient-derived mAbs, which induced both D1R G protein- and -arrestin transduced signals. Furthermore, patient AAbs and mAbs enhanced D1R signaling mechanisms mediated by the neurotransmitter dopamine. Our findings suggest that AAb-mediated D1R signaling may contribute to the pathogenesis of neuropsychiatric sequelae and inform new options for diagnosis and treatment of GAS sequelae and related disorders. .

Competing Interests: Competing interests: None declared.

Introduction: Exposure to a range of stressful life events (SLE) is implicated in youth psychopathology. Previous studies point to a discrepancy between parents'/children's reports regarding stressful life events. No study systematically assessed the correlation between such discrepancies and psychopathology in depressed youth. This study was designed to assess parent-youth discrepancies regarding stressful life events and its association with severity of psychopathology at baseline and response to selective serotonin reuptake inhibitor (SSRI) treatment in depressed youth. Methods: Reports regarding stressful life events were assessed in children/adolescents suffering from depressive/anxiety disorders using the life events checklist (LEC), a self-report questionnaire measuring the impact of negative life events (NLE) and positive life events (PLE), as reported by the children and their parents. The severity of depression/anxiety disorders and response to antidepressant treatment were evaluated and correlated with both measures of LEC. Results: Participants were 96 parent-child dyads (39 boys, 57 girls) aged 6-18 years (mean = 13.90 years, SD = 2.41). Parents reported more NLE and higher severity of NLE events than their children (number of NLE: 7.51 ± 4.17 vs. 6.04 ± 5.32; Cumulative severity of NLE: 24.95 ± 14.83 vs. 17.24 ± 12.94). Discrepancy in PLE, but not NLE, was associated with more severe psychopathology and reduced response to treatment. Discussion: Discrepancy in informant reports regarding life events in depressed/anxious youth, especially regarding PLE, is associated with more severe psychopathology and reduced response to pharmacotherapy. It is essential to use multiple reporters in assessing stressful life events in children.

Objective: The presence of comorbidities can substantially affect patients' quality of life, but data regarding their impact on idiopathic inflammatory myopathies (IIMs) are limited., Methods: We examined the prevalence of comorbidities in IIM patients, other autoimmune rheumatic diseases (oAIRDs), and healthy controls (HCs), using data from the self-reported COVAD-2 survey. We defined Basic Multimorbidity (BM) as the presence of ≥ 2 non-rheumatic chronic conditions and Complex Multimorbidity (CM) as the presence of ≥ 3 non-rheumatic chronic conditions affecting ≥3 organ systems. Hierarchical Clustering on Principal Components was performed for grouping., Results: Among the COVAD respondents, 1558 IIMs, 4591 oAIRDs, and 3652 HCs were analysed. IIMs exhibited a high burden of comorbidities (OR: 1.62 vs oAIRDs and 2.95 vs HCs, p< 0.01), BM (OR 1.66 vs oAIRDs and 3.52 vs HCs, p< 0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs, p< 0.01), and mental health disorders (MHDs) (OR 1.33 vs oAIRDs and 2.63 vs HCs, p< 0.01). Among the IIM patients, those with comorbidities or MHDs had lower PROMIS Global Physical (PGP), PROMIS Global Mental (PGM), and PROMIS Physical Function (SF10) scores, and higher fatigue (F4a) scores (all p< 0.001). PGP, PGM, SF10a and F4a were influenced by age, active disease, BM, and MHDs. Four distinct clusters were identified among the IIMs according to comorbidities and PROMIS scores., Conclusion: Patients with IIMs have a higher burden of comorbidities that influence physical and mental health, identifiable as clinical clusters for optimized and holistic management approaches., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

For millions of years, barnacles and mussels have successfully adhered to wet rocks near tide-swept seashores. While the chemistry and mechanics of their underwater adhesives are being thoroughly investigated, an overlooked aspect of marine organismal adhesion is their ability to remove underlying biofilms from rocks and prepare clean surfaces before the deposition of adhesive anchors. Herein, we demonstrate that nonionic, coacervating synthetic polymers that mimic the physicochemical features of marine underwater adhesives remove ∼99% of Pseudomonas aeruginosa ( P. aeruginosa ) biofilm biomass from underwater surfaces. The efficiency of biofilm removal appears to align with the compositional differences between various bacterial biofilms. In addition, the surface energy influences the ability of the polymer to displace the biofilm, with biofilm removal efficiency decreasing for surfaces with lower surface energies. These synthetic polymers weaken the biofilm-surface interactions and exert shear stress to fracture the biofilms grown on surfaces with diverse surface energies. Since bacterial biofilms are 1000-fold more tolerant to common antimicrobial agents and pose immense health and economic risks, we anticipate that our unconventional approach inspired by marine underwater adhesion will open a new paradigm in creating antibiofilm agents that target the interfacial and viscoelastic properties of established bacterial biofilms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, emerged in December 2019, sparking a global health crisis. While initially recognized as a respiratory illness, it has become evident that Coronavirus disease 2019 (COVID-19) also affects the central nervous system. This comprehensive review focuses on the neurological manifestations of COVID-19 and its impact on patients with preexisting neurological disorders, particularly those with multiple sclerosis (MS) receiving disease-modifying therapies. Advancements in management, including vaccinations, antiviral therapy, and targeted prophylaxis, have led to a decline in the incidence and severity of COVID-19. Nevertheless, significant complications persist, particularly in patients with advanced MS, who are highly vulnerable to infectious agents like SARS-CoV-2. This review explores the evolving understanding of MS and its association with SARS-CoV-2, encompassing neuroinvasiveness, pathogenesis, disease severity, and outcomes. Research findings reveal substantial neurological implications for some MS patients with COVID-19, with a potential risk of disease relapse and severity. A notable proportion of MS patients experiencing COVID-19 may manifest new symptoms, experience exacerbation of existing symptoms, or encounter both simultaneously, underscoring the diverse neurological effects of the virus. While vaccination and therapeutics have mitigated the overall impact, specific subgroups, especially those on anti-CD20 therapy and with existing disability, remain at higher risk, necessitating ongoing vigilance and tailored care., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Telomere biology disorders (TBD), caused by pathogenic germline variants in telomere-related genes, present with multi-organ disease and a predisposition to cancer. Clonal hematopoiesis (CH) as a marker of cancer development and survival in TBD is poorly understood. Here, we characterized the clonal landscape of a large cohort of 207 TBD patients with a broad range of age and phenotype. CH occurred predominantly in symptomatic patients and in signature genes typically associated with cancers: PPM1D, POT1, TERT promoter (TERTp), U2AF1S34, and/or TP53. Chromosome 1q gain (Chr1q+) was the commonest karyotypic abnormality. Clinically, multiorgan involvement and CH in TERTp, TP53, and splicing factor genes associated with poorer overall survival. Chr1q+, and splicing factor or TP53 mutations significantly increased the risk of hematologic malignancies, regardless of the clonal burden. Chr1q+ and U2AF1S34 mutated clones were pre-malignant events associated with the secondary acquisition of mutations in genes related to hematologic malignancies. Like known effects of Chr1q+ and TP53-CH, functional studies demonstrated that U2AF1S34 mutations primarily compensated for aberrant upregulation of TP53 and interferon pathways in telomere-dysfunctional hematopoietic stem cells, highlighting the TP53 pathway as a canonical route of malignancy in TBD. In contrast, somatic POT1/PPM1D/TERTp-CH had distinct trajectories unrelated to cancer development. With implications beyond TBD, our data show that telomere dysfunction is a strong selective pressure for CH. In TBD, CH is a poor prognostic marker associated with worse overall survival. The identification of key regulatory pathways that drive clonal transformation in TBD allows the identification of patients at a higher risk of cancer development., (Copyright © 2024 American Society of Hematology.)

Objective: Mastoidectomy surgical training is challenging due to the complex nature of the anatomical structures involved. Traditional training methods based on direct patient care and cadaveric temporal bone training have practical shortcomings. 3D-printed temporal bone models and augmented reality (AR) have emerged as promising solutions, particularly for mastoidectomy surgery, which demands an understanding of intricate anatomical structures. Evidence is needed to explore the potential of AR technology in addressing these training challenges., Methods: 21 medical students in their clinical clerkship were recruited for this prospective, randomized controlled trial assessing mastoidectomy skills. The participants were randomly assigned to the AR group, which received real-time guidance during drilling on 3D-printed temporal bone models, or to the control group, which received traditional training methods. Skills were assessed on a modified Welling scale and evaluated independently by two senior otologists., Results: The AR group outperformed the control group, with a mean overall drilling score of 19.5 out of 25, compared with the control group's score of 12 (p < 0.01). The AR group was significantly better at defining mastoidectomy margins (p < 0.01), exposing the antrum, preserving the lateral semicircular canal (p < 0.05), sharpening the sinodural angle (p < 0.01), exposing the tegmen and attic, preserving the ossicles (p < 0.01), and thinning and preserving the external auditory canal (p < 0.05)., Conclusion: AR simulation in mastoidectomy, even in a single session, improved the proficiency of novice surgeons compared with traditional methods., Level of Evidence: NA Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Here, we employ polymer physics models of chromatin to investigate the 3D folding of a 2 Mb wide genomic region encompassing the human LTN1 gene, a crucial DNA locus involved in key cellular functions. Through extensive Molecular Dynamics simulations, we reconstruct in silico the ensemble of single-molecule LTN1 3D structures, which we benchmark against recent in situ Hi-C 2.0 data. The model-derived single molecules are then used to predict structural folding features at the single-cell level, providing testable predictions for super-resolution microscopy experiments.

This research's main objective is to identify the level of contamination in drinking water in Adama town and its environs by employing PIG, GIS and HHRA. The physical-chemical parameters of groundwater were determined, and the results were compared to regional and global drinking water quality guidelines. The pH of groundwater is alkaline, and the contents of Ca 2+ , Na + , HCO 3 - , and F - in the majority of samples surpassed the permissible drinking limit. The hydrochemical facies were identified in the following order: Ca-Mg-HCO 3 , Na-Ca-HCO 3 , and Na-HCO 3 . Cation exchange and Rock-water interaction are the major dominant natural mechanisms controlling groundwater chemistry. Using IDW interpolation methods with Arc GIS 10.8, spatial analysis of the physico-geochemical content of water divulged that TDS, pH, TH, EC, Mg 2+ , Ca 2+ , K + , Na + , Cl - , HCO 3 - all exhibit a positive trend in the direction of groundwater flow from the upland to the lowland (rift floor). As per PIG, the results show that 57%, 33%, 7% and 3% of the samples were found in the insignificant, low, moderate and high, correspondingly. The total hazard index (THI) is calculated from hazard quotients (HQIntake and HQDermal) results showing 83%, 73%, and 57% of the samples exceed the non-carcinogenic health threat of fluoride THI >1 in drinking water for children, women and men. Children are more susceptible to danger than either males or women, according to the THI data, based on body weights and consumption rates. Similarly, females are also more vulnerable to health risks than men.- , and SO 4 2- all exhibit a positive trend in the direction of groundwater flow from the upland to the lowland (rift floor). As per PIG, the results show that 57%, 33%, 7% and 3% of the samples were found in the insignificant, low, moderate and high, correspondingly. The total hazard index (THI) is calculated from hazard quotients (HQIntake and HQDermal) results showing 83%, 73%, and 57% of the samples exceed the non-carcinogenic health threat of fluoride THI >1 in drinking water for children, women and men. Children are more susceptible to danger than either males or women, according to the THI data, based on body weights and consumption rates. Similarly, females are also more vulnerable to health risks than men., Competing Interests: The authors confirm no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Smilax genus possesses bioactive properties attributed to phenolic compounds, which may exhibit antioxidant effects and inhibit the advanced glycation end products (AGEs). However, identifying these phenolic compounds and AGEs has become increasingly relevant to understanding such activities. This study aimed to identify phenolic compounds in extracts of Smilax spp. and evaluate their antioxidant and AGEs inhibitory activities. To achieve this, the Smilax genus was identified via PCR, and phenolic compounds including chlorogenic acid, naringenin-6-C-glucoside, quercetin, quercetin-3-O-glucoside, and myricetin were identified using HPLC-MS/MS. Antioxidant activity was assessed by ferric reducing antioxidant power (FRAP), and radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azino-bis-[3-ethyl-benzothiazoline]-6-sulfonic acid (ABTS), while AGEs inhibition was evaluated using a model system formed by bovine serum albumin-glucose. The highest antioxidant activity was 3612.18 mM TE/g, and the inhibition of AGEs was 52.44 %. These results demonstrate that Smilax spp. can inhibit AGEs, neutralize free radicals, and reduce compounds associated with antioxidant capacity., Competing Interests: Declaration of competing interest There are no activities that may have any conflict of interest If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The group of authors declares no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Synthesizing perceivable artificial neural inputs independent of typical sensory channels remains a fundamental challenge in the development of next-generation brain-machine interfaces. Establishing a minimally invasive, wirelessly effective, and miniaturized platform with long-term stability is crucial for creating a clinically meaningful interface capable of mediating artificial perceptual feedback. In this study, we demonstrate a miniaturized fully implantable wireless transcranial optogenetic encoder designed to generate artificial perceptions through digitized optogenetic manipulation of large cortical ensembles. This platform enables the spatiotemporal orchestration of large-scale cortical activity for remote perception genesis via real-time wireless communication and control, with optimized device performance achieved by simulation-guided methods addressing light and heat propagation during operation. Cue discrimination during operant learning demonstrates the wireless genesis of artificial percepts sensed by mice, where spatial distance across large cortical networks and sequential order-based analyses of discrimination performance reveal principles that adhere to general perceptual rules. These conceptual and technical advancements expand our understanding of artificial neural syntax and its perception by the brain, guiding the evolution of next-generation brain-machine communication.

Populations in rural communities have more limited access to health care and attention than urban populations. The present study aimed to evaluate barriers to access to health care in mothers and caregivers of children under five years of age, twelve months after an educational intervention. The study was carried out from February to September 2022, and 472 mothers from eight communities in the state of Yucatán, in the southeast of the United Mexican States, participated. A comparative analysis was carried out on help-seeking times, obstacles to reaching it, and illnesses in children. The results revealed that the main barriers to access to care were long times to decide to seek help, lack of financial resources to pay for the transfer to another health unit, lack of someone to accompany the mother or caregiver when the child needed be transferred, and lack of transportation for the transfer. Disease knowledge remained at different levels in the eight communities; the significant differences occurred in four communities, one specifically for heart defects. It was concluded that, in the rural populations studied, there are barriers to access to health care which have to do with neglected social determinants, such as those related to conditions of gender, income, social support network, and the health system. Access to health care must be universal, so public health interventions should be aimed at reducing the barriers that prevent the population from demanding and using services in a timely manner.

Background: Basic sanitation services and practices are crucial for the well-being and health of a community. However, little is known about the determinants of basic sanitation services in Ethiopia, particularly in the study area., Objectives: To identify the determinants of basic sanitation service coverage among households in the Shashogo district, Hadiya Zone, and Central Ethiopia in 2023., Methods: A case-control investigation was carried out in households in Shashogo District from August 8, 2023, to December 10, 2023. Ten Kebeles were chosen randomly from a total of 34 Kebeles in the district. A total of 579 households (193 cases and 386 controls) were included in the study. The data were gathered with pretested and structured questionnaires in digital form with a smartphone. The data were analyzed with SPSS. Independent t tests and regression models were used to determine predictors of basic sanitation services., Results: The mean (±SD) age of the study participants was 38.2 (±8.9) years. After controlling for confounders in the multivariate analysis, the adoption of improved latrine services among households was found to be associated with greater average monthly income (AOR = 1.841, 95% CI (1.043, 3.251)), the study respondents who had access to the necessary materials for latrine construction/upgrade were approximately 3.5 times more likely to adopt improved latrine services among households with (AOR = 3.477 (95% CI = 1.314, 9.202) than among those who lacked access to the necessary materials for latrine construction, the study respondents who had training in sanitation and hygiene (AOR = 4.744, 95% CI (2.984, 7.542)) and who had sufficient knowledge about the adoption of improved latrine services (AOR = 2.020, 95% CI (1.125, 3.628)) were found to be determinants of the adoption of improved latrine services among households., Conclusion: This study revealed that economics, knowledge, attitudes and practices, infrastructure, and culture were identified as determinants of the adoption of improved latrines in the study area. Poor sanitation significantly impacts economic, social, environmental and many other direct and indirect impacts on the well-being of citizens. Therefore, policies on sanitation and contextual initiatives and focused actions are needed by stakeholders and policy implementers to improve knowledge gaps, access to necessary materials and the income capacity of those lagging to adopt services., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Purpose: CheckMate 914 is a two-part, randomized phase III trial evaluating adjuvant nivolumab plus ipilimumab (part A) or adjuvant nivolumab monotherapy (part B) versus placebo in mutually exclusive populations of patients with localized renal cell carcinoma (RCC) at high risk of postnephrectomy recurrence. Part A showed no disease-free survival (DFS) benefit for adjuvant nivolumab plus ipilimumab versus placebo. We report results from part B., Methods: Patients were randomly assigned (2:1:1) to nivolumab (240 mg once every 2 weeks for up to 12 doses), placebo, or nivolumab (240 mg once every 2 weeks for up to 12 doses) plus ipilimumab (1 mg/kg once every 6 weeks for up to four doses). The planned treatment duration was 24 weeks (approximately 5.5 months). The primary end point was DFS per blinded independent central review (BICR) for nivolumab versus placebo; safety was a secondary end point., Results: Overall, 825 patients were randomly assigned to nivolumab (n = 411), placebo (n = 208), or nivolumab plus ipilimumab (n = 206). With a median follow-up of 27.0 months (range, 18.0-42.4), the primary end point of improved DFS per BICR with nivolumab versus placebo was not met (hazard ratio [HR], 0.87 [95% CI, 0.62 to 1.21]; P = .40); the median DFS was not reached in either arm, and 18-month DFS rates were 78.4% versus 75.4%. The HR for DFS per investigator was 0.80 (95% CI, 0.58 to 1.12; P = .19). Grade 3-4 all-cause adverse events (AEs) occurred in 17.2%, 15.0%, and 28.9% of patients with nivolumab, placebo, and nivolumab plus ipilimumab, respectively. Any-grade treatment-related AEs led to discontinuation in 9.6%, 1.0%, and 28.4%, respectively., Conclusion: Part B of CheckMate 914 did not meet the primary end point of improved DFS for nivolumab versus placebo in patients with localized RCC at high risk of postnephrectomy recurrence.

Background: Attendance to neonatal follow-up programs presents a significant factor associated with positive long-term outcomes of high-risk infants. Strategies to maximize participation benefit not only future interventions' effectiveness but also healthcare systems and society. While a number of studies have focused on attrition or loss to follow-up, no studies have focused on the contributive risk factors to abstaining from neonatal follow-up programs specifically during the COVID-19 pandemic. This study aims to reveal the main factors linked to non-compliance in a neonatal follow-up program of a tertiary hospital., Methods: In this ambidirectional observational study, data from 1137 high-risk neonates who participated in a hospital follow-up program were collected (573 before and 564 after the COVID-19 pandemic). The study sample was grouped to three groups: G1 (N = 831), who maintained participation in the program; G2 (N = 196), who discontinued; and G3 (N = 110), who never visited the outpatient clinics. Data were obtained from the hospital's Systems Applications and Products (SAP) Software and a structured questionnaire, answered by parents of newborns either discontinuing (G2) or not attending (G3) the follow-up program through a telephone contact., Results: The most frequently reported reason for discontinuance before the pandemic onset was the parents' perception of no necessity to maintain participation (44.12%). During the COVID-19 pandemic, provider-related barriers to maintaining hospital access, inability to provide high-quality services (37.14%), and feelings of fear and insecurity (18.5%) emerged as factors for non-attendance. Citizenship and morbidity (respiratory distress syndrome, sepsis, necrotic enterocolitis, jaundice) acted as incentives to join the follow-up program during both study periods. Multiple regression analysis showed that multiple-gestation infants had higher odds of maintaining participation during the COVID-19 period (OR, 4.04; CI, 1.09-14.9)., Conclusions: Understanding the potential impact of COVID-19 and the transformative changes in neonatal follow-up clinics is crucial for applying compliance strategies. Removing barriers to maintain family participation can lead to increased attendance rates., Competing Interests: The authors declare no conflicts of interest.

The UNAIDS 95-95-95 targets are an important metric for guiding national HIV programs and measuring progress towards ending the HIV epidemic as a public health threat by 2030. Nevertheless, as proportional targets, the outcome of reaching the 95-95-95 targets will vary greatly across, and within, countries owing to the geographic diversity of the HIV epidemic. Countries and subnational units with a higher initial prevalence and number of people living with HIV (PLHIV) will remain with a larger number and higher prevalence of virally unsuppressed PLHIV-persons who may experience excess morbidity and mortality and can transmit the virus to others. Reliance on achievement of uniform proportional targets as a measure of program success can potentially mislead resource allocation and progress towards equitable epidemic control. More granular surveillance information on the HIV epidemic is required to effectively calibrate strategies and intensity of HIV programs across geographies and address current and projected health disparities that may undermine efforts to reach and sustain HIV epidemic control even after the 95 targets are achieved., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Finding an ovary and/or fallopian tube within an indirect inguinal hernia is a rare occurrence that can be detected incidentally during elective surgery or present as a medical emergency requiring immediate intervention. Hence, it poses a difficult clinical picture in a reproductive-age woman with groin mass., Clinical Presentation: We describe the case of a 45-year-old Ethiopian woman of Amhara ethnicity who presented with a left inguinal swelling that persisted for 5 years. Physical examination revealed an irreducible, non-tender lump in the left groin and an ultrasonography scan confirmed the presence of an indirect inguinal hernia. The patient was then scheduled for elective hernia repair. During the surgery, both her left ovary and fallopian tube were found within the hernial sac. The contents were released from the sac, high ligation performed, and the inguinal floor repaired with mesh., Discussion: Inguinal hernias in women are rare and often present a diagnostic challenge. Although the exact pathogenesis of inguinal hernias containing female genital organs is unknown, some risk factors have been postulated. Diagnosis should start with a physical exam and imaging, but many of the cases have been intraoperative surprises. Management is primarily surgical, ranging from simple reduction and hernia repair to salpingo-oophorectomy depending on the status of the hernia contents., Conclusion: This report emphasizes the importance of maintaining a high index of suspicion when examining females with inguinal hernias to ensure accurate diagnosis and management of tubo-ovarian hernias. Although rare, inguinal hernias containing female genital organs should be considered in the differential diagnosis of inguinal hernias, as early detection and appropriate surgical management can prevent potential complications., (© 2024. The Author(s).)

Drug delivery to the esophagus through systemic administration remains challenging, as minimal drug reaches the desired target. Local delivery offers the potential for improved efficacy while minimizing off-target toxicities but necessitates bioadhesive properties for mucosal delivery. Herein, we describe the synthesis of two new mucoadhesive amphiphilic copolymers prepared by sequential ring-opening copolymerization or postpolymerization click conjugation. Both strategies yield block copolymers containing a hydrophilic amine-functionalized poly-amido-saccharide and either a hydrophobic alkyl derivatized poly-amido-saccharide or poly(lactic acid), respectively. The latter resulting copolymers readily self-assemble into spherical, ≈200 nm diameter, positively charged mucoadhesive nanoparticles. The NPs entrap ultrahigh levels of paclitaxel via encapsulation of free paclitaxel and paclitaxel conjugated to a biodegradable, biocompatible poly(1,2-glycerol carbonate). Paclitaxel-loaded NPs rapidly enter cells, release paclitaxel, are cytotoxic to esophageal OE33 and OE19 tumor cells in vitro, and, importantly, demonstrate improved mucoadhesion compared to conventional poly(ethylene glycol)-poly(lactic acid) nanoparticles to ex vivo esophageal tissue.

Introduction: Out-of-hospital cardiac arrest (OHCA) has a high global incidence and mortality rate, with early defibrillation significantly improving survival. Our aim was to assess the feasibility of autonomous drone delivery of automated external defibrillators (AED) in a non-urban area with physical barriers and compare the time to defibrillate (TTD) with bystander retrieval from a public access defibrillator (PAD) point and helicopter emergency medical services (HEMS) physician performed defibrillation., Methods: This randomized simulation-based trial with a cross-over design included bystanders performing AED retrievals either delivered by automated drone flight or on foot from a PAD point, and simulated HEMS interventions. The primary outcome was the time to defibrillation, with secondary outcomes comparing workload, perceived physical effort, and ease of use., Results: Thirty-six simulations were performed. Drone-delivered AED intervention had a significantly shorter TTD [2.2 (95 % CI 2.0-2.3) min] compared to PAD retrieval [12.4 (95 % CI 10.4-14.4) min] and HEMS [18.2 (95 % CI 17.1-19.2) min]. The self-reported physical effort on a visual analogue scale for drone-delivered AED was significantly lower versus PAD [2.5 (1 - 22) mm vs. 81 (65-99) mm, p = 0.02]. The overall mean workload measured by NASA-TLX was also significantly lower for drone delivery compared to PAD [4.3 (1.2-11.7) vs. 11.9 (5.5-14.5), p = 0.018]., Conclusion: The use of drones for automated AED delivery in a non-urban area with physical barriers is feasible and leads to a shorter time to defibrillation. Drone-delivered AEDs also involve a lower workload and perceived physical effort than AED retrieval on foot., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Context: The critical role of hospice and palliative care in response to the COVID-19 pandemic is well recognized, but there is limited evidence to guide healthcare leadership through future crises., Objectives: Our goal was to support future organizational resilience by exploring hospice and palliative team members' perspectives on crisis leadership during the COVID-19 pandemic in New York City (NYC)., Methods: This qualitative descriptive study used individual, semi-structured interviews of purposively sampled interdisciplinary team members. Enrollment sites were two large NYC metro hospice care organizations and one outpatient palliative care practice. We asked participants to complete a demographic form and a 45-60 minute interview. We used descriptive statistics and thematic analysis, respectively, for data analysis. We triangulated the data by presenting preliminary study findings to a group of clinicians (n=21) from one of the referring organizations., Results: Participants (n=30) were professionally diverse (e.g., nurses, physicians, social workers, chaplains, administrators), experienced (mean=17 years; 10 years in hospice), and highly educated (83% ≥ master's degree). About half (n=15) self-identified as white, non-Hispanic, and nearly half (n=13) self-identified as being from a racial/ethnic minoritized group. Two (n=2) did not wish to self-identify. We identified four themes that reflected challenges and adaptive responses to providing care during a crisis: Stay Open and Stay Safe; Act Flexibly; Lead Adaptively; and Create a Culture of Solidarity., Conclusion: While additional work is indicated, findings offer direction for a crisis management playbook to guide leadership in hospice, palliative care, and other healthcare settings in future crises., Competing Interests: Disclosure/Conflict of Interest The authors have no conflicts to report. DD acknowledges support from the National Palliative Care Research Center – Kornfeld Scholar, and the Cambia Sojourns Scholar Program. This paper does not represent the views of the Department of Veterans Affairs or the U.S. government., (Copyright © 2024. Published by Elsevier Inc.)