A Recipe for a Great Meal: A Benchtop Route from Elemental Se to Superior Thermoelectric ß-Ag2Se.

The low-temperature modification of ß-Ag2Se has proven to be useful as a near-room-temperature thermoelectric material. Over the past years, research has been devoted to interstitial, vacancy, and substitutional doping into the parent ß-Ag2Se structure, aiming at tuning the material's charge and heat transport properties to enhance thermoelectric performance. The transformation of ß-Ag2Se into α-Ag2Se at ∼134 °C and the low solubility of dopants are the main obstacles for the doping approach. Herein, we report a facile, safe, scalable, and cost-effective benchtop approach to successfully produce metal-doped ß-Ag2Se. The doped materials display a remarkable enhancement of thermoelectric performance with a record-high peak zT of 1.30 at 120 °C and an average zT of ∼1.15 in the 25-120 °C range for 0.2 at. % Zn-doped Ag2Se. The enhancement in zT is attributed to point defects created by Zn doping into Ag vacancies/interstitials, which enhances the scattering of phonons and tunes the charge carrier properties, leading to the significant suppression of thermal conductivity. The simplicity of the synthetic method developed herein and the high performance of the final products provide an avenue to produce high-quality Ag2Se-based thermoelectric materials.

Late Paleozoic oxygenation of marine environments supported by dolomite U-Pb dating.

Understanding causal relationships between evolution and ocean oxygenation hinges on reliable reconstructions of marine oxygen levels, typically from redox-sensitive geochemical proxies. Here, we develop a proxy, using dolomite U-Pb geochronology, to reconstruct seawater U/Pb ratios. Dolomite samples consistently give U-Pb dates and initial 207Pb/206Pb ratios lower than expected from their stratigraphic ages. These observations are explained by resetting of the U-Pb system long after deposition; the magnitude of deviations from expected initial 207Pb/206Pb are a function of the redox-sensitive U/Pb ratios during deposition. Reconstructed initial U/Pb ratios increased notably in the late-Paleozoic, reflecting an increase in oxygenation of marine environments at that time. This timeline is consistent with documented shifts in some other redox proxies and supports evolution-driven mechanisms for the oxygenation of late-Paleozoic marine environments, as well as suggestions that early animals thrived in oceans that on long time scales were oxygen-limited compared to today.

Hyperexcitability and translational phenotypes in a preclinical mouse model of SYNGAP1-Related Intellectual Disability.

Disruption of SYNGAP1 directly causes a genetically identifiable neurodevelopmental disorder (NDD) called SYNGAP1-related intellectual disability (SRID). Without functional SynGAP1 protein, individuals are developmentally delayed and have prominent features of intellectual disability, motor impairments, and epilepsy. Over the past two decades, there have been numerous discoveries indicting the critical role of Syngap1. Several rodent models with a loss of Syngap1 have been engineered identifying precise roles in neuronal structure and function, as well as key biochemical pathways key for synapse integrity. Homozygous loss of SYNGAP1/Syngap1 is lethal. Heterozygous mutations of Syngap1 result in a broad range of behavioral phenotypes. Our in vivo functional data, using the original mouse model from the Huganir laboratory, corroborated behaviors including robust hyperactivity and deficits in learning and memory in young adults. Furthermore, we described impairments in the domain of sleep, characterized using neurophysiological data collected with wireless, telemetric electroencephalography (EEG). Syngap1+/- mice exhibited elevated spiking events and spike trains, in addition to elevated power, most notably in the delta power frequency. For the first time, we illustrated primary neurons from Syngap1+/- mice displayed increased network firing activity, greater bursts, and shorter inter-burst intervals between peaks by employing high density microelectrode arrays (HD-MEA). Our work bridges in-vitro electrophysiological neuronal activity and function with in vivo neurophysiological brain activity and function. These data elucidate quantitative, translational biomarkers in vivo and in vitro that can be utilized for the development and efficacy assessment of targeted treatments for SRID.

Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model.

Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus. We also characterize immune responses elicited following administration of the phage cocktail. While minimal innate responses are observed after phage administration, two rounds of treatment induces phage-specific neutralizing antibodies and accelerate phage clearance from tissues. Interestingly, the myophages in our cocktail induce a more robust neutralizing antibody response than the siphophages. This anti-phage immunity reduces the effectiveness of the phage cocktail in our murine model. Collectively, this study shows phage-specific immune responses may be an important consideration in the development of phage cocktails for therapeutic use.

Impact of the COVID-19 pandemic in childhood and adolescent cancer care in northern Tanzania: a cross-sectional study.

INTRODUCTION: The SARS-CoV-2 (COVID-19) pandemic has strained healthcare systems and presented unique challenges for children requiring cancer care, particularly in low- and middle-income countries. This study aimed to assess the impact of the COVID-19 pandemic on access to cancer care for children and adolescents in Northern Tanzania. METHODS: In this cross-sectional study, we assessed the demographic and clinical characteristics of 547 pediatric and adolescent cancer patients (ages 0-19 years old) between 2016 and 2022 using the population-based Kilimanjaro Cancer Registry (KCR). We categorized data into pre-COVID-19 (2016-2019) and COVID-19 (2020-2022) eras, and performed descriptive analyses of diagnostic, treatment, and demographic information. A secondary analysis was conducted on a subset of 167 patients with stage of diagnosis at presentation. RESULTS: Overall admissions nearly doubled during the pandemic (n = 190 versus 357). The variety of diagnoses attended at KCMC increased during the pandemic, with only five groups of diseases reported in 2016 to twelve groups of diseases in 2021. Most patients were diagnosed at a late stage (stage III or IV) across eras, with the proportion of under-five years old patients increasing late-diagnoses from 29.4% (before the pandemic), 52.8% (during the pandemic), when compared to the overall cohort. Around 95% of children in this age category reported late-stage diagnosis during the pandemic. Six out of the twelve cancer site groups also reported an increase in late-stage diagnosis. During the pandemic, the proportion of children receiving surgery increased from 15.8 to 30.8% (p < 0.001). CONCLUSION: Childhood and adolescent cancer care changed in Northern Tanzania during the COVID-19 pandemic, with increased late-stage diagnoses presentations among younger patients and the increased use of surgical therapies in the context of a growing practice. Understanding the impact of the COVID-19 pandemic on pediatric and adolescent cancer care can help us better adapt healthcare systems and interventions to the emerging needs of children and adolescents with cancer in the midst of a health crisis.

Salivary Gland Tumors: A 20 Year Review From a Single Community Practice.

Objective: Salivary gland tumors are a heterogenous group of lesions with variable pathology and clinical outcomes. Most published data are derived from studies conducted at tertiary care centers. Our study analyzed the experience from a community setting to determine significant differences, if any, in pathological distribution and clinical outcomes compared to the existing literature. Methods: We performed a retrospective analysis of all major salivary gland tumors that presented to a large community practice over a 20 year period. Retrospective chart analysis was performed for demographics, clinical presentation, imaging, cytology, histopathology, and clinical outcome data. Results: Of 806 patients, the parotid gland was the most common site in 683 patients (84.7%), followed by submandibular in 78 (9.7%) and sublingual in 45 (5.6%). A total of 203 patients were managed conservatively with observation without definitive diagnosis or lost to follow-up. A total of 495 patients underwent surgical intervention within the community practice. Twenty-six patients underwent surgical excision at an outside hospital. Eighty-two patients were determined to have a benign diagnosis based on ultrasound-guided fine needle aspiration or excisional biopsy alone. Final histopathology was benign in 505 cases (83.7%), while 98 tumors (16.3%) received a diagnosis of primary or secondary malignancy. For the parotid gland, pleomorphic adenoma (155) and Warthin's tumor (155) were the most common benign diagnoses, while mucoepidermoid carcinoma (13), adenocarcinoma (8), and acinic cell carcinoma (8) were the most common primary malignancies. Conclusions: We found a higher rate of benign tumor pathology compared to the existing literature. While the outcome data on surgical treatment of benign tumors are comparable to the existing literature, the same conclusion cannot be drawn for malignant tumors, given relatively small numbers in our series and likely disparity in the complexity of the surgical cases in tertiary care centers.

Health Disparities in Young Adults: A Direct Comparison of Distress and Unmet Needs Across Cancer Centers.

PURPOSE: Information on concerns that young adults (YAs) with cancer face when receiving care outside of specialized treatment centers is needed to increase equitable care to YAs at greater risk of marginalization by the health care system. The current study compared distress and unmet needs at the time of clinic visit between YAs receiving care from three different cancer clinics: (1) a National Cancer Institute-designated center, (2) a community-based clinic, and (3) a county hospital outpatient clinic. METHODS: The Adolescent and Young Adult Psycho-Oncology Screening Tool (AYA-POST) was administered to measure distress and cancer-related concerns of YAs in active treatment. A one-way analysis of variance (ANOVA) compared distress scores by treatment site. A Fisher's exact test compared the number of participants endorsing each item on the Needs Assessment Checklist from each site. A simple linear regression determined the association between distress and number of items endorsed on the Needs Assessment Checklist. RESULTS: Ninety-seven participants completed the AYA-POST, endorsing, on average, 11 concerns. Fisher's exact test showed significant differences between sites in the proportion of participants endorsing eight items: boredom (P < .001), eating/appetite (P < .001), nausea/vomiting (P < .001), financial concern (P = .002), hopelessness/helplessness (P = .03), confidentiality (P = .04), sibling concern (P = .04), and insurance (P = .05). The simple linear regression model was significant (F(1, 94) = 39.772, P < .001, R2 = 0.297), indicating the number of unmet needs accounted for almost 30% of the variance in distress. The one-way ANOVA was not significant (F(2, 93) = 1.34, P = .267). CONCLUSION: Social determinants of health can influence the number and type of unmet needs experienced, affecting distress and other outcomes and underscoring the importance of timely, effective, age-appropriate screening and intervention for distress and unmet needs in YAs with cancer.

Neurocognitive correlates of metabolic dysregulation in individuals with mood disorders: a systematic review and meta-analysis.

Individuals with mood disorders are predisposed to metabolic dysfunction, while those with metabolic dysregulation such as diabetes and obesity experience more severe depressive symptoms. Both metabolic dysfunction and mood disorders are independently associated with cognitive deficits. Therefore, given their close association, this study aimed to explore the association between metabolic dysfunction in individuals with mood disorders in relation to cognitive outcomes. A comprehensive search comprised of these three domains was carried out; a random-effects meta-analysis pooling mean cognitive outcomes was conducted (PROSPERO ID: CRD42022295765). Sixty-three studies were included in this review; 26 were synthesized in a quantitative meta-analysis. Comorbid metabolic dysregulation was associated with significantly lower global cognition among individuals with mood disorders. These trends were significant within each mood disorder subgroup, including major depressive disorder, bipolar disorder, and self-report depression/depressive symptoms. Type 2 diabetes was associated with the lowest cognitive performance in individuals with mood disorders, followed by peripheral insulin resistance, body mass index ⩾25 kg/m2, and metabolic syndrome. Significant reduction in scores was also observed among individual cognitive domains (in descending order) of working memory, attention, executive function, processing speed, verbal memory, and visual memory. These findings demonstrate the detrimental effects of comorbid metabolic dysfunction in individuals with mood disorders. Further research is required to understand the underlying mechanisms connecting mood disorders, metabolism, and cognition.

Postoperative permanent section evaluation of Mohs micrographic surgery debulk specimens does not result in upstaging of cutaneous squamous cell carcinoma compared to stage at the completion of surgery: A retrospective case series.

Background: Mohs micrographic surgery (MMS) is used for the treatment of high-risk cutaneous squamous cell carcinoma (cSCC). MMS examines the surgical margins in real time and does not commonly examine the central component of the tumor. Objective: To determine if debulk specimens provide additional details relevant to tumor staging not gained from routine MMS. Methods: A retrospective chart review of debulk specimens taken during MMS for cSCC was performed. Dermatopathology reports were analyzed and tumors were staged using Brigham and Women's Hospital and American Joint Committee on Cancer's 8th edition staging systems. Results: Permanent section evaluation of debulk specimens did not result in clinically meaningful information for staging that could not be gained from MMS layers or initial biopsy analysis. Limitations: A single institution, and a small sample size of 39 tumors. Conclusions: Evaluation of debulk specimens during MMS may not always be an effective use of time or health care resources.

Multiple primary dermatofibrosarcoma protuberans tumors in a single patient with chromosomal microarray analysis: A case report and review.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with a high propensity for local invasion and recurrence. Although it is a rare event, the occurrence of multiple tumors in a single patient raises a diagnostic dilemma, as metastatic disease should be differentiated from multiple primary malignant events. In more than 90% of DFSP, a pathogenic t(17;22) translocation leads to the expression of COL1A1::PDGFB fusion transcripts. Karyotype analysis, fluorescence in situ hybridization, and RT-PCR can be useful ancillary studies in detecting this characteristic rearrangement, and sequencing of the fusion transcript can be used to support a clonal origin in metastatic and multifocal disease. However, previous reports have demonstrated variable sensitivity of these assays, in part due to the high sequence variability of the COL1A1::PDGFB fusion. Here, we report a patient who developed two distinct DFSP tumors over the course of 7 years. Chromosomal microarray analysis identified distinctive genomic alterations in the two tumors, supporting the occurrence of multiple primary malignant events.

Considering a Utility-Centric Framework Based on "Minimum Orthophosphate" Criteria for Mitigation of Elevated Cuprosolvency in Drinking Water.

Gaps in the United States Environmental Protection Agency (US EPA) Lead and Copper Rule (LCR) leave some consumers and their pets vulnerable to high cuprosolvency in drinking water. This study seeks to help proactive utilities who wish to mitigate cuprosolvency problems through the addition of orthophosphate corrosion inhibitors. The minimum doses of orthophosphate necessary to achieve acceptable cuprosolvency in relatively new copper pipe were estimated as a function of alkalinity via linear regressions for the 90th, 95th, and 100th percentile copper tube segments (R2 > 0.98, n = 4). Orthophosphate was very effective at reducing cuprosolvency in the short term but, in some cases, resulted in higher long-term copper concentrations than the corresponding condition without orthophosphate. Alternatives to predicting "long-term" results for copper tubes using simpler bench tests starting with fresh Cu(OH)2 solids showed promise but would require further vetting to overcome limitations such as maintaining water chemistry and orthophosphate residuals and to ensure comparability to results using copper tube.

Association of maternal pre-pregnancy or first trimester body mass index with neurodevelopmental impairment or death in extremely low gestational age neonates.

OBJECTIVE: To compare the rates of death or survival with severe neurodevelopmental impairment (sNDI) at 2 years among extremely preterm infants in relation to pre-pregnancy or first-trimester maternal body mass index (BMI). METHODS: This retrospective cohort study included extremely preterm infants (gestational age 220/7-266/7 weeks). The study was conducted at National Institute of Child Health and Human Development Neonatal Research Network sites. The primary outcome was death or sNDI at 2 years. RESULTS: Data on the primary outcome were available for 1208 children. Death or sNDI was not different among the three groups: 54.9% in normal, 56.1% in overweight, and 53.4% in obese group (p = 0.39). There was no significant difference in mortality, sNDI, moderate/severe cerebral palsy, Bayley Scales of Infant Development (BSID)-III cognitive composite score <70, BSID-III language composite score <70 in adjusted models. CONCLUSION: Neurodevelopmental outcome was not significantly associated with maternal pre-pregnancy BMI among extreme preterm infants.

Remote monitoring of patients with rheumatoid arthritis: a mixed methods evaluation across six hospitals in London, UK.

OBJECTIVES: This study evaluated the scale-up of a remote monitoring (RM) service, capturing monthly Rheumatoid Arthritis Impact of Disease scores and patient-generated text messages, for patients with rheumatoid arthritis (RA; in remission or with low disease activity) attending routine outpatient clinics across six hospitals. We explored patients and staff experiences and implementation outcomes. METHODS: A pragmatic, mixed methods approach was used, with active patient involvement throughout. We undertook a rapid review, analysed service-level data, and conducted a patient survey and patient and staff interviews, informed by the Capability, Opportunity, Motivation, Behaviour (COM-B) and Exploration, Preparation, Implementation, Sustainment (EPIS) theoretical frameworks. RESULTS: The review included 37 articles, covering themes of patient and clinician acceptability, engagement, feasibility and clinical impact. Service-level data (n = 202) showed high levels of patient engagement with the service. The patient survey (n = 155) showed patients felt the service was easy to use, had confidence in it and felt it improved access to care. Patient interview (n = 22) findings mirrored those of the survey. Motivating factors included increased responsiveness and ease of contact with clinical teams. Views from staff interviews (n = 16) were more mixed. Some implementation barriers were specific to roll-out sites. Prioritisation of staff needs was emphasised. CONCLUSION: Patients were positive about the service and engagement was high. Staff views and engagement were more mixed. Results suggest that equal levels of patient and staff engagement are required for sustainability. These findings further our understanding of the implementation challenges to scaling RM interventions for patients with RA in routine care settings.

Adult neuro-oncology trials in the United States over 5 decades: Analysis of trials completion rate to guide the path forward.

Background: Clinical trials are important to close the gap between therapeutic unmet needs and scientific advances in neuro-oncology. This study analyzes the landscape of neuro-oncology trials to identify completion rates and guide strategies for the path forward. Methods: US-registered adult neuro-oncology clinical trials were extracted from www.clinicaltrials.gov (1966-2019), including funding source, trial type, scope, phase, and subjects' demographics. Completed trials defined as those that had completed participants' examinations or intervention administration for the purpose of the final collection of data for the primary outcome were dichotomized against those that failed to reach completion. Univariate and multivariate analyses were used to detect differences across factors comparing the last 2 decades (2000-2009, 2010-2019). Results: Our search yielded 4522 trials, of which 1257 are eligible for this study. In 25 US states, neuro-oncology trial availability is <0.85/100,000 population. Comparing the past 2 decades, trial completion rate decreased from 88% to 64% (P < .001) and National Institutes of Health funding decreased from 47% to 24% (P < .001). Inclusion of subjects >65-year-old and women increased, while inclusion of Hispanic subjects decreased (P < .001). The top 2 reasons for lack of completion included accrual and operational difficulties. A larger proportion of women, non-Hispanic subjects, and older adults were enrolled in completed trials than in those that failed completion. Conclusions: Our study is the first report on the neuro-oncology clinical trial landscape in the United States and supports the development of strategies to further improve access to these trials. Additionally, attention is needed to identify and modify other factors contributing to lack of completion.

Interpersonal violence and suicide risk: Examining buffering effects of school and community connectedness.

Background: Exposure to interpersonal violence is associated with elevated suicide risk. Preventing suicide among high-risk adolescents is most often discussed from a clinical treatment perspective, resulting in a gap in research examining whether school and community connectedness can buffer the relationships between forms of interpersonal violence and suicide risk in clinical samples of adolescents. Methods: Baseline data from 294 adolescents who received substance use treatment were analyzed to help fill this gap in research. Adolescents in this sample were at greater risk for suicidal thoughts and behaviors given their histories of substance use disorders and high rates of interpersonal violence, with 57% reporting experiencing at least one form of abuse/violence. Independent variables included lifetime exposure to physical abuse, sexual abuse, and weapon violence; moderators included various measures of school and community connectedness. Multinomial logistic regression models were estimated to examine the main and interaction effects predicting a three-category measure of suicide risk: non-suicidal, suicidal ideation only, and prior suicide attempts. Results: Sexual abuse survivors had the highest predicted probability of a prior suicide attempt when reporting lower levels of teacher support, school-based positive peer interactions, or neighborhood social connection, but at higher levels of these protective factors, their predicted probability was similar to those not exposed to sexual abuse. The same protective pattern was observed for physical abuse survivors with high neighborhood social connection. Conclusion: The buffering effects observed in this study identified dimensions of school and community social connectedness as protective factors for youth exposed to abuse. Although promoting social connectedness is often cited as a universal suicide prevention approach, tailored efforts to enhance connectedness within this population may also be a promising secondary prevention strategy. Thus, in addition to clinical treatment, more emphasis should be placed on systems-level approaches to reducing risk among youth most vulnerable to suicide.

Intensive glycaemic targets in overweight and obese individuals with gestational diabetes mellitus: clinical trial protocol for the iGDM study.

INTRODUCTION: The prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy and caesarean delivery. Women with GDM who are also overweight or obese have higher rates of pregnancy complications when compared with normal-weight women with GDM, which may occur in part due to suboptimal glycaemic control. The current recommendations for glycaemic targets in pregnant women with diabetes are based on limited evidence and exceed the mean fasting (70.9±7.8 mg/dL) and 1-hour postprandial (108.9±12.9 mg/dL) glucose values in pregnant individuals without diabetes. Our prior work demonstrated that the use of intensive (fasting <90 mg/dL and 1-hour postprandial <120 mg/dL) compared with standard (fasting <95 mg/dL and 1-hour postprandial <140 mg/dL) glycaemic targets resulted in improved glycaemic control without increasing the risk for hypoglycaemia in pregnant individuals with GDM, but the impact of intensive glycaemic targets on perinatal outcomes is unknown. METHODS AND ANALYSIS: The Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus: A Multicenter Randomized Trial (iGDM Trial) is a large, pragmatic randomised clinical trial designed to investigate the impact of intensive versus standard glycaemic targets on perinatal outcomes in women with GDM who are overweight and obese. During the 5-year project period, a multidisciplinary team of investigators from five medical centres representing regions of the USA with high rates of obesity will randomise 828 overweight and obese women with GDM to either intensive or standard glycaemic targets. We will test the central hypothesis that intensive glycaemic targets will result in lower rates of neonatal composite morbidity including large for gestational age birth weight, neonatal hypoglycaemia, respiratory distress syndrome and need for phototherapy when compared with standard glycaemic targets using the intention-to-treat approach to analysis. ETHICS AND DISSEMINATION: The Institutional Review Board (IRB) at Indiana University School of Medicine approved this study (IRB# 11435; initial approval date 25 August 2021). We will submit the results of the trial for publication in peer-reviewed journals and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT05124808.

Investigating the Interplay Between Mental Health Conditions and Social Connectedness on Suicide Risk: Findings from a Clinical Sample of Adolescents.

This study examined whether school and community connectedness buffer the relationships between mental health conditions and suicide risk in a clinical sample of adolescents with histories of substance use disorders. Data from 294 adolescents were examined, with approximately 58% reporting lifetime suicidal ideation and/or prior attempts. Multinomial logistic regression was used to examine main and interaction effects on a three-category measure of suicide risk. Depression severity and panic disorder were associated with elevated suicidal ideation risk, whereas disordered eating was associated with elevated risk of attempts. Higher school-based positive peer interactions, school safety, and neighborhood social connection levels were associated with reduced suicide attempt risk. Moderation analyses revealed that high neighborhood social connection levels may partially mitigate the elevated likelihood of attempting suicide associated with disordered eating. Findings suggest clinical populations of adolescents may benefit from approaches aiming to promote social connectedness, further supporting a comprehensive approach to suicide prevention.

Equine Embryonic Stem Cell-Derived Tenocytes are Insensitive to a Combination of Inflammatory Cytokines and Have Distinct Molecular Responses Compared to Primary Tenocytes.

Tissue fibrosis following tendon injury is a major clinical problem due to the increased risk of re-injury and limited treatment options; however, its mechanism remains unclear. Evidence suggests that insufficient resolution of inflammation contributes to fibrotic healing by disrupting tenocyte activity, with the NF-κB pathway being identified as a potential mediator. Equine embryonic stem cell (ESC) derived tenocytes may offer a potential cell-based therapy to improve tendon regeneration, but how they respond to an inflammatory environment is largely unknown. Our findings reveal for the first time that, unlike adult tenocytes, ESC-tenocytes are unaffected by IFN-γ, TNFα, and IL-1ß stimulation; producing minimal changes to tendon-associated gene expression and generating 3-D collagen gel constructs indistinguishable from unstimulated controls. Inflammatory pathway analysis found these inflammatory cytokines failed to activate NF-κB in the ESC-tenocytes. However, NF-κB could be activated to induce changes in gene expression following stimulation with NF-κB pharmaceutical activators. Transcriptomic analysis revealed differences between cytokine and NF-κB signalling components between adult and ESC-tenocytes, which may contribute to the mechanism by which ESC-tenocytes escape inflammatory stimuli. Further investigation of these molecular mechanisms will help guide novel therapies to reduce fibrosis and encourage superior tendon healing.

Modeling the global impact of reducing out-of-pocket costs for children's surgical care.

Over 1.7 billion children lack access to surgical care, mostly in low- and middle-income countries (LMICs), with substantial risks of catastrophic health expenditures (CHE) and impoverishment. Increasing interest in reducing out-of-pocket (OOP) expenditures as a tool to reduce the rate of poverty is growing. However, the impact of reducing OOP expenditures on CHE remains poorly understood. The purpose of this study was to estimate the global impact of reducing OOP expenditures for pediatric surgical care on the risk of CHE within and between countries. Our goal was to estimate the impact of reducing OOP expenditures for surgical care in children for 149 countries by modeling the risk of CHE under various scale-up scenarios using publicly available World Bank data. Scenarios included reducing OOP expenditures from baseline levels to paying 70%, 50%, 30%, and 10% of OOP expenditures. We also compared the impact of these reductions across income quintiles (poorest, poor, middle, rich, richest) and differences by country income level (low-income, lower-middle-income, upper-middle-income, and high-income countries).Reducing OOP expenditures benefited people from all countries and income quintiles, although the benefits were not equal. The risk of CHE due to a surgical procedure for children was highest in low-income countries. An unexpected observation was that upper-middle income countries were at higher risk for CHE than LMICs. The most vulnerable regions were Africa and Latin America. Across all countries, the poorest quintile had the greatest risk for CHE. Increasing interest in financial protection programs to reduce OOP expenditures is growing in many areas of global health. Reducing OOP expenditures benefited people from all countries and income quintiles, although the benefits were not equal across countries, wealth groups, or even by wealth groups within countries. Understanding these complexities is critical to develop appropriate policies to minimize the risks of poverty.