Human CD8+ T cell cross-reactivity across influenza A, B and C viruses.

Influenza A, B and C viruses (IAV, IBV and ICV, respectively) circulate globally and infect humans, with IAV and IBV causing the most severe disease. CD8+ T cells confer cross-protection against IAV strains, however the responses of CD8+ T cells to IBV and ICV are understudied. We investigated the breadth of CD8+ T cell cross-recognition and provide evidence of CD8+ T cell cross-reactivity across IAV, IBV and ICV. We identified immunodominant CD8+ T cell epitopes from IBVs that were protective in mice and found memory CD8+ T cells directed against universal and influenza-virus-type-specific epitopes in the blood and lungs of healthy humans. Lung-derived CD8+ T cells displayed tissue-resident memory phenotypes. Notably, CD38+Ki67+CD8+ effector T cells directed against novel epitopes were readily detected in IAV- or IBV-infected pediatric and adult subjects. Our study introduces a new paradigm whereby CD8+ T cells confer unprecedented cross-reactivity across all influenza viruses, a key finding for the design of universal vaccines.

A Neandertal dietary conundrum: Insights provided by tooth enamel Zn isotopes from Gabasa, Spain.

The characterization of Neandertals' diets has mostly relied on nitrogen isotope analyses of bone and tooth collagen. However, few nitrogen isotope data have been recovered from bones or teeth from Iberia due to poor collagen preservation at Paleolithic sites in the region. Zinc isotopes have been shown to be a reliable method for reconstructing trophic levels in the absence of organic matter preservation. Here, we present the results of zinc (Zn), strontium (Sr), carbon (C), and oxygen (O) isotope and trace element ratio analysis measured in dental enamel on a Pleistocene food web in Gabasa, Spain, to characterize the diet and ecology of a Middle Paleolithic Neandertal individual. Based on the extremely low δ66Zn value observed in the Neandertal's tooth enamel, our results support the interpretation of Neandertals as carnivores as already suggested by δ15N isotope values of specimens from other regions. Further work could help identify if such isotopic peculiarities (lowest δ66Zn and highest δ15N of the food web) are due to a metabolic and/or dietary specificity of the Neandertals.

Training labor and treatment behavior: Evidence from physician residency programs.

Public and private investments in physician human capital support a healthcare workforce to provide future medical services nationwide. Yet, little is known about how introducing training labor influences hospitals' provision of care. We leverage all-payer data and emergency medicine (EM) and obstetrics (OBGYN) residency program debuts to estimate local access and treatment intensity effects. We find that the introduction of EM programs coincides with less treatment intensity and suggestive increases in throughput. OBGYN programs adopt the pre-existing surgical tendencies of the hospital but may also relax some capacity constraints-allowing the marginal mother to avoid a riskier nearby hospital.

Prevalence of Buprenorphine Providers Requiring Cash Payment From Insured Women Seeking Opioid Use Disorder Treatment.

CONTEXT: Medications for opioid use disorder (OUD) are known to be effective, especially in reducing the risk of overdose death. Yet, many individuals suffering from OUD are not receiving treatment. One potential barrier can be the patient's ability to access providers through their insurance plans. DATA AND METHODS: We used an audit (simulated patient) study methodology to examine appointment-granting behavior by buprenorphine prescribers in 10 different US states. Trained callers posed as women with OUD and were randomly assigned Medicaid or private insurance status. Callers request an OUD treatment appointment and then asked whether they would be able to use their insurance to cover the cost of care, or alternatively, whether they would be required to pay fully out-of-pocket. FINDINGS: We found that Medicaid and privately insured women were often asked to pay cash for OUD treatment--40% of the time over the full study sample. Such buprenorphine provider requests happened more than 60% of the time in some states. Areas with more providers or with more generous provider payments were not obviously more willing to accept the patient's insurance benefits for OUD treatment. Rural providers were less likely to require payment in cash in order for the woman to receive care. CONCLUSIONS: State-to-state variation was the most striking pattern in our field experiment data. The wide variation suggests that women of reproductive age with OUD in certain states face even greater challenges to treatment access than perhaps previously thought; however, it also reveals that some states have found ways to curtail this problem. Our findings encourage greater attention to this public health challenge and possibly opportunities for shared learning across states.

County-level Factors and Treatment Access Among Insured Women With Opioid Use Disorder.

BACKGROUND: An over 40% increase in overdose deaths within the past 2 years and low levels of engagement in treatment call for a better understanding of factors that influence access to medication for opioid use disorder (OUD). OBJECTIVE: To examine whether county-level characteristics influence a caller's ability to secure an appointment with an OUD treatment practitioner, either a buprenorphine-waivered prescriber or an opioid treatment program (OTP). RESEARCH DESIGN AND SUBJECTS: We leveraged data from a randomized field experiment comprised of simulated pregnant and nonpregnant women of reproductive age seeking treatment for OUD among 10 states in the US. We employed a mixed-effects logistic regression model with random intercepts for counties to examine the relationship between appointments received and salient county-level factors related to OUD. MEASURES: Our primary outcome was the caller's ability to secure an appointment with an OUD treatment practitioner. County-level predictor variables included socioeconomic disadvantage rankings, rurality, and OUD treatment/practitioner density. RESULTS: Our sample comprised 3956 reproductive-aged callers; 86% reached a buprenorphine-waivered prescriber and 14% an OTP. We found that 1 additional OTP per 100,000 population was associated with an increase (OR=1.36, 95% CI: 1.08 to 1.71) in the likelihood that a nonpregnant caller receives an OUD treatment appointment from any practitioner. CONCLUSIONS: When OTPs are highly concentrated within a county, women of reproductive age with OUD have an easier time securing an appointment with any practitioner. This finding may suggest greater practitioners' comfort in prescribing when there are robust OUD specialty safety nets in the county.

Three-year results from phase I of ZUMA-4: KTE-X19 in pediatric relapsed/refractory acute lymphoblastic leukemia.

Here we present the 3-year results of ZUMA-4, a phase I/II multicenter study evaluating the safety and efficacy of KTEX19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Phase I explored two dose levels and formulations. The primary endpoint was the incidence of dose-limiting toxicities. Thirty-one patients were enrolled; KTE-X19 was administered to 24 patients (median age 13.5 years, range 3-20; median follow-up 36.1 months). No dose-limiting toxicities were observed. All treated patients had grade ≥3 adverse events, commonly hypotension (50%) and anemia (42%). Grade 3 cytokine release syndrome rates were 33% in all treated patients, 75% in patients given the dose of 2×106 CAR T cells/kg, 27% in patients given the dose of 1×106 cells/kg in the 68 mL formulation, and 22% in patients given the dose of 1×106 cells/kg in the 40 mL formulation; the percentages of patients experiencing grade ≥3 neurologic events were 21%, 25%, 27%, and 11% respectively. Overall complete remission rates (including complete remission with incomplete hematologic recovery) were 67% in all treated patients, 75% in patients given 2×106 CAR T cells/kg, 64% in patients given 1×106 cells/kg in the 68 mL formulation, and 67% in patients given 1×106 cells/kg in the 40 mL formulation. Overall minimal residual diseasenegativity rates were 100% among responders; 88% of responders underwent subsequent allogeneic stem-cell transplantation. In the 1×106 (40 mL) group (recommended phase II dose), the median duration of remission censored at allogeneic stem-cell transplantation and median overall survival were not reached. Pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia achieved high minimal residual disease-negative remission rates with a manageable safety profile after a single dose of KTE-X19. Phase II of the study is ongoing at the dose of 1×106 CAR T cells/kg in the 40 mL formulation. ClinicalTrials.gov: NCT02625480.

Genetic origins of the Minoans and Mycenaeans.

The origins of the Bronze Age Minoan and Mycenaean cultures have puzzled archaeologists for more than a century. We have assembled genome-wide data from 19 ancient individuals, including Minoans from Crete, Mycenaeans from mainland Greece, and their eastern neighbours from southwestern Anatolia. Here we show that Minoans and Mycenaeans were genetically similar, having at least three-quarters of their ancestry from the first Neolithic farmers of western Anatolia and the Aegean, and most of the remainder from ancient populations related to those of the Caucasus and Iran. However, the Mycenaeans differed from Minoans in deriving additional ancestry from an ultimate source related to the hunter-gatherers of eastern Europe and Siberia, introduced via a proximal source related to the inhabitants of either the Eurasian steppe or Armenia. Modern Greeks resemble the Mycenaeans, but with some additional dilution of the Early Neolithic ancestry. Our results support the idea of continuity but not isolation in the history of populations of the Aegean, before and after the time of its earliest civilizations.

Dance movement therapy for dementia.

BACKGROUND: Dementia is a syndrome of acquired cognitive impairment which is severe enough to interfere with independent living. Over the course of the illness, people with dementia also experience changes in emotions, behaviour and social relationships. According to Alzheimer's Disease International, dementia affects approximately 55 million people worldwide. The latest NICE guideline for dementia highlights the value of diverse treatment options for the different stages and symptoms of dementia, including non-pharmacological treatments. Relevant literature also argues for the value of interventions that acknowledge the complexity of the condition and address the person as a whole, including their physical, emotional, social and cognitive processes. A growing literature highlights the capacity of the arts and has embodied practices to address this complexity. Dance movement therapy (DMT) is an embodied psychological intervention that can address complexity and thus may be useful for people with dementia, but its effectiveness remains unclear. OBJECTIVES: To assess the effects of dance movement therapy on behavioural, social, cognitive and emotional symptoms of people with dementia in comparison to no treatment, standard care or any other treatment. Also, to compare different forms of dance movement therapy (e.g. Laban-based dance movement therapy, Chacian dance movement therapy or Authentic Movement) SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (Clarivate), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization's meta-register of the International Clinical Trials Registry Portal until 8 December 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that included people with dementia, of any age and in any setting. The DMT intervention had to be delivered by a dance movement therapy practitioner who (i) had received formal training (ii) was a dance movement therapist in training or (iii) was otherwise recognised as a dance movement therapist in the country in which the study was conducted. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data and evaluated methodological quality. We expressed effect estimates using the mean difference (MD) between intervention groups and presented associated confidence intervals (CIs). We used GRADE methods to rate our certainty in the results. MAIN RESULTS: We found only one study eligible for inclusion in this review. This was a 3-arm parallel-group RCT conducted in Hong Kong involving 204 adults with mild neurocognitive disorder or dementia. The study examined the effects of short-term (12 weeks) group DMT in comparison with exercise and a waiting-list control group immediately post-intervention and three and nine months later. We found that, at the end of the intervention, DMT may result in little to no difference in neuropsychiatric symptoms assessed with the 12-item Neuropsychiatric Inventory when compared with waiting list (MD 0.3, 95% CI -0.96 to 1.56; low-certainty evidence) or exercise (MD -0.30, 95% CI -1.83 to 1.23; low-certainty evidence). Nor was there any evidence of effects at later time points. Cognitive functioning was assessed with a variety of instruments and there were no statistically significant between-group differences (low-certainty evidence). When compared to exercise or waiting list, DMT may result in little to no difference in cognitive function immediately after the intervention or at follow-up. In comparison to waiting list, DMT may result in a slight reduction in depression assessed with the 4-item Geriatric Depression Scale at the end of therapy (MD -0.60, 95% CI -0.96 to -0.24; low-certainty evidence). This slight positive effect of DMT on depression scores was sustained at three and nine months after the completion of the intervention. DMT may also reduce depression slightly in comparison with exercise at the end of therapy (MD -0.40, 95% CI -0.76 to -0.04, low-certainty evidence), an effect also sustained at three and nine months. Our fourth primary outcome, quality of life, was not assessed in the included study. There were data for two of our secondary outcomes, social and occupational functioning and dropouts (which we used as a proxy for acceptability), but in both cases the evidence was of very low certainty and hence our confidence in the results was very low. For all outcomes, we considered the certainty of the evidence in relation to our review objectives to be low or very low in GRADE terms due to indirectness (because not all participants in the included study had a diagnosis of dementia) and imprecision. AUTHORS' CONCLUSIONS: This review included one RCT with a low risk of bias. Due to the low certainty of the evidence, the true effects of DMT as an intervention for dementia may be substantially different from those found. More RCTs are needed to determine with any confidence whether DMT has beneficial effects on dementia.

"The Perception of Visiting Holocaust Sites on Undergraduate Students Learning Process".

This paper presents the main findings of a qualitative research project. The aim of the research was to explore undergraduate students' perceived knowledge acquisition and awareness of the Holocaust, after visiting Auschwitz concentration camp in Poland. The qualitative study (focus groups & semi-structured questionnaires) involved three cohorts of students and lecturers from a university in the North West of England. The participants visited the Holocaust-related sites in Poland from 2016 to 2019. Findings indicate that students' who actively engaged in visits to Holocaust related sites developed knowledge and awareness of the Holocaust. For many participants, this knowledge and awareness was facilitated via a reflective process that enabled empathic connection between these historical events and the students. The study also highlighted practical strategies that could be implemented to enhance the experience for future cohorts of undergraduate students visiting holocaust related sites. By adding to the limited literature on Holocaust education with undergraduate students, the study highlighted the importance and directions for future research in this area to inform future pedagogic practice.

Impact of isolation method on cellular activation and presence of specific tendon cell subpopulations during in vitro culture.

Tendon injuries are common and heal poorly, due in part to a lack of understanding of fundamental tendon cell biology. A major impediment to the study of tendon cells is the absence of robust, well-characterized in vitro models. Unlike other tissue systems, current tendon cell models do not account for how differences in isolation methodology may affect the activation state of tendon cells or the presence of various tendon cell subpopulations. The objective of this study was to characterize how common isolation methods affect the behavior, fate, and lineage composition of tendon cell cultures. Tendon cells isolated by explant exhibited reduced proliferative capacity, decreased expression of tendon marker genes, and increased expression of genes associated with fibroblast activation compared to digested cells. Consistently, explanted cells also displayed an increased propensity to differentiate to myofibroblasts compared to digested cells. Explanted cultures from multiple different tendons were substantially enriched for the presence of scleraxis-lineage (Scx-lin+) cells compared to digested cultures, while the overall percentage of S100a4-lineage (S100a4-lin+) cells was dependent on both isolation method and tendon of origin. Neither isolation methods preserved the ratios of Scx-lin+ or S100a4-lin+ to non-lineage cells seen in tendons in vivo. Combined, these data indicate that further refinement of in vitro cultures models is required in order to more accurately understand the effects of various stimuli on tendon cell behavior. Statement of clinical significance: The development of informed in vitro tendon cell models will facilitate enhanced screening of potential therapeutic candidates to improve tendon healing.

Micro-punches versus micro-slices for serial sampling of human dentine: Striking a balance between improved temporal resolution and measuring additional isotope systems.

RATIONALE: The last decade has seen a dramatic increase in the application of serial sampling of human dentine in archaeology. Rapid development in the field has provided many improvements in the methodology, in terms of both time resolution as well as the ability to integrate more isotope systems in the analysis. This study provides a comparison of two common sampling approaches, allowing researchers to select the most suitable approach for addressing specific research questions. METHODS: Two common approaches for sequential sampling of human dentine (micro-punches and micro-slices) are compared in terms of viability and efficacy. Using archaeological deciduous second molars and permanent first molars, this study demonstrates how the two approaches capture aspects of the weaning process in different ways. In addition, different aspects related to the extraction protocols, such as the thickness of the central slide and the solubilisation step, are also evaluated. RESULTS: While both approaches show similar intra-tooth isotopic patterns, the micro-punches approach is preferable for research that requires a very fine temporal resolution, while the micro-slices approach is best for research where δ34 S values are needed, or when the samples are poorly preserved. In addition, the solubilisation step has a large effect on collagen yield, and, to a lesser extent, on isotopic compositions. Therefore, it is important to ensure that only samples that have undergone the same pre-treatment protocol are directly compared. CONCLUSIONS: We present the pros and cons of the two micro-sampling approaches and offer possible mitigation strategies to address some of the most important issues related to each approach.

Exceptionally high δ15N values in collagen single amino acids confirm Neandertals as high-trophic level carnivores.

Isotope and archeological analyses of Paleolithic food webs have suggested that Neandertal subsistence relied mainly on the consumption of large herbivores. This conclusion was primarily based on elevated nitrogen isotope ratios in Neandertal bone collagen and has been significantly debated. This discussion relies on the observation that similar high nitrogen isotopes values could also be the result of the consumption of mammoths, young animals, putrid meat, cooked food, freshwater fish, carnivores, or mushrooms. Recently, compound-specific C and N isotope analyses of bone collagen amino acids have been demonstrated to add significantly more information about trophic levels and aquatic food consumption. We undertook single amino acid C and N isotope analysis on two Neandertals, which were characterized by exceptionally high N isotope ratios in their bulk bone or tooth collagen. We report here both C and N isotope ratios on single amino acids of collagen samples for these two Neandertals and associated fauna. The samples come from two sites dating to the Middle to Upper Paleolithic transition period (Les Cottés and Grotte du Renne, France). Our results reinforce the interpretation of Neandertal dietary adaptations as successful top-level carnivores, even after the arrival of modern humans in Europe. They also demonstrate that high δ15N values of bone collagen can solely be explained by mammal meat consumption, as supported by archeological and zooarcheological evidence, without necessarily invoking explanations including the processing of food (cooking, fermenting), the consumption of mammoths or young mammals, or additional (freshwater fish, mushrooms) dietary protein sources.

Association between physician practice Medicaid acceptance and employing nurse practitioners and physician assistants: A longitudinal analysis.

BACKGROUND: Access to care is often a challenge for Medicaid beneficiaries due to low practice participation. As demand increases, practices will likely look for ways to see Medicaid patients while keeping costs low. Employing nurse practitioners (NPs) and physician assistants (PAs) is one low-cost and effective means to achieve this. However, there are no longitudinal studies examining the relationship between practice Medicaid acceptance and NP/PA employment. PURPOSE: The purpose of this study was to examine the association of practice Medicaid acceptance with NP/PA employment over time. METHODS: Using SK&A data (2009-2015), we constructed a panel of 102,453 unique physician practices to assess for changes in Medicaid acceptance after newly employing NPs and PAs. We employed practice-level fixed effects linear regressions. RESULTS: Our results showed that, among practices employing both NPs and PAs, there was a roughly 2% increase in the likelihood of Medicaid participation over time. When stratifying our sample by practice size and specialty, the positive correlation localized to small primary care and medical practices. When both NPs and PAs were present, small primary care practices had a 3.3% increase and small medical practices had a 6.9% increase in the likelihood of accepting Medicaid. CONCLUSION: NP and PA employment was positively associated with increases in Medicaid participation. PRACTICE IMPLICATIONS: As more individuals gain coverage under Medicaid, organizations will need to decide how to adapt to greater patient demand. Our results suggest that hiring NPs and PAs may be a potential lower cost strategy to accommodate new Medicaid patients.

Dietary evidence from Central Asian Neanderthals: A combined isotope and plant microremains approach at Chagyrskaya Cave (Altai, Russia).

Neanderthals are known primarily from their habitation of Western Eurasia, but they also populated large expanses of Northern Asia for thousands of years. Owing to a sparse archaeological record, relatively little is known about these eastern Neanderthal populations. Unlike in their western range, there are limited zooarchaeological and paleobotanical studies that inform us about the nature of their subsistence. Here, we perform a combined analysis of carbon and nitrogen stable isotopes on bone collagen and microbotanical remains in dental calculus to reconstruct the diet of eastern Neanderthals at Chagyrskaya Cave in the Altai Mountains of Southern Siberia, Russia. Stable isotopes identify one individual as possessing a high trophic level due to the hunting of large- and medium-sized ungulates, while the analysis of dental calculus also indicates the presence of plants in the diet of this individual and others from the site. These findings indicate eastern Neanderthals may have had broadly similar subsistence patterns to those elsewhere in their range.

Immune tolerance induction in severe haemophilia A: A UKHCDO inhibitor and paediatric working party consensus update.

INTRODUCTION: In good risk patients (historic inhibitor peak < 200BU), the International Immune Tolerance Study demonstrated equal efficacy to induce tolerance between high (200iu/kg/day) and low dose (50iu/kg ×3 times/week) immune tolerance induction (ITI) regimens. However, the trial stopped early on account of the excessive bleed rate in the low dose ITI arm. METHODS: United Kingdom Haemophilia Centre Doctors' Organization (UKHCDO) Paediatric and Inhibitor working parties considered available ITI data alongside the bi-phenotypic antibody emicizumab (Hemlibra®) efficacy and safety data to develop a consensus guideline for the future UK ITI guideline. RESULTS: This revision of UKHCDO ITI guidance incorporates the recommendation to use emicizumab as a prophylaxis haemostatic agent to reduce bleeding rates and to facilitate low dose and reduced frequency of FVIII CFC for ITI in the majority of children. CONCLUSION: This consensus protocol will facilitate future evaluation of ITI outcomes in the evolving landscape of haemophilia therapeutics and ITI strategies.

Private coverage mandates, business cycles, and provider treatment intensity.

The Affordable Care Act (ACA) is the source of multiple large-scale health insurance expansions affecting various segments of the US population. Although much has been done to quantify the first-order effects of these policies, less empirical investigation has been devoted to the effects on the supply-side of health care. We focus on a well-known ACA initiative (the young adult dependent coverage mandate) to offer novel evidence on two fronts: the policy's heterogeneous effect across different labor markets and the potential for the policy-induced shift in payer mix to influence provider treatment decisions. First, we show that the federal mandate's direct effect on young adult private insurance take-up is strongly mitigated by the Great Recession. Second, we demonstrate that providers do not treat young adults more aggressively when more of them hold private coverage. Policymakers should keep these broader considerations and more diffuse risk protection implications in mind when contemplating changes to the law.

Prenatal metal mixtures and fetal size in mid-pregnancy in the MADRES study.

BACKGROUND: Fetal growth is predictive of health later in life. Both toxic and essential metals influence fetal growth, but most studies have focused on these elements individually and used birth weight as an indicator of fetal growth. The objective of the current study was to investigate the impact of a mixture of metals on fetal size in mid-pregnancy in a predominately lower income Hispanic pregnancy cohort in Los Angeles. METHODS: For our primary analysis, we focused on six elements that have previously been associated individually with fetal size, including arsenic (As), barium (Ba), cadmium (Cd), mercury (Hg), molybdenum (Mo), and tin (Sn), measured in maternal urine samples collected in early pregnancy (median: 12.4 weeks gestation). In an exploratory analysis, we additionally included cobalt (Co), nickel (Ni), antimony (Sb), and thallium (Tl). Using covariate-adjusted Bayesian Kernel Machine Regression (BKMR) as our main mixture modeling approach, we examined the impact of these metals on fetal biometry measures obtained between 18 and 22 weeks gestation, with a focus on estimated fetal weight (EFW). RESULTS: BKMR identified Mo and Ba as the mixture components that contributed most to associations with EFW. Linear associations were observed for both metals. An increase in Mo from the 25th to 75th percentile was associated with a 0.114 (95% credible interval (CI): 0.019, 0.247) SD higher EFW, equivalent to a 7.4 g difference. Similar associations were observed between Mo and the other fetal measures evaluated. In contrast, an increase in Ba from the 25th to 75th percentile was associated with a -0.076 (95% CI: 0.217, 0.066) SD lower EFW, equivalent to a 4.9 g difference. Similar inverse associations were observed for Ba in relation to abdominal circumference and biparietal diameter. BKMR also identified a possible interaction between Ba and Mo in relation to head circumference, suggesting that the positive associations between Mo and this outcome may be attenuated at high levels of Ba, which was consistent with findings from linear regression (Pinteraction = 0.03). In an exploratory analysis accounting for a larger mixture of metals, Mo and Ba consistently contributed most to associations with EFW. An inverse association was also identified between Sb and EFW. CONCLUSIONS: Our results suggest that Mo may promote fetal growth, while Ba and Sb may reduce fetal growth, in this population.

In Pursuit of an Opioid-Free Pediatric Ambulatory Surgery Center: A Quality Improvement Initiative.

BACKGROUND: Opioids have been a central component of routine adult and pediatric anesthesia for decades. However, the long-term effects of perioperative opioids are concerning. Recent studies show a 4.8%-6.5% incidence of persistent opioid use after surgery in older children and adults. This means that >2 million of the 50 million patients undergoing elective surgeries in the United States each year are likely to develop persistent opioid use. With this in mind, anesthesiologists at Bellevue Clinic and Surgery Center assembled an interdisciplinary quality improvement team focused on 2 goals: (1) develop effective anesthesia protocols that minimize perioperative opioids and (2) add value to clinical services by maintaining or improving perioperative outcomes while reducing costs. This article describes our project and findings but does not attempt to make inferences or generalizations about populations outside our facility. METHODS: We performed a large-scale implementation of opioid-sparing protocols at our standalone pediatric clinic and ambulatory surgery facility, based in part on the prior success of our previously published tonsillectomy and adenoidectomy protocol. Multiple Plan-Do-Study-Act cycles were performed using data captured from the electronic medical record. The percentage of surgical patients receiving intraoperative opioids and postoperative morphine preintervention and postintervention were compared. The following measures were evaluated using statistical process control charts: maximum postoperative pain score, postoperative morphine rescue rate, total postanesthesia care unit minutes, total anesthesia minutes, and postoperative nausea and vomiting rescue rate. Intraoperative analgesic costs were calculated. RESULTS: Between January 2017 and June 2019, 10,948 surgeries were performed at Bellevue, with 10,733 cases included in the analyses. Between December 2017 and June 2019, intraoperative opioid administration at our institution decreased from 84% to 8%, and postoperative morphine administration declined from 11% to 6% using analgesics such as dexmedetomidine, nonsteroidal anti-inflammatory drugs, and regional anesthesia. Postoperative nausea and vomiting rescue rate decreased, while maximum postoperative pain scores, total anesthesia minutes, and total postanesthesia care unit minutes remained stable per control chart analyses. Costs improved. CONCLUSIONS: By utilizing dexmedetomidine, nonsteroidal anti-inflammatory drugs, and regional anesthesia for pediatric ambulatory surgeries at our facility, perioperative opioids were minimized without compromising patient outcomes or value.

The effects of high oxygen partial pressure on vegetable Allium seeds with a short shelf-life.

MAIN CONCLUSION: Storage at an elevated partial pressure of oxygen and classical artificial ageing cause a rapid loss of seed viability of short-lived vegetable seeds. Prolonging seed longevity during storage is of major importance for gene banks and the horticultural industry. Slowing down biochemical deterioration, including oxygen-dependent deterioration caused by oxidative processes can boost longevity. This can be affected by the seed structure and the oxygen permeability of seed coat layers. Classical artificial seed ageing assays are used to estimate seed 'shelf-life' by mimicking seed ageing via incubating seeds at elevated temperature and elevated relative humidity (causing elevated equilibrium seed moisture content). In this study, we show that seed lots of vegetable Allium species are short-lived both during dry storage for several months and in seed ageing assays at elevated seed moisture levels. Micromorphological analysis of the Allium cepa x Allium fistulosum salad onion seed identified intact seed coat and endosperm layers. Allium seeds equilibrated at 70% relative humidity were used to investigate seed ageing at tenfold elevated partial pressure of oxygen (high pO2) at room temperature (22 ºC) in comparison to classical artificial ageing at elevated temperature (42 ºC). Our results reveal that 30 days high pO2 treatment causes a rapid loss of seed viability which quantitatively corresponded to the seed viability loss observed by ~ 7 days classical artificial ageing. A similar number of normal seedlings develop from the germinating (viable) proportion of seeds in the population. Many long-lived seeds first exhibit a seed vigour loss, evident from a reduced germination speed, preceding the loss in seed viability. In contrast to this, seed ageing of our short-lived Allium vegetable seems to be characterised by a rapid loss in seed viability.

Evidence that reduction in volume protects in situ articular chondrocytes from mechanical impact.

Chondrocytes, the resident cells in articular cartilage, carry the burden of producing and maintaining the extracellular matrix (ECM). However, as these cells have a low proliferative capacity and are not readily replaced, chondrocyte death due to extreme forces may contribute to the pathogenesis of osteoarthritis (OA) after injury or may inhibit healing after osteochondral transplantation, a restorative procedure for damaged cartilage that requires a series of mechanical impacts to insert the graft. Consequently, there is a need to understand what factors influence the vulnerability of in situ chondrocytes to mechanical trauma. To this end, the objective of this study was to investigate how altering cell volume by different means (hydrostatic pressure, uniaxial load, and osmotic challenge with and without inhibition of regulatory volume decrease) affects the vulnerability of in situ chondrocytes to extreme mechanical forces. Using a custom experimental platform enabling testing of viable and intact murine cartilage-on-bone explants, we established a strong correlation between chondrocyte volume and vulnerability to impact injury wherein reduced volume was protective. Moreover, we found that the volume-perturbing interventions did not affect cartilage ECM mechanical properties, suggesting that their effects on chondrocyte vulnerability occurred at the cellular level. The findings of this study offer new avenues for novel strategies aimed at preventing chondrocyte loss during osteochondral grafting or to halting the progression of cell death after a joint destabilizing injury.