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BACKGROUND: Persons who speak languages other than English are underrepresented in clinical trials, likely in part because of inadequate multilevel resources. We conducted a survey of institutions affiliated with the Childrens Oncology Group (COG) to characterize current research recruitment practices and resources regarding translation and interpretation services. METHODS: In October 2022, a 20-item survey was distributed electronically to institutions affiliated with COG to assess consent practices and resources for recruiting participants who speak languages other than English to COG trials. Descriptive statistics were used to summarize responses; responses were compared by institution size and type as well as respondent role. RESULTS: The survey was sent to 230 institutions, and the response rate was 60% (n = 139). In total, 60% (n = 83) of those respondents had access to short-form consent forms. Full consent form translation was required at 50% of institutions, and 12% of institutional review boards restricted use of centrally translated consent forms. Forty-six percent (n = 64) of institutions reported insufficient funding to support translation costs; 19% (n = 26) had access to no-cost translation services. Forty-four percent (n = 61) were required to use in-person interpreters for consent discussions; the most frequently cited barrier (56%) to obtaining consent was lack of available in-person interpreters. Forty-seven percent (n = 65) reported that recruiting persons who speak languages other than English to clinical trials was somewhat or very difficult. CONCLUSIONS: Institutions affiliated with COG face resource-specific challenges that impede recruitment of participants who speak languages other than English for clinical trials. These findings indicate an urgent need to identify strategies aimed at reducing recruitment barriers to ensure equitable access to clinical trials.

Abstract Background Most insects are poikilotherms and ectotherms, so their body temperature is predicated by environmental temperature. With climate change, insect body temperature is rising, which affects how insects develop, survive, and respond to infection. Aging also affects insect physiology by deteriorating body condition and weakening immune proficiency via senescence. Aging is usually considered in terms of time, or chronological age, but it can also be conceptualized in terms of body function, or physiological age. We hypothesized that warmer temperature decouples chronological and physiological age in insects by accelerating senescence. To investigate this, we reared the African malaria mosquito, Anopheles gambiae, at 27 °C, 30 °C and 32 °C, and measured survival starting at 1-, 5-, 10- and 15-days of adulthood after no manipulation, injury, or a hemocoelic infection with Escherichia coli or Micrococcus luteus. Then, we measured the intensity of an E. coli infection to determine how the interaction between environmental temperature and aging shapes a mosquito’s response to infection. Results We demonstrate that longevity declines when a mosquito is infected with bacteria, mosquitoes have shorter lifespans when the temperature is warmer, older mosquitoes are more likely to die, and warmer temperature marginally accelerates the aging-dependent decline in survival. Furthermore, we discovered that E. coli infection intensity increases when the temperature is warmer and with aging, and that warmer temperature accelerates the aging-dependent increase in infection intensity. Finally, we uncovered that warmer temperature affects both bacterial and mosquito physiology. Conclusions Warmer environmental temperature accelerates aging in mosquitoes, negatively affecting both longevity and infection outcomes. These findings have implications for how insects will serve as pollinators, agricultural pests, and disease vectors in our warming world.

ABSTRACTInhalation of ambient particulate matter (PM) can disrupt the gut microbiome, while exercise independently influences the gut microbiome by promoting beneficial bacteria. In this study, we analyzed changes in gut microbial diversity and composition in response to combined interventions of PM exposure and aerobic exercise, extending up to 12 weeks. This investigation was conducted using mice, categorized into five groups: control group (Con), exercise group (EXE), exercise group followed by 3-day exposure to PM (EXE + 3-day PM), particulate matter exposure (PM), and PM exposure with concurrent treadmill exercise (PME). Notably, the PM group exhibited markedly lower alpha diversity and richness compared to the Con group and our analysis of beta diversity revealed significant variations among the intervention groups. Members of the Lachnospiraceae family showed significant enhancement in the exercise intervention groups (EXE and PME) compared to the Con and PM groups. The biomarker Lactobacillus, Coriobacteraceae, and Anaerofustis were enriched in the EXE group, while Desulfovibrionaceae, Mucispirillum schaedleri, Lactococcus and Anaeroplasma were highly enriched in the PM group. Differential abundance analysis revealed that Paraprevotella, Bacteroides, and Blautia were less abundant in the 12-week PM exposure group than in the 3-day PM exposure group. Moreover, both the 3-day and 12-week PM exposure groups exhibited a reduced relative abundance of Bacteroides uniformis, SMB53, and Staphylococcus compared to non-PM exposure groups. These findings will help delineate the possible roles and associations of altered microbiota resulting from the studied interventions, paving the way for future mechanistic research.

Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent public health threat, according to the CDC. This pathogen has few treatment options and causes severe nosocomial infections with > 50% fatality rate. Although previous studies have examined the proteome of CRAb, there have been no focused analyses of dynamic changes to β-lactamase expression that may occur due to drug exposure. Here, we present our initial proteomic study of variation in β-lactamase expression that occurs in CRAb with different β-lactam antibiotics. Briefly, drug resistance to Ab (ATCC 19606) was induced by the administration of various classes of β-lactam antibiotics, and the cell-free supernatant was isolated, concentrated, separated by SDS-PAGE, digested with trypsin, and identified by label-free LC-MS-based quantitative proteomics. Thirteen proteins were identified and evaluated using a 1789 sequence database of Ab β-lactamases from UniProt, the majority of which were Class C β-lactamases (≥ 80%). Importantly, different antibiotics, even those of the same class (e.g. penicillin and amoxicillin), induced non-equivalent responses comprising various isoforms of Class C and D serine-β-lactamases, resulting in unique resistomes. These results open the door to a new approach of analyzing and studying the problem of multi-drug resistance in bacteria that rely strongly on β-lactamase expression.

Lysine succinylation (Ksu) has recently emerged as a protein modification that regulates diverse functions in various biological processes. However, the systemically and precise role of lysine succinylation in erythropoiesis remains to be fully elucidated. In this study, we noted a prominent increase of succinyl-CoA and lysine succinylation during human erythroid differentiation. To explore the functional significance of succinylation, we inhibited succinylation by either knock downing key succinyltransferases or overexpressing desuccinylases. Succinylation inhibition led to suppressed cell proliferation, increased apoptosis, and disrupted erythroid differentiation. In vivo overexpression of the desuccinylases SIRT5 delayed erythroid differentiation. Furthermore, integrative proteome and succinylome analysis identifies 939 succinylated proteins with 3,562 Ksu sites, distributed across various cellular compartments and involved in multiple cellular processes. Significantly, inconsistencies between protein expression levels and succinylation levels were observed, indicating that the succinylation of certain proteins may function independently of expression. Mechanistically, we implicated KAT2A-mediated succinylation of histone H3 K79, leading to chromatin remodeling and subsequently erythropoiesis regulation. Specially, we identified CYCS as a key regulator of erythropoiesis, which depends on its succinylation sites K28/K40. Taken together, our comprehensive investigation of the succinylation landscape during erythropoiesis provides valuable insights into its regulatory role and offer potential implications for erythroid-related diseases.

Background. Organ donation registration rates in the United States are lowest among Asian Americans. This study aimed to investigate the reasons for low organ donation registration rates among Asian Americans and develop educational material to help improve organ donation rates and awareness. Methods. We conducted a 2-phase study. In phase 1, a cross-sectional observational survey was distributed in-person on an iPad to members of the Asian community in Queens, New York, to investigate their knowledge, attitudes, and beliefs toward organ donation. Based on the results, an educational video was developed, and the efficacy of the video was assessed with an independent cohort of participants in phase 2 using a pre-/post-video comprehension assessment survey. Results. Among 514 Chinese or Korean Americans who participated in the phase 1 survey, 97 participants (19%) reported being registered organ donors. Registered donors were more likely to have previously discussed their organ donation wishes with their family (adjusted odds ratio [aOR], 4.77; 95% confidence interval [CI], 2.56-8.85; P

OBJECTIVES:. Our study aimed to assess the time to positivity (TTP) of clinically significant blood cultures in critically ill children admitted to the PICU. DESIGN:. Retrospective review of positive blood cultures in patients admitted or transferred to the PICU. SETTING:. Large tertiary-care medical center with over 90 PICU beds. PATIENTS:. Patients 0–20 years old with bacteremia admitted or transferred to the PICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. The primary endpoint was the TTP, defined as time from blood culture draw to initial Gram stain result. Secondary endpoints included percentage of cultures reported by elapsed time, as well as the impact of pathogen and host immune status on TTP. Host immune status was classified as previously healthy, standard risk, or immunocompromised. Linear regression for TTP was performed to account for age, blood volume, and Gram stain. Among 164 episodes of clinically significant bacteremia, the median TTP was 13.3 hours (interquartile range, 10.7–16.8 hr). Enterobacterales, Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus pneumoniae were most commonly identified. By 12, 24, 36, and 48 hours, 37%, 89%, 95%, and 97% of positive cultures had resulted positive, respectively. Median TTP stratified by host immune status was 13.2 hours for previously healthy patients, 14.0 hours for those considered standard risk, and 10.6 hours for immunocompromised patients (p = 0.001). Median TTP was found to be independent of blood volume. No difference was seen in TTP for Gram-negative vs. Gram-positive organisms (12.2 vs. 13.9 hr; p = 0.2). CONCLUSIONS:. Among critically ill children, 95% of clinically significant blood cultures had an initial positive result within 36 hours, regardless of host immune status. Need for antimicrobial therapy should be frequently reassessed and implementation of a shorter duration of empiric antibiotics should be considered in patients with low suspicion for infection.

PurposeRepeated mild traumatic brain injuries (mTBI) are a continuing healthcare concern worldwide, given its potential for enduring adverse neurodegenerative conditions. Past research suggests a potential protective effect of n-3 polyunsaturated fatty acids (PUFA) in experimental models of mTBI. The aim of this study was to investigate whether the neuroprotective benefits of n-3 PUFA persist following repetitive weight drop injury (WDI).MethodsMale fat-1 mice (n = 12), able to endogenously convert n-6 PUFA to n-3 PUFA, and their wild type (WT) counterparts (n = 12) were maintained on a 10% w/w safflower diet. At 9–10 weeks of age, both groups received one mild low-impact WDI on the closed cranium daily, for three consecutive days. Following each WDI, time to righting reflex and seeking behaviour were measured. Neurological recovery, cognitive, motor, and neurobehavioural outcomes were assessed using the Neurological Severity Score (NSS) over 7 days (168 h) post-last WDI. Brains were assessed for cerebral microhemorrhages by Prussian blue and cellular damage by glial fibrillary acidic protein (GFAP) staining.ResultsFat-1 mice exhibited significantly faster righting reflex and seeking behaviour time, and lower mean NSS scores and at all post-WDI time points (p ≤ 0.05) compared to WT mice. Immunohistochemistry showed no significant difference in presence of cerebral microhemorrhage however, fat-1 mice had significantly lower GFAP staining in comparison to WT mice (p ≤ 0.05).Conclusionn-3 PUFA is effective in restoring cognitive, motor, and behavioural function after repetitive WDI, which may be mediated through reduced cellular damage of the brain.

Social work education is considered an important venue for advancing the field's commitment to anti-racism. This research employed collective autobiographical methods within a Critical Race Theory framework to explore Black social work students' experiences of anti-Black racism in the learning environment of a Predominantly White Institution. Data was analyzed through a collaborative, inductive approach. Analysis revealed four interrelated themes: 1) racial microaggressions directed at Black students; 2) the perceived complicity of school administration in maintaining a racist environment; 3) the harm that an anti-Black racist learning environment caused to Black students; and 4) a relational approach to challenging anti-Black racism in the learning environment. Findings underscore the need for increased attention to racism in the implicit social work curriculum.

The five-year rule must die. Despite an extensive literature search, the origins of the five-year rule remain unknown. In an era when the nursing profession is so focused on evidence-based practice, any approach that arbitrarily limits literature searches to articles published in the previous five years lacks scientific basis. We explore some reasons for the pervasiveness of the practice and suggest that librarians need to engage with nursing faculty, who are well-positioned to be change agents in this practice.

The rising interest and success in deploying inherited microorganisms and cytoplasmic incompatibility (CI) for vector control strategies necessitate an explanation of the CI mechanism. Wolbachia-induced CI manifests in the form of embryonic lethality when sperm from Wolbachia-bearing testes fertilize eggs from uninfected females. Embryos from infected females however survive to sustain the maternally inherited symbiont. Previously in Drosophila melanogaster flies, we demonstrated that CI modifies chromatin integrity in developing sperm to bestow the embryonic lethality. Here, we validate these findings using wMel-transinfected Aedes aegypti mosquitoes released to control vector-borne diseases. Once again, the prophage WO CI proteins, CifA and CifB, target male gametic nuclei to modify chromatin integrity via an aberrant histone-to-protamine transition. Cifs are not detected in the embryo, and thus elicit CI via the nucleoprotein modifications established pre-fertilization. The rescue protein CifA in oogenesis localizes to stem cell, nurse cell, and oocyte nuclei, as well as embryonic DNA during embryogenesis. Discovery of the nuclear targeting Cifs and altered histone-to-protamine transition in both Aedes aegypti mosquitoes and D. melanogaster flies affirm the Host Modification Model of CI is conserved across these host species. The study also newly uncovers the cell biology of Cif proteins in the ovaries, CifA localization in the embryos, and an impaired histone-to-protamine transition during spermiogenesis of any mosquito species. Overall, these sperm modification findings may enable future optimization of CI efficacy in vectors or pests that are refractory to Wolbachia transinfections.

BackgroundDiabetes is a chronic disease that requires lifelong management and care, affecting around 422 million people worldwide and roughly 37 million in the United States. Patients newly diagnosed with diabetes must work with health care providers to formulate a management plan, including lifestyle modifications and regular office visits, to improve metabolic control, prevent or delay complications, optimize quality of life, and promote well-being. ObjectiveOur aim is to investigate one component of system-wide access to timely health care for people with diabetes in New York City (NYC), namely the length of time for someone with newly diagnosed diabetes to obtain an appointment with 3 diabetes care specialists: a cardiologist, an endocrinologist, and an ophthalmologist, respectively. MethodsWe contacted the offices of 3 different kinds of specialists: cardiologists, endocrinologists, and ophthalmologists, by telephone, for this descriptive cross-sectional study, to determine the number of days required to schedule an appointment for a new patient with diabetes. The sampling frame included all specialists affiliated with any private or public hospital in NYC. The number of days to obtain an appointment with each specialist was documented, along with “time on hold” when attempting to schedule an appointment and the presence of online booking capabilities. ResultsOf the 1639 unique physicians affiliated with (private and public) hospitals in the 3 subspecialties, 1032 (cardiologists, endocrinologists, and ophthalmologists) were in active practice and did not require a referral. The mean wait time for scheduling an appointment was 36 (SD 36.4; IQR 12-51.5) days for cardiologists; 82 (SD 47; IQR 56-101) days for endocrinologists; and 50.4 (SD 56; IQR 10-72) days for ophthalmologists. The median wait time was 27 days for cardiologists, 72 days for endocrinologists, and 30 days for ophthalmologists. The mean time on hold while attempting to schedule an appointment with these specialists was 2.6 (SD 5.5) minutes for cardiologists, 5.4 (SD 4.3) minutes for endocrinologists, and 3.2 (SD 4.8) minutes for ophthalmologists, respectively. Over 46% (158/341) of cardiologists enabled patients to schedule an appointment on the web, and over 55% (128/228) of endocrinologists enabled patients to schedule an appointment on the web. In contrast, only approximately 25% (117/463) of ophthalmologists offered web-based appointment scheduling options. ConclusionsThe results indicate considerable variation in wait times between and within the 3 specialties examined for a new patient in NYC. Given the paucity of research on wait times for newly diagnosed people with diabetes to obtain an appointment with different specialists, this study provides preliminary estimates that can serve as an initial reference. Additional research is needed to document the extent to which wait times are associated with complications and the demographic and socio-economic characteristics of people served by different providers.

Abstract Background Larvicides are critical for the control of mosquito-borne diseases. However, even sublethal exposure to a larvicide can alter development and life history traits, which can then affect population density and disease transmission dynamics. Photosensitive insecticides (PSIs) are a promising class of larvicide that are toxic when ingested and activated by light. We investigated whether the time of day when exposure occurs, or the process of pupation, affects larval susceptibility to PSI phototoxicity in the mosquito Anopheles gambiae, and whether sublethal exposure to PSIs alters life history traits. Methods Larvae were treated with lethal concentrations of the PSIs methylene blue (MB) and rose bengal (RB), and larval survival was measured at various times of day. Additionally, larvae were exposed to two concentrations of each PSI that resulted in low and medium mortality, and the life history traits of the surviving larvae were measured. Results Pupation, which predominantly occurs in the evening, protected larvae from PSI toxicity, but the toxicity of PSIs against larvae that had yet to pupate was unaffected by time of day. Larval exposure to a sublethal concentration of MB, but not RB, shortened the time to pupation. However, larval exposure to a sublethal concentration of RB, but not MB, increased pupal mortality. Neither PSI had a meaningful effect on the time to eclosion, adult longevity, or adult melanization potential. Conclusions PSIs are lethal larvicides. Sublethal PSI exposure alters mosquito development, but does not affect adult life history traits. Graphical Abstract

Calciphylaxis is a rare and serious complication of chronic renal failure characterized by vascular calcium overload. It has a high mortality rate. Penile calciphylaxis is an extremely rare condition of penile necrosis due to calciphylaxis of the penile arterioles. Presented here is a severe case of systemic calciphylaxis initially presented as penile necrosis treated with sodium thiosulfate and amputation.

Bleeding resulting from surgical procedures or trauma, including gunshot wounds, represents a life-threatening health issue. Therefore, the development of safe, effective, and convenient hemostatic agents is critical in securing the “golden time” to save patients’ lives. Plant-derived compounds and plant extracts have been regarded as promising sources of hemostatic agents in previous studies, regulating hemostatic function with low toxicity and minimal side effects within the human body. Aloe vera-based hydrogels, which are characterized by flexible strength and high functionality, have emerged as a promising platform for wound applications due to their unique biocompatibility features. This study provides a comprehensive exploration of the utilization of thickening agents and natural agents such as xanthan gum, carrageenan, Carbomer, and alginate in applying aloe vera-based hydrogels as a hemostatic. Furthermore, it also tests the use of aloe vera-based hydrogels for therapeutic delivery at wound sites through the incorporation of various antimicrobial agents to extend the utility of the hydrogels beyond hemostasis. Our novel applied research utilizes aloe vera-based hydrogel as an antimicrobial hemostatic agent, providing valuable insights for a wide range of applications and highlighting its potential to enhance hemorrhage control in various emergency scenarios.

Abstract Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent public health threat, according to the CDC. This pathogen has few treatment options and causes severe nosocomial infections with > 50% fatality rate. Although previous studies have examined the proteome of CRAb, there have been no focused analyses of dynamic changes to β-lactamase expression that may occur due to drug exposure. Here, we present our initial proteomic study of variation in β-lactamase expression that occurs in CRAb with different β-lactam antibiotics. Briefly, drug resistance to Ab (ATCC 19606) was induced by the administration of various classes of β-lactam antibiotics, and the cell-free supernatant was isolated, concentrated, separated by SDS-PAGE, digested with trypsin, and identified by label-free LC–MS-based quantitative proteomics. Thirteen proteins were identified and evaluated using a 1789 sequence database of Ab β-lactamases from UniProt, the majority of which were Class C β-lactamases (≥ 80%). Importantly, different antibiotics, even those of the same class (e.g. penicillin and amoxicillin), induced non-equivalent responses comprising various isoforms of Class C and D serine-β-lactamases, resulting in unique resistomes. These results open the door to a new approach of analyzing and studying the problem of multi-drug resistance in bacteria that rely strongly on β-lactamase expression.

The body temperature of mosquitoes, like most insects, is dictated by the environmental temperature. Climate change is increasing the body temperature of insects and thereby altering physiological processes such as immune proficiency. Aging also alters insect physiology, resulting in the weakening of the immune system in a process called senescence. Although both temperature and aging independently affect the immune system, it is unknown whether temperature alters the rate of immune senescence. Here, we evaluated the independent and combined effects of temperature (27°C, 30°C and 32°C) and aging (1, 5, 10 and 15 days old) on the melanization immune response of the adult female mosquito, Anopheles gambiae. Using a spectrophotometric assay that measures phenoloxidase activity (a rate limiting enzyme) in hemolymph, and therefore, the melanization potential of the mosquito, we discovered that the strength of melanization decreases with higher temperature, aging, and infection. Moreover, when the temperature is higher, the aging-dependent decline in melanization begins at a younger age. Using an optical assay that measures melanin deposition on the abdominal wall and in the periostial regions of the heart, we found that melanin is deposited after infection, that this deposition decreases with aging, and that this aging-dependent decline is accelerated by higher temperature. This study demonstrates that higher temperature accelerates immune senescence in mosquitoes, with higher temperature uncoupling physiological age from chronological age. These findings highlight the importance of investigating the consequences of climate change on how disease transmission by mosquitoes is affected by aging.

Beta-lactam antibiotics have been a major climacteric in medicine for being the first bactericidal compound available for clinical use. They have continually been prescribed since their development in the 1940s, and their application has saved an immeasurable number of lives. With such immense use, the rise in antibiotic resistance has truncated the clinical efficacy of these compounds. Nevertheless, the synergism of combinational antibiotic therapy has allowed these drugs to burgeon once again. Here, the development of meropenem with vaborbactam—a recently FDA-approved beta-lactam combinational therapy—is reviewed in terms of structure rationale, activity gamut, pharmacodynamic/pharmacokinetic properties, and toxicity to provide insight into the future development of analogous therapies.

Altered intestinal health is also associated with the incidence and severity of many chronic inflammatory conditions, which could be attenuated via dietary n-3 PUFA interventions. However, little is known about the effect of lifelong exposure to n-3 PUFA from plant and marine sources (beginning in utero via the maternal diet) on early life biomarkers of intestinal health. Harems of C57Bl/6 mice were randomly assigned to one of three isocaloric AIN-93G modified diets differing in their fat sources consisting of the following: (i) 10% safflower oil (SO, enriched in n-6 PUFA), (ii) 3% flaxseed oil + 7% safflower oil (FX, plant-based n-3 PUFA-enriched diet), or (iii) 3% menhaden fish oil + 7% safflower oil (MO, marine-based n-3 PUFA-enriched diet). Mothers remained on these diets throughout pregnancy and offspring (n = 14/diet) continued on the same parental diet until termination at 3 weeks of age. In ileum, villi:crypt length ratios were increased in both the FX and MO dietary groups compared to SO (p < 0.05). Ileum mRNA expression of critical intestinal health biomarkers was increased by both n-3 PUFA-enriched diets including Relmβ and REG3γ compared to SO (p < 0.05), whereas only the FX diet increased mRNA expression of TFF3 and Muc2 (p < 0.05) and only the MO diet increased mRNA expression of ZO-1 (p < 0.05). In the proximal colon, both the FX and MO diets increased crypt lengths compared to SO (p < 0.05), whereas only the MO diet increased goblet cell numbers compared to SO (p < 0.05). Further, the MO diet increased proximal colon mRNA expression of Relmβ and REG3γ (p < 0.05) and both MO and FX increased mRNA expression of Muc2 compared to SO (p < 0.05). Collectively, these results demonstrate that lifelong exposure to dietary n-3 PUFA, beginning in utero, from both plant and marine sources, can support intestinal health development in early life. The differential effects between plant and marine sources warrants further investigation for optimizing health.

The current discourse around Open Science has tended to focus on the creation of new technological platforms and tools to facilitate sharing and reuse of a wide range of research outputs. There is an assumption that once these new tools are in place, researchers-and at times, members of the general public-will be able to participate in the creation of scientific knowledge in more accessible and efficient ways. While many of these new tools have indeed assisted in the ease of collaboration through online spaces and mechanisms, the narrowness of how infrastructure is imagined by open science practitioners tends to put the use of technology ahead of the issues that people are actually trying to solve and fails to acknowledge the systemic constraints that exist within and between some communities. Drawing on an analytical framework grounded in Black feminist intersectionality (Noble 2016), this paper highlights the need for more inclusive knowledge infrastructures, particularly in the context of sustainable development. Three case studies from the Open and Collaborative Science in Development Network (OCSDNet), are outlined in order to illustrate the importance of moving beyond a definition of infrastructure as merely a technical or physical entity. These cases, arising from research conducted in South Africa, Brazil, and the Caribbean, demonstrate how more sustainable and nuanced forms of collaboration and participation may be enabled through broader understandings of knowledge infrastructures. This paper further argues that leveraging the feminist concept of intersectionality when conceptualizing the development of knowledge infrastructures could be one way to move from narrow assumptions about standardized knowledge “users” towards more inclusive reimaginings of how knowledges can be produced and shared via networked technologies.

Background: The modern-day cardiac intensive care unit (CICU) has evolved to care for patients with acute critical cardiac illness. We describe the current population of cardiac patients in a quaternary CICU. Methods: Consecutive CICU patients admitted to the CICU at the Toronto General Hospital from 2014 to 2020 were studied. Patient demographics, admission diagnosis, critical care resources, complications, in-hospital mortality, and CICU and hospital length of stay were recorded. Results: A total of 8865 consecutive admissions occurred, with a median age of 64.9 years. The most common primary cardiac diagnoses were acute decompensated heart failure (17.8%), non ST-elevation myocardial infarction (16.8%), ST-elevation myocardial infarction (15.5%), and arrhythmias (14.7%). Cardiogenic shock was seen in 13.2%, and out-of-hospital cardiac arrest in 4.1%. A noncardiovascular admission diagnosis accounted for 13.9% of the cases. Over the period studied, rates of admission were higher for cardiogenic shock (P < 0.001 for trend), with a higher use of critical care resources. Additionally, rates of admission were higher in female patients and those who had chronic kidney disease and diabetes. The in-hospital mortality rate of all CICU admissions was 13.2%, and it was highest in those with noncardiac conditions, compared to the rate in those with cardiac diagnoses (29.4% vs 10.6%, P < 0.001). Conclusions: Given the trends of higher acuity of patients with cardiac critical illness, with higher use of critical care resources, education streams for critical care within cardiology, and alternative pathways of care for patients who have lower-acuity cardiac disease remain imperative to manage this evolving population. Résumé: Introduction: L’unité de soins intensifs de cardiologie (USIC) d’aujourd’hui a évolué vers des soins aux patients atteints d’une maladie cardiaque aiguë en phase critique. Nous décrivons la population actuelle de patients cardiaques d’une USIC quaternaires. Méthodes: Les patients consécutifs d’USIC admis à l’USIC de l’Hôpital général de Toronto de 2014 à 2020 ont fait l’objet de l’étude. Les données démographiques des patients, le diagnostic à l’admission, les ressources en soins aux patients en phase critique, les complications, la mortalité intrahospitalière, et la durée de séjour à l’hôpital et à l’USIC ont été enregistrés. Résultats: Il y a eu un total de 8 865 admissions consécutives dont les patients avaient un âge médian de 64,9 ans. Les diagnostics principaux les plus fréquents de maladies cardiaques étaient l'insuffisance cardiaque aiguë décompensée (17,8 %), l’infarctus du myocarde sans élévation du segment ST (16,8 %), l’infarctus du myocarde avec élévation du segment ST (15,5 %) et les arythmies (14,7 %). Le choc cardiogénique a été observé chez 13,2 %, et l’arrêt cardiaque hors de l’hôpital, chez 4,1 %. Un diagnostic d’admission de maladie non cardiovasculaire représente 13,9 % des cas. Durant la période étudiée, les taux d’admission en raison d’un choc cardiogénique étaient plus élevés (P < 0,001 pour la tendance), et entraînaient une utilisation plus élevée de ressources en soins aux patients en phase critique. De plus, les taux d’admission étaient plus élevés chez les patientes, et chez ceux qui avaient une insuffisance rénale chronique et un diabète. Le taux de mortalité intrahospitalière de toutes les admissions à l’USIC était de 13,2 %, et il constituait le taux le plus élevé chez ceux qui avaient des maladies non cardiaques comparativement au taux chez ceux qui avaient des diagnostics de maladies cardiaques (29,4 % vs 10,6 %, P < 0,001). Conclusions: Compte tenu des tendances d’accroissement de la gravité de l’état des patients atteints d’une maladie cardiaque en phase critique et de la plus grande utilisation des ressources en soins aux patients en phase critique, des volets de formation en soins aux patients en phase critique en cardiologie et d’autres protocoles de soins des patients qui ont une maladie cardiaque de plus faible gravité demeurent essentiels à la prise en charge de cette population grandissante.

In this forum, three educators spanning elementary and secondary contexts reflect on their experiences as they respond to the following question: How has the pandemic impacted issues of access in your teaching practice, and what are some implications for teaching in the post-pandemic return to physical spaces of literacy learning? Across their accounts, the authors describe how their experiences have re(shaped) their perspectives about students and learning as well as prompted questions about the digitalization of pedagogy and the creation of inclusive, equitable learning spaces for all learners.

Abstract Background Epidemiological research of events related to labor and delivery frequently uses maternal interview or birth certificates as a primary method of data collection; however, the validity of these data are rarely confirmed. This study aimed to examine the validity of birth certificate data and maternal interview of maternal demographics and events related to labor and delivery with data abstracted from medical records in a US setting. Methods Birth certificate and maternal recall data from the Iowa Health in Pregnancy Study (IHIPS), a population-based case-control study of risk factors for preterm and small-for-gestational age births, were linked to medical record data to assess the validity of events that occurred during labor and delivery along with reported maternal demographics. Sensitivity, specificity, positive and negative predictive values, and kappa scores were calculated. Results Postpartum maternal recall and birth certificate data were excellent for infant characteristics (birth weight, gestational age, infant sex) and variables related to labor and delivery (mode of delivery) when compared with medical records. Birth certificate data for labor induction had low sensitivity (46.3%) and positive predictive value (18.3%) compared to medical records. Compared to maternal interview, birth certificate data also had poor agreement for smoking and alcohol use during pregnancy. Agreement between all three methods of data collection was very low for pregnancy weight gain (kappa = 0.07-0.08). Conclusions Maternal interview and birth certificate data can be a valid source for collecting data on infant characteristics and events that occurred during labor and delivery. However, caution should be used if solely using birth certificate data to gather data on maternal demographic and/or lifestyle factors.

The tolerance model rests on the thesis of a physiologically regulated, albeit unsustainable, systemic attempt to adapt to the catabolic challenge posed by acute prepubescent malnutrition even in its severe forms. The model centers on the immunological component of the attempt, positing reorientation toward a non-inflammatory form of competence in place of the classic paradigm of immunological attrition and exhaustion. The foundation of the model was laid in 1990, and sixteen years later it was articulated formally on the basis of a body of evidence centered on T cell cytokines and interventions with cytokine and hormonal mediators. The benefit originally suggested was a reduced risk of autoimmune pathologies consequent to the catabolic release of self-antigens, hence the designation highlighting immune tolerance. Herein, the emergence of the tolerance model is traced from its roots in the recognition that acute malnutrition elicits an endocrine-based systemic adaptive attempt. Thereafter, the growth of the evidence base supporting the model is outlined, and its potential to shed new light on existing information is tested by application to the findings of a published clinical study of acutely malnourished children. Finally, some knowledge gaps pertinent to the model are identified and its potential for growth consonant with evolving perceptions of immunobiology is illustrated.

Among the various mechanisms that bacteria use to develop antibiotic resistance, the multiple expression of β-lactamases is particularly problematic, threatening public health and increasing patient mortality rates. Even if a combination therapy—in which a β-lactamase inhibitor is administered together with a β-lactam antibiotic—has proven effective against serine-β-lactamases, there are no currently approved metallo-β-lactamase inhibitors. Herein, we demonstrate that quercetin and its analogs are promising starting points for the further development of safe and effective metallo-β-lactamase inhibitors. Through a combined computational and in vitro approach, taxifolin was found to inhibit VIM-2 expressing P. aeruginosa cell proliferation at

Abstract Background Racial and ethnic minority groups experience a disproportionate burden of SARS‐CoV‐2 illness and studies suggest that cancer patients are at a particular risk for severe SARS‐CoV‐2 infection. Aims The objective of this study was examine the association between neighborhood characteristics and SARS‐CoV‐2 infection among patients with cancer. Methods and Results We performed a cross‐sectional study of New York City residents receiving treatment for cancer at a tertiary cancer center. Patients were linked by their address to data from the US Census Bureau's American Community Survey and to real estate tax data from New York's Department of City Planning. Models were used to both to estimate odds ratios (ORs) per unit increase and to predict probabilities (and 95% CI) of SARS‐CoV2 infection. We identified 2350 New York City residents with cancer receiving treatment. Overall, 214 (9.1%) were infected with SARS‐CoV‐2. In adjusted models, the percentage of Hispanic/Latino population (aOR = 1.01; 95% CI, 1.005–1.02), unemployment rate (aOR = 1.10; 95% CI, 1.05–1.16), poverty rates (aOR = 1.02; 95% CI, 1.0002–1.03), rate of >1 person per room (aOR = 1.04; 95% CI, 1.01–1.07), average household size (aOR = 1.79; 95% CI, 1.23–2.59) and population density (aOR = 1.86; 95% CI, 1.27–2.72) were associated with SARS‐CoV‐2 infection. Conclusion Among cancer patients in New York City receiving anti‐cancer therapy, SARS‐CoV‐2 infection was associated with neighborhood‐ and building‐level markers of larger household membership, household crowding, and low socioeconomic status. Novelty and impact We performed a cross‐sectional analysis of residents of New York City receiving treatment for cancer in which we linked subjects to census and real estate date. This linkage is a novel way to examine the neighborhood characteristics that influence SARS‐COV‐2 infection. We found that among patients receiving anti‐cancer therapy, SARS‐CoV‐2 infection was associated with building and neighborhood‐level markers of household crowding, larger household membership, and low socioeconomic status. With ongoing surges of SARS‐CoV‐2 infections, these data may help in the development of interventions to decrease the morbidity and mortality associated with SARS‐CoV‐2 among cancer patients.

The high degree of endemism on Sulawesi has previously been suggested to have vicariant origins, dating back to 40 Ma. Recent studies, however, suggest that much of Sulawesis fauna assembled over the last 15 Myr. Here, we test the hypothesis that more recent uplift of previously submerged portions of land on Sulawesi promoted diversification and that much of its faunal assemblage is much younger than the island itself. To do so, we combined palaeogeographical reconstructions with genetic and morphometric datasets derived from Sulawesis three largest mammals: the babirusa, anoa and Sulawesi warty pig. Our results indicate that although these species most likely colonized the area that is now Sulawesi at different times (14 Ma to 2-3 Ma), they experienced an almost synchronous expansion from the central part of the island. Geological reconstructions indicate that this area was above sea level for most of the last 4 Myr, unlike most parts of the island. We conclude that emergence of land on Sulawesi (approx. 1-2 Myr) may have allowed species to expand synchronously. Altogether, our results indicate that the establishment of the highly endemic faunal assemblage on Sulawesi was driven by geological events over the last few million years.