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Although results from studies of first-trimester influenza vaccination and congenital heart defects (CHDs) have been reassuring, data are limited for specific CHDs.We assessed associations between reported maternal influenza vaccination, 1 month before pregnancy (B1) through end of third pregnancy month (P3), and specific CHDs using data from a multisite, population-based case-control study. Analysis included 2,982 case children diagnosed with a simple CHD (no other cardiac involvement with or without extracardiac defects) and 4,937 control children without a birth defect with estimated delivery dates during 2006-2011. For defects with ≥5 exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; and maternal age at delivery, race/ethnicity, low folate intake, and smoking and alcohol use during B1P3.Overall, 124 (4.2%) simple CHD case mothers and 197 (4.0%) control mothers reported influenza vaccination from 1 month before through the third pregnancy month. The aOR for any simple CHD was 0.97 (95% CI: 0.76-1.23). Adjusted ORs for specific simple CHDs ranged from 0.62 for hypoplastic left heart syndrome to 2.34 for total anomalous pulmonary venous return (TAPVR). All adjusted CIs included the null except for TAPVR.Although we cannot fully exclude that exposure misclassification may have masked risks for some CHDs, findings add to existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. The TAPVR result may be due to chance, but it may help inform future studies.

Arsenic crosses the placenta and accumulates in fetal tissues. In the United States, diet is the predominant route of arsenic exposure, but epidemiologic data are sparse regarding this exposure and development of birth defects. Using data from a large case-control study, we explored associations between maternal dietary arsenic exposure and congenital heart defects (CHDs), the most prevalent birth defects.We used maternal self-reported dietary assessments and arsenic concentration estimates in food items to estimate average daily exposure to dietary arsenic during the year before pregnancy for mothers of 10,446 unaffected control children and 6,483 case children diagnosed with CHDs. Using tertiles of dietary exposure to total arsenic (all species) and inorganic arsenic, we applied logistic regression analysis to estimate associations for middle and high tertiles, compared with the low tertile.Positive associations (odds ratio [OR] ≥ 1.2) for total arsenic were observed in both tertiles for perimembranous ventricular septal defect (VSD) and high tertile only for double outlet right ventricle-transposition of the great arteries (DORV-TGA), partial anomalous pulmonary venous return (PAPVR), and tricuspid atresia. Positive associations were also observed in both tertiles (tricuspid atresia) and high tertile only (DORV-TGA, conoventricular VSD, PAPVR, and pulmonary atresia) for inorganic arsenic. Most remaining associations were near or below unity.Exploration of maternal dietary exposure to total and inorganic arsenic and CHDs produced few positive associations but was limited by available food item concentrations. Future research requires expanded collection of dietary data, improved estimates of concentrations, and consideration of nondietary sources of arsenic exposure.

Aneurysmal extension of abdominal aortic aneurysms (AAAs) to the common iliac artery (CIA) presents a technical challenge to successful endovascular abdominal aortic aneurysm repair (EVAR). In the present study, we compared sac shrinkage and perioperative outcomes after the bell-bottom technique (BBT), internal iliac artery embolization and external iliac artery extension (EIE), and iliac branch endoprosthesis (IBE).Using the Vascular Quality Initiative database, a retrospective analysis was conducted for patients who had undergone EVAR from 2013 to 2019. The demographic, anatomic, and perioperative data were analyzed. All patients with a proximal aortic neck length 10 mm and aortic graft diameter32 mm were excluded from the analysis. The patients were subdivided into four groups according to the distal limb strategy: group 1, control group with a bilateral common iliac artery limb 20 mm; group 2, BBT with either a unilateral or bilateral limb20 mm; group 3, EIE technique; and group 4, IBE. The primary endpoint was the maximal change in the aortic diameter during follow-up. The secondary endpoints included postoperative complications and the rate of endoleak.The records for 14,455 patients who had undergone EVAR were queried and 5788 met the anatomic criteria. The average age was 73 years, and 86.3% were men. The maximal change in the aortic diameter in the control, BBT, IBE, and EIE groups was -7.2 mm, -6.1 mm, -4.6 mm, and -6.8 mm, respectively (P = .06). The differences were not statistically significant on univariate analysis at an average follow-up of 405 days. However, on multivariable analysis (P = .01), compared with the control group, the BBT and IBE groups were 18.4% (odds ratio [OR], 0.816; 95% confidence interval [CI], 0.68-0.98) and 48.0% (OR, 0.52; 95% CI, 0.33-0.82) less likely to experience aneurysmal shrinkage, respectively. In contrast, the EIE group showed no significant difference in shrinkage compared with that in the control group. Multivariable analysis of the groups also revealed that compared directly with the BBT group, the EIE group was 69.5% more likely to have experienced shrinkage in the aortic aneurysmal diameter (OR, 1.70; 95% CI, 1.05-2.75). The BBT and IBE groups had a significantly higher rate of type II endoleaks (17.63% and 16.95%, respectively; P = .03). The EIE group had a higher rate of type Ib endoleaks (1.9%) compared with the BBT (1.1%), IBE (1.7%), and control (0.3%) groups (P = .01). No differences were found between the groups in terms of postoperative myocardial infarction (P = .47) or respiratory (P = .61) or intestinal (P = .71) complications. However, the rates of limb complications and reoperation were higher in the EIE group.The present study revealed that the EIE technique was more likely to demonstrate shrinkage in the aortic aneurysmal diameter than were the BBT and IBE groups compared with the control group on multivariable analysis. The EIE technique was also more likely to result in aneurysmal sac shrinkage than was the BBT group, albeit with greater rates of limb-related complications.

Population-based estimates of survival among individuals with Duchenne muscular dystrophy (DMD) living in the United States are lacking. It is also unclear whether the association between glucocorticoid use and all-cause mortality persists in the context of other common treatments (cardiac medication, cough-assist, bilevel positive airway pressure, and scoliosis surgery) observed to delay mortality. Among 526 individuals identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network, the estimated median survival time from birth was 23.7 years. Current glucocorticoid users had a lower hazard of mortality than non-users. Individuals who ever had scoliosis surgery had a lower hazard of mortality than individuals who did not have scoliosis surgery. Individuals who ever used cough assist had a lower hazard of mortality than individuals who never used cough assist. Non-Hispanic Black individuals had a higher hazard of mortality than non-Hispanic White individuals. No differences in hazards of mortality were observed between ever versus never use of cardiac medication and ever versus never use of bilevel positive airway pressure. The glucocorticoid observation is consistent with the 2018 Care Considerations statement that glucocorticoid use continues in the non-ambulatory phase. Our observations may inform the clinical care of individuals living with DMD.

To assess associations between influenza vaccination during etiologically-relevant windows and selected major structural non-cardiac birth defects.We analyzed data from the National Birth Defects Prevention Study, a multisite, population-based case-control study, for 8233 case children diagnosed with a birth defect and 4937 control children without a birth defect with delivery dates during 2006-2011. For all analyses except for neural tube defects (NTDs), we classified mothers who reported influenza vaccination 1 month before through the third pregnancy month as exposed; the exposure window for NTDs was 1 month before through the first pregnancy month. For defects with five or more exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; maternal age, race/ethnicity, smoking and alcohol use, low folate intake; and, for NTDs, folate antagonist medications.There were 334 (4.1%) case and 197 (4.0%) control mothers who reported influenza vaccination from 1 month before through the third pregnancy month. Adjusted ORs ranged from 0.53 for omphalocele to 1.74 for duodenal atresia/stenosis. Most aORs (11 of 19) were ≤1 and all adjusted CIs included the null. The unadjusted CIs for two defects, hypospadias and craniosynostosis, excluded the null. These estimates were attenuated upon covariate adjustment (hypospadias aOR: 1.25 (95% CI 0.89, 1.76); craniosynostosis aOR: 1.23 (95% CI: 0.88, 1.74)).Results for several non-cardiac major birth defects add to the existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. Under-reporting of vaccination may have biased estimates downward.

With current and anticipated disease-modifying treatments, including gene therapy, an early diagnosis for Duchenne muscular dystrophy (DMD) is crucial to assure maximum benefit. In 2009, a study from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) showed an average diagnosis age of 5 years among males with DMD born from January 1, 1982 to December 31, 2000. Initiatives were implemented by the US Centers for Disease Control and Prevention (CDC) and patient organizations to reduce time to diagnosis. We conducted a follow-up study in a surveillance cohort born after January 1, 2000 to determine whether there has been an improvement in time to diagnosis.We assessed the age of diagnosis among males with DMD born from January 1, 2000 to December 31, 2015 using data collected by six US MD STARnet surveillance sites (Colorado, Iowa, western New York State, the Piedmont region of North Carolina, South Carolina, and Utah). The analytic cohort included 221 males with definite or probable DMD diagnosis without a documented family history. We computed frequency count and percentage for categorical variables, and mean, median, and standard deviation (SD) for continuous variables.The mean [median] ages in years of diagnostic milestones were: first signs, 2.7 [2.0]; first creatine kinase (CK), 4.6 [4.6]; DNA/muscle biopsy testing, 4.9 [4.8]; and time from first signs to diagnostic confirmation, 2.2 [1.4].The time interval between first signs of DMD and diagnosis remains unchanged at 2.2 years. This results in lost opportunities for timely genetic counseling, implementation of standards of care, initiation of glucocorticoids, and participation in clinical trials.

This study examined the perceptions of nine music teachers regarding teacher professional development (PD) for new and experienced teachers over the past 20 years. Data included reflections on past research studies that participants were a part of 20 and 10 years ago, respectively, as part of two individual interviews and a focus group interview conducted between fall 2019 and winter 2020. Findings are presented in the following categories: (a) new teacher PD support, (b) forms of PD, and (c) emerging topics within PD (including diversity, equity, and inclusion; technology; trauma-information pedagogies; and social and emotional learning). These findings are discussed in relation to past research in these areas.

Exposure of blood to a foreign surface in the form of a diagnostic or therapeutic biomaterial device or implanted cells or tissue elicits an immediate, evolutionarily conserved thromboinflammatory response from the host. Primarily designed to protect against invading organisms after an injury, this innate response features instantaneous activation of several blood-borne, highly interactive, well-orchestrated cascades and cellular events that limit bleeding, destroy and eliminate the foreign substance or cells, and promote healing and a return to homeostasis via delicately balanced regenerative processes. In the setting of blood-contacting synthetic or natural biomaterials and implantation of foreign cells or tissues, innate responses are robust, albeit highly context specific. Unfortunately, they tend to be less than adequately regulated by the host’s natural anticoagulant or anti-inflammatory pathways, thereby jeopardizing the functional integrity of the device, as well as the health of the host. Strategies to achieve biocompatibility with a sustained return to homeostasis, particularly while the device remains in situ and functional, continue to elude scientists and clinicians. In this review, some of the complex mechanisms by which biomaterials and cellular transplants provide a “hub” for activation and amplification of coagulation and immunity, thromboinflammation, are discussed, with a view toward the development of innovative means of overcoming the innate challenges.

BACKGROUND: Sacral agenesis (SA) consists of partial or complete absence of the caudal end of the spine and often presents with additional birth defects. Several studies have examined gene variants for syndromic forms of SA, but only one has examined exomes of children with non-syndromic SA. METHODS: Using buccal cell specimens from families of children with non-syndromic SA, exomes of 28 child-parent trios (eight with and 20 without a maternal diagnosis of pregestational diabetes) and two child-father duos (neither with diagnosis of maternal pregestational diabetes) were exome sequenced. RESULTS: Three children had heterozygous missense variants in ID1 (Inhibitor of DNA Binding 1), with CADD scores >20 (top 1% of deleterious variants in the genome); two children inherited the variant from their fathers and one from the child’s mother. Rare missense variants were also detected in PDZD2 (PDZ Domain Containing 2; N=1) and SPTBN5 (Spectrin Beta, Non-erythrocytic 5; N=2), two genes previously suggested to be associated with SA etiology. Examination of variants with autosomal recessive and X-linked recessive inheritance identified five and two missense variants, respectively. Compound heterozygous variants were identified in several genes. In addition, 12 de novo variants were identified, all in different genes in different children. CONCLUSIONS: To our knowledge, this is the first study reporting a possible association between ID1 and non-syndromic SA. Although maternal pregestational diabetes has been strongly associated with SA, the missense variants in ID1 identified in two of three children were paternally inherited. These findings add to the knowledge of gene variants associated with non-syndromic SA and provide data for future studies.

Recent mouse knockout studies identified adapter protein-2-associated kinase 1 (AAK1) as a viable target for treating neuropathic pain. BMS-986176/LX-9211 (

Introduction : Hospitalists can be instrumental in management of inpatients with multiple comorbidities requiring complex medical care such as vascular surgery patients, as well as an expertise in health care delivery. We instituted a unique hospitalist co-management program and assessed length of stay, 30-day readmission rates and mortality, and performed an overall cost-analysis. Methods : Hospitalist co-management of vascular surgery inpatients was implemented beginning April 2019, and data was studied until March 2020. We compared this data to an eight-month period prior to implementing co-management (7/2018 – 3/2019). Patient-related outcomes that were assessed include length of stay, re-admission index, mortality index, case-mix index. Cost-analysis was performed to look at indirect and direct cost of care. Results : A total of 1,062 patients were included in the study 520 pre co-management and 542 patients were post-comanagement. Baseline case-mix index was 2.47, and post-comanagement was 2.46 (p>0.05). In terms of average length of stay (aLOS), the baseline aLOS was 5.16 days per patient, while after co-management it was significantly decreased by 1.25 days to 3.91 days (p Conclusions : Hospitalist co-management improves outcomes for vascular surgery inpatients, decreases length of stay, re-admission and mortality while providing a significant cost-savings. The overall average variable direct cost decreased by $1,732 per patient. Conclusion : Hospitalist co-management improves outcomes for vascular surgery inpatients, decreases length of stay, re-admission and mortality while providing a significant cost-savings.

Background and purposeCongenital clubfoot is a common musculoskeletal anomaly, with a suspected multifactorial etiopathogenesis. To begin examining its etiopathogenesis in a nationwide Danish population, liveborn infants with clubfoot were ascertained to classify co-occurring congenital anomalies, estimate annual prevalence, and compare occurrence with maternal smoking rates, a commonly reported risk factor.Patients and methodsThis case-cohort study used data from the Danish National Patient Register and Danish Civil Registration System to identify 1,315,282 liveborn infants delivered during 1994–2021 in Denmark to Danish parents. Among these, 2,358 infants (65.1% male) were ascertained with clubfoot and classified as syndromic (co-occurring chromosomal, genetic, or teratogenic syndromes) and nonsyndromic (isolated or co-occurring multiple congenital anomalies [MCA]). Annual prevalence estimates and corresponding 95% confidence intervals (CIs) for children with nonsyndromic clubfoot were estimated using Poisson regression and compared with population-based, maternal annual smoking rates obtained from publicly available resources.ResultsInfants most often presented with nonsyndromic clubfoot (isolated=84.6%; MCA=10.9%); limb and heart anomalies were the most frequently identified MCAs. Prevalence (per 1,000 liveborn infants) was 1.52 (CI 1.45 – 1.58) for isolated and 0.19 (CI 0.17 – 0.22) for MCA clubfoot. Prevalence estimates for both isolated and MCA clubfoot remained stable during the study period, despite marked decreases in population-based maternal smoking rates.InterpretationFrom 1994-2021, prevalence of nonsyndromic clubfoot in Denmark was reasonably stable. Reduction in population-level maternal smoking rates did not seem to impact prevalence estimates. Ascertainment and characterization of this cohort provides a population-based clinical and biological resource for etiopathogenic investigations.

Current treatments to prevent thrombosis, namely anticoagulants and platelets antagonists, remain complicated by the persistent risk of bleeding. Improved therapeutic strategies that diminish this risk would have a huge clinical impact. Antithrombotic agents that neutralize and inhibit polyphosphate (polyP) can be a powerful approach towards such a goal. Here, we report a design concept towards polyP inhibition, termed macromolecular polyanion inhibitors (MPI), with high binding affinity and specificity. Lead antithrombotic candidates are identified through a library screening of molecules which possess low charge density at physiological pH but which increase their charge upon binding to polyP, providing a smart way to enhance their activity and selectivity. The lead MPI candidates demonstrates antithrombotic activity in mouse models of thrombosis, does not give rise to bleeding, and is well tolerated in mice even at very high doses. The developed inhibitor is anticipated to open avenues in thrombosis prevention without bleeding risk, a challenge not addressed by current therapies.

Background: Germline genetic variants in PLCE1 (10q23) have demonstrated consistent associations with risk of esophageal squamous cell carcinoma (ESCC) and gastric cancer among Chinese. We evaluated PLCE1 mRNA and protein expression in paired tumor-normal tissues, and their relationship with survival.Methods:PLCE1 mRNA was profiled using three probes in the Affymetrix GeneChip U133 for paired tumor-normal tissues of ESCC (n = 132), gastric cardia adenocarcinoma (GCA, n = 62), and gastric noncardia adenocarcinoma (GNCA, n = 72). We used immunohistochemistry to detect PLCE1 protein on slides from tissue microarrays in paired tumor-normal tissues of ESCC (n = 303), and tumors of GCA (n = 298) and GNCA (n = 124).Results: Compared with normal tissues, PLCE1 mRNA expression was significantly reduced in ESCC tumors (P = 0.03, probe_205112_at), as well as in GCA and GNCA tumors (P < 0.0001, each probe). Protein expression was nonsignificantly reduced in ESCC tumors (P = 0.51). Increased tumor-normal mRNA fold change (probe_205112_at) was associated with longer survival in ESCC (9.6 months for highest vs. lowest quartile; Ptrend = 0.02). Increased mRNA tumor-normal fold change (probe_205111_at) was associated with longer survival for GCA (10.7 months for highest quartile; Ptrend = 0.04), but not for GNCA cases (P = 0.72). Similar to mRNA, elevated tumor-normal fold change for protein in ESCC was also associated with improved survival (8.1 months for highest quartile; Ptrend = 0.04).Conclusions: Dysregulated PLCE1 mRNA expression was observed for both ESCC (one probe only) and GCA tumors, and the altered PLCE1 expression seems to be associated with cancer prognosis.Impact: A potential role for PLCE1 in the early detection and/or therapy of ESCC and GCA warrants further investigation. Cancer Epidemiol Biomarkers Prev; 23(8); 1579–88. ©2014 AACR.

PDF - 194K, Supplementary Figure S1. Immunohistochemistry for PLCE1 protein expression with areas of annotation selected for image quantification (20x.)Supplementary Table S1. PLCE1 mRNA expression in GCA, GNCA and ESCC tumor tissues and tumor-normal expression fold change by characteristics of the subjects. Supplementary Table S2. PLCE1 protein expression in GCA, GNCA and ESCC tumor tissues and tumor-normal expression fold change in ESCC by characteristics of the participants. Supplementary Table S3. The probe-specific association between PLCE1 mRNA expression in tumors and tumor-normal fold change and mortality of ESCC, GCA, and GNCAs. Supplementary Table S4. Spearman correlation coefficients (P values) between PLCE1 mRNA expression in normal tissues of ESCC, GCA, and GNCA and selected PLCE1 SNPs.

Enkephalins are opioid peptides that modulate analgesia, reward, and stress.In vivodetection of enkephalins remains difficult due to transient and low endogenous concentrations and inherent sequence similarity. We present an analytical method for Met- and Leu-Enkephalin detection in the mouse Nucleus Accumbens shell after acute stress. This approach increases spatiotemporal resolution, optimizes the detection of Met-Enkephalin through methionine oxidation, and provides insight into the relationship between Met- and Leu-Enkephalin following stress.

BackgroundStudies indicate that workers’ compensation claim processes may affect patients’ health negatively. However, few studies focus on patients with mental health claims, and the claim process varies between countries.AimsThe aims of this study were to examine whether being notified to the Danish Labour Market Insurance with an occupational mental health condition was associated with changes in visits to the general practitioner (GP), use of medicine and annual income.MethodsStudy participants were 965 patients with a mental disorder examined at a department of occupational medicine. Of these, 669 patients were notified with an occupational mental disorder, 296 were not. Health-related outcomes, including GP visits and prescriptions of psychotropic drugs, were estimated at baseline during the year of medical examination, while annual income was estimated a year before the examination. The follow-up was the year after the year of examination for all outcomes. Outcomes were collected from the Danish National Bureau of Statistics. Analyses were conducted using Poisson regression and conditional logistic regression.ResultsAll measured outcomes decreased from baseline to follow-up in both groups. These changes were not significantly different depending on notification status at baseline.ConclusionsThis study suggests that being notified with an occupational mental disorder does not significantly affect health-related outcomes. A significant decrease in annual income over time was seen in both groups, the notified and the unnotified group, highlighting the importance of providing support to all employees with a mental disorder.

INTRODUCTION/AIMS: The multidisciplinary Duchenne muscular dystrophy (DMD) Care Considerations were developed to standardize care and improve outcomes. We provide cumulative cost estimates for selected key preventive (ie, excluding new molecular therapies and acute care) elements of the care considerations in eight domains (neuromuscular, rehabilitation, respiratory, cardiac, orthopedic, gastrointestinal, endocrine, psychosocial management) independent of completeness of uptake or provision of nonpreventive care. METHODS: We used de-identified insurance claims data from a large midwestern commercial health insurer during 2018. We used Current Procedural Terminology and national drug codes to extract unit costs for clinical encounters representing key preventive elements of the DMD Care Considerations. We projected per-patient cumulative costs from ages 5 to 25 years for these elements by multiplying a schedule of recommended frequencies of preventive services by unit costs in 2018 US dollars. RESULTS: Assuming a diagnosis at age 5 years, independent ambulation until age 11, and survival until age 25, we estimated 670 billable clinical events. The 20-year per-patient cumulative cost was $174 701 with prednisone ($2.3 million with deflazacort) and an expected total of $12 643 ($29 194) for out-of-pocket expenses associated with those events and medications. DISCUSSION: Standardized monitoring of disease progression and treatments may reduce overall costs of illness. Costs associated with these services would be needed to quantify potential savings. Our approach demonstrates a method to estimate costs associated with implementation of preventive care schedules.

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) phenotypes are used to describe disease progression in affected individuals. However, considerable heterogeneity has been observed across and within these two phenotypes, suggesting a spectrum of severity rather than distinct conditions. Characterizing the phenotypes and subphenotypes aids researchers in the design of clinical studies and clinicians in providing anticipatory guidance to affected individuals and their families. Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), we used K-means cluster analysis to group phenotypically similar males with pediatric-onset dystrophinopathy. We identified four dystrophinopathy clusters: Classical BMD, Classical DMD, late ambulatory DMD, and severe DMD. The clusters that we identified align with both ‘classical’ and ‘non-classical’ dystrophinopathy described in the literature. Individuals with dystrophinopathies have heterogenous clinical presentations that cluster into phenotypically similar groups. Use of clinically-derived phenotyping may provide a clearer understanding of disease trajectories, reduce variability in study results, and prevent exclusion of certain cohorts from analysis. Findings from studying subphenotypes may ultimately improve our ability to predict disease progression.

Mechanisms underlying the SARS-CoV-2-triggered hyperacute thrombo-inflammatory response that causes multi-organ damage in coronavirus disease 2019 (COVID-19) are poorly understood. Several lines of evidence implicate overactivation of complement. To delineate the involvement of complement in COVID-19, we prospectively studied 25 ICU-hospitalized patients for up to 21 days. Complement biomarkers in patient sera and healthy controls were quantified by enzyme-linked immunosorbent assays. Correlations with respiratory function and mortality were analyzed. Activation of complement via the classical/lectin pathways was variably increased. Strikingly, all patients had increased activation of the alternative pathway (AP) with elevated levels of activation fragments, Ba and Bb. This was associated with a reduction of the AP negative regulator, factor (F) H. Correspondingly, terminal pathway biomarkers of complement activation, C5a and sC5b-9, were significantly elevated in all COVID-19 patient sera. C5a and AP constituents Ba and Bb, were significantly associated with hypoxemia. Ba and FD at the time of ICU admission were strong independent predictors of mortality in the following 30 days. Levels of all complement activation markers were sustained throughout the patients’ ICU stays, contrasting with the varying serum levels of IL-6, C-reactive protein, and ferritin. Severely ill COVID-19 patients have increased and persistent activation of complement, mediated strongly via the AP. Complement activation biomarkers may be valuable measures of severity of lung disease and the risk of mortality. Large-scale studies will reveal the relevance of these findings to thrombo-inflammation in acute and post-acute COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s00430-021-00725-2.

Empirical data do not support the conclusion of a crisis of public trust in science. They do support the conclusion of a crisis of conservative trust in science: polls show that American attitudes toward science are highly polarized along political lines. In this essay, we argue that conservative hostility toward science is rooted in conservative hostility toward government regulation of the marketplace, which has morphed in recent decades into conservative hostility to government, tout court. This distrust was cultivated by conservative business leaders for nearly a century, but took strong hold during the Reagan administration, largely in response to scientific evidence of environmental crises that invited governmental response. Thus, science-particularly environmental and public health science-became the target of conservative anti-regulatory attitudes. We argue that contemporary distrust of science is mostly collateral damage, a spillover from carefully orchestrated conservative distrust of government.

The issue of hydrophilicity of the surface of gas permeable contact lenses remains one of the persistent problems. Tangible Hydra-PEG™ surface coating is applied to gas permeable contact lenses to significantly improve wettability and wearing comfort. Although it is mainly used to alleviate dry eye symptoms in scleral and corneal lens users, particularly for those patients with corneal ectasia and/or Ocular Surface Disease (OSD), it can be used in other modalities. This article describes the development of the product and describes the benefits of its use in a clinical case.

INTRODUCTION/AIMS Scoliosis is a common comorbidity among individuals diagnosed with a dystrophinopathy. We examined associations between clinical predictors and scoliosis in childhood-onset dystrophinopathy. METHODS The progression and treatment of scoliosis were obtained from data collected by the US population-based Muscular Dystrophy Surveillance, Tracking, and Research Network. Associations between loss of independent ambulation (LoA) and corticosteroid use and scoliosis outcomes (ages at or exceeding Cobb angle thresholds [10°, 20°, 30°]; surgery) were estimated using Kaplan-Meier curve estimation and extended Cox regression modeling. RESULTS We analyzed curvature data for 513 of 1054 individuals ascertained. Overall, approximately one-half had at least one radiograph and one-quarter had a curvature of at least 20°. The average maximum curvature was 25.0° (SD = 21.5°) among all individuals and 42.8° (SD = 18.8°) among those recommended for surgery. Higher adjusted hazards ratio of curvature (aHR(curvature) [95% confidence interval]) were found among individuals with LoA compared to those without LoA (aHR(10) = 6.2 [4.4, 8.7], aHR(20) = 15.3 [7.4, 31.7], aHR(30) = 31.6 [7.7, 128.9]), among individuals who did not use corticosteroids compared to those who did (aHR(10) = 1.2 [0.9, 1.7], aHR(20) = 1.8 [1.1, 2.7], aHR(30) = 2.3 [1.3, 4.0]), and among non-ambulatory individuals who used corticosteroids after LoA compared to those who did not (aHR(10) = 1.8 [1.2, 2.8], aHR(20) = 1.6 [1.0, 2.6], aHR(30) = 3.6 [1.6, 7.9]). Scoliosis surgery among individuals with LoA who did not use corticosteroids was more than double compared to those who used (aHR = 2.3 [1.3, 4.2]). DISCUSSION Our retrospective observational study suggests corticosteroids may delay spinal curvature progression and need for scoliosis surgery. Continuing corticosteroids after LoA also showed potential benefits of delaying curvature progression, additional studies are needed to confirm this finding or address the magnitude of benefit.

The endogenous opioid peptide systems are critical for analgesia, reward processing, and affect, but research on their release dynamics and function has been challenging. Here, we have developed microimmunoelectrodes (MIEs) for the electrochemical detection of opioid peptides using square-wave voltammetry. Briefly, a voltage is applied to the electrode to cause oxidation of the tyrosine residue on the opioid peptide of interest, which is detected as current. To provide selectivity to these voltammetric measurements, the carbon fiber surface of the MIE is coated with an antiserum selective to the opioid peptide of interest. To test the sensitivity of the MIEs, electrodes are immersed in solutions containing different concentrations of opioid peptides, and peak oxidative current is measured. We show that dynorphin antiserum-coated electrodes are sensitive to increasing concentrations of dynorphin in the attomolar range. To confirm selectivity, we also measured the oxidative current from exposure to tyrosine and other opioid peptides in solution. Our data show that dynorphin antiserum-coated MIEs are sensitive and selective for dynorphin with little to no oxidative current observed in met-enkephalin and tyrosine solutions. Additionally, we demonstrate the utility of these MIEs in anin vitrobrain slice preparation using bath application of dynorphin as well as optogenetic activation of dynorphin release. Future work aims to use MIEsin vivofor real-time, rapid detection of endogenous opioid peptide release in awake, behaving animals.

Introduction: Racial/ethnic differences in diagnostic and treatment services have been identified for a range of health conditions and outcomes. The current study aimed to analyze whether there are racial/ethnic differences in the timing of diagnostic testing and treatments for males with Duchenne Muscular Dystrophy (DMD). Methods: Diagnostic and clinical data for male individuals with DMD born during 1990-2010 were analyzed from eight sites (Arizona, Colorado, Georgia, Iowa, Piedmont Region of North Carolina, western New York, South Carolina, Utah) of the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet). Seven milestones related to diagnosis/treatment experiences were selected as outcomes. Times to each milestone were estimated and compared by four racial/ethnic groups using Kaplan-Meier estimation and Cox proportional hazard models. Times between initial evaluation or diagnostic testing and later milestones were also compared by race/ethnicity. Results: We identified 682 males with definite or probable DMD of whom 61.7% were non-Hispanic White, 20.5% Hispanic, 10.6% other, and 7.2% non-Hispanic Black. Seven milestone events were studied (initial evaluation, first neurology/neuromuscular visit, diagnosis, corticosteroid treatment first offered, corticosteroid treatment started, first electrocardiogram or echocardiogram, and first pulmonary function testing). The first five milestone events occurred at an older age for non-Hispanic Black individuals compared to non-Hispanic White individuals. Time from diagnosis to first offering of corticosteroids and initiation of corticosteroid therapy was later for Hispanic individuals compared to non-Hispanic White individuals. When accounting for timing of initial evaluation/diagnosis, offering of corticosteroids continued to occur later, but first pulmonary testing occurred earlier, among Hispanic individuals compared to non-Hispanic Whites. No significant delays remained for non-Hispanic Black individuals after accounting for later initial evaluation/diagnosis. Conclusion: We described racial/ethnic differences in ages at selected diagnostic and treatment milestones. The most notable differences were significant delays for five of seven milestones in non-Hispanic Black individuals, which appeared to be attributable to later initial evaluation/diagnosis. Findings for Hispanic individuals were less consistent. Efforts to address barriers to early evaluation and diagnosis for non-Hispanic Black children with DMD may promote more timely initiation of recommended disease monitoring and interventions.

The use of mechanical metamaterials in engineering applications is often limited because of uncertainty regarding their deformation behavior. This uncertainty necessitates large safety factors and assumptions about their behavior to be included in mechanical designs including metamaterials, which detracts from their greatest benefit, viz. their ultralight weight. In this study, a yield envelope was created for both a bending-dominated and a stretching-dominated cellular material topology to improve the understanding of the response of cellular materials under various load types and orientations. Experimental studies revealed that the shear strength of a cellular material is significantly lower than that predicted by Mohr’s criterion, necessitating a modification of the Mohr’s yield criterion for cellular materials. All topologies experienced tension–compression anisotropy and topology orientation anisotropy during loading, with the stretching-dominated topology experiencing the largest anisotropies.

Pathological angiogenesis (PA) contributes to various ocular diseases, including age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity, which are major causes of blindness over the world. Current treatments focus on anti-vascular endothelial growth factor (VEGF) therapy, but persistent avascular retina, recurrent intravitreal neovascularization, and general adverse effects are reported. We have previously found that recombinant thrombomodulin domain 1 (rTMD1) can suppress vascular inflammation. However, the function of rTMD1 in VEGF-induced PA remains unknown. In this study, we found that rTMD1 inhibited VEGF-induced angiogenesis in vitro. In an oxygen induced retinopathy (OIR) animal model, rTMD1 treatment significantly decreased retinal neovascularization but spared normal physiological vessel growth. Furthermore, loss of TMD1 significantly promoted PA in OIR. Meanwhile, hypoxia-inducible factor-1α, the transcription factor that upregulates VEGF, was suppressed after rTMD1 treatment. The levels of interleukin-6, and intercellular adhesion molecule-1 were also significantly suppressed. In conclusion, our results indicate that rTMD1 not only has dual effects to suppress PA and inflammation in OIR, but also can be a potential HIF-1α inhibitor for clinical use. These data bring forth the possibility of rTMD1 as a novel therapeutic agent for PA.

OBJECTIVES Venous thromboembolism (VTE) is a major cause of morbidity and mortality for surgical patients. This article aims to determine factors that may have contributed to the development of VTE in patients undergoing lateral skull base surgery, to assess the validity of the Caprini Risk Assessment Model (RAM) score in this subset of patients, and to determine the efficacy of mechanical DVT prophylaxis alone in preventing VTE. STUDY DESIGN Retrospective chart review. METHODS A retrospective chart review was conducted of patients who underwent skull base surgery for vestibular schwannoma, and the rate of VTE was assessed. Patient demographics, comorbidities, and treatment factors were examined to determine risk factors associated with the development of a postoperative thrombotic event. Caprini RAM scores were compared for patients who developed a VTE. RESULTS Among 197 patients, the rate of VTE formation was 3.5%. No individual risk factor independently contributed to the development of a thrombotic event. The mean Caprini RAM score was 4.06 in patients who did not develop a VTE and 5.14 in the patients that did develop a VTE (P = .005). The Caprini score was significant for the risk of VTE formation, with an odds ratio of 2.8 (P = .009, 95% CI = 1.3-6.2). CONCLUSION Venous thromboembolism rates are relatively low following lateral skull base surgery. While there is no individual risk factor associated with increased VTE risk, the Caprini RAM score appears to be a useful predictor of risk. The Caprini score may be useful in identifying high-risk patients who may benefit from chemoprophylaxis for VTE prevention. LEVEL OF EVIDENCE Level III-This is a retrospective chart review study Laryngoscope, 2021.

OBJECTIVE To evaluate the audiologic outcomes of microdrill fenestration for obliterative otosclerosis compared to traditional stapedotomy technique. STUDY DESIGN Retrospective chart review. SETTING Tertiary referral center. PATIENTS Adult patients undergoing stapedotomy for otosclerosis. MAIN OUTCOME MEASURES Patients were separated into groups that underwent either microdrill or laser fenestration based on intraoperative severity of disease. Audiologic outcomes and complications were compared between the two groups. RESULTS There were 588 ears in 519 patients that were evaluated. There was a significant postoperative improvement in pure tone average, air-bone gap, and mean bone conduction thresholds for both the obliterative and nonobliterative group (p

Counterproductive work behavior (CWB) is a topic of considerable importance for organizational scholars and practitioners. Yet, despite a wide-ranging consensus that negative affect (NA) is a precursor to CWB, there is surprisingly little consensus as to whether CWB enactment will subsequently lead to lower or higher levels of NA. That is, scholars disagree as to whether CWB has a reparative (negative) or generative (positive) effect on subsequent NA. We submit that both perspectives have validity, and thus the question should not be whether CWB is associated with lower or higher subsequent levels of NA, but rather for whom. This article is dedicated to answering this question. Drawing from the behavioral concordance model, we position empathy as a moderator of this relationship, such that CWB will be reparative for those with lower levels of empathy and generative for those with higher levels of empathy. Findings across 3 experience-sampling studies support our hypotheses and highlight a number of interesting directions for future research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

We report results from a dataset consisting of all courses taken by students at the City University of New York [CUNY] in fall 2019 and spring 2020. This time frame covers the semester prior to the wide-spread onset of the COVID-19 pandemic in New York City (i.e., pre-pandemic), and the semester when the coronavirus precipitated a rapid and unprecedented forced shift of all courses within the university system to a fully-online mode of instruction early in the term (i.e., pandemic term). Findings indicate that students at two-year colleges, men, and certain racial/ethnic groups had less resilient course outcomes when comparing their rates of pre-pandemic vs. pandemic course outcomes. However, these differences were observed primarily among those students who had not originally chosen to enrol in any fully online courses that year. In contrast, students who had originally chosen to enrol in fully online courses that year were much more resilient, with differences by institution type, gender, and race/ethnicity by and large not exacerbated by the pandemic.

Marine oxygen deficient zones (ODZs) promote unique plankton communities and redox environments which impact the cycling of biologically essential trace metals in the ocean. Here we use measurements of dissolved and particulate Ni concentrations and isotopes to investigate the biotic and abiotic processes controlling Ni cycling in the world’s largest ODZ, located in the Eastern Tropical North Pacific (ETNP). We observed a negative correlation between dissolved Ni concentrations and isotopic composition (δ60Ni) throughout the water column, such that Ni concentrations increased from roughly 3 nmol kg−1 to 8 nmol kg−1 over the upper 1000 m, while δ60Ni values decreased by 0.2‰ from about +1.6‰ to +1.4‰. These vertical patterns are characteristic of both the subtropical North and South Pacific, and can be explained by a combination of physical mixing of water masses and biological uptake and export, either with all of the Ni being bioavailable or with separate bioavailable and non-bioavailable Ni pools. Although evidence for additional Ni cycling processes such as sulfide precipitation or Ni sorption/desorption through Fe/Mn redox chemistry have been observed in other ODZs and euxinic waters, we found no clear evidence for these in either the redoxcline or low oxygen waters of the ETNP. Indeed, the relationship between dissolved [Ni] and δ60Ni observed in the ETNP is similar to results reported elsewhere in the subtropical North and South Pacific, falling generally on a mixing line between a surface water endmember (dissolved [Ni] = 2 nmol kg−1 and δ60Ni = +1.7‰) and a deep-water endmember (dissolved [Ni] = 6–10 nmol kg−1 and δ60Ni = ~+1.4‰). While this surface water endmember is similar to that of the Atlantic, the deep endmember in the Pacific is approximately 0.1‰ heavier than deep Atlantic Ni. This subtle isotopic difference suggests gradual accumulation of isotopically heavy Ni isotopes in the deep ocean, consistent with recent evidence of heavy Ni remobilization during early diagenesis. Lastly, in the ETNP, particulate δ60Ni is generally ~0.5‰ lighter than the dissolved Ni pool, and this pattern is consistent across both the euphotic zone and redoxcline, suggesting that biological export from the euphotic zone is the primary source of particulate Ni to the deep ocean.

OBJECTIVE: To examine the associations between social determinants of health (SDOH) and prevalent overweight/obesity status and change in adiposity status among American Indian and Alaska Native (AI/AN) children. METHODS: The study sample includes 23,950 AI/AN children 2–11 years of age, who used Indian Health Service (IHS) from 2010 to 2014. Multivariate generalized linear mixed models were used to examine the following: (1) cross-sectional associations between SDOH and prevalent overweight/obesity status and (2) longitudinal associations between SDOH and change in adiposity status over time. RESULTS: Approximately 49% of children had prevalent overweight/obesity status; 18% had overweight status and 31% had obesity status. Prevalent severe obesity status was 20% in 6–11-year olds. In adjusted cross-sectional models, children living in counties with higher levels of poverty had 28% higher odds of prevalent overweight/obesity status. In adjusted longitudinal models, children 2–5 years old living in counties with more children eligible for free or reduced-priced lunch had 15% lower odds for transitioning from normal-weight status to overweight/obesity status. CONCLUSIONS: This work contributes to accumulating knowledge that economic instability, especially poverty, appears to play a large role in overweight/obesity status in AI/AN children. Research, clinical practice, and policy decisions should aim to address and eliminate economic instability in childhood.

The micronutrient iron plays a major role in setting the magnitude and distribution of primary production across the global ocean. As such, an understanding of the sources, sinks, and internal cycling processes that drive the oceanic distribution of iron is key to unlocking iron's role in the global carbon cycle and climate, both today and in the geologic past. Iron isotopic analyses of seawater have emerged as a transformative tool for diagnosing iron sources to the ocean and tracing biogeochemical processes. In this review, we summarize the end-member isotope signatures of different iron source fluxes and highlight the novel insights into iron provenance gained using this tracer. We also review ways in which iron isotope fractionation might be used to understand internal oceanic cycling of iron, including speciation changes, biological uptake, and particle scavenging. We conclude with an overview of future research needed to expand the utilization of this cutting-edge tracer. Expected final online publication date for the

Green infrastructure (GI) initiatives, including programs to plant trees and install bioswales, have been adopted by a growing number of local government and non-governmental organizations. While the details of these programs vary, a common characteristic of most Canadian and US GI initiatives is a distributed approach that includes both public and private land. To date, little research has explored residents’ knowledge of GI or their engagement with related initiatives even though residents’ installation of GI is often key to creating distributed GI networks. In this study, we (1) assess residents’ knowledge of the term GI, (2) identify residents’ level of engagement with GI initiatives, and (3) examine whether factors like level of concern about local environmental issues can predict GI knowledge or level of engagement with GI initiatives. We explored these objectives through a survey of residents in Toronto (Ontario, Canada) and Philadelphia (Pennsylvania, US). We found that about a quarter of survey respondents in both cities had previously heard the term “green infrastructure”. Neither knowledge of GI nor level of engagement with GI initiatives could be predicted by the level of concern about local environmental issues, but residents’ interest in using their outdoor space for nature activities (e.g., gardening) predicted GI knowledge in both cities and level of initiative engagement in Philadelphia. Our results suggest the need for widespread education campaigns that clearly define GI so that residents can be participants in policy discussions, link it with their needs, and identify ways to manage GI to create desired benefits.