Search

Background We describe the clinical course of medical and surgical patients who received naloxone on general hospital wards for suspected opioid-induced respiratory depression (OIRD). Methods From May 2018 through October 2020, patients who received naloxone on hospital wards were identified and their records reviewed for incidence and clinical course. Results There were 86,030 medical and 106,807 surgical admissions. Naloxone was administered to 99 (incidence 11.5 [95% confidence interval 9.4–14.0] per 10,000 admissions) medical and 63 (5.9 [95% confidence interval 4.5–7.5]) surgical patients (P Conclusion Medical inpatients are more likely to suffer OIRD than are surgical inpatients despite lower opioid doses. Definitive OIRD was confirmed in 77% of patients because of immediate naloxone response, whereas 23% of patients did not respond, and this subset was more likely to need a higher level of care and had a higher 30-day mortality rate. Careful monitoring of mental and respiratory variables is necessary when opiates are used in hospital.

In congenital diaphragmatic hernia (CDH), ultrasound (U/S) measurements of the contralateral lung commonly provide the observed-to-expected lung-to-head ratio (O/E LHR) and are used to determine the severity of pulmonary hypoplasia. Fetal magnetic resonance imaging (MRI) measurement of the observed-to-expected total lung volume (O/E TLV) has been used as an adjunct to O/E LHR in predicting outcomes. Since O/E LHR only measures the contralateral lung, we sought to investigate if MRI measurements of the contralateral lung volume (O/E CLV) can accurately predict outcomes in CDH. We hypothesize that O/E CLV is a better predictor of CDH outcomes than O/E LHR. We identified all infants with a prenatal diagnosis of CDH at our fetal center who had both MRI and U/S measurements. Using lung volume ratios of right–left 55:45, we calculated O/E CLV from O/E TLV. We used receiver-operating characteristic (ROC) curves to calculate the area under the curve (AUC) to compare the predictive accuracy of O/E CLV to O/E LHR for ECMO support, as well as survival to both discharge and 1 year. Seventy-four patients had complete prenatal imaging with 39% requiring ECMO support. The median O/E CLV was 48.0% and the median O/E LHR was 42.3%. O/E CLV was a better predictor of the need for ECMO support (AUC 0.81 vs. 0.74). O/E CLV was a better predictor of survival to discharge (AUC 0.84 vs. 0.64) and 1-year survival (AUC 0.83 vs. 0.63) than O/E LHR. O/E LHR is a well-validated standard for predicting outcomes and guiding prenatal counseling in CDH. We provide evidence that fetal MRI measurements of the contralateral lung volume corrected for gestational age were more accurate in predicting the need for ECMO and survival. Future prospective studies validating O/E CLV regarding outcomes and ECMO utilization are warranted. Level III, retrospective comparative study.

A 62-year-old woman with human T-lymphotropic virus type 1 cell lymphoma developed heart failure after mogamulizumab, an immunotherapy agent. Clinical presentation and cardiac magnetic resonance imaging were consistent with myocarditis, and a recurrence of heart failure occurred after rechallenge with the therapy. (Level of Difficulty: Advanced.), Central Illustration

BACKGROUND The frequency and temporal distribution of postoperative respiratory depression (RD) events are not completely understood. This study determined the temporal distribution and frequency of RD episodes in postsurgical patients continuously monitored by bedside capnography and pulse oximetry. METHODS This was a post hoc study of a subset of postsurgical patients enrolled in The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) trial from 2 sites in the United States. These patients had undergone continuous bedside monitoring on general care wards. These data were adjudicated for potential RD episodes. The number of RD episodes per patient and the time of each RD episode were determined. The first RD episode experienced by a patient was classified as an "initial" episode, and the initial and all subsequent RD episodes experienced by a patient were classified as "all" episodes. A PRODIGY risk score was calculated. RESULTS Data analyzed from 250 patients contained 2539 RD episodes in 155 (62.0%, 95% confidence interval, 55.7-68.0) patients with median 2 [0-8], range of 0-545 RD episodes per patient, with a PRODIGY risk score distribution of 100 (40.0%) low, 79 (31.6%) intermediate, 70 (28.0%) high (missing data from 1 patient). Median time to the initial RD episode was 8.8 [5.1-18.0] hours postoperatively. There was a peak occurrence of initial RD events between 14:00 and 20:00 on the day of surgery, and these were associated with a large number of subsequent events in the same timeframe. The peak time of all RD episodes occurred from 02:00 to 06:00. Patients with high PRODIGY risk scores had higher incidence and greater number of RD episodes per patient (P < .001, overall comparisons between groups for both incidence [χ2] and number of episodes [Kruskal-Wallis test]). CONCLUSIONS Continuous monitoring of surgical patients demonstrates that RD episodes are common, and risk increases with higher PRODIGY scores. In this patient cohort, the rate of initial RD episodes peaked in the afternoon to early evening, while peak rate of all RD episodes occurred in early morning. Further, among patients with RD episodes, the number of episodes increased with higher PRODIGY scores.

The goal of this study was to determine the feasibility of identifying the anal dimple (AD) on routine prenatal ultrasound. Using the presence, absence, appearance, and location of the anal dimple as an indirect sign for possible underlying anorectal malformations (ARM), we hypothesize that evaluation of the anal dimple as part of the fetal anatomic survey may increase the sensitivity in detecting less severe ARMs. In a prospective longitudinal observational study, pregnant women who underwent prenatal ultrasound (US) at the Colorado Fetal Care Center between January 2019 and 2020 were enrolled. The variables recorded included gestational age, singleton versus multiple pregnancy, gender of the fetus, visualization of the AD, and reason for non-visualization of the AD. A total of 900 ultrasounds were performed, evaluating 1044 fetuses, in 372 different pregnant women. Gestational ages ranged from 16 to 38 weeks. The AD was visualized in 612 fetuses (58.6%) and not seen in 432 (41.4%). The two most common reasons for non-visualization were extremes in gestational age (n = 155; 36%) and fetal position (n = 152; 35.3%). The optimal gestational age range for AD visualization was 28–33 weeks + 6 days, with 78.1% visualization rate. Visualization of the anal dimple by ultrasound is feasible and may aid in the detection of less severe ARMs, ultimately impacting pregnancy management and family counseling. The optimal timing for anal dimple visualization is late second and third trimester.

Resumo Fundamento A doença de Chagas (DC) constitui uma causa potencial negligenciada de doença microvascular coronariana (DMC). Objetivos Comparar pacientes com DMC relacionada à DC (DMC-DC) com pacientes com DMC ligada a outras etiologias (DMC-OE). Métodos De 1292 pacientes estáveis, encaminhados para angiografia coronária invasiva para elucidar o padrão hemodinâmico e a causa de angina, 247 apresentaram coronárias subepicárdicas normais, e 101 foram incluídos após aplicação dos critérios de exclusão. Desses, 15 compuseram o grupo de DMC-DC e suas características clínicas, hemodinâmicas, angiográficas, e cintilográficas foram comparadas às do grupo de 86 pacientes com DMC-OE. O nível de significância estatística para todas as comparações adotado foi de 0,05. Resultados Pacientes com suspeita de DMC-DC apresentaram características antropométricas, clínicas e angiográficas, além de alterações hemodinâmicas e de perfusão miocárdica estatisticamente comparáveis às detectadas nos 86 pacientes com DMC-OE. Disfunção ventricular diastólica, expressa por elevada pressão telediastólica do ventrículo esquerdo, foi igualmente encontrada nos dois grupos. Entretanto, em comparação a esse grupo com DMC-OE, o grupo com DMC-DC exibiu fração de ejeção ventricular esquerda mais baixa (61,1 ± 11,9 vs 54,8 ± 15,9; p= 0,049) e mais elevado escore de mobilidade da parede ventricular (1,77 ± 0,35 vs 1,18 ± 0,26; p= 0,02). Conclusão A cardiomiopatia crônica da doença de Chagas esteve associada à etiologia de possível doença microvascular coronariana em 15% de amostra de 101 pacientes estáveis, cujo sintoma principal era angina requerendo elucidação por angiografia invasiva. Embora os grupos DMC-DC e DMC-OE apresentassem características clínicas, hemodinâmicas, e de perfusão miocárdica em comum, a disfunção global e segmentar do ventrículo esquerdo foi mais grave nos pacientes com DMC associada à DC em comparação à DMC por outras etiologias. (Arq Bras Cardiol. 2020; 115(6):1094-1101) Abstract Background Chagas disease (CD) as neglected secondary form of suspected coronary microvascular dysfunction (CMD). Objectives Comparison of patients with CMD related to CD (CMD-CE) versus patients with CMD caused by other etiologies (CMD-OE). Methods Of 1292 stable patients referred for invasive coronary angiography to elucidate the hemodynamic pattern and the cause of angina as a cardinal symptom in their medical history, 247 presented normal epicardial coronary arteries and 101 were included after strict exclusion criteria. Of those, 15 had suspected CMD-CE, and their clinical, hemodynamic, angiographic and scintigraphic characteristics were compared to those of the other 86 patients with suspected CDM-OE. Level of significance for all comparisons was p < 0.05. Results Patients with suspected CMD-CE showed most anthropometric, clinical, angiographic hemodynamic and myocardial perfusion abnormalities that were statistically similar to those detected in the remaining 86 patients with suspected CMD-OE. LV diastolic dysfunction, expressed by elevated LV end-diastolic pressure was equally found in both groups. However, as compared to the group of CMD-OE the group with CMD-CE exhibited lower left ventricular ejection fraction (54.8 ± 15.9 vs 61.1 ± 11.9, p= 0.049) and a more severely impaired index of regional wall motion abnormalities (1.77 ± 0.35 vs 1.18 ± 0.26, p= 0.02) respectively for the CMD-OE and CMD-CE groups. Conclusion Chronic Chagas cardiomyopathy was a secondary cause of suspected coronary microvascular disease in 15% of 101 stable patients whose cardinal symptom was anginal pain warranting coronary angiography. Although sharing several clinical, hemodynamic, and myocardial perfusion characteristics with patients whose suspected CMD was due to other etiologies, impairment of LV segmental and global systolic function was significantly more severe in the patients with suspected CMD related to Chagas cardiomyopathy. (Arq Bras Cardiol. 2020; 115(6):1094-1101)

Background Postoperative in-hospital pneumonia is a serious complication. This study aims to investigate the association between 3 preoperative stratification tools (American Society of Anesthesiologists Physical Status [ASA-PS] score, Charlson Comorbidity Index [CCI], and Rockwood Frailty Deficit Index [FI]) and risk for postoperative pneumonia. Methods We identified adult patients who developed postoperative pneumonia following noncardiothoracic surgery under general anesthesia, between January 1, 2016 and December 31, 2017. Patients with postoperative pneumonia were 1:1 matched to control subjects based on age, sex, and the exact type of operations. Medical records were reviewed to identify variables that may be associated with risk for developing postoperative pneumonia. Analyses adjusted for clinical characteristics were performed using the conditional logistic regression, taking into account 1:1 matched set case-control study design. Results We identified 211 cases of postoperative pneumonia, and all 3 tested stratification tools were associated with increased risk: ASA-PS (after all adjustments of American Society of Anesthesiologists (ASA) III, odds ratio 4.17 [95% confidence interval 1.74-10.01]; ASA > III 24.03 [6.54-88.32]), CCI (CCI values > 3, 1.29 [1.02-1.63] per unit CCI score), and frail FI score 3.25 (1.45-7.27). Because of incomplete intake documentation, the FI could not be calculated in 57 (13.5%) patients, but these “unknown frailty” patients were also at increased risk for postoperative pneumonia, 3.15 (1.29-7.72). Discussion Three commonly used stratification indices (ASA-PS score, CCI, and FI) were associated with increased risk for postoperative pneumonia. Patients unable to complete intake form to calculate the FI were also at increased risk.

Objective To determine the rate and clinical factors associated with postoperative nausea and vomiting (PONV) and severe pain after robotic-assisted mitral valve repair. Design Retrospective chart review. Setting Major quaternary academic medical center. Participants Adult patients undergoing robotic-assisted mitral valve repair from May 5, 2018 through September 13, 2019. Interventions Participant electronic medical records were abstracted for clinical characteristics, PONV within the first 72 postoperative hours, episodes of severe pain (defined as pain score ≥7 using an 11-point numerical pain rating scale), and opioid use within the first 24 postoperative hours. Multivariate analyses were performed. Measurements and Main Results Of 124 participants, PONV was noted in 83 (67%; 95% confidence interval [CI] 58%-75%) patients and severe pain in 96 (77%, 95% CI 69%-84%) patients. The median (interquartile range) time to PONV was 6.1 (3.7-14.7) hours. After adjusting for age, sex, and duration of surgery, pre-incisional use of methadone was associated with reduced risk for severe pain (odds ratio 0.40 [95% CI 0.16-0.99]; p = 0.048) and a lower 24-postoperative hour opioid requirement (estimate –29.0 mg intravenous morphine equivalents [95% CI –46.7 to –11.3]; p = 0.006). However, methadone was not associated with a reduction of the cumulative opioid dose (intraoperative and 24-hour postoperative opioid dose; p = 0.248). Both severe pain and PONV were associated with longer hospital stay. Conclusion PONV and severe pain are common after robotic-assisted mitral valve repair. Peri-incisional methadone is associated with a modest decrease in the severe pain rate but without a reduction in opioid dose or hospital stay.

With the advent of routine prenatal imaging, the number of renal anomalies identified prenatally has significantly increased; however, the underlying etiologies of these anomalies and the clinical significance of these findings remains unclear. This confusion is especially true for the prenatal diagnosis of cystic renal changes. The terms “cystic kidney disease” and “renal cystic dysplasia” encompass myriad renal diseases. Although renal cystic dysplasia in infants shares many similarities with multicystic dysplastic kidney (MCDK), it is important to distinguish MCDK from other etiologies that would lead to renal cysts, to ensure proper patient diagnosis and appropriate counseling regarding risks and to guide clinical management. The purpose of this review is to highlight the multiple etiologies of cystic kidney disease, including genetic associations, associations with underlying syndromes, and associations with underlying anatomical abnormalities. Here we focus on prenatal imaging, associated pathological findings, and clinical significance, with an emphasis on the defining characteristics of MCDK as compared to other forms of cystic renal disease.

Background Atopic dermatitis (AD) patients are often colonized with Staphylococcus aureus, and staphylococcal biofilms have been reported on adult AD skin lesions. The commensal S epidermidis can antagonize S aureus, although its role in AD is unclear. We sought to characterize S aureus and S epidermidis colonization and biofilm propensity and determine their associations with AD severity, barrier function, and epidermal gene expression in the first US early-life cohort of children with AD, the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH). Methods The biofilm propensity of staphylococcal isolates was assessed by crystal violet assays. Gene expression of filaggrin and antimicrobial alarmins S100A8 and S100A9 was measured in keratinocyte RNA extracted from skin tape strips. Staphylococcal biofilms sampled from MPAACH skin were visualized using scanning electron microscopy. Results Sixty-two percent of staphylococcal isolates (sampled from 400 subjects) formed moderate/strong biofilms. Sixty-eight percent of subjects co-colonized with both staphylococcal species exhibited strains that formed cooperative mixed-species biofilms. Scanning electron microscopy verified the presence of staphylococcal biofilms on the skin of MPAACH children. Staphylococcus aureus strains showing higher relative biofilm propensity compared with S epidermidis were associated with increased AD severity (P = .03) and increased lesional and nonlesional transepidermal water loss (P = .01, P = .03). Conclusions Our data suggest a pathogenic role for S aureus biofilms in AD. We found that strain-level variation in staphylococcal isolates governs the interactions between S epidermidis and S aureus and that the balance between these two species, and their biofilm propensity, has important implications for AD.

This work was supported by Fundação para a Ciência e a Tecnologia and Programa Operacional de Potencial Humano/Fundo Social Europeu (SFRH/BD/77592/2011 to Mariana L. Carrito). Previous studies have highlighted the influence of conditional mating strategies in attractiveness preferences. "Good genes" and dominance cues are perceived as attractive when considering short-term relationships. In contrast, cues for better parenting abilities and trustworthiness are considered more attractive when participants ponder a long-term relationship. We investigated women's and men's attractiveness preferences in other-sex faces that were structurally altered along a continuum of apparent trustworthiness. Faces were adjusted in shape toward the perceived trustworthy-untrustworthy extremes defined on the basis of previously created prototypes. We anticipated that perceived trustworthiness would be more important for long-term than short-term relationships because of the greater costs of exploitation. Also, we explored individual differences in preferences, anticipating that participants with high social interaction anxiety would prefer more trustworthy-looking faces. As expected, we found a preference for more trustworthy-looking faces when participants considered a long-term versus a short-term relationship. Social interaction anxiety correlated positively with trustworthiness preferences, probably reflecting an avoidance response in anxious individuals, induced by untrustworthy cues. Collectively, these findings constitute novel evidence of the influence of individual differences in mate choice-relevant face preferences. Postprint

In our introduction to this Special Issue on early modern cities and globalization, we explore the current place of cities before 1850 in global urban history and address the promise of a greater focus on their role. We argue that the interplay between the large scale and the small scale in the imperial global city is an essential dialogical force in the formation of each city's relationship to the wider early modern world. Furthermore, early modern global urban history can help explain the creation of spaces that facilitated connections between distant, global locations, as well as illuminate the emergence of networks of exchange between city communities around the globe. Yet, it also reveals the tense, messy negotiation of the meaning of these urban spaces, as well as the incredibly diverse communities they harboured.

Objectives: There is a paucity of evidence to guide the perinatal management of difficult airways in fetuses with micrognathia. We aimed to (1) develop a postnatal grading system based on the extent of airway intervention required at birth to assess the severity of micrognathic airways and (2) compare trends in airway management and outcomes by location of birth [nonfetal center (NFC), defined as a hospital with or without an NICU and no fetal team, versus fetal center (FC), defined as a hospital with an NICU and fetal team]. Methods: We retrospectively reviewed the prenatal and postnatal records of all neonates diagnosed with micrognathia from January 2010 to April 2018 at a quaternary children’s hospital. We developed a novel grading scale, the Micrognathia Grading Scale (MGS), to grade the extent of airway intervention at birth from 0 (no airway intervention) to 4 (requirement of EXIT or advanced airway instrumentation for airway securement). Results: We identified 118 patients with micrognathia. Eighty-nine percent (105/118) were eligible for grading using the MGS. When the MGS was applied, the airway grades were as follows: grade 0 (30%), grade 1 (10%), grade 2 (9%), grade 3 (48%), and grade 4 (4%). A quarter of micrognathic patients with grade 0–2 airways had postnatal hospital readmissions for airway obstruction after birth, of which all were born at NFC. Over 40% of patients with grade 3–4 micrognathic airways required airway intervention within 24 h of birth. Overall, NFC patients had a readmission rate of (27%) for airway obstruction after birth compared to FC patients (17%). Conclusions: Due to the high incidence of grade 3–4 airways on the MGS in micrognathic patients, fetuses with prenatal findings suggestive of micrognathia should be referred to a comprehensive fetal care center capable of handling complex neonatal airways. For grade 0–2 airways, infants frequently had postnatal complications necessitating airway intervention; early referral to a multidisciplinary team for both prenatal and postnatal airway management is recommended.

Background Periodontitis has been associated with coronary artery disease, but the impact of a periodontal treatment on the endothelial function of patients with a recent ST-segment elevation myocardial infarction (STEMI) was not investigated. Methods Randomized controlled trial ( NCT02543502 ). Patients admitted between August 2012 and January 2015 were included. Patients were screened during the index hospitalization for STEMI, and those with severe periodontal disease were randomized 2 weeks later to periodontal treatment or to control. The primary endpoint of this trial was the between group difference in the variation of flow-mediated vasodilation (FMD) in the brachial artery assessed by ultrasound from baseline to the 6-month follow-up. Secondary outcomes were cardiovascular events, adverse effects of periodontal treatment and inflammatory markers. Results Baseline characteristics were balanced between patients in the intervention (n = 24) and control groups (n = 24). There was a significant FMD improvement in the intervention group (3.05%; p = .01), but not in the control group (−0.29%; p = .79) (p = .03 for the intergroup comparison). Periodontal treatment was not associated with any adverse events and the inflammatory profile and cardiovascular events were not significantly different between both groups. Conclusions Treatment of periodontal disease improves the endothelial function of patients with a recent myocardial infarction, without adverse clinical events. Larger trials are needed to assess the benefit of periodontal treatment on clinical outcomes. Clinical trial registration NCT02543502 ( https://clinicaltrials.gov/ct2/show/NCT02543502?term=NCT02543502&rank=1 ).

Summary Background Patients with rheumatoid arthritis have increased risk of seasonal influenza and influenza-related complications but have reduced vaccine immunogenicity. It is unknown whether patients with rheumatoid arthritis would benefit from more immunogenic vaccine formulations. This study investigated the immunogenicity and safety of a high-dose trivalent inactivated influenza vaccine (HD-TIV) in patients with rheumatoid arthritis compared to a standard-dose quadrivalent influenza vaccine (SD-QIV). Methods This study was a treatment-stratified, randomised, double-blind trial to compare the immunogenicity and safety of SD-QIV (15 μg of haemagglutinin [HA] per strain) versus HD-TIV (60 μg of HA per strain) in adults with rheumatoid arthritis who are positive for rheumatoid factor or anti-cyclic citrullinated peptide, or both, recruited during the 2016–17 and 2017–18 influenza seasons at three hospitals affiliated with McGill University (Montreal, QC, Canada). Participants had received treatment for rheumatoid arthritis with conventional or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) or biological DMARDs, or combinations of them, were still on treatment at the time of enrolment, and their treatment had not been modified during the 3 months before enrolment. They were stratified into one of three groups according to treatment. Patients who, at enrolment, were taking conventional or targeted synthetic DMARDs (methotrexate, hydroxychloroquine, and sulfasalazine) as monotherapy or in combination were stratified to group 1; those who were taking a biological DMARD (anti-tumour necrosis factor or anti-interleukin 6), with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 2; and those who were taking abatacept, tofacitinib, or rituximab, with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 3. Participants were randomly allocated (1:1) to receive the SD-QIV or HD-TIV vaccine. Randomisation was based on a computer-generated allocation sequence, and participants, investigators, and research nurses responsible for safety assessments were masked to vaccine assignment. The primary outcome was the seroconversion rate (as measured by haemagglutination-inhibition assay) per strain at day 28. Analysis was done in the modified intention-to-treat population, which included all randomly assigned participants for whom seroconversion status was available. Safety was assessed throughout the surveillance period (day 0–186). This trial is registered at ClinicalTrials.gov , number NCT02936180 . Findings Between Oct 24, 2016, and Dec 6, 2017, 696 patients with rheumatoid arthritis were invited to participate in the study and 279 were randomly assigned and vaccinated (140 [50%] received SD-QIV and 139 [50%] HD-TIV). 136 patients who received SD-QIV and 138 who received HD-TIV were included in the modified intention-to-treat anaysis. Patients who received HD-TIV were more likely to seroconvert than those who received SD-QIV: the odds ratio was 2·99 (95% CI 1·46–6·11) for seroconversion to strain A/H3N2, 1·95 (1·19–3·22) for seroconversion to strain B/Bris, 3·21 (1·57–6·56) for seroconversion to strain A/H1N1 (in 2016–2017), and 2·44 (1·18–5·06) for seroconversion to strain A/H1N1 (in 2017–2018). Similar results were observed in patients from groups 1 and 2; the number of individuals in group 3 was insufficient to draw conclusions. Local and systemic adverse events were similar in both vaccine groups, no serious adverse events were reported between days 0 and 28 in any group, and neither vaccine increased rheumatoid arthritis disease activity. Interpretation Our data suggest that in patients with seropositive rheumatoid arthritis, HD-TIV is safe and more immunogenic than SD-QIV. These results are the first evidence to support the use of the HD-TIV in these patients. Funding The Arthritis Society-Canada.

Made available in DSpace on 2022-04-28T19:47:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Deutsche Forschungsgemeinschaft The genus Brachycephalus is a fascinating group of miniaturized anurans from the Brazilian Atlantic Forest, comprising the conspicuous, brightly colored pumpkin-toadlets and the cryptic flea-toads. Pumpkin-toadlets are known to contain tetrodotoxins and therefore, their bright colors may perform an aposematic function. Previous studies based on a limited number of mitochondrial and nuclear-encoded markers supported the existence of two clades containing species of pumpkin-toadlet phenotype, but deep nodes remained largely unresolved or conflicting between data sets. We use new RNAseq data of 17 individuals from nine Brachycephalus species to infer their evolutionary relationships from a phylogenomic perspective. Analyses of almost 5300 nuclear-encoded ortholog protein-coding genes and full mitochondrial genomes confirmed the existence of two separate pumpkin-toadlet clades, suggesting the convergent evolution (or multiple reversals) of the bufoniform morphology, conspicuous coloration, and probably toxicity. In addition, the study of the mitochondrial gene order revealed that three species (B. hermogenesi, B. pitanga, and B. rotenbergae) display translocations of different tRNAs (NCY and CYA) from the WANCY tRNA cluster to a position between the genes ATP6 and COIII, showing a new mitochondrial gene order arrangement for vertebrates. The newly clarified phylogeny suggests that Brachycephalus has the potential to become a promising model taxon to understand the evolution of coloration, body plan and toxicity. Given that toxicity information is available for only few species of Brachycephalus, without data for any flea-toad species, we also emphasize the need for a wider screening of toxicity across species, together with more in-depth functional and ecological study of their phenotypes. Instituto de Biociências Departamento de Biodiversidade (Campus Rio Claro) Universidade Estadual Paulista (UNESP), Avenida 24A, N 1515, Bela Vista, SP Zoological Institute Technische Universität Braunschweig Institute for Microbiology and Genetics Department of Applied Bioinformatics University of Goettingen, Goldschmidtstr, 1 Max Planck Institute for Evolutionary Biology Unidade Passos Universidade do Estado de Minas Gerais (UEMG), Avenida Juca Stockler 1130, MG Laboratório de Sistemática de Vertebrados Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga 6681, RS Departamento de Ciências Biológicas Universidade Estadual de Santa Cruz, BA Laboratório de História Natural de Anfíbios Brasileiros (LaHNAB) Departamento de Biologia Animal Instituto de Biologia Universidade Estadual de Campinas, SP Instituto de Biociências Departamento de Biodiversidade (Campus Rio Claro) Universidade Estadual Paulista (UNESP), Avenida 24A, N 1515, Bela Vista, SP CNPq: 163546/2020-7 FAPESP: 2018/09691-0 CNPq: 300896/2016-6 CNPq: 302834/2020-6 CNPq: 304999/2015-6 CAPES: 88881.062205/2014-01 Deutsche Forschungsgemeinschaft: VE247/16-1–HO 3492/6-1

BACKGROUND The atopic march has been studied mostly in White populations, biasing our current paradigms. OBJECTIVE We sought to define the atopic march in Black and White children and explore mechanisms for racial differences. METHODS Utilizing the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort (n = 601), we assessed longitudinal sensitization, food allergy (FA), allergic rhinitis, risk of asthma development (through the Pediatric Asthma Risk Score), Scoring for Atopic Dermatitis (SCORAD), transepidermal water loss, skin filaggrin (FLG) expression, exposures, and genetic heritability to define AD progression endotypes in Black and White children. RESULTS White MPAACH children were more likely to be sensitized to aero and food allergens (P = .0001) and over 3 times more likely to develop FA and/or allergic rhinitis (AR) without asthma risk (P < .0001). In contrast, Black children were over 6 times more likely to proceed to high asthma risk without FA, sensitization, or AR (P < .0001). White children had higher lesional and nonlesional transepidermal water loss (both P < .001) as well as decreased nonlesional keratinocyte FLG expression (P = .02). Black children had increased genetic heritability for asthma risk and higher rates of exposures to secondhand smoke and traffic-related air pollution. CONCLUSIONS Black and White children with AD have distinct allergic trajectories defined by different longitudinal endotypes. Black children exhibit higher asthma risk despite a more intact skin barrier and less sensitization, FA, and AR. White children have less asthma risk, despite a more dysfunctional skin barrier, and more FA, AR, and sensitization. The observed racial differences are likely due in part to increased genetic heritability for asthma risk and harmful environmental exposures in Black children. Collectively, our findings provide a new paradigm for an atopic march that is inclusive of Black children.

This study tested the hypothesis that exposure of children prior to their third birthday to procedures requiring general anesthesia is associated with an increased incidence of autism spectrum disorder (ASD) in later life. This study employed a nested, 1:2 matched-case control study design using ASD cases identified in a population-based birth cohort of children born in Olmsted County, MN from 1976 to 2000. Matching variables included sex, date of birth, and mother’s age in conditional logistic regression including 499 ASD cases and 998 controls. After adjusting for birth weight and health status, there was no significant association between exposure and ASD (OR 1.27 [95% CI 0.92–1.76]), indicating that general anesthesia is not associated with an increased risk of ASD.

Background: microRNAs (miRNAs) are directly associated with inflammatory response, but their direct role in CRSwNP (chronic rhinosinusitis with nasal polyps) remains evasive. This study aimed to compare the expression of several miRNAs in tissue samples obtained from patients with CRSwNP and controls and to evaluate if miRNAs correlate to a specific inflammatory pattern (T1, T2, T17, and Treg) or intensity of symptoms in CRSwNP. Methods: nasal polyps (from patients with CRSwNP – n=36) and middle turbinate mucosa (from control patients – n=41) were collected. Microarray determined human mature miRNA expression, and the results obtained were validated by qPCR. miRNAs that were differentially expressed were then correlated to cytokine proteins (by Luminex), tissue eosinophilia, and SNOT-22. Results: After microarray and qPCR analyses, six microRNAs were up-regulated in CRSwNP samples when compared with controls: miR-205-5p, miR-221-3p, miR-222-3p, miR-378a-3p, miR-449a and miR-449b-5p. All these miRNAs are directly implicated with cell cycle regulation and apoptosis, and to a minor extent, with inflammation. Importantly, miR-205-5p showed a significantly positive correlation with IL-5 concentration and eosinophil count at the tissue and with the worst SNOT-22 score. Conclusions: miRNA 205-5p was increased in CRSwNP compared to controls, and it was especially expressed in CRSwNP patients with higher T2 inflammation (measured by both IL-5 levels and local eosinophilia) and worst clinical presentation. This miRNA may be an interesting target to be explored in patients with CRSwNP.

BackgroundDomoic acid (DA) is a naturally occurring neurotoxin harmful to marine animals and humans. California sea lions exposed to DA in prey during algal blooms along the Pacific coast exhibit significant neurological symptoms, including epilepsy with hippocampal atrophy.ObservationsHere we describe a xenotransplantation procedure to deliver interneuron progenitor cells into the damaged hippocampus of an epileptic sea lion with suspected DA toxicosis. The sea lion has had no evidence of seizures following the procedure, and clinical measures of well-being including weight and feeding habits have stabilized.LessonsThese preliminary results suggest xenotransplantation has improved the quality-of-life (QOL) for this animal and holds tremendous therapeutic promise.

OBJECTIVES Excessive adiposity is associated with cardiovascular disease (CVD). Anthropometric indices are useful in screening individuals at higher risk for these diseases. However, there are no studies that show which of these indices has the best discriminatory power among Afro-descendant Brazilian women. The objective of this study was to assess the accuracy of anthropometric indices in identifying risk factors for CVD in Afro-descendant Brazilian women and define the one most suitable for use under the operating conditions prevailing in Quilombola communities. METHODS A household random sample of 1661 women descendants of African slaves were analyzed. The anthropometric predictors analyzed were waist circumference (WC), body mass index, waist-to-height ratio, conicity index (C-index), body shape index, and percentage of body fat (%BF; estimated by bioimpedance). The assessed risk factors for CVD were arterial hypertension, diabetes mellitus, and dyslipidemias (hypertriglyceridemia; hypercholesterolemia; low high-density lipoprotein). To identify the statistical significance between the differences in the areas under the ROC curves (AUC) obtained with the different predictors and outcomes, was used the Bonferroni test adjusted for multiple analyses by the Sidak method. RESULTS The AUC obtained with WC was higher (p .05) to those obtained with the other predictors 29 times out of 30 possibilities (six predictors x five outcomes). Only the AUC obtained with C-index in identifying hypercholesterolemia was significantly higher than that with WC. CONCLUSION Due to its accuracy and greater operational simplicity, WC was the most adequate predictor for identifying Afro-descendant women at greatest risk for CVD.

Introduction Preclinical studies suggest that inhalational anesthetics may induce neuropathology changes in the nigrostriatal system, leading to development of α-synucleinopathies. We explored the role of general anesthesia in the development of Parkinson disease (PD) and other α-synucleinopathies. Methods All α-synucleinopathy cases in Olmsted County, Minnesota, from January 1991, to December 2010, were identified from diagnostic codes, and then reviewed for type and index date of diagnosis. Cases were matched by sex and age (±1 year) to a referent control, a resident living in Olmsted County, and free of α-synucleinopathies before the index date (year of onset of the α-synucleinopathy). Medical records of both cases and controls were reviewed for lifetime exposure to anesthesia prior to the index date. Results A total of 431 cases with clinically defined α-synucleinopathies were identified. Of these, 321 (74%) underwent 1,069 procedures under anesthesia before the diagnosis date, and in the control group, 341 (79%) underwent 986 procedures. When assessed as a dichotomous variable, anesthetic exposure was not significantly associated with α-synucleinopathies (odds ratio [OR], 0.75; 95% CI, 0.54-1.05; P=.094). No association was observed when anesthetic exposure was quantified by the number of exposures (OR, 0.64, 0.89, and 0.74, for 1, 2–3, and ≥4 exposures, respectively, compared to no exposure as the reference; P=.137) or quantified by the cumulative duration of exposure assessed as a continuous variable (OR, 1.00; 95% CI, 0.97-1.02 per 1-h increase of anesthetic exposure; P=.776). Conclusions We did not observe a significant association between exposure to general anesthesia and risk for the development of α-synucleinopathies.

Background Housing is a growing challenge for US adults in an increasingly unaffordable housing market. These housing challenges can create barriers to effective management and control of Type II Diabetes. However, little is known about how housing challenges are perceived and navigated by clinicians who care for patients with Type II Diabetes. Objective To examine how primary care clinicians perceive and navigate their patients’ housing challenges in the context of Type II Diabetes management. Methods We conducted semi-structured interviews with 18 primary care clinicians practising in four clinical settings in New Haven, Connecticut. Two investigators systematically coded the interviews. Analysis of coded data was used to determine themes. Results Participants considered housing as significant to their patients’ health and a potential barrier to optimal diabetes management. Participants sought to improve their patients’ housing through advocacy, referrals and interdisciplinary collaborations. They also adjusted clinical decisions to adapt to patients’ housing challenges. In making clinical adjustments, participants struggled to find a balance between what they perceived to be feasible for unstably housed patients and maintaining a standard of care. Some participants navigated this balanced by employing creative strategies and individualized care. Conclusion In highlighting the challenges that clinicians face in maintaining a standard of care for unstably housed diabetes patients, our findings speak to the need for more guidance, resources and support to address housing in a clinical setting.

A virtual screening conducted with nearly 4 000 000 compounds from lead-like and fragment-like subsets enabled the identification of a small-molecule inhibitor (1) of the Trypanosoma cruzi cruzain enzyme, a validated drug target for Chagas disease. Subsequent comprehensive structure-based drug design and structure–activity relationship studies led to the discovery of carbamoyl imidazoles as potent, reversible, and competitive cruzain inhibitors. The most potent carbamoyl imidazole inhibitor (45) exhibited high affinity with a Ki value of 20 nM, presenting both in vitro and in vivo activity against T. cruzi. Furthermore, the most promising compounds reduced parasite burden in vivo and showed no toxicity at a dose of 100 mg/kg. These carbamoyl imidazoles are structurally attractive, nonpeptidic, and easy to prepare and synthetically modify. Finally, these results further advance our understanding of the noncovalent mode of inhibition of this pharmaceutically relevant enzyme, building strong foundations for ...

Due to the rarity of Wilms tumor (WT) and the relative urgency with which pediatric renal tumors are treated, there is little reported data on the natural history and growth of WTs. Historical reports of estimated doubling times of WTs were based on time to disease recurrence after initial diagnosis and treatment, and were published before the current advancements in molecular biomarker testing. We compare 2 cases of WT with sequential imaging, and postulate how the growth parameters of these tumors may be associated with differing chromosomal traits.