Research Training and Scholarly Activity during General Pediatric Residency in Canada.

OBJECTIVE: To describe the characteristics of research training and scholarly activity during pediatrics residency in Canada and identify facilitators and barriers to resident scholarly activity. STUDY DESIGN: We conducted a mixed-methods, cross-sectional survey of pediatrics residents in Canada from April to June 2023. Trainees and medical education experts developed the 55-item survey, pilot tested, and distributed electronically to residents in all 17 Canadian residency programs. Responses were complemented with program-level data from pediatrics residency program directors. RESULTS: Of 644 Canadian pediatrics residents, 230 (36%) responded. Resident respondents conducted various types of scholarly projects, including retrospective clinical study (22%), qualitative research (15%), quality improvement (13%), and medical education research (12%). Discordance between the field of career interests and primary scholarly projects was common. Among respondents, 20% had abstracts accepted at national or international conferences, and 12% had manuscripts submitted to peer-reviewed journals. Resident respondents' self-perceived progress in their scholarly projects were discrepant from their actual progress. Key themes related to barriers and facilitators to scholarly activity included protected time for research, mentorship, and research skills training. CONCLUSIONS: The research training and scholarly activity of pediatrics residents in Canada is variable. Establishing national standards, implementing progress monitoring mechanisms with tailored support, and offering flexible protected research time are important next steps.

Impact of the superimposition reference area on intraoral scanning accuracy in a partially dentate maxilla.

STATEMENT OF PROBLEM: The alignment of 3-dimensional (3D) files involves selecting a reference area before performing a local best fit alignment during the digital scan superimposition and is essential for comparing digital scans. Scan alignment relies on both reference area location and the alignment algorithm. However, a consensus on the impact of different reference areas on intraoral scanning accuracy is lacking. PURPOSE: The purpose of this in vitro study was to assess the impact of 3 superimposition reference areas on the accuracy of 3 intraoral scanners for a partially dentate maxilla. MATERIAL AND METHODS: A Kennedy class II resin cast was scanned using 3 intraoral scanners (Primescan, TRIOS 3, and Emerald) outputting 30 digital scans (10 per scanner). Test scans from intraoral scanners were subsequently compared with a reference digital standard tessellation language file generated by a laboratory scanner with validated accuracy. The files were superimposed using best fit alignment for each intraoral scanner using 3 different superimposition reference areas (whole region of interest, palate, and all teeth). Accuracy was assessed by using a 3D analysis program (Geomagic Control X; 3D systems) for each scanner at 4 preselected areas. Test and reference scan differences were depicted on color maps and quantified via root mean square deviations. Differences were analyzed using regression analysis with the post hoc student t test and Bonferroni correction (α=.05). RESULTS: The TRIOS 3 and Emerald produced positive deviations in the palatal color maps, whereas Primescan produced more uniform color maps, regardless of the superimposition strategy used. Primescan exhibited the best accuracy (trueness and precision) in both palatal and bounded edentulous areas, regardless of the superimposition reference area. The TRIOS 3 recorded the highest distal extension trueness (ranging from 42.9±7.7 µm to 65 ±19.5 µm), and Primescan achieved the highest precision (ranging from 28.5 ±9.8 µm to 48.9 ±16.9 µm), regardless of the superimposition area. Emerald demonstrated the highest teeth trueness (ranging from 31.6 ±6.8 µm to 69.6 ±11.5 µm), while Primescan produced the highest precision (ranging from 17.9 ±6.1 µm to 30.7 ±9.2 µm), regardless of the reference area used. CONCLUSIONS: The chosen reference area for best fit alignment significantly influenced digital scan accuracy (P<.001). Primescan displayed the highest palatal and bounded edentulous area accuracy, with TRIOS 3 recording the highest distal extension trueness. Emerald recorded the highest teeth trueness and Primescan recorded the highest distal extension and tooth precision. All conclusions were independent of the superimposition strategy used.

Bend or Twist? What Plectonemes Reveal about the Mysterious Motility of Spiroplasma.

Spiroplasma is a unique, helical bacterium that lacks a cell wall and swims using propagating helix hand inversions. These deformations are likely driven by a set of cytoskeletal filaments, but how remains perplexing. Here, we probe the underlying mechanism using a model where either twist or bend drive spiroplasma's chirality inversions. We show that Spiroplasma should wrap into plectonemes at different values of the length and external viscosity, depending on the mechanism. Then, by experimentally measuring the bending modulus of Spiroplasma and if and when plectonemes form, we show that Spiroplasma's helix hand inversions are likely driven by bending.

Quality improvement strategies for diabetes care: Effects on outcomes for adults living with diabetes.

BACKGROUND: There is a large body of evidence evaluating quality improvement (QI) programmes to improve care for adults living with diabetes. These programmes are often comprised of multiple QI strategies, which may be implemented in various combinations. Decision-makers planning to implement or evaluate a new QI programme, or both, need reliable evidence on the relative effectiveness of different QI strategies (individually and in combination) for different patient populations. OBJECTIVES: To update existing systematic reviews of diabetes QI programmes and apply novel meta-analytical techniques to estimate the effectiveness of QI strategies (individually and in combination) on diabetes quality of care. SEARCH METHODS: We searched databases (CENTRAL, MEDLINE, Embase and CINAHL) and trials registers (ClinicalTrials.gov and WHO ICTRP) to 4 June 2019. We conducted a top-up search to 23 September 2021; we screened these search results and 42 studies meeting our eligibility criteria are available in the awaiting classification section. SELECTION CRITERIA: We included randomised trials that assessed a QI programme to improve care in outpatient settings for people living with diabetes. QI programmes needed to evaluate at least one system- or provider-targeted QI strategy alone or in combination with a patient-targeted strategy. - System-targeted: case management (CM); team changes (TC); electronic patient registry (EPR); facilitated relay of clinical information (FR); continuous quality improvement (CQI). - Provider-targeted: audit and feedback (AF); clinician education (CE); clinician reminders (CR); financial incentives (FI). - Patient-targeted: patient education (PE); promotion of self-management (PSM); patient reminders (PR). Patient-targeted QI strategies needed to occur with a minimum of one provider or system-targeted strategy. DATA COLLECTION AND ANALYSIS: We dual-screened search results and abstracted data on study design, study population and QI strategies. We assessed the impact of the programmes on 13 measures of diabetes care, including: glycaemic control (e.g. mean glycated haemoglobin (HbA1c)); cardiovascular risk factor management (e.g. mean systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), proportion of people living with diabetes that quit smoking or receiving cardiovascular medications); and screening/prevention of microvascular complications (e.g. proportion of patients receiving retinopathy or foot screening); and harms (e.g. proportion of patients experiencing adverse hypoglycaemia or hyperglycaemia). We modelled the association of each QI strategy with outcomes using a series of hierarchical multivariable meta-regression models in a Bayesian framework. The previous version of this review identified that different strategies were more or less effective depending on baseline levels of outcomes. To explore this further, we extended the main additive model for continuous outcomes (HbA1c, SBP and LDL-C) to include an interaction term between each strategy and average baseline risk for each study (baseline thresholds were based on a data-driven approach; we used the median of all baseline values reported in the trials). Based on model diagnostics, the baseline interaction models for HbA1c, SBP and LDL-C performed better than the main model and are therefore presented as the primary analyses for these outcomes. Based on the model results, we qualitatively ordered each QI strategy within three tiers (Top, Middle, Bottom) based on its magnitude of effect relative to the other QI strategies, where 'Top' indicates that the QI strategy was likely one of the most effective strategies for that specific outcome. Secondary analyses explored the sensitivity of results to choices in model specification and priors.  Additional information about the methods and results of the review are available as Appendices in an online repository. This review will be maintained as a living systematic review; we will update our syntheses as more data become available. MAIN RESULTS: We identified 553 trials (428 patient-randomised and 125 cluster-randomised trials), including a total of 412,161 participants. Of the included studies, 66% involved people living with type 2 diabetes only. Participants were 50% female and the median age of participants was 58.4 years. The mean duration of follow-up was 12.5 months. HbA1c was the commonest reported outcome; screening outcomes and outcomes related to cardiovascular medications, smoking and harms were reported infrequently. The most frequently evaluated QI strategies across all study arms were PE, PSM and CM, while the least frequently evaluated QI strategies included AF, FI and CQI. Our confidence in the evidence is limited due to a lack of information on how studies were conducted.  Four QI strategies (CM, TC, PE, PSM) were consistently identified as 'Top' across the majority of outcomes. All QI strategies were ranked as 'Top' for at least one key outcome. The majority of effects of individual QI strategies were modest, but when used in combination could result in meaningful population-level improvements across the majority of outcomes. The median number of QI strategies in multicomponent QI programmes was three.  Combinations of the three most effective QI strategies were estimated to lead to the below effects:  - PR + PSM + CE: decrease in HbA1c by 0.41% (credibility interval (CrI) -0.61 to -0.22) when baseline HbA1c < 8.3%; - CM + PE + EPR: decrease in HbA1c by 0.62% (CrI -0.84 to -0.39) when baseline HbA1c > 8.3%;  - PE + TC + PSM: reduction in SBP by 2.14 mmHg (CrI -3.80 to -0.52) when baseline SBP < 136 mmHg; - CM + TC + PSM: reduction in SBP by 4.39 mmHg (CrI -6.20 to -2.56) when baseline SBP > 136 mmHg;  - TC + PE + CM: LDL-C lowering of 5.73 mg/dL (CrI -7.93 to -3.61) when baseline LDL < 107 mg/dL; - TC + CM + CR: LDL-C lowering by 5.52 mg/dL (CrI -9.24 to -1.89) when baseline LDL > 107 mg/dL. Assuming a baseline screening rate of 50%, the three most effective QI strategies were estimated to lead to an absolute improvement of 33% in retinopathy screening (PE + PR + TC) and 38% absolute increase in foot screening (PE + TC + Other). AUTHORS' CONCLUSIONS: There is a significant body of evidence about QI programmes to improve the management of diabetes. Multicomponent QI programmes for diabetes care (comprised of effective QI strategies) may achieve meaningful population-level improvements across the majority of outcomes. For health system decision-makers, the evidence summarised in this review can be used to identify strategies to include in QI programmes. For researchers, this synthesis identifies higher-priority QI strategies to examine in further research regarding how to optimise their evaluation and effects. We will maintain this as a living systematic review.

Probiotics and non-alcoholic fatty liver disease in children and adolescents: a systematic review.

BACKGROUND: non-alcoholic fatty liver disease (NAFLD) in childhood is an increasing global public health issue with significant long-term consequences. NAFLD management mainly consists of lifestyle modifications, however, adjunct pharmacological therapies are currently lacking. Gut microbiota manipulation via probiotics may alter the course of pediatric NAFLD. The objective of this systematic review was to synthesize all the available literature on the use of probiotics in children and adolescents with NAFLD. METHODS: PubMed, EBSCOhost, Scopus, Web of Science, and Cochrane Library were systematically searched for trials on the use of probiotics in pediatric NAFLD. A quantitative DerSimonian Laird random effects meta-analysis was performed when possible; otherwise, a narrative summary of the study outcomes was presented and discussed. A separate search was completed to include all the ongoing registered trials on probiotics use in pediatric NAFLD. RESULTS: five randomized controlled trials met the inclusion criteria. Of these, four trials were included in the final quantitative analysis. Probiotic therapy significantly reduced the levels of alanine aminotransferase (ALT) (mean difference: -10.39 [-19.85, -0.93]), however significant heterogeneity between studies was identified (I2, 93 %). CONCLUSIONS: there is insufficient evidence to support probiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials. Lifestyle modifications focusing on maintaining a normal BMI and regular exercise continue to be the gold standard approach to treating NAFLD in children.

High-fidelity porcine models of metabolic syndrome: a contemporary synthesis.

This review aims to describe and compare porcine models of metabolic syndrome. This syndrome and its associated secondary comorbidities are set to become the greatest challenge to healthcare providers and policy makers in the coming century. However, an incomplete understanding of the pathogenesis has left significant knowledge gaps in terms of efficacious therapeutics. To further our comprehension and, in turn, management of metabolic syndrome, appropriate high-fidelity models of the disease complex are of great importance. In this context, our review aims to assess the most promising porcine models of metabolic syndrome currently available for their similarity to the human phenotype. In addition, we aim to highlight the strengths and shortcomings of each model in an attempt to identify the most appropriate application of each. Although no porcine model perfectly recapitulates the human metabolic syndrome, several pose satisfactory approximations. The Ossabaw miniature swine in particular represents a highly translatable model that develops each of the core parameters of the syndrome with many of the associated secondary comorbidities. Future high-fidelity porcine models of metabolic syndrome need to focus on secondary sequelae replication, which may require extended induction period to reveal.

Inborn Errors of Immunity on the Island of Ireland - a Cross-Jurisdictional UKPID/ESID Registry Report.

The epidemiology of inborn errors of immunity (IEI) in the Republic of Ireland was first published in 2005 but has not been updated since. IEI prevalence data from Northern Ireland was last published in 2018. Using data from the United Kingdom Primary Immune Deficiency (UKPID) and European Society for Immunodeficiencies (ESID) registries, we reviewed all registered cases of IEI affecting adult patients ≥ 18 years of age from the two largest immunology specialist centres in Northern Ireland and the Republic of Ireland, respectively and calculated the combined minimum adult prevalence of IEI on the island of Ireland for the first time. We also recorded data pertaining to presenting symptoms of IEI, diagnostic delay, immunoglobulin data, and genetic testing, as well as briefly reporting data pertaining to secondary immunodeficiency in both countries. As of 1 May 2020, we identified a minimum adult IEI prevalence in Ireland of 8.85/100,000 population.

Body mass index and risk of Parkinson, Alzheimer, Dementia, and Dementia mortality: a systematic review and dose-response meta-analysis of cohort studies among 5 million participants.

Objective: Inconsistent results regarding the association between the Body Mass Index (BMI) and brain disorders have been reported. We performed this study to investigate the association between BMI and risk of Parkinson, Alzheimer, Dementia and Dementia-mortality.Methods: A systematic search was conducted up to April 2019 in MEDLINE/PubMed, SCOPUS, and Cochrane Library. Results pooled with random-effects model.Results: Totally, 29 articles which were included in this study with4,978,621 participants. The pooled HR for Parkinson's in the underweight person was 1.20 (95%CI1.10-1.30). The pooled HR for dementia in underweight and overweight category was 1.23 (95%CI = 1.05-1.45) and 0.88 (95%CI = 0.83-0.94), respectively. There is not any significant relation between each categories of BMI and Alzheimer disease. The pooled HR for dementia in underweight and overweight category was 1.36 (95%CI = 1.14-1.63) and 0.81 (95%CI = 0.49-1.33), respectively. The non-linear association between BMI and risk of Dementia-mortality was significant (p = 0.001,Coeff = 0.003).Conclusion: This study highlights underweight related to increase incidence of Parkinson, Dementia, and Dementia mortality but no on Alzheimer disease.

'I miss being honest': sex workers' accounts of silence and disclosure with health care providers in Ireland.

In this paper, female sex workers tell stories of their interactions with health care providers (HCP) in four cities in the Republic of Ireland. While Irish society has made great progress in listening to the sexual stories of women that were historically silenced (e.g. stories of abortion, sexual abuse), sex workers have not benefited from this new climate. Regularly silenced by parliamentarians and non-governmental organisations who speak upon their behalf, sex workers are consigned within a narrative of victimhood and coercion. This paper draws from a participant action research study conducted in 2019-20 and explores women's motivations in whether to disclose their sex work, and the strategies deployed to conceal it while seeking access to sexual health care. These strategies included traveling beyond their own communities for health care and STI home testing. The paper identifies women, particularly, migrants who felt their precarious position made it impossible for them to be truthful about their sex work to health care providers, exposing them to greater health risk. The paper understands this marginality within a context of structural violence where sex worker health is shaped by institutional power relations creating unequal health outcomes but is also challenged by stories of solidarity.

Cord-Blood High-Sensitivity Troponin-I Reference Interval and Association with Early Neonatal Outcomes.

OBJECTIVE: This study was aimed to establish a reference interval for high-sensitivity cardiac troponin I (hs-cTnI) in umbilical cord blood of infants and to assess its association with the risk of predetermined early neonatal outcomes in a high-acuity tertiary care hospital. STUDY DESIGN: Umbilical cord-blood samples were collected and hs-cTnI was measured in all infants born between August 2015 and September 2015 at McMaster Children's Hospital (n = 256). Gestational age, birth weight, Apgar's scores, age in days at which feeding was established, neonatal intensive care unit (NICU) admission, and discharge in days after birth were recorded. RESULTS: The 90th, 95th, and 99th percentiles for the term infant subcohort were 19.75, 41.45, and 166.30 ng/L, respectively. We observed decreased mean gestational ages and birth weights in both the 90th (37.7 weeks; 2,961.4 g) and 95th percentiles (37.1 weeks; 2,709.9 g) when compared with the remaining infants. Moreover, levels of hs-cTnI were significantly higher in infants with respiratory distress requiring intervention (p < 0.05), low birth weight infants (p < 0.01), preterm infants (p < 0.001), and those requiring NICU admission (p < 0.01). Multiple linear regression of the recorded demographic factors revealed prematurity (gestational age <35 weeks: coefficient 0.346 ± 0.160, p < 0.05; gestational age <37 weeks: coefficient 0.253 ± 0.105, p < 0.05) and male sex (coefficient 0.138 ± 0.047; p < 0.01) to be most predictive of log-hs-cTnI levels. CONCLUSION: This study establishes the reference values for cord-blood hs-cTnI in infants at a tertiary care center. Premature and sick infants requiring NICU admission had significantly higher levels of hs-cTnI. KEY POINTS: · Established the 90th, 95th, and 99th percentiles of neonatal cord-blood hs-cTnI in term infants as 19.75, 41.45, and 166.30 ng/L, respectively.. · Infants with hs-cTnI levels exceeding the 90th percentile had lower gestational ages and birth weights with higher rates of NICU admissions.. · Infants with respiratory distress or requiring NICU admission were found to have higher levels of hs-cTnI..

Assembly and Manipulation of a Prototypical N-Heterocyclic Carbene with a Metalloporphyrin Pedestal on a Solid Surface.

The controlled arrangement of N-heterocyclic carbenes (NHCs) on solid surfaces is a current challenge of surface functionalization. We introduce a strategy of using Ru porphyrins in order to control both the orientation and lateral arrangement of NHCs on a planar surface. The coupling of the NHC to the Ru porphyrin is a facile process which takes place on the interface: we apply NHCs as functional, robust pillars on well-defined, preassembled Ru porphyrin monolayers on silver and characterize these interfaces with atomic precision via a battery of experimental techniques and theoretical considerations. The NHCs assemble at room temperature modularly and reversibly on the Ru porphyrin arrays. We demonstrate a selective and complete functionalization of the Ru centers. With its binding, the NHC modifies the interaction of the Ru porphyrin with the Ag surface, displacing the Ru atom by 1 Å away from the surface. This arrangement of NHCs allows us to address individual ligands by controlled manipulation with the tip of a scanning tunneling microscope, creating patterned structures on the nanometer scale.

Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity: A Meta-Analysis.

OBJECTIVES: To determine the weight, body mass index (BMI), cardiometabolic, and gastrointestinal effects of glucagon-like peptide-1 (GLP-1) receptor agonists in children with obesity. STUDY DESIGN: Web of Science, PubMed/MEDLINE, and Scopus databases from 01/01/1994-01/01/2021 for randomized control trials examining the weight, BMI, cardiometabolic, or gastrointestinal effects of GLP-1 receptor agonists in children and adolescents with obesity. Data were extracted by 2 independent surveyors and a random effects model was applied to meta-analyze generic inverse variance outcomes. Primary outcomes were related to weight and cardiometabolic profile, and secondary outcomes of interest were gastrointestinal-related treatment-emergent adverse events. RESULTS: Nine studies involving 574 participants were identified, of which 3 involved exenatide and 6 involved liraglutide. GLP-1 receptor agonists use caused a modest reduction in body weight (mean difference [MD] -1.50 [-2.50,-0.50] kg, I2 64%), BMI (MD -1.24 [-1.71,-0.77] kg/m2, I2 0%), and BMI z score (MD -0.14 [-0.23,-0.06], I2 43%). Glycemic control was improved in children with proven insulin resistance (glycated hemoglobin A1c MD -1.05 [-1.93,-0.18] %, I2 76%). Although no lipid profile improvements were noted, a modest decrease in systolic blood pressure was detected (MD -2.30 [-4.11,-0.49] mm Hg; I2 0%). Finally, analysis of gastrointestinal-related treatment-emergent adverse events revealed an increased risk of nausea (risk ratio 2.11 [1.44, 3.09]; I2 0%), without significant increases in other gastrointestinal symptoms. CONCLUSIONS: This meta-analysis indicates that GLP-1 receptor agonists are safe and effective in modestly reducing weight, BMI, glycated hemoglobin A1c, and systolic blood pressure in children and adolescents with obesity in a clinical setting, albeit with increased rates of nausea. PROSPERO ID: CRD42020195869.

Central venous catheters are an important factor in paediatric thrombosis.

AIM: To establish the incidence and characteristics of paediatric thrombosis (PT) in a Canadian tertiary care centre during the era of low molecular weight heparin (LMWH). METHODS: A retrospective observational case study of all patients <18 years of age evaluated for arterial and venous thrombosis from May 2008 to July 2018 at McMaster Children's Hospital was conducted through the electronic medical record. RESULTS: The incidence of PT was 52.2 per 10 000 hospital admissions (n = 477/91 462). Provoked thrombosis was more prevalent (88.9%, n = 424/477) than unprovoked (2.9%, n = 14/477) or idiopathic thrombosis (4%, n = 19/477). Half of PT were in children <2 years (51.2%, n = 244/477). Central vascular catheterisation was a contributory factor in more than half of thrombotic events (56.2%, n = 268/477), while trauma (1.1%, n = 5/477), oral contraceptives (4%, n = 19/477), infection (4%, n = 19/477), surgery (6.9%, n = 33/477) and malignancy (8.4%, n = 40/477) were also risk factors. Arterial ischaemic stroke was diagnosed in 11.1% of cases (n = 53/477), while pulmonary embolism was identified in 7.1% (n = 34/477) and 1.7% of cases were fatal (n = 8/477). LMWH was the first-line therapeutic of choice (47.8%, n = 228/477), with 28.1% (n = 134/477) requiring no intervention. CONCLUSION: These data reiterate the elevated thrombosis risk to which infants and children with central vascular access are exposed.

Emergency department attendances during the COVID-19 pandemic: a retrospective analysis of attendances following Irish governmental pandemic measures.

BACKGROUND: COVID-19 has resulted in the death of over 1 million people to date. Following government-implemented regulations, there has been concern over the apparent decline in emergency department (ED) attendances and the resultant health legacy. Therefore, we aimed to characterise the attendances to an Irish tertiary hospital ED following the implementation of these regulations during the COVID-19 pandemic. METHODS: This retrospective observational study investigated all attendances to the Cork University Hospital ED from 15 February to 11 April in 2020 and 2017-2019. Attendances were stratified into four periods: Before COVID (BC) (15 February to 5 March), After COVID (AC) (6 March to 12 March), Educational Closure (EC) (13 March to 27 March) and Stay Home (SH) (28 March to 11 April), as per government regulations. Triage presentations of abdominal pain, shortness of breath, chest pain, headache and trauma were examined. Data were analysed by independent t-tests and χ2 analysis. RESULTS: There were 8261 attendances to the ED in the 2020 time period compared with a mean of 10 389 attendances during the corresponding periods in 2017-2019. There was a significant decrease in daily attendances in 2020 compared with 2017-2019 in the AC (142 vs 188, p=0.02), EC (122 vs 184, p<0.001) and SH (121 vs 181, p<0.001) periods, including significant decreases in abdominal pain (AC: 9 vs 22, EC: 10 vs 19, SH: 11 vs 18, p<0.001), chest pain (AC: 9 vs 15, EC: 8 vs 15, SH: 9 vs 15, p<0.01), headache (AC: 5 vs 11, EC: 4 vs 9, SH: 4 vs 9, p<0.01) and trauma (AC: 3 vs 5, EC: 2 vs 6, SH: 3 vs 5, p<0.01). CONCLUSION: Our findings suggest that the combination of government-imposed restrictions and perceived risk of attending an ED during a pandemic may contribute to reduced attendances. Public confidence in EDs is necessary to reduce collateral damage caused by failure to seek medical attention during a pandemic; adequate infrastructure to allow social distancing and isolation capacity in EDs is a necessity.

Management of COVID-19-associated multisystem inflammatory syndrome in children: A comprehensive literature review.

BACKGROUND: The prevalence and severity of COVID-19 are greatly reduced in children, yet some pediatric patients develop a syndrome resembling Kawasaki Disease (KD), termed Multisystem Inflammatory Syndrome in Children (MIS-C). With an estimated incidence of 2/100,000 children, MIS-C is relatively rare but can be fatal. Clinical features can include fever, hyperinflammatory state, gastrointestinal symptoms, myocardial dysfunction, and shock. The pathogenesis of MIS-C, although yet to be completely elucidated, appears to be distinct from KD in terms of epidemiology, severity, and biochemical signature. AIM OF REVIEW: Although efficacy of treatments for MIS-C have largely not yet been investigated, we aim to conduct a comprehensive literature search of numerous medical databases (AMED, EBM Reviews, Embase, Healthstar, MEDLINE, ERIC, and Cochrane) to highlight treatments used around the world, their rationale, and outcomes to better inform guidelines in the future. Using the findings, an approach to MIS-C management will be outlined. KEY SCIENTIFIC CONCEPTS OF REVIEW: •MIS-C appears to be a SARS-CoV-2 related post-infection phenomenon that is distinct from Kawasaki disease.•Although outcomes are largely favorable, there is significant variation in MIS-C treatment. Most management regimens reported to date mirror that of KD; however, targeted therapy based on specific MIS-C phenotypes may have the potential to improve outcomes.•We recommend close monitoring by a multidisciplinary team, symptomatic treatment (e.g., intravenous immunoglobulin for KD-like symptoms, steroids/immunotherapy for multisystem inflammation), and long-term follow-up.•Further research is required to evaluate the effectiveness of current MIS-C treatments and to determine more refined therapies.

Return to run rates following hallux valgus correction: A retrospective comparison of metatarsal shaft osteotomies versus the modified lapidus procedure.

BACKGROUND: Hallux valgus affects 23-36% in general populations. The purpose of this study was to evaluate return to run following either a modified Lapidus procedure or a metatarsal osteotomy. We hypothesized that there would be no difference in the ability to return to running. METHODS: A Retrospective review of a consecutive series of patients at a single institution with surgical correction was performed. 51 patients were identified. 35 were treated with a metatarsal shaft osteotomy and 16 with a modified Lapidus. RESULTS: No difference was found between the cohorts in terms of age, sex, or preoperative hallux valgus angle (HVA). 27/35 (77%) with metatarsal shaft osteotomy were able to return to running versus 13/16 (81%) with modified Lapidus. There was no significant difference in the ability to return to running between cohorts (p =1.00). CONCLUSION: Our study showed no statistical difference for the modified Lapidus versus metatarsal osteotomies relative to return to running.

Conformational Control of Chemical Reactivity for Surface-Confined Ru-Porphyrins.

We assess the crucial role of tetrapyrrole flexibility in the CO ligation to distinct Ru-porphyrins supported on an atomistically well-defined Ag(111) substrate. Our systematic real-space visualisation and manipulation experiments with scanning tunnelling microscopy directly probe the ligation, while bond-resolving atomic force microscopy and X-ray standing-wave measurements characterise the geometry, X-ray and ultraviolet photoelectron spectroscopy the electronic structure, and temperature-programmed desorption the binding strength. Density-functional-theory calculations provide additional insight into the functional interface. We unambiguously demonstrate that the substituents regulate the interfacial conformational adaptability, either promoting or obstructing the uptake of axial CO adducts.

On-Surface Synthesis of Nonmetal Porphyrins.

We report the on-surface synthesis of a nonmetal porphyrin, namely, silicon tetraphenylporphyrin (Si-TPP), by the deposition of atomic silicon onto a free-base TPP layer on a Ag(100) surface under ultrahigh vacuum (UHV) conditions. Scanning tunneling microscopy provides insights into the self-assembly of the TPP molecules before and after Si insertion. Silicon coordinates with all four nitrogen atoms of the TPP macrocycle and interacts with a silver atom of the substrate as confirmed by scanning tunneling spectroscopy, X-ray photoelectron spectroscopy, and complementary density functional theory calculations. The Si-TPP complex presents a saddle-shaped conformation that is stable under STM manipulation. Our study shows how protocols established for the on-surface metalation of tetrapyrroles can be adopted to achieve nonmetal porphyrins. Complementary experiments yielding Si-TPP and Ge-TPP on Ag(111) highlight the applicability to different main group elements and supports. The success of our nonmetal porphyrin synthesis procedure is further corroborated by a temperature-programmed desorption experiment, revealing the desorption of Ge-TPP. This extension of interfacial complex formation beyond metal elements opens promising prospects for new tetrapyrrole architectures with distinct properties and functionalities.

Gut microbiome of a porcine model of metabolic syndrome and HF-pEF.

Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease.NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.

Classifying Nearest-Neighbor Interactions and Deformations of AdS.

We classify all regular solutions of the Yang-Baxter equation of eight-vertex type. Regular solutions correspond to spin chains with nearest-neighbor interactions. We find a total of four independent solutions. Two are related to the usual six- and eight-vertex models that have R matrices of difference form. We find two new solutions of the Yang-Baxter equation, which are manifestly of nondifference form. These new solutions contain the S-matrices of the AdS_{2} and AdS_{3} integrable models as a special case. This can be used as a starting point to study and classify integrable deformations of these holographic integrable systems.