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Gender-harassment is well-described in academic medicine, including pediatrics. We explored academic pediatricians' qualitative descriptions of: 1) workplace gender-harassment; 2) its professional and emotional tolls; 3) barriers to and outcomes of reporting gender-harassment; and 4) tools to intervene.We conducted a cross-sectional, anonymous, survey-based study within a single, large pediatrics department. Surveys included demographic items, validated measures to assess prevalence of gender-harassment, and optional, free-text boxes to elaborate. Here, we present the directed content analyses of free-text responses. Two trained qualitative researchers coded participant comments to identify types of gender-harassment, its impact, and participants' experiences reporting it. Final agreement between coders was outstanding (Kappa0.9). A secondary, inductive analysis illustrated the emotional burdens of and opportunities to interrupt gender-harassment.Of 524 total faculty, 290 (55%) completed the survey and 144 (27% of total, 50% of survey-respondents) provided text-responses. This sub-cohort was predominantly white women5 years on-faculty. Compared to the full cohort, sub-cohort participants had more commonly witnessed/experienced workplace-harassment; 92% of sub-cohort women and 52% of men endorsed fear of reporting it. Respondents described harassment by institutional staff (24% of respondents), patients/families (35%), colleagues (50%), supervisors/leadership (50%), and the system (63%). Women used stronger emotional descriptors than men (ie, "humiliated" vs "uncomfortable"). Only 19% of women (and no men) had reported witnessed/experienced harassment; 24% of those described a negative consequence and 95% noted that no changes were made thereafter.This single-center study suggests gender-harassment in academic pediatrics is common. Faculty feel fear and futility reporting it.

Background Conduction system pacing (CSP) (His bundle pacing and left bundle pacing) is a group of techniques intended to achieve cardiac pacing with a narrow QRS complex through a lead directly inserted in conduction system structures. The safety and effectiveness of this technique are not yet fully understood. Purpose To describe the short-term implant findings and safety profile of CSP as a first option after 4 years in a single center. Methods In a period of 42 months, 214 patients were submitted to CSP as a first strategy to restore AV synchrony (pacemakers for AV block or sinus node dysfunction) or as a resynchronization (CRT) strategy (for patients with heart failure and bundle branch block). CSP lead was implanted in lieu of a conventional right ventricular lead in pacemaker cases, and in addition or in lieu of a coronary sinus lead, in CRT cases, depending on the technical and anatomical possibilities. Results The mean age was 76.7±16.4 years, 65% males. 162 patients implanted a CSP lead for a dual-chamber pacemaker, 3 patients for a single chamber pacemaker, 32 patients for CRT-D (CSP lead replacing the coronary sinus lead with a defibrillator), and 13 patients for an optimized CRT (CSP lead plus coronary sinus lead). In 16 patients (7.4%) the technique of choice was His bundle pacing, two of them presented with subacute elevated thresholds, requiring new lead implantation at the moment of generator pulse replacement. One patient submitted to left bundle branch pacing (0.4%) had subacute lead dislodgement, being submitted to lead revision. Four patients intended for CRT (1.8%) didn't meet the criteria for His bundle pacing or left bundle branch pacing, being submitted to conventional coronary sinus lead placement. There were 10 cases (4.6%) of confirmed lead perforation during the lead septum insertion, with prompt repositioning, all uneventful. No pericardium effusion related to lead perforation was observed. One patient (0.4%) had a pneumothorax, requiring chest tube drainage. Conclusion Conduction system pacing as a first strategy is a feasible, effective and safe technique, both for pacing and for resynchronization purposes, with a complication rate comparable to conventional implantation. Funding Acknowledgement Type of funding sources: None.

The last substantial description of gender discrimination and harassment described in the journal Pediatrics was in 2019. It is unclear whether the field has made progress toward its goal of equity. We aimed to describe: (1) the recent gender-equity climate according to women and men faculty in the department of pediatrics at a single, large academic center, and (2) institutional efforts to address persistent gender discrimination and harassment. In late 2020, we distributed an anonymous survey to all department faculty that included demographic data, a modified version of the Overt Gender Discrimination at Work Scale, questions about experiences/witnessed discriminatory treatment and sexual harassment, and if those experiences negatively affected career advancement. Of 524 pediatrics faculty, 290 (55%) responded. Compared with men, women more commonly reported gender discrimination (50% vs. 4%, P < .01) and that their gender negatively affected their career advancement (50% vs 9%, P < .01). More than 50% of women reported discriminatory treatment at least annually and 38% recognized specific sexist statements; only 4% and 17% of men reported the same (P < .01 for both). We concluded that a disproportionately low number of male faculty recognized the harassment female faculty experienced. In the 18 months since, our department and university have made efforts to improve salary equity and parity in leadership representation, created an anonymous bias-reporting portal, mandated bias training, and implemented new benchmarks of “professionalism” that focus on diversity. Although we acknowledge that culture change will take time, we hope our lessons learned help promote gender equity in pediatrics more broadly.

Background: Cluster-randomized trials allow for the evaluation of a community-level or group-/cluster-level intervention. For studies that require a cluster-randomized trial design to evaluate cluster-level interventions aimed at controlling vector-borne diseases, it may be difficult to assess a large number of clusters while performing the additional work needed to monitor participants, vectors, and environmental factors associated with the disease. One such example of a cluster-randomized trial with few clusters was the “efficacy and risk of harms of repeated ivermectin mass drug administrations for control of malaria” trial. Although previous work has provided recommendations for analyzing trials like repeated ivermectin mass drug administrations for control of malaria, additional evaluation of the multiple approaches for analysis is needed for study designs with count outcomes. Methods: Using a simulation study, we applied three analysis frameworks to three cluster-randomized trial designs (single-year, 2-year parallel, and 2-year crossover) in the context of a 2-year parallel follow-up of repeated ivermectin mass drug administrations for control of malaria. Mixed-effects models, generalized estimating equations, and cluster-level analyses were evaluated. Additional 2-year parallel designs with different numbers of clusters and different cluster correlations were also explored. Results: Mixed-effects models with a small sample correction and unweighted cluster-level summaries yielded both high power and control of the Type I error rate. Generalized estimating equation approaches that utilized small sample corrections controlled the Type I error rate but did not confer greater power when compared to a mixed model approach with small sample correction. The crossover design generally yielded higher power relative to the parallel equivalent. Differences in power between analysis methods became less pronounced as the number of clusters increased. The strength of within-cluster correlation impacted the relative differences in power. Conclusion: Regardless of study design, cluster-level analyses as well as individual-level analyses like mixed-effects models or generalized estimating equations with small sample size corrections can both provide reliable results in small cluster settings. For 2-year parallel follow-up of repeated ivermectin mass drug administrations for control of malaria, we recommend a mixed-effects model with a pseudo-likelihood approximation method and Kenward–Roger correction. Similarly designed studies with small sample sizes and count outcomes should consider adjustments for small sample sizes when using a mixed-effects model or generalized estimating equation for analysis. Although the 2-year parallel follow-up of repeated ivermectin mass drug administrations for control of malaria is already underway as a parallel trial, applying the simulation parameters to a crossover design yielded improved power, suggesting that crossover designs may be valuable in settings where the number of available clusters is limited. Finally, the sensitivity of the analysis approach to the strength of within-cluster correlation should be carefully considered when selecting the primary analysis for a cluster-randomized trial.

BACKGROUND The gains made against malaria have stagnated since 2015, threatened further by increasing resistance to insecticides and antimalarials. Improvement in malaria control necessitates a multipronged strategy, which includes the development of novel tools. One such tool is mass drug administration (MDA) with endectocides, primarily ivermectin, which has shown promise in reducing malaria transmission through lethal and sublethal impacts on the mosquito vector. OBJECTIVE The primary objective of the study is to assess the impact of repeated ivermectin MDA on malaria incidence in children aged ≤10 years. METHODS Repeat Ivermectin MDA for Malaria Control II is a double-blind, placebo-controlled, cluster-randomized, and parallel-group trial conducted in a setting with intense seasonal malaria transmission in Southwest Burkina Faso. The study included 14 discrete villages: 7 (50%) randomized to receive standard measures (seasonal malaria chemoprevention [SMC] and bed net use for children aged 3 to 59 months) and placebo, and 7 (50%) randomized to receive standard measures and monthly ivermectin MDA at 300 μg/kg for 3 consecutive days, provided under supervision to all eligible village inhabitants, over 2 successive rainy seasons. Nonpregnant individuals >90 cm in height were eligible for ivermectin MDA, and cotreatment with ivermectin and SMC was not permitted. The primary outcome is malaria incidence in children aged ≤10 years, as assessed by active case surveillance. The secondary safety outcome of repeated ivermectin MDA was assessed through active and passive adverse event monitoring. RESULTS The trial intervention was conducted from July to November in 2019 and 2020, with additional sampling of humans and mosquitoes occurring through February 2022 to assess postintervention changes in transmission patterns. Additional human and entomological assessments were performed over the 2 years in a subset of households from 6 cross-sectional villages. A subset of individuals underwent additional sampling in 2020 to characterize ivermectin pharmacokinetics and pharmacodynamics. Analysis and unblinding will commence once the database has been completed, cleaned, and locked. CONCLUSIONS Our trial represents the first study to directly assess the impact of a novel approach for malaria control, ivermectin MDA as a mosquitocidal agent, layered into existing standard-of-care interventions. The study was designed to leverage the current SMC deployment infrastructure and will provide evidence regarding the additional benefit of ivermectin MDA in reducing malaria incidence in children. CLINICALTRIAL ClinicalTrials.gov NCT03967054; https://clinicaltrials.gov/ct2/show/NCT03967054; Pan African Clinical Trials Registry PACT201907479787308 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/41197

Substantial progress has been made globally to control malaria, however there is a growing need for innovative new tools to ensure continued progress. One approach is to harness genetic sequencing and accompanying methodological approaches as have been used in the control of other infectious diseases. However, to utilize these methodologies for malaria, we first need to extend the methods to capture the complex interactions between parasites, human and vector hosts, and environment, which all impact the level of genetic diversity and relatedness of malaria parasites. We develop an individual-based transmission model to simulate malaria parasite genetics parameterized using estimated relationships between complexity of infection and age from five regions in Uganda and Kenya. We predict that cotransmission and superinfection contribute equally to within-host parasite genetic diversity at 11.5% PCR prevalence, above which superinfections dominate. Finally, we characterize the predictive power of six metrics of parasite genetics for detecting changes in transmission intensity, before grouping them in an ensemble statistical model. The model predicted malaria prevalence with a mean absolute error of 0.055. Different assumptions about the availability of sample metadata were considered, with the most accurate predictions of malaria prevalence made when the clinical status and age of sampled individuals is known. Parasite genetics may provide a novel surveillance tool for estimating the prevalence of malaria in areas in which prevalence surveys are not feasible. However, the findings presented here reinforce the need for patient metadata to be recorded and made available within all future attempts to use parasite genetics for surveillance.

BACKGROUND NlmCategory: BACKGROUND content: In 2016, the Zambian National Malaria Elimination Centre started programmatic mass drug administration (pMDA) campaigns with dihydroartemisinin-piperaquine as a malaria elimination tool in Southern Province. Two rounds were administered, two months apart (coverage 70% and 57% respectively). We evaluated the impact of one year of pMDA on malaria incidence using routine data. - Label: METHODS NlmCategory: METHODS content: We conducted an interrupted time series with comparison group analysis on monthly incidence data collected at the health facility catchment area (HFCA) level, with a negative binomial model using generalized estimating equations. pMDA was conducted in HFCAs with greater than 50 cases/1,000 people/year. Ten HFCAs with incidence rates marginally above this threshold (pMDA group) were compared to 20 HFCAs marginally below (comparison group). - Label: RESULTS NlmCategory: RESULTS content: "The pMDA HFCAs saw a 46% greater decrease in incidence at the time of intervention than the comparison areas (incidence rate ratio: 0.536 [0.337-0.852]); however, incidence increased toward the end of the season. No HFCAs saw a transmission interruption." - Label: CONCLUSION NlmCategory: CONCLUSIONS content: pMDA, implemented during one year with imperfect coverage in low transmission areas with sub-optimal vector control coverage, significantly reduced incidence. However, elimination will require additional tools. Routine data are important resources for programmatic impact evaluations and should be considered for future analyses.

The overall aim of the current investigation was to develop and validate the initial version of the Minnesota Inference Assessment (MIA). MIA is a web-based measure of inference processes in Grades K–2. MIA leverages the affordances of different media to evaluate inference processes in a nonreading context, using age-appropriate fiction and nonfiction videos coupled with questioning. We evaluated MIA’s technical adequacy in a proof-of-concept study. Taken together, the results support the interpretation that MIA shows promise as a valid and reliable measure of inferencing in a nonreading context for students in Grades K–2. Future directions involve further development of multiple, parallel forms that can be used for progress monitoring in K–2.

This study used integrative data analysis (Curran & Hussong, 2009), which allows combining data from different studies, to examine the generalizability of a research-based mathematics program, sche...

The study of zebrafish skin pattern development could lead to a better understanding of how these patterns are generated and how they evolved. To compare and contrast wild-type (WT) stripe...

Accurate diagnosis of fracture-related infection (FRI) is critical for preventing poor outcomes such as loss of function or amputation. Due to the multiple variables associated with FRI, however, accurate diagnosis is challenging and complicated by a lack of standardized diagnostic criteria. Limitations with the current gold standard for diagnosis, which is routine microbiology culture, further complicate the diagnostic and management process. Efforts to optimize the process rely on a foundation of data derived from prosthetic joint infections (PJI), but differences in PJI and FRI make it clear that unique approaches for these distinct infections are required. A more concerted effort focusing on FRI has dominated more recent investigations and publications leading to a consensus definition by the American Orthopedics (AO) Foundation and the European Bone and Joint Infection Society (EBJIS). This has the potential to better standardize the diagnostic process, which will not only improve patient care but also facilitate more robust and reproducible research related to the diagnosis and management of FRI. The purpose of this minireview is to explore the consensus definition, describe the foundation of data supporting current FRI diagnostic techniques, and identify pathways for optimization of clinical microbiology-based strategies and data.

Cellular senescence is a fate-determined state, accompanied by reorganization of heterochromatin. While lineage-appropriate genes can be temporarily repressed through facultative heterochromatin, stable silencing of lineage-inappropriate genes often involves the constitutive heterochromatic mark, histone H3K9me3. The fate of these heterochromatic genes during the chromatin reorganization accompanying senescence is unclear. Here we show a small number of lineage-inappropriate genes are derepressed in senescent cells from H3K9me3 regions that gain open chromatin marks. DNA FISH experiments reveal that these gene loci, which are tightly condensed at the nuclear periphery in proliferative cells, are physically decompacted during senescence. Among these gene loci, NLRP3 is predominantly expressed in immune cells, such as macrophages, where it resides within an open topologically associated domain (TAD). In contrast, NLRP3 is derepressed in senescent fibroblasts, potentially due to the local disruption of the H3K9me3-rich TAD that contains it. The role of NLRP3 has been implicated in the amplification of inflammatory cytokine signalling in senescence and aging, underscoring the functional relevance of gene induction from ‘permissive’ H3K9me3 regions in senescent cells.

Introduction Patient positioning, notably positioning patients in “anti-deformity positioning”, is a standard practice in burn rehabilitation as it assists with edema management, scar contracture prevention, and wound healing. Successfully and consistently providing proper positioning of burn patients requires the combined effort of the multi-disciplinary burn team. The primary goal at our center was to increase the frequency that patients were correctly positioned to over 90% at the time of random audits. Methods At a medium-sized, academic burn unit, once to twice weekly audits were conducted by burn lead therapists on the compliance of proper patient positioning over a 6-month period. Using this data as a trigger, a quality improvement project was designed using the PDSA (Plan-Do-Study-Act) cycle to help identify reasons behind lack of compliance. Surveys were distributed to the therapy and nursing staff to identify any barriers to care. Effects on positioning compliance post-intervention were monitored. Results In the 6 months prior to intervention, our patients were positioned correctly an average of 76% of the time. Therapy and nursing surveys identified the following barriers to care: Nursing needed more education on positioning, and the approach was too heavily reliant on nursing efforts alone. To address these barriers, therapists provided education to both day and night shift nurses, communicated daily about positioning expectations, shifted the project from a nursing approach to a multidisciplinary approach, and made changes in therapy workflow. Immediately following the intervention, the compliance rates were 91% for the first month and 85% for the second month. Conclusions Coordinating efforts of the entire burn team improves consistency for positioning in burn patients. Utilizing the PDSA cycle allowed us to identify areas for improvement and to develop appropriate interventions aimed at both increased education for nursing staff and workflow improvements for our therapists. Following the completion of our interventions we were able to obtain an immediate improvement in our compliance with proper positioning of burn patients.

The purpose of this replication study was to provide replication evidence not currently available of the effects of a research-based mathematics program, schema-based instruction, on the mathematical problem-solving performance of 7th-grade students. The replication was implemented in 36 schools in 5 districts; 59 mathematics teachers and their students (N = 1,492) participated in the study. Multilevel hierarchical linear analyses revealed statistically significant differences between conditions on proximal and distal measures of mathematics problem solving, with effects sizes similar to those reported in Jitendra et al. (2015). (PsycINFO Database Record (c) 2019 APA, all rights reserved)

BackgroundA new more highly sensitive rapid diagnostic test (HS-RDT) forPlasmodium falciparummalaria (Alere™/Abbott Malaria Ag P.f RDT [05FK140], now calledNxTek™Eliminate Malaria Ag Pf) was launched in 2017. The test has already been used in many research studies in a wide range of geographies and use cases.MethodsIn this study, we collate all published and available unpublished studies that use the HS-RDT and assess its performance in (i) prevalence surveys, (ii) clinical diagnosis, (iii) screening pregnant women, and (iv) active case detection. Two individual-level data sets from asymptomatic populations are used to fit logistic regression models to estimate the probability of HS-RDT positivity based on histidine-rich protein 2 (HRP2) concentration and parasite density. The performance of the HS-RDT in prevalence surveys is estimated by calculating the sensitivity and positive proportion in comparison to polymerase chain reaction (PCR) and conventional malaria RDTs.ResultsWe find that across 18 studies, in prevalence surveys, the mean sensitivity of the HS-RDT is estimated to be 56.1% (95% confidence interval [CI] 46.9–65.4%) compared to 44.3% (95% CI 32.6–56.0%) for a conventional RDT (co-RDT) when using nucleic acid amplification techniques as the reference standard. In studies where prevalence was estimated using both the HS-RDT and a co-RDT, we found that prevalence was on average 46% higher using a HS-RDT compared to a co-RDT. For use in clinical diagnosis and screening pregnant women, the HS-RDT was not significantly more sensitive than a co-RDT.ConclusionsOverall, the evidence presented here suggests that the HS-RDT is more sensitive in asymptomatic populations and could provide a marginal improvement in clinical diagnosis and screening pregnant women. Although the HS-RDT has limited temperature stability and shelf-life claims compared to co-RDTs, there is no evidence to suggest, given this test has the same cost as current RDTs, it would have any negative impacts in terms of malaria misdiagnosis if it were widely used in all four population groups explored here.

Contains fulltext : 238223.pdf (Publisher’s version ) (Open Access) BACKGROUND: Adoption of molecular techniques to detect Plasmodium falciparum infection has revealed many previously undetected (by microscopy) yet transmissible low-density infections. The proportion of these infections is typically highest in low transmission settings, but drivers of submicroscopic infection remain unclear. Here, we updated a previous systematic review of asexual P falciparum prevalence by microscopy PCR in the same population. We aimed to explore potential drivers of submicroscopic infection and to identify the locations where submicroscopic infections are most common. METHODS: In this systematic review and meta-analysis we searched PubMed and Web of Science from Jan 1, 2010, until Oct 11, 2020, for cross-sectional studies reporting data on asexual P falciparum prevalence by both microscopy and PCR. Surveys of pregnant women, surveys in which participants had been chosen based on symptoms or treatment, or surveys that did not involve a population from a defined location were excluded. Both the number of individuals tested and the number of individuals who tested positive by microscopy or PCR, or both, for P falciparum infection were extracted. Bayesian regression modelling was used to explore determinants of the size of the submicroscopic reservoir including geographical location, seasonality, age, methodology, and current or historical patterns of transmission. FINDINGS: Of 4893 identified studies, we retained 121 after screening and removal of duplicates. 45 studies from a previous systematic review were included giving 166 studies containing 551 cross-sectional survey microscopy and PCR prevalence pairs. Our results show that submicroscopic infections predominate in low-transmission settings across all regions, but also reveal marked geographical variation, with the proportion of infections that are submicroscopic being highest in South American surveys and lowest in west African surveys. Although current transmission levels partly explain these results, we find that historical transmission intensity also represents a crucial determinant of the size of the submicroscopic reservoir, as does the demographic structure of the infected population (with submicroscopic infection more likely to occur in adults than in children) and the PCR or microscopy methodology used. We also observed a small yet significant influence of seasonality, with fewer submicroscopic infections observed in the wet season than the dry season. Integrating these results with estimates of infectivity in relation to parasite density suggests the contribution of submicroscopic infections to transmission across different settings is likely to be highly variable. INTERPRETATION: Significant variation in the prevalence of submicroscopic infection exists even across settings characterised by similar current levels of transmission. These differences in submicroscopic epidemiology potentially warrant different approaches to targeting this infected subgroup across different settings to eliminate malaria. FUNDING: Bill & Melinda Gates Foundation, The Royal Society, and the UK Medical Research Council.

Aims: To ascertain if human pericytes produce SPARC (acronym for Secreted Protein Acidic and Cysteine Rich), a matricellular protein implicated in the regulation of cell proliferation, migration, and cell-matrix interactions; clarify if SPARC expression in cardiac pericytes is modulated by hypoxia; and determine the functional consequences of SPARC silencing. Results: Starting from the recognition that the conditioned media (CM) of human pericytes promote proliferation and migration of cardiac stromal cells, we screened candidate mediators by mass-spectrometry analysis. Of the 14 high-confidence proteins (

BackgroundPericytes are attracting much attention as potential candidates for successful cell therapy of myocardial ischaemia. Intramyocardially delivered adventitial pericytes (APCs) secrete paracrine factors which stimulate angiogenesis and recruitment of cardiac stromal cells, reduce fibrosis and promote cardiomyocyte proliferation and viability. However, factors responsible for these biological effects have not been elucidated yet.PurposeTo exploit the components of APC secretome exerting a biological effect on cardiac cells with the aim to discover new druggable targets with potential therapeutic activity.Methods and resultsAPCs were derived from saphenous veins of adult patients (n=13, 68±11 yrs, all with coronary artery disease - CAD). The APC-conditioned medium (CM) stimulated the proliferation of human iPS-derived cardiomyocytes compared with unconditioned medium (UCM) (EdU incorporation, 1.3-fold increases, P=0.004). Stimulation with APC-CM increased the number of mitotic figures in cardiomyocytes (Aurora B, 1.5-fold increases compared to UCM, P=0.002). Furthermore, APC-CM abrogated the hypoxia-induced apoptosis in cardiomyocytes (2-fold increase in Caspase 3/7 activity in hypoxic cells exposed to UCM compared to normoxic cells, P=0.002). We also found that APC-CM stimulates the migration of human cardiac stromal cells (CSCs) obtained from healthy donors (n=6, 54±11 yrs) in both a transwell and scratch migration assays (n=6, P30KDa. The pro-migratory fractions of the APC-CM obtained from size exclusion chromatography underwent mass spectrometry analysis (n=3 APCs). This identified 14 proteins uniquely present in the pro-migratory fractions. The two most relevant candidates were SPARC and TGFBI, both confirmed by ELISA. Intriguingly, the recombinant SPARC and TGFBI failed to reproduce the biological effect of APC-CM on CSC migration, suggesting that the secreted proteins may carry unique post-translational modifications not found in synthetic peptides. Further analyses are being carried out to reveal the biological properties of the endogenous SPARC and TGFBI.ConclusionsThis study suggests a fascinating approach based on the use of the active component of the APC-CM as a surrogate of APC therapy. If the biological properties of the cellular proteins will be successfully reproduced in synthetic peptides in vitro, this innovative approach may extend the benefits of APC therapy to all those patients with CAD for whom cell therapy is not an available option.

Aims: Tissue engineering aims to improve the longevity of prosthetic heart valves. However, the optimal cell source has yet to be determined. This study aimed to establish a mechanistic rationale supporting the suitability of human adventitial pericytes (APCs).Methods and Results: APCs were immunomagnetically sorted from saphenous vein leftovers of patients undergoing coronary artery bypass graft surgery and antigenically characterized for purity. Unlike bone marrow-derived mesenchymal stromal cells (BM-MSCs), APCs were resistant to calcification and delayed osteochondrogenic differentiation upon high phosphate (HP) induction, as assessed by cytochemistry and expression of osteogenic markers. Moreover, glycolysis was activated during osteogenic differentiation of BM-MSCs, whereas APCs showed no increase in glycolysis upon HP challenge. The microRNA-132-3p (miR-132), a known inhibitor of osteogenesis, was found constitutively expressed by APCs and upregulated following HP stimulation. The anti-calcific role of miR-132 was further corroborated by in silico analysis, luciferase assays in HEK293 cells, and transfecting APCs with miR-132 agomir and antagomir, followed by assessment of osteochondrogenic markers. Interestingly, treatment of swine cardiac valves with APC-derived conditioned medium conferred them with resistance to HP-induced osteogenesis, with this effect being negated when using the medium of miR-132-silenced APCs. Additionally, as an initial bioengineering step, APCs were successfully engrafted onto pericardium sheets, where they proliferated and promoted aortic endothelial cells attraction, a process mimicking valve endothelialization. Conclusions: Human APCs are resistant to calcification compared with BM-MSCs and convey the anti-calcific phenotype to heart valves through miR-132. These findings may open new important avenues for prosthetic valve cellularization.

Given ever increasing ease of access to technology, the majority of adults first turn to the internet for medical advice. The world wide web is filled with user-generated content within multiple social media platforms that lack a governing body to validate the information’s accuracy and reliability. The authors performed a qualitative review of first-aid burn resources available on YouTube using two validated scales: Modified Discern and Global Quality Scale. A search was conducted using the term “burn treatment” on September 18, 2019. Of 120 reviewed videos, 59 met their inclusion criteria. 36% (n = 21) of the speakers had formal medical training, with only 12% (n = 7) identified as burn care professionals. The mean views originating from nonmedical speakers (162,675) were more than eight times that originating from burn centers (14,975). The quality of the videos was compared by video source, speaker, and specialty. Burn centers had the highest Modified Discern and Global Quality Scale scores, 2.91 and 2.86, respectively (P < .05). Additionally, the authors were able to demonstrate that there was a statistically significant higher quality of videos when the speaker was a burn care professional or had formal medical training. Unfortunately, their review demonstrated that videos originating from hospital systems and burn centers made up a minority of the online media content. These results illustrate an opportunity for improvement by way of increased content creation to bolster the online presence of the burn community and provide patients with more accurate information.

The burden of malaria is heavily concentrated in sub-Saharan Africa (SSA) where cases and deaths associated with COVID-19 are rising1. In response, countries are implementing societal measures aimed at curtailing transmission of SARS-CoV-22,3. Despite these measures, the COVID-19 epidemic could still result in millions of deaths as local health facilities become overwhelmed4. Advances in malaria control this century have been largely due to distribution of long-lasting insecticidal nets (LLINs)5, with many SSA countries having planned campaigns for 2020. In the present study, we use COVID-19 and malaria transmission models to estimate the impact of disruption of malaria prevention activities and other core health services under four different COVID-19 epidemic scenarios. If activities are halted, the malaria burden in 2020 could be more than double that of 2019. In Nigeria alone, reducing case management for 6 months and delaying LLIN campaigns could result in 81,000 (44,000–119,000) additional deaths. Mitigating these negative impacts is achievable, and LLIN distributions in particular should be prioritized alongside access to antimalarial treatments to prevent substantial malaria epidemics. Transmission dynamics models of COVID-19 and malaria reveal how different scenarios of COVID-19 spread and varying levels of interruption to antimalarial programs could result in increased deaths in sub-Saharan Africa.

MicroRNAs (miRs) regulate complex processes, including angiogenesis, by targeting multiple mRNAs. miR-24-3p-3p directly represses eNOS, GATA2, and PAK4 in endothelial cells (ECs), thus inhibiting angiogenesis during development and in the infarcted heart. miR-24-3p is widely expressed in cardiovascular cells, suggesting that it could additionally regulate angiogenesis by acting on vascular mural cells. Here, we have investigated: 1) new miR-24-3p targets, 2) the expression and the function of miR-24-3p in human vascular ECs, 3) the impact of miR-24-3p inhibition in the angiogenesis reparative response to limb ischemia in mice. Using bioinformatics target prediction platforms and 3&prime, UTR luciferase assays, we newly identified Notch1 and its Delta-like ligand 1 (Dll1) to be directly targeted by miR-24-3p. miR-24-3p was expressed in human ECs and pericytes cultured under normal conditions. Exposure to hypoxia increased miR-24-3p in ECs but not in pericytes. Transfection with a miR-24-3p precursor (pre-miR-24-3p) increased miR-24-3p expression in ECs, reducing the cell survival, proliferation, and angiogenic capacity. Opposite effects were caused by miR-24-3p inhibition. The anti-angiogenic action of miR-24-3p overexpression could be prevented by simultaneous adenovirus (Ad)-mediated delivery of constitutively active Notch intracellular domain (NICD) into cultured ECs. We next demonstrated that reduced Notch signalling contributes to the anti-angiogenic effect of miR-24-3p in vitro. In a mouse unilateral limb ischemia model, local miR-24-3p inhibition (by adenovirus-mediated miR-24-3p decoy delivery) restored endothelial Notch signalling and increased capillary density. However, the new vessels appeared disorganised and twisted, worsening post-ischemic blood perfusion recovery. To better understand the underpinning mechanisms, we widened the search for miR-24-3p target genes, identifying several contributors to vascular morphogenesis, such as several members of the Wingless (Wnt) signalling pathway, &beta, catenin signalling components, and VE-cadherin, which synergise to regulate angiogenesis, pericytes recruitment to neoformed capillaries, maturation, and stabilization of newly formed vessels. Among those, we next focussed on &beta, catenin to demonstrate that miR-24-3p inhibition reduces &beta, catenin expression in hypoxic ECs, which is accompanied by reduced adhesion of pericytes to ECs. In summary, miR-24-3p differentially targets several angiogenesis modulators and contributes to autonomous and non-autonomous EC crosstalk. In ischemic limbs, miR-24-3p inhibition increases the production of dysfunctional microvessels, impairing perfusion. Caution should be observed in therapeutic targeting of miR-24-3p.

Blade-mounted strain gages are vital during rig and engine development to ensure safe engine operation. However, they also enable a change in dynamics of integrally bladed rotors (IBRs). State-of-the-art IBR dynamic response predictions are accomplished using as-manufactured models (AMMs) generated via optical topography measurements and mesh morphing. Two AMM finite element models (FEMs) are created of a 20-bladed IBR. One FEM has no strain gages present, where the second FEM includes strain gages on six blades. Traditionally, strain gages and lead wires are treated as the same material property as the IBR itself. It will be shown that the inclusion of strain gages in AMM's using this method changes the IBR's predicted mistuning. An alternative AMM approach is developed that changes the material properties of the finite elements attributed to the strain gages. The predicted mistuning for each AMM is accomplished using the fundamental mistuning model identification (FMM ID), where the predicted mistuning will be compared to both traveling wave excitation (TWE) experiments and a rotating, single stage compressor rig. Findings show mistuning predictions of the nonstrain gaged AMM compare far better to the experiments compared to the inclusion of the strain gages in the AMM. Additionally, altering material properties of the strain gages in the AMM improve mistuning prediction compared to treating the strain gages as the parent IBR material. Therefore, AMM should be acquired using clean, nonstrain gaged rotors or the material properties of strain gaged elements need to be altered to more accurately model the component.