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Background Youth violence is a major public health concern in the United States. Hospital-based Violence Intervention Programs (HVIPs) are integral in connecting youth sustaining interpersonal violence-related injuries to medical, mental health, and social services. At our pediatric emergency department, our baseline referral rate to the established HVIP was 32.5%. From November 2018–2019, we aimed to increase the percent of eligible patients referred to our HVIP from 32.5 to 70% for patients aged 7–18 years who present to our Level 1 emergency department/trauma center with a violent injury. Methods For this quality improvement project, we recorded key aspects of the referral process, such as patient eligibility, who placed referrals, and when referrals were placed in relation to the ED admission. Key stakeholders were interviewed to identify specific interventions. Our key interventions were: 1. Educating providers on eligibility requirements. 2. Encouraging nurses to enter consults at the time of admission. 3. Publishing information about program referrals in the weekly nursing newsletter. 4. Updating social workers on eligibility requirements for the HVIP. We used PDSA cycles to inform our project. Our primary outcome measure was the number of eligible patients referred to our HVIP and measures were analyzed using statistical process control charts. Results The HVIP-eligible population had the following demographics: 31.1% female and a mean age 14.3 ± 2.7, 82.6% assaults and 17.4% gunshot wounds. From 11/2018 to 11/2019, there were 78 referrals to the HVIP, out of 167 eligible patients. The referral rate improved from 32.5% pre-interventions to 61.1% post-interventions, showing an 88% increase. Conclusion(s) We noted an increase in referrals to our HVIP following our interventions that centered on educating, advertising, and encouraging. Future studies will focus on analyzing other aspects of the enrollment process, such as obtaining patient consent.

Technology bears important relationships to our health and wellness and has been utilized over the past two decades as an aid to support both self-management goals as well as collaboration among treatment teams.However, when chronic illnesses such as eating disorders (ED) are managed outside of institutionalized care settings, designing effective technology to support collaboration in treatment necessitates that we understand the relationships between patients, clinicians, and support networks. We conducted in-depth, semi-structured, interviews with 9 ED patients and 10 clinicians to understand the ED journey through the lens of collaborative efforts, technology use, and potential detriments. Based on our analysis of these 19 interviews, we present novel findings on various underlying disconnects within the collaborative ED treatment process disconnects among clinicians, between treatment foci, among preferences in tracking, within support networks, and inpatients' own identities. Our findings highlight how these various disconnects are concomitant with and gaps can stem from a lack of collaboration between different stakeholders in the ED journey. We also identify methods of facilitating collaboration in these disconnects through technological mediators.

Crystallization of concomitant polymorphs is a very intriguing process that is difficult to be studied experimentally. A comprehensive study of two polymorphic modifications of acetyl 2-(N-(2-fluorophenyl)imino)coumarin-3-carboxamide using quantum chemical methods has revealed molecular and crystal structure dependence on crystallization conditions. Fast crystallization associated with a kinetically controlled process results in the formation of a columnar structure with a nonequilibrium molecular conformation and more isotropic topology of interaction energies between molecules. Slow crystallization may be considered as a thermodynamically controlled process and leads to the formation of a layered crystal structure with the conformation of the molecule corresponding to local minima and anisotropic topology of interaction energies. Fast crystallization results in the formation of a lot of weak intermolecular interactions, while slow crystallization leads to the formation of small amounts of stronger interactions.

Circumstances of the COVID-19 pandemic have mandated a change to standard management of infantile spasms. On April 6, 2020, the Child Neurology Society issued an online statement of immediate recommendations to streamline diagnosis and treatment of infantile spasms with utilization of telemedicine, outpatient studies, and selection of first-line oral therapies as initial treatment. The rationale for the recommendations and specific guidance including follow-up assessment are provided in this manuscript. These recommendations are indicated as enduring if intended to outlast the pandemic, and limited if intended only for the pandemic health care crisis but may be applicable to future disruptions of health care delivery.

Lacosamide, an antiepileptic drug prescribed for children with refractory focal epilepsy, is generally well tolerated, with dose-dependent adverse effects. We describe 4 children who developed a movement disorder in conjunction with the initiation and/or uptitration of lacosamide. Three patients developed dyskinesias involving the face or upper extremity whereas the fourth had substantial worsening of chronic facial tics. The patients all had histories suggestive of opercular dysfunction: 3 had seizure semiologies including hypersalivation, facial and upper extremity clonus while the fourth underwent resection of polymicrogyria involving the opercula. Onset, severity, and resolution of dyskinesias correlated with lacosamide dosing. These cases suggest that pediatric patients with dysfunction of the opercular cortex are at increased risk for developing drug-induced dyskinesias on high-dose lacosamide therapy. Practitioners should be aware of this potential side effect and consider weaning lacosamide or video electroencephalography (EEG) for differential diagnosis, particularly in pediatric patients with underlying opercular dysfunction.

BACKGROUND: Post-surgical changes in adjacent segment motion are considered a factor in further development of degeneration and cervical radiculopathy. The objective was to examine the extent of correlations between physiological motion of cervical foramina and long-term patient reported outcomes (PRO). METHODS: Biplane X-ray imaging and CT-based markerless tracking were used to measure 3D static and dynamic dimensions during neck axial rotation and extension from 18 patients treated for C5–6 radiculopathy with fusion or arthroplasty. Minimum foraminal height (FH.Min) and width (FW.Min), and their range (FH.Range and FW.Range) achieved during a motion task were calculated for adjacent levels (C4–5 and C6–7) at 2.0±0.6 years post-surgery. The modified Japanese Orthopedic Association score (mJOAS), the Neck Disability Index (NDI) including the visual analogue scale (VAS) for neck and arm pain, and the EuroQol EQ-5D score were recorded at 6.5±1.1 years post-surgery. The relationships between 6.5-year outcomes and 2-year foraminal motion were examined using regression. RESULTS: Worsening patient-reported outcomes were generally associated with lower values of FW.Min (P

Purpose Children with benign epilepsy with centrotemporal spikes have rare seizures emerging from the motor cortex, which they outgrow in adolescence, and additionally may have language deficits of unclear etiology. We piloted the use of transcranial magnetic stimulation paired with EMG and EEG (TMS-EMG, TMS-EEG) to test the hypotheses that net cortical excitability decreases with age and that use-dependent plasticity predicts learning. Methods We assessed language and motor learning in 14 right-handed children with benign epilepsy with centrotemporal spikes. We quantified two TMS metrics of left motor cortex excitability: the resting motor threshold (measure of neuronal membrane excitability) and amplitude of the N100-evoked potential (an EEG measure of GABAergic tone). To test plasticity, we applied 1 Hz repetitive TMS to the motor cortex to induce long-term depression-like changes in EMG- and EEG-evoked potentials. Results Children with benign epilepsy with centrotemporal spikes tolerate TMS; no seizures were provoked. Resting motor threshold decreases with age but is elevated above maximal stimulator output for half the group. N100 amplitude decreases with age after controlling for resting motor threshold. Motor cortex plasticity correlates significantly with language learning and at a trend level with motor learning. Conclusions Transcranial magnetic stimulation is safe and feasible for children with benign epilepsy with centrotemporal spikes, and TMS-EEG provides more reliable outcome measures than TMS-EMG in this group because many children have unmeasurably high resting motor thresholds. Net cortical excitability decreases with age, and motor cortex plasticity predicts not only motor learning but also language learning, suggesting a mechanism by which motor cortex seizures may interact with language development.

Since 2018, a scientific research project, the “Lilybaeum Project”, is being carried out by a collaboration of physicists and archaeologists. The goal is to apply forefront analysis techniques to the investigation of archaeological artefacts, both in situ and in the laboratory. The first case study presented in this paper concerns the original investigation through X-ray computed tomography of a collection of objects from the Regional Archaeological Museum of Lilybaeum, in Marsala, Italy. In addition to a very significant collection of clay jars mostly from children's graves of the ancient Lilybaeum necropolis, an unprecedented analysis of wooden planks belonging to the only existing wreck of a Punic Ship kept in the Museum is presented.

The OCA2-HERC2 locus is responsible for the greatest proportion of eye color variation in humans. Numerous studies extensively described both functional SNPs and associated patterns of variation over this region. The goal of our study is to examine how these haplotype structures and allelic associations vary when highly variable markers such as microsatellites are used. Eleven microsatellites spanning 357 Kb of OCA2-HERC2 genes are analyzed in 3029 individuals from worldwide populations. We found that several markers display large differences in allele frequency (10% to 35% difference) among Europeans, East Asians and Africans. In Europe, the alleles showing increased frequency can also discriminate individuals with (IrisPlex) predicted blue and brown eyes. Distinct haplotypes are identified around the variants C and T of the functional SNP rs12913832 (associated to blue eyes), with linkage disequilibrium r2 values significant up to 237 Kb. The haplotype carrying the allele rs12913832 C has high frequency (76%) in blue eye predicted individuals (30% in brown eye predicted individuals), while the haplotype associated to the allele rs12913832 T is restricted to brown eye predicted individuals. Finally, homozygosity values reach levels of 91% near rs12913832. Odds ratios show values of 4.2, 7.4 and 10.4 for four markers around rs12913832 and 7.1 for their core haplotype. Hence, this study provides an example on the informativeness of multiallelic markers that, despite their current limited potential contribution to forensic eye color prediction, supports the use of microsatellites for identifying causing variants showing similar genetic features and history.

Background Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients’ clinical phenotypes and analyse the differential clinical course. Methods We performed a hierarchical cluster analysis based on Ward’s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients’ prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P < .001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27–3.62; HR 3.42, 95%CI 2.72–4.31; HR 2.79, 95%CI 2.32–3.35), and Cluster 1 (HR 1.88, 95%CI 1.48–2.38; HR 2.50, 95%CI 1.98–3.15; HR 2.09, 95%CI 1.74–2.51) reported a higher risk for the three outcomes respectively. Conclusions In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes.

OBJECTIVE In patients treated for DKA, decrease the rate of visits experiencing one or more BG

Supplemental Digital Content is available in the text., Introduction: The COVID-19 pandemic has posed a significant threat to US healthcare workers’ mental and physical health. The US Food and Drug Administration approved the first mRNA COVID-19 vaccine for Emergency Use Authorization on December 11, 2020. High-risk healthcare workers were determined to be Phase 1a. Goal: Complete the two-dose vaccine series in all interested phase 1a staff immediately after the COVID-19 vaccine was available and distributed to our institution, December 14, 2020. Methods: A multidisciplinary team involving key stakeholders performed process mapping to develop four key drivers for vaccination success: rapid vaccine procurement, proper storage and handling, well-defined vaccine administration and follow-up plan, and system preparation. We tested interventions using plan-do-study-act cycles. We included employees and providers with direct patient care responsibilities, age 18 years or older, employed at the children’s health system, or the affiliated academic medical center. We examined the total number of dose 1 and dose 2 vaccines administered for our primary outcome, and the balancing measure included the percent of wasted vaccines. Results: Three thousand nine-hundred twenty-one healthcare personnel completed the survey, and 73% reported intent to receive the COVID-19 vaccine immediately or at a later time. After 57 clinic days, we vaccinated 83% (n = 5,231) of healthcare personnel at our institution, and 99% completed the two-dose series. Due to surplus vaccines, we vaccinated an additional 1,258 community members with 99% completion of the two-dose series. Vaccine waste was minimal 0.1%. Conclusion: We describe the development and implementation of a successful COVID-19 employee and community vaccination program.

Cholesterol crystals (CCs) were first discovered in atherosclerotic plaque tissue in the early 1900 and have since been observed and implicated in many diseases and conditions, including myocardial infarction, abdominal aortic aneurism, kidney disease, ocular diseases, and even central nervous system anomalies. Despite the widespread involvement of CCs in many pathologies, the mechanisms involved in their formation and their role in various diseases are still not fully understood. Current knowledge concerning the formation of CCs, as well as the molecular pathways activated upon cellular exposure to CCs, will be explored in this review. As CC formation is tightly associated with lipid metabolism, the role of cellular lipid homeostasis in the formation of CCs is highlighted, including the role of lysosomes. In addition, cellular pathways and processes known to be affected by CCs are described. In particular, CC-induced activation of the inflammasome and production of reactive oxygen species, along with the role of CCs in complement-mediated inflammation is discussed. Moreover, the clinical manifestation of embolized CCs is described with a focus on renal and skin diseases associated with CC embolism. Lastly, potential therapeutic measures that target either the formation of CCs or their impact on different cell types and tissues are highlighted.

Backgound and aims The low-density lipoprotein receptor-deficient (Ldlr−/−) mouse has been utilized by cardiovascular researchers for more than two decades to study atherosclerosis. However, there has not yet been a systematic effort to document the ultrastructural changes that accompany the progression of atherosclerotic plaque in this model. Methods Employing several different staining and microscopic techniques, including immunohistochemistry, as well as electron and polarized microscopy, we analyzed atherosclerotic lesion development in Ldlr−/− mice fed an atherogenic diet over time. Results Lipid-like deposits occurred in the subendothelial space after only one week of atherogenic diet. At two weeks, cholesterol crystals (CC) formed and increased thereafter. Lipid, CC, vascular smooth muscles cells, and collagen progressively increased over time, while after 4 weeks, relative macrophage content decreased. Accelerated accumulation of plate- and needle-shaped CC accompanied plaque core necrosis. Lastly, CC were surrounded by cholesterol microdomains, which co-localized with CC through all stages of atherosclerosis, indicating that the cholesterol microdomains may be a source of CC. Conclusions Here, we have documented, for the first time in a comprehensive way, atherosclerotic plaque morphology and composition from early to advanced stages in the Ldlr−/− mouse, one of the most commonly used animal models utilized in atherosclerosis research.

Purpose Anterior cruciate ligament (ACL) ruptures are common and are frequently reconstructed using a patellar tendon (PT) autograft. Unfortunately, the time course of PT healing after ACL reconstruction is not particularly well understood. Thus, the primary objective of this study was to use shear wave elastography (SWE) to evaluate the extent to which shear wave speed (SWS) is associated with time after ACL reconstruction. Methods Longitudinal SWE images were acquired from lateral, central, and medial regions of the PT from two groups: 30 patients who had undergone ACL reconstruction with a PT autograft within the preceding 40 months, and 30 age-matched asymptomatic control subjects. SWE images were acquired at 20° and 90° of passive flexion from both knees. In each subject group, statistical analyses assessed changes in mean SWS with time post-surgery, as well as differences in mean SWS between PT regions and limbs. Results In the ACL reconstruction patients, mean SWS increased with time post-surgery in the lateral region of the involved knee (p = 0.025) and decreased with time post-surgery in the central region of the contralateral knee (p = 0.022). Conclusion The findings suggest that there is an association between the mechanical properties of the PT and time post-surgery in both the involved and contralateral limbs after ACL reconstruction. These changes are likely due to maturation of the donor site tissue and changes in gait/loading patterns following ACL rupture and reconstruction. Level of evidence Level II — Prospective Cohort.

Visual Abstract, Highlights • LDGs are a subset of neutrophils that were elevated in psoriasis and associated with the severity of disease. • In psoriasis, LDGs associated with noncalcified coronary plaque burden beyond cardiovascular risk factors and in vitro, induced endothelial cell damage. • Compared to normal-density granulocyte neutrophils, platelet-associated biological pathways were upregulated in LDGs, suggesting enhanced platelet adherence to the LDG surface. • LDGs co-localized with platelets in circulation, and the LDG-platelet interaction associated more strongly with non-calcified coronary burden by coronary CTA compared to LDGs alone., Summary Psoriasis is an inflammatory skin disease associated with increased cardiovascular risk and serves as a reliable model to study inflammatory atherogenesis. Because neutrophils are implicated in atherosclerosis development, this study reports that the interaction among low-density granulocytes, a subset of neutrophils, and platelets is associated with a noncalcified coronary plaque burden assessed by coronary computed tomography angiography. Because early atherosclerotic noncalcified burden can lead to fatal myocardial infarction, the low-density granulocyte−platelet interaction may play a crucial target for clinical intervention.

Background Motor impairment after stroke is due not only to direct tissue loss but also to disrupted connectivity within the motor network. Mixed results from studies attempting to enhance motor recovery with Transcranial Magnetic Stimulation (TMS) highlight the need for a better understanding of both connectivity after stroke and the impact of TMS on this connectivity. This study used TMS-EEG to map the causal information flow in the motor network of healthy adult subjects and define how stroke alters these circuits. Methods Fourteen stroke patients and 12 controls received TMS to two sites (bilateral primary motor cortices) during two motor tasks (paretic/dominant hand movement vs. rest) while EEG measured the cortical response to TMS pulses. TMS-EEG based connectivity measurements were derived for each hemisphere and the change in connectivity (ΔC) between the two motor tasks was calculated. We analyzed if ΔC for each hemisphere differed between the stroke and control groups or across TMS sites, and whether ΔC correlated with arm function in stroke patients. Results Right hand movement increased connectivity in the left compared to the right hemisphere in controls, while hand movement did not significantly change connectivity in either hemisphere in stroke. Stroke patients with the largest increase in healthy hemisphere connectivity during paretic hand movement had the best arm function. Conclusions TMS-EEG measurements are sensitive to movement-induced changes in brain connectivity. These measurements may characterize clinically meaningful changes in circuit dynamics after stroke, thus providing specific targets for trials of TMS in post-stroke rehabilitation.

Chronic exposure to psychosocial and environmental stressors (PSES) has been shown to increase risk for diabetes, obesity, and cardiovascular disease and alter immune cell distribution and function. In Natural Killer (NK) cells, the impact of PSES has been demonstrated by a loss of NK cell numbers or function and a shift in NK cell subpopulations. NKp46 is an activating receptor on NK cells crucial for NK cell function. In this study, we aimed to determine if PSES is associated with NKp46 expression. We recruited 27 African-American women (age 59.85±1.91; BMI 34.06±1.67), characterized NKp46 expression from blood samples using flow cytometry, and determined serum cytokine levels using Luminex. Furthermore, study participants answered questionnaires to determine various psychosocial measures, socioeconomic status (SES), and home address for neighborhood deprivation (NDI). First, we determined that social isolation significantly associated with NKp46 expression (β=-0.51, p=0.02), while NDI and SES did not. Second, we identified biomarkers associated with social isolation. Social isolation significantly associated with the cytokine RANTES (β=0.64, p=0.01) after adjustment for cardiovascular risk and BMI. Third, we determined that RANTES also associated with NKp46 expression after adjustment (β=-0.54, p=0.01). We performed a mediation analysis using structural equation modeling to determine if RANTES could be a potential biological mediator between social isolation and NKp46 expression levels; this revealed that RANTES mediates 51.07% of the association (Figure). Thus, our study highlights the importance of further understanding the impact of PSES on immune cells and inflammation. Work to unravel the biology of adversity is crucial to address health disparities. In the future, larger studies should be conducted to identify underlying signaling molecules and pathways altering NK cells during chronic PSES that accelerate disease development and progression and ultimately, serve as targets for intervention.

Eating disorders (EDs) constitute a mental illness with the highest mortality. Today, mobile health apps provide promising means to ED patients for managing their condition. Apps enable users to monitor their eating habits, thoughts, and feelings, and offer analytic insights for behavior change. However, not only have scholars critiqued the clinical validity of these apps, their underlying design principles are not well understood. Through a review of 34 ED apps, we uncovered 11 different data types ED apps collect, and 9 strategies they employ to support collection and reflection. Drawing upon personal health informatics and visualization frameworks, we found that most apps did not adhere to best practices on what and how data should be collected from and reflected to users, or how data-driven insights should be communicated. Our review offers suggestions for improving the design of ED apps such that they can be useful and meaningful in ED recovery.

Intermittent fasting and fasting mimetic diets ameliorate inflammation. Similarly, serum extracted from fasted healthy and asthmatic subjects’ blunt inflammation in vitro, implicating serum components in this immunomodulation. To identify the proteins orchestrating these effects, SOMAScan technology was employed to evaluate serum protein levels in healthy subjects following an overnight, 24-h fast and 3 h after refeeding. Partial least square discriminant analysis identified several serum proteins as potential candidates to confer feeding status immunomodulation. The characterization of recombinant IGFBP1 (elevated following 24 h of fasting) and PYY (elevated following refeeding) in primary human CD4+ T cells found that they blunted and induced immune activation, respectively. Furthermore, integrated univariate serum protein analysis compared to RNA-seq analysis from peripheral blood mononuclear cells identified the induction of IL1RL1 and MFGE8 levels in refeeding compared to the 24-h fasting in the same study. Subsequent quantitation of these candidate proteins in lean versus obese individuals identified an inverse regulation of serum levels in the fasted subjects compared to the obese subjects. In parallel, IL1RL1 and MFGE8 supplementation promoted increased CD4+ T responsiveness to T cell receptor activation. Together, these data show that caloric load-linked conditions evoke serological protein changes, which in turn confer biological effects on circulating CD4+ T cell immune responsiveness.

Background: Neighborhoods and the microbiome are linked to cardiovascular disease (CVD), yet investigations to identify microbiome-related factors at neighborhood levels have not been widely investigated. We sought to explore relationships between neighborhood deprivation index (NDI) and the microbial metabolite, trimethylamine-N-oxide. We hypothesized that inflammatory markers and dietary intake would be mediators of the relationship. Methods: African-American adults at risk for CVD living in the Washington, DC area were recruited to participate in a cross-sectional community-based study. US census-based neighborhood deprivation index (NDI) measures (at the census-tract level) were determined. Serum samples were analyzed for CVD risk factors, cytokines, and the microbial metabolite, trimethylamine-N-oxide (TMAO). Self-reported dietary intake based on food groups was collected. Results: Study participants (n = 60) were predominantly female (93.3%), with a mean (SD) age of 60.83 (+/−10.52) years. Mean (SD) NDI was −1.54 (2.94), and mean (SD) TMAO level was 4.99 (9.65) µmol/L. Adjusting for CVD risk factors and BMI, NDI was positively associated with TMAO (β = 0.31, p = 0.02). Using mediation analysis, the relationship between NDI and TMAO was significantly mediated by TNF-α (60.15%) and interleukin)-1 β (IL, 49.96%). When controlling for clustering within neighborhoods, the NDI-TMAO association was no longer significant (β = 5.11, p = 0.11). However, the association between NDI and IL-1 β (β = 0.04, p = 0.004) and TNF-α (β = 0.17, p = 0.003) remained. Neither NDI nor TMAO was significantly associated with daily dietary intake. Conclusion and Relevance: Among a small sample of African-American adults at risk for CVD, there was a significant positive relationship with NDI and TMAO mediated by inflammation. These hypothesis-generating results are initial and need to be confirmed in larger studies.

Introduction Vaccine hesitancy and delays in vaccine administration time have limited the success of prior influenza vaccination initiatives in the pediatric emergency department (ED). In 2018-2019, season 1, this ED implemented mandatory vaccine screening and offered the vaccine to all eligible patients; however, only 9% of the eligible population received the vaccine. In 2019-2020, season 2, the team sought to improve influenza vaccination rates from 9% to 15% and administer over 2,000 vaccines to eligible ED patients. Methods Key drivers included: identifying vaccine hesitancy, providing counseling, reducing administration delays, and developing reminders for vaccine administration. We tested interventions using plan-do-study-act cycles. We included discharged ED patients, age 6 months-18 years old, emergency severity index score 2-5, and no prior vaccine this season. Process measures included percent of patients screened, eligible, accepting the vaccine, and leaving before vaccination. Outcome measures were the percent of eligible patients vaccinated and the total number of vaccines administered. Vaccination time was the balancing measure. Results We included 57,804 children in this study. Comparing season 1 to 2, screening rates (84%) and eligibility rates (58%) were similar. Vaccine acceptance rates improved from 13% to 22%, the proportion of patients leaving before vaccination decreased from 32% to 17%, and vaccination rates improved from 9% to 20%. Total vaccines administered increased from 1,309 to 3,180, and vaccination time was 5 minutes faster in season 2. Conclusions This ED influenza vaccination process provides a model to overcome vaccine hesitancy and can be adapted and replicated for any vaccine-preventable illness.

Ogden syndrome is a rare lethal X‐linked recessive disorder caused by a recurrent missense variant (Ser37Pro) in the NAA10 gene, encoding the catalytic subunit of the N‐terminal acetyltransferase A complex (NatA). So far eight boys of two different families have been described in the literature, all presenting the distinctive and recognizable phenotype, which includes mostly postnatal growth retardation, global severe developmental delay, characteristic craniofacial features, and structural cardiac anomalies and/or arrhythmias. Here, we report the ninth case of Ogden syndrome with an independent recurrence of the Ser37Pro variant. We were able to follow the clinical course of the affected boy and delineate the evolving phenotype from his birth until his unfortunate death at 7 months. We could confirm the associated phenotype as well as the natural history of this severe disease. By describing new presenting features, we are further expanding the clinical spectrum associated with Ogden syndrome and review other phenotypes associated with NAA10 variants.

Background: Psychosocial stress correlates with cardiovascular (CV) events; however, associations between physiologic measures of stressors and CVD remain incompletely understood, especially in racial/ethnic minority populations in resource-limited neighborhoods. We examined associations between chronic stress-related neural activity, measured by amygdalar 18Fluorodeoxyglucose (18FDG) uptake, and aortic vascular FDG uptake (arterial inflammation measure) in a community-based cohort.Methods: Forty participants from the Washington, DC CV Health and Needs Assessment (DC-CHNA), a study of a predominantly African-American population in resource-limited urban areas and 25 healthy volunteers underwent detailed phenotyping, including 18FDG PET/CT for assessing amygdalar activity (AmygA), vascular FDG uptake, and hematopoietic (leukopoietic) tissue activity. Mediation analysis was used to test whether the link between AmygA and vascular FDG uptake was mediated by hematopoietic activity.Results: AmygA (1.11 ± 0.09 vs. 1.05 ± 0.09, p = 0.004) and vascular FDG uptake (1.63 ± 0.22 vs. 1.55 ± 0.17, p = 0.05) were greater in the DC-CHNA cohort compared to volunteers. Within the DC-CHNA cohort, AmygA associated with vascular FDG uptake after adjustment for Framingham score and body mass index (β = 0.41, p = 0.015). The AmygA and aortic vascular FDG uptake relationship was in part mediated by splenic (20.2%) and bone marrow (11.8%) activity.Conclusions: AmygA, or chronic stress-related neural activity, associates with subclinical CVD risk in a community-based cohort. This may in part be mediated by the hematopoietic system. Our findings of this hypothesis-generating study are suggestive of a potential relationship between chronic stress-related neural activity and subclinical CVD in an African American community-based population. Taken together, these findings suggest a potential mechanism by which chronic psychosocial stress, such as stressors that can be experienced in adverse social conditions, promotes greater cardiovascular risk amongst resource-limited, community-based populations most impacted by cardiovascular health disparities. However, larger prospective studies examining these findings in other racially and ethnically diverse populations are necessary to confirm and extend these findings.

There are approximately 38 million people globally living with Human immunodeficiency virus 1 (HIV-1) and given the tremendous success of combination antiretroviral therapy (cART) this has dramatically reduced mortality and morbidity with prevention benefits. However, HIV-1 persists during cART within the human body and re-appears upon cART interruption. This HIV-1 reservoir remains a barrier to cure with cellular sites of viral persistence not fully understood. In this study we provide evidence corroborating a recently published article in STM demonstrating the role of platelets as a novel cellular disseminator of HIV-1 particles in the setting of viral suppression. Using classical transmission electron microscopy with and without immunogold labeling, we visualize HIV-1 in both platelets and monocytes in cART suppressed HIV donors. Our study suggests that due to the close proximity of platelets and monocytes an alternative life cycle of HIV-1 cycling within monocytes and platelets without the need of active replication under cART occurs. Our findings are supported by the lack of detectable HIV-1 particles in platelets derived from HIV uninfected donors or the ���Berlin��� patient suggesting that platelets may serve as an underappreciated hidden bearer for HIV-1 and should be considered in HIV remission studies and trials.

IntroductionAlthough physical activity (PA) reduces cardiovascular disease (CVD) risk, physical inactivity remains a pressing public health concern, especially among African American (AA) women in the USA. PA interventions focused on AA women living in resource-limited communities with scarce PA infrastructure are needed. Mobile health (mHealth) technology can increase access to PA interventions. We describe the development of a clinical protocol for a multilevel, community-based, mHealth PA intervention for AA women.Methods and analysisAn mHealth intervention targeting AA women living in resource-limited Washington, DC communities was developed based on the socioecological framework for PA. Over 6 months, we will use a Sequential Multi-Assignment, Randomized Trial approach to compare the effects on PA of location-based remote messaging (named ‘tailored-to-place’) to standard remote messaging in an mHealth intervention. Participants will be randomised to a remote messaging intervention for 3 months, at which point the intervention strategy will adapt based on individuals’ PA levels. Those who do not meet the PA goal will be rerandomised to more intensive treatment. Participants will be followed for another 3 months to determine the contribution of each mHealth intervention to PA level. This protocol will use novel statistical approaches to account for the adaptive strategy. Finally, effects of PA changes on CVD risk biomarkers will be characterised.Ethics and disseminationThis protocol has been developed in partnership with a Washington, DC-area community advisory board to ensure feasibility and acceptability to community members. The National Institutes of Health Intramural IRB approved this research and the National Heart, Lung, and Blood Institute provided funding. Once published, results of this work will be disseminated to community members through presentations at community advisory board meetings and our quarterly newsletter.Trial registration numberNCT03288207.

Cigarette smoking causes adverse health effects that might occur shortly after smoking initiation and lead to the development of inflammation and cardiorespiratory disease. Emerging studies have demonstrated the role of the intestinal microbiome in disease pathogenesis. The intestinal microbiome is susceptible to the influence of environmental factors such as smoking, and recent studies have indicated microbiome changes in smokers. Candidate modified risk tobacco products (CMRTP) are being developed to provide substitute products to lower smoking-related health risks in smokers who are unable or unwilling to quit. In this study, the ApoE–/– mouse model was used to investigate the impact of cigarette smoke (CS) from the reference cigarette 3R4F and aerosols from two CMRTPs based on the heat-not-burn principle [carbon-heated tobacco product 1.2 (CHTP 1.2) and tobacco heating system 2.2 (THS 2.2)] on the intestinal microbiome over a 6-month period. The effect of cessation or switching to CHTP 1.2 after 3 months of CS exposure was also assessed. Next-generation sequencing was used to evaluate the impact of CMRTP aerosols in comparison to CS on microbiome composition and gene expression in the digestive tract of mice. Our analyses highlighted significant gene dysregulation in response to 3R4F exposure at 4 and 6 months. The findings showed an increase in the abundance of Akkermansiaceae upon CS exposure, which was reversed upon cessation. Cessation resulted in a significant decrease in Akkemansiaceae abundance, whereas switching to CHTP 1.2 resulted in an increase in Lactobacillaceae abundance. These microbial changes could be important for understanding the effect of CS on gut function and its relevance to disease pathogenesis via the microbiome.

Objectives: Little is understood about associations between neighborhood characteristics and depression, a cardiovascular disease (CVD) risk factor, in diverse populations. We examined relationships between perceived/objective neighborhood characteristics, depression, and CVD markers within the Washington, DC CV Health/Needs Assessment, an evaluation among predominantly African-American (AA) adults in resource-limited DC communities. Method: Factor analysis of overall neighborhood environment perception (NEP) identified three NEP sub-scores:1) violence; 2) physical/social environment; 3) social cohesion (higher score = more favorable perception). Objective neighborhood characteristics were measured by geospatially-derived scores of walkability, transportation, and crime. Depression was defined by the revised Center for Epidemiologic Studies Depression Scale (CESD-R). We used linear-regression modeling to examine neighborhood measures and CESD-R associations. To investigate a subsequent connection with CVD risk, we examined relationships between CESD-R and CVD-associated cytokines in a population subset. Results: Participants (N = 99; mean age = 59.06; 99% AA) had a mean CESD-R score 5.8(SD = 8.88). In adjusted models, CESD-R scores decreased by 0.20 units (p = 0.01) for every overall NEP unit-increase. Perceived physical/social environment (β = −0.34, p = 0.04) and social cohesion (β = −0.82, p = 0.01) were related to CESD-R while perceived violence was not (β = −0.28, p = 0.1). Of objective neighborhood environment measures (i.e. walk, transit, bike, personal crime, and property crime scores), only property crime score was associated with depression (β = 4.99, p < 0.03). In population subset (n = 42), higher CESD-R associated with higher IL-1β (β = 21.25, p < 0.01) and IL-18 (β = 0.006, p = 0.01). Conclusion: Favorable neighborhood perceptions are related to lower depressive symptoms in a predominantly AA cohort from Washington, DC resource-limited communities. Neighborhood perceptions appear to be strongly associated with depressive symptoms compared to objective characteristics. Increasing CESD-R scores were related to higher pro-inflammatory markers. Improving neighborhood perceptions may be beneficial to psychological well-being and CV health for urban minority residents.

Supplemental Digital Content is available in the text., Introduction: Annual influenza vaccination is recommended for all US children 6 months and older to prevent morbidity and mortality. Despite these recommendations, only ~50% of US children are vaccinated annually. Influenza vaccine administration in the pediatric emergency department (ED) is an innovative solution to improve vaccination rates. However, during the 2017–2018 influenza season, only 75 influenza vaccinations were given in this tertiary care ED. We aimed to increase the number of influenza vaccines administered to ED patients from 75 to 1,000 between August 2018 and March 2019.s Methods: Process mapping identified potential barriers and solutions. Key interventions included mandatory vaccine screening, creation of a vaccine administration protocol, education for family, provider, and nursing, a revised pharmacy workflow, and weekly staff feedback. Interventions were tested using plan-do-study-act cycles. The process measure was the percent of patients screened for vaccine status. The primary outcome was the number of influenza vaccines administered. The balancing measures were ED length of stay (LOS), wasted vaccines, and financial impact on the institution. Results: We included 33,311 children in this study. Screening for vaccine status improved from 0% to 90%. Of those screened, 58% were eligible for vaccination, and 8.5% of eligible patients were vaccinated in the ED. In total, 1,323 vaccines were administered with no significant change in ED LOS (139 min) and no lost revenue to the hospital. Conclusions: We implemented an efficient, cost-effective, influenza vaccination program in the pediatric ED and successfully increased vaccinations in a population that might not otherwise receive the vaccine.

Mechanisms explaining the link between psoriasis, a pro-inflammatory condition, and cardiovascular disease (CVD) are not fully known. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is predominantly expressed in hepatocytes as a critical regulator of lipid metabolism and clinical trials targeting PCSK9 reduce CVD. Independent of its role in lipid metabolism, PCSK9 levels associate with endothelial dysfunction and predict CV events. We used two separate human psoriasis cohorts and the K14-Rac1V12(−/+) murine model of psoriasis to investigate PCSK9 and CV risk in psoriasis. In both psoriasis cohorts, (n=88 and n=20), PCSK9 levels were 20% and 13% higher than age, sex, and cholesterol matched controls respectively (p

On the 9th March 2020, the first patient with COVID-19 was admitted to ICU in the Royal Gwent Hospital, Newport, Wales. We prospectively recorded the rate of ICU admissions of 52 patients with COVID-19 over 60 days, focusing on the epidemiology of ethnicity and deprivation. Patients were 65% (34 of 52) male and had a median (IQR) age of 55 (48-62) years. Prevalent comorbidities included obesity (52%); diabetes (33%), and asthma (23%). COVID-19 hospital and ICU inpatient numbers peaked on days 23 and 39, respectively – a lag of 16 days. The ICU mortality rate was 33% (17 of 52). Black, Asian and Minority Ethnics (BAME) population represented 35% of ICU COVID-19 admissions (18 of 52) and 35% of deaths (6 of 17). Within the BAME group, 72% (13 of 18) were found to reside in geographical areas representing the 20% most deprived in Wales, versus 27% of Caucasians (9 of 33). Less than 5% of the population within the hospital catchment area are of BAME descent, yet they represent a disproportionately high proportion of patients with ICU admission and mortality suffering from COVID-19. The interplay between ethnicity and deprivation, which is complex, may be a factor in our findings. This in turn could be related to an increased prevalence of co-morbidities; higher community exposure; or genetic polymorphisms.

It is evident that health disparities exist during the COVID-19 pandemic, a pandemic caused by the novel coronavirus SARS-CoV-2. Underlying reasons for COVID-19 health disparities are multi-factorial. However, social determinants, including those regarding socioeconomic status, social inequalities, health behaviors, and stress, may have implications on these disparities. Exposure to one or more of these social determinants is associated with heightened inflammatory responses, particularly increases in the cytokine interleukin-6 (IL-6), as well as immune system dysfunction. Thus, an amplified effect during COVID-19 could occur, potentially resulting in vulnerable patients experiencing an intensified cytokine storm due to a hyperactive and dysfunctional immune response. Further understanding how social determinants play a mechanistic role in COVID-19 disparities could potentially help reduce health disparities overall and in future pandemics.

Name of the disease (synonyms) Simpson-Golabi-Behmel syndrome (SGBS). OMIM# OF THE DISEASE: 312870. Name of the analysed genes or dna/chromosome segments GPC3. OMIM# OF THE GENE(S): 300037. Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for mutations in the GPC3 gene(s) in ⊠ diagnostic, ☐ predictive and ⊠ prenatal settings and for ⊠ risk assessment in relatives.

OBJECTIVE:To compare changes in foraminal motion at two time points post-surgery between artificial disc replacement (ADR) and anterior cervical discectomy and fusion (ACDF). METHODS:Eight ACDF and 6 ADR patients (all single-level C5-6) were tested at 2 years (T1) and 6.5 years (T2) post-surgery. The minimum foraminal height (FH.Min) and width (FW.Min) achieved during neck axial rotation and extension, and the range of these dimensions during motion (FH.Rn and FW.Rn, respectively) were measured using a biplane dynamic x-ray system, CT imaging and model-based tracking while patients performed neck axial rotation and extension tasks. Two-way mixed ANOVA was employed for analysis. RESULTS:In neck extension, significant interactions were found between year post-surgery and type of surgery for FW.Rn at C5-6 (p0.7). CONCLUSIONS:Changes were observed in the range of foraminal geometry at adjacent levels from 2 years to 6.5 years post-surgery that were different between ACDF and ADR for neck extension. These changes are contrary to the notion that motion at adjacent levels continue to increase following ACDF as compared to ADR over the long term.

Rationale: Psoriasis is a systemic inflammatory skin disease associated with cardiovascular disease and lipid dysfunction. However, traditional lipid parameters have limited prognostic value, whereas assessing oxidation-modified lipids in this inflammatory driven condition may capture additional risk. Recently, a study showed that psoriasis was associated with increased lipid-rich coronary plaques; therefore, investigating potential relationships with oxidation-modified lipids may speed understanding of increased cardiovascular disease in psoriasis. Objective: To understand whether oxidation-modified lipids associate with traditional lipid phenotypes, cardiometabolic disease biomarkers, and total coronary plaque, with focus on noncalcified burden (NCB) by coronary computed tomographic angiography in psoriasis. Methods and Results: Psoriasis subjects and controls (n=252) had profiling for oxidation-modified LDL (low-density lipoprotein), HDL (high-density lipoprotein), Lp(a) (lipoprotein[a]), cholesterol efflux capacity, lipoprotein particle size and number by NMR spectroscopy, and PON-1 (paraoxonase-1) activity. Blinded coronary computed tomographic angiography coronary artery disease characterization included total burden, NCB, and dense-calcified burden. Compared with healthy volunteers, psoriasis subjects were older (mean age, 50.1), had increased body mass index , and homeostatic model assessment of insulin resistance. Psoriasis subjects had increase in oxidized Lp(a), Lp(a), and oxidized HDL (oxHDL; P P =0.020) and oxHDL (β=−0.11; P =0.007) with NCB. Moreover, psoriasis subjects expressed significantly higher PON-1 (kU/µL) activity compared with healthy volunteers (8.55±3.21 versus 6.24±3.82; P =0.01). Finally, psoriasis treatment was associated with a reduction in oxHDL (U/mL; 203.79±88.40 versus 116.36±85.03; P P =0.03). Conclusions: Traditional lipids did not capture risk of lipid-rich plaque as assessed by NCB, whereas assaying oxidation-modification of lipids revealed significant association with oxidized LDL and oxHDL. The PON-1 activity was increased in psoriasis suggesting possible compensatory antioxidative effect. Psoriasis treatment was associated with a reduction in oxHDL. These findings support performance of larger studies to understand oxidation-modified lipids in inflammatory states.

Structure and thermolysis of NiC2O4·2H2O (I) and Ni(HCO2)2·2H2O (II) were studied for the precipitated powders from the water solutions of precursors. The compound (I) has a disordered structure (C2/c, a=11.7916(5), b= 5.31798(14), c= 9.7806(7) A, β = 127.014(6)°, V= 489.73(4)A3) which is described via the displacement vector applied to the basis atoms and the part of the shifted atoms. Thermal dehydration of (I) leads to formation of the disordered β-NiC2O4 (III), the structure of which (P21/n, a=5.8294(9), b= 5.1685(13), c= 5.2712(4) A, β = 117.793(12)°, V= 140.50(5)A3) was refined from the powder diffraction. Oxalates (I) and (III) are both characterized by the essential part of the shifted atoms causing the extinction of some lines in XRPD pattern. The final product of thermal decomposition of (I) in air is NiO, whereas thermolysis of (II) leads to formation of Ni/NiO mixture. The content of Ni in the latter depends on the thickness of the decaying layer in the sample because the gaseous products of the reaction prevent the oxidation of the nickel formed initially.