BTLA+ Dendritic Cells: The Regulatory T Cell Force Awakens.

The role of dendritic cells (DCs) in the induction of antigen-specific tolerance mediated by extrathymic regulatory T (Treg) cells remains incompletely defined. In this issue of Immunity, Jones et al. (2016) show that BTLA+DEC205+CD8+CD11c+ DCs efficiently induce peripheral Treg cells via the engagement of HVEM, a receptor for BTLA.

Aluminum Cayley trees as scalable, broadband, multiresonant optical antennas.

An optical antenna can convert a propagative optical radiation into a localized excitation and the reciprocal. Although optical antennas can be readily created using resonant nanoparticles (metallic or dielectric) as elementary building blocks, the realization of antennas sustaining multiple resonances over a broad range of frequencies remains a challenging task. Here, we use aluminum self-similar, fractal-like structures as broadband optical antennas. Using electron energy loss spectroscopy, we experimentally evidence that a single aluminum Cayley tree, a simple self-similar structure, sustains multiple plasmonic resonances. The spectral position of these resonances is scalable over a broad spectral range spanning two decades, from ultraviolet to midinfrared. Such multiresonant structures are highly desirable for applications ranging from nonlinear optics to light harvesting and photodetection, as well as surface-enhanced infrared absorption spectroscopy.

Firearm Storage Behaviors - Behavioral Risk Factor Surveillance System, Eight States, 2021-2022.

Secure firearm storage might help reduce access by children and other unauthorized users and the related risk for injury or death. Information about state-specific prevalence of firearm storage practices can be used to develop secure storage messages and programs; however, such information is often unavailable. Data from the Behavioral Risk Factor Surveillance System, by respondent characteristics, were used to estimate prevalence of keeping firearms in or around the home and related storage practices for eight states that administered the firearm safety module in 2021 or 2022. Overall, 18.4% (California) to 50.6% (Alaska) of respondents reported that a firearm was kept in or around their home. Among those with a firearm in or around the home, 19.5% (Minnesota) to 43.8% (North Carolina) reported that a firearm was stored loaded. Across all eight states, approximately one half of those with a loaded firearm stored at least one loaded firearm unlocked. Among respondents with a child and a loaded firearm in the home, 25.2% (Ohio) to 41.4% (Alaska) reported that a loaded firearm was stored unlocked. Variability in firearm storage practices highlights the importance of local data and suggests opportunities to tailor prevention efforts to specific population groups to reduce risk for firearm handling by children without adult supervision, and other unauthorized persons.

Challenging Ancient DNA Results About Putative HLA Protection or Susceptibility to Yersinia pestis.

In a recent article, Immel et al. (Immel A, Key FM, Szolek A, Barquera R, Robinson MK, Harrison GF, Palmer WH, Spyrou MA, Susat J, Krause-Kyora B, et al. 2021. Analysis of genomic DNA from medieval plague victims suggests long-term effect of Yersinia pestis on human immunity genes. Mol Biol Evol. 38:4059-4076) extracted DNA from 36 individuals dead from plague in Ellwangen, Southern Germany, during the 16th century. By comparing their human leukocyte antigen (HLA) genotypes with those of 50 present-day Ellwangen inhabitants, the authors reported a significant decrease of HLA-B*51:01 and HLA-C*06:02 and a significant increase of HLA-DRB1*13:01/13:02 frequencies from ancient to modern populations. After comparing these frequencies with a larger sample of 8,862 modern Germans and performing simulations of natural selection, they concluded that these changes had been driven by natural selection. In an attempt to provide more evidence on such stimulating results, we explored the HLA frequency patterns over all of Europe, we predicted binding affinities of HLA-B/C/DRB1 alleles to 106,515 Yersinia pestis-derived peptides, and we performed forward simulations of HLA genetic profiles under neutrality. Our analyses do not sustain the conclusions of HLA protection or susceptibility to plague based on ancient DNA.

Environmental signals perceived by the brain abate pro-metastatic monocytes by dampening glucocorticoids receptor signaling.

While positive social-behavioral factors predict longer survival in cancer patients, the underlying mechanisms are unknown. Since tumor metastasis are the major cancer mortality factor, we investigated how an enriched environment (EE) conductive to enhanced sensory, cognitive and motor stimulation impact metastatic progression in lungs following intravasation in the circulation. We find that mice housed in EE exhibited reduced number of lung metastatic foci compared to control mice housed in a standard environment (SE). Compared to SE mice, EE mice increased lung inflammation as early as 4 days after circulating tumor cells extravasation. The impact of environmental signals on lung metastasis is independent of adrenergic receptors signaling. By contrast, we find that serum corticosterone levels are lower in EE mice and that glucocorticoid receptor (GR) antagonist reduces the number of lung metastasis in SE mice. In addition, the difference of the number of lung metastasis between SE and EE mice is abolished when inflammatory monocytes are rendered deficient in GR signaling. This decreased GR signaling in inflammatory monocytes of SE mice results in an exacerbated inflammatory profile in the lung. Our study shows that not only EE reduces late stages of metastatic progression in lungs but disclose a novel anti-tumor mechanism whereby GR-dependent reprogramming of inflammatory monocytes can inhibit metastatic progression in lungs. Moreover, while inflammatory monocytes have been shown to promote cancer progression, they also have an anti-tumor effect, suggesting that their role is more complex than currently thought.

Prevalence of Adverse Childhood Experiences Among U.S. Adults - Behavioral Risk Factor Surveillance System, 2011-2020.

Adverse childhood experiences (ACEs) are defined as preventable, potentially traumatic events that occur among persons aged <18 years and are associated with numerous negative outcomes; data from 25 states indicate that ACEs are common among U.S. adults (1). Disparities in ACEs are often attributable to social and economic environments in which some families live (2,3). Understanding the prevalence of ACEs, stratified by sociodemographic characteristics, is essential to addressing and preventing ACEs and eliminating disparities, but population-level ACEs data collection has been sporadic (1). Using 2011-2020 Behavioral Risk Factor Surveillance System (BRFSS) data, CDC provides estimates of ACEs prevalence among U.S. adults in all 50 states and the District of Columbia, and by key sociodemographic characteristics. Overall, 63.9% of U.S. adults reported at least one ACE; 17.3% reported four or more ACEs. Experiencing four or more ACEs was most common among females (19.2%), adults aged 25-34 years (25.2%), non-Hispanic American Indian or Alaska Native (AI/AN) adults (32.4%), non-Hispanic multiracial adults (31.5%), adults with less than a high school education (20.5%), and those who were unemployed (25.8%) or unable to work (28.8%). Prevalence of experiencing four or more ACEs varied substantially across jurisdictions, from 11.9% (New Jersey) to 22.7% (Oregon). Patterns in prevalence of individual and total number of ACEs varied by jurisdiction and sociodemographic characteristics, reinforcing the importance of jurisdiction and local collection of ACEs data to guide targeted prevention and decrease inequities. CDC has released prevention resources, including Preventing Adverse Childhood Experiences: Leveraging the Best Available Evidence, to help provide jurisdictions and communities with the best available strategies to prevent violence and other ACEs, including guidance on how to implement those strategies for maximum impact (4-6).

Emergency Department Visits for Firearm Injuries Before and During the COVID-19 Pandemic - United States, January 2019-December 2022.

During the COVID-19 pandemic, the U.S. firearm homicide rate increased by nearly 35%, and the firearm suicide rate remained high during 2019-2020 (1). Provisional mortality data from the National Vital Statistics System indicate that rates continued to increase in 2021: the rates of firearm homicide and firearm suicide in 2021 were the highest recorded since 1993 and 1990, respectively (2). Firearm injuries treated in emergency departments (EDs), the primary setting for the immediate medical treatment of such injuries, gradually increased during 2018-2019 (3); however, more recent patterns of ED visits for firearm injuries, particularly during the COVID-19 pandemic, are unknown. Using data from the National Syndromic Surveillance Program (NSSP),* CDC examined changes in ED visits for initial firearm injury encounters during January 2019-December 2022, by year, patient sex, and age group. Increases in the overall weekly number of firearm injury ED visits were detected at certain periods during the COVID-19 pandemic. One such period during which there was a gradual increase was March 2020, which coincided with both the declaration of COVID-19 as a national emergency† and a pronounced decrease in the total number of ED visits. Another increase in firearm injury ED visits occurred in late May 2020, concurrent with a period marked by public outcry related to social injustice and structural racism (4), changes in state-level COVID-19-specific prevention strategies,§ decreased engagement in COVID-19 mitigation behaviors (5), and reported increases in some types of crime (4). Compared with 2019, the average number of weekly ED visits for firearm injury was 37% higher in 2020, 36% higher in 2021, and 20% higher in 2022. A comprehensive approach is needed to prevent and respond to firearm injuries in communities, including strategies that engage community and street outreach programs, implement hospital-based violence prevention programs, improve community physical environments, enhance secure storage of firearms, and strengthen social and economic supports.

SARS-CoV-2 Vaccination-Induced Immunogenicity in Heart Transplant Recipients.

Among heart transplant (HT) recipients, a reduced immunological response to SARS-CoV-2 vaccination has been reported. We aimed to assess the humoral and T-cell response to SARS-CoV-2 vaccination in HT recipients to understand determinants of immunogenicity. HT recipients were prospectively enrolled from January 2021 until March 2022. Anti-SARS-CoV-2-Spike IgG levels were quantified after two and three doses of a SARS-CoV-2 vaccine (BNT162b2, mRNA1273, or AZD1222). Spike-specific T-cell responses were assessed using flow cytometry. Ninety-one patients were included in the study (69% male, median age 55 years, median time from HT to first vaccination 6.1 years). Seroconversion rates were 34% after two and 63% after three doses. Older patient age (p = 0.003) and shorter time since HT (p = 0.001) were associated with lower antibody concentrations after three vaccinations. There were no associations between vaccine types or immunosuppressive regimens and humoral response, except for prednisolone, which was predictive of a reduced response after two (p = 0.001), but not after three doses (p = 0.434). A T-cell response was observed in 50% after two and in 74% after three doses. Despite three vaccine doses, a large proportion of HT recipients exhibits a reduced immune response. Additional strategies are desirable to improve vaccine immunogenicity in this vulnerable group of patients.

Violent Victimization During Childhood in the United States: Associations With Revictimization and Health.

Childhood violence victimization is a serious adverse childhood experience with lasting health impacts. This study examined the prevalence and characteristics of five forms of childhood violence victimization and their association with revictimization and negative health conditions among adults. Data are from the 2010-2012 National Intimate Partner and Sexual Violence Survey. Age at first victimization and perpetrator sex were assessed; adjusted odds ratios assessed associations with revictimization and health. Ages 14-17 were the most common age at first victimization for most violence types; almost half of male (46.7%) and a quarter of female (27.0%) rape victims reported first victimization before age 10. Most victimization was associated with revictimization and negative health, controlling for adult victimization. Primary prevention of childhood violence may reduce later health risks.

A Single Dose of BNT162b2 Messenger RNA Vaccine Induces Airway Immunity in Severe Acute Respiratory Syndrome Coronavirus 2 Naive and Recovered Coronavirus Disease 2019 Subjects.

BACKGROUND: Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and therefore virus shedding. Parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior mucosal infection compared with injections of a parenteral vaccine in a mucosally naive subject. We investigated whether this was also the case for the BNT162b2 coronavirus disease 2019 (COVID-19) messenger RNA vaccine. METHODS: Twenty recovered COVID-19 subjects (RCSs) and 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive subjects were vaccinated with, respectively, 1 and 2 doses of the BNT162b2 COVID-19 vaccine. Nasal epithelial lining fluid (NELF) and plasma were collected before and after vaccination and assessed for immunoglobulin G (IgG) and IgA antibody levels to Spike and for their ability to neutralize binding of Spike to angiotensin-converting enzyme-2 receptor. Blood was analyzed 1 week after vaccination for the number of Spike-specific antibody-secreting cells (ASCs) with a mucosal tropism. RESULTS: All RCSs had both nasal and blood SARS-CoV-2-specific antibodies at least 90 days after initial diagnosis. In RCSs, a single dose of vaccine amplified preexisting Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including Delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2-naive subjects after 2 vaccine doses compared with RCSs after 1 dose. CONCLUSIONS: Mucosal immune response to the SARS-CoV-2 Spike protein is higher in RCSs after a single vaccine dose compared with SARS-CoV-2-naive subjects after 2 doses.

Hypoxia briefly increases diuresis but reduces plasma volume by fluid redistribution in women.

We have recently reported that hypobaric hypoxia (HH) reduces plasma volume (PV) in men by decreasing total circulating plasma protein (TCPP). Here, we investigated whether this applies to women and whether an inflammatory response and/or endothelial glycocalyx shedding could facilitate the TCCP reduction. We further investigated whether acute HH induces a short-lived diuretic response that was overlooked in our recent study, where only 24-h urine volumes were evaluated. In a strictly controlled crossover protocol, 12 women underwent two 4-day sojourns in a hypobaric chamber: one in normoxia (NX) and one in HH equivalent to 3,500-m altitude. PV, urine output, TCPP, and markers for inflammation and glycocalyx shedding were repeatedly measured. Total body water (TBW) was determined pre- and postsojourns by deuterium dilution. PV was reduced after 12 h of HH and thereafter remained 230-330 mL lower than in NX (P < 0.0001). Urine flow was 45% higher in HH than in NX throughout the first 6 h (P = 0.01) but lower during the second half of the first day (P < 0.001). Twenty-four-hour urine volumes (P ≥ 0.37) and TBW (P ≥ 0.14) were not different between the sojourns. TCPP was lower in HH than in NX at the same time points as PV (P < 0.001), but inflammatory or glycocalyx shedding markers were not consistently increased. As in men, and despite initially increased diuresis, HH-induced PV contraction in women is driven by a loss of TCPP and ensuing fluid redistribution, rather than by fluid loss. The mechanism underlying the TCPP reduction remains unclear but does not seem to involve inflammation or glycocalyx shedding.NEW & NOTEWORTHY This study is the first to investigate the mechanisms underlying plasma volume (PV) contraction in response to hypoxia in women while strictly controlling for confounders. PV contraction in women has a similar time course and magnitude as in men and is driven by the same mechanism, namely, oncotically driven redistribution rather than loss of fluid. We further report that hypoxia facilitates an increase in diuresis, that is, however, short-lived and of little relevance for PV regulation.

Electrical stimulation of the splenic nerve bundle ameliorates dextran sulfate sodium-induced colitis in mice.

BACKGROUND: Vagus nerve stimulation has been suggested to affect immune responses, partly through a neuronal circuit requiring sympathetic innervation of the splenic nerve bundle and norepinephrine (NE) release. Molecular and cellular mechanisms of action remain elusive. Here, we investigated the therapeutic value of this neuromodulation in inflammatory bowel disease (IBD) by applying electrical splenic nerve bundle stimulation (SpNS) in mice with dextran sulfate sodium (DSS)-induced colitis. METHODS: Cuff electrodes were implanted around the splenic nerve bundle in mice, whereupon mice received SpNS or sham stimulation. Stimulation was applied 6 times daily for 12 days during DSS-induced colitis. Colonic and splenic tissues were collected for transcriptional analyses by qPCR and RNA-sequencing (RNA-seq). In addition, murine and human splenocytes were stimulated with lipopolysaccharide (LPS) in the absence or presence of NE. Single-cell RNA-seq data from publicly available data sets were analyzed for expression of ß-adrenergic receptors (ß-ARs). RESULTS: Colitic mice undergoing SpNS displayed reduced colon weight/length ratios and showed improved Disease Activity Index scores with reduced Tumor Necrosis Factor α mRNA expression in the colon compared with sham stimulated mice. Analyses of splenocytes from SpNS mice using RNA-seq demonstrated specific immune metabolism transcriptome profile changes in myeloid cells. Splenocytes showed expression of ß-ARs in myeloid and T cells. Cytokine production was reduced by NE in mouse and human LPS-stimulated splenocytes. CONCLUSIONS: Together, our results demonstrate that SpNS reduces clinical features of colonic inflammation in mice with DSS-induced colitis possibly by inhibiting splenic myeloid cell activation. Our data further support exploration of the clinical use of SpNS for patients with IBD.

Gun Carrying Among Youths, by Demographic Characteristics, Associated Violence Experiences, and Risk Behaviors - United States, 2017-2019.

Suicide and homicide are the second and third leading causes of death, respectively, among youths aged 14-17 years (1); nearly one half (46%) of youth suicides and most (93%) youth homicides result from firearm injuries (1). Understanding youth gun carrying and associated outcomes can guide prevention initiatives (2). This study used the updated measure of gun carrying in the 2017 and 2019 administrations of CDC's Youth Risk Behavior Survey* (YRBS) to describe the national prevalence of gun carrying for reasons other than hunting or sport among high school students aged <18 years and to examine the associations between gun carrying and experiencing violence, suicidal ideation or attempts, or substance use. Gun carrying during the previous 12 months was reported by one in 15 males and one in 50 females. Gun carrying was significantly more likely among youths with violence-related experiences (adjusted prevalence ratio [aPR] range = 1.5-10.1), suicidal ideation or attempts (aPR range = 1.8-3.5), or substance use (aPR range = 4.2-5.6). These results underscore the importance of comprehensive approaches to preventing youth violence and suicide, including strategies that focus on preventing youth substance use and gun carrying (3).

County-Level Social Vulnerability and Emergency Department Visits for Firearm Injuries - 10 U.S. Jurisdictions, January 1, 2018-December 31, 2021.

At least 100,000 persons in the United States experience a fatal or nonfatal firearm injury each year.* CDC examined rates of firearm injury emergency department (ED) visits by community social vulnerability using data from CDC's Firearm Injury Surveillance Through Emergency Rooms (FASTER) program.† ED visit data, shared with CDC's National Syndromic Surveillance Program (NSSP)§ during 2018-2021, were analyzed for 647 counties in 10 FASTER-funded jurisdictions.¶ County-level social vulnerability data were obtained from the 2018 Social Vulnerability Index (SVI).** Rates of ED visits for firearm injuries (number of firearm injury ED visits per 100,000 ED visits) were calculated across tertile levels of social vulnerability. Negative binomial regression models were used to estimate rate ratios (RRs) and associated 95% CIs comparing rates of ED visits across social vulnerability levels. During 2018-2021, compared with rates in counties with low overall social vulnerability, the firearm injury ED visit rate was 1.34 times as high in counties with medium social vulnerability and 1.80 times as high in counties with high social vulnerability. Similar patterns were observed for the SVI themes of socioeconomic status and housing type and transportation, but not for the themes of household composition and disability status or racial and ethnic minority status and language proficiency. More timely data†† on firearm injury ED visits by social vulnerability can help identify communities disproportionately experiencing elevated firearm injury rates. States and communities can use the best available evidence to implement comprehensive prevention strategies that address inequities in the social and structural conditions that contribute to risk for violence, including creating protective community environments, strengthening economic supports, and intervening to reduce harms and prevent future risk (e.g., with hospital-based violence intervention programs) (1,2).

Vital Signs: Changes in Firearm Homicide and Suicide Rates - United States, 2019-2020.

INTRODUCTION: The majority of homicides (79%) and suicides (53%) in the United States involved a firearm in 2020. High firearm homicide and suicide rates and corresponding inequities by race and ethnicity and poverty level represent important public health concerns. This study examined changes in firearm homicide and firearm suicide rates coinciding with the emergence of the COVID-19 pandemic in 2020. METHODS: National vital statistics and population data were integrated with urbanization and poverty measures at the county level. Population-based firearm homicide and suicide rates were examined by age, sex, race and ethnicity, geographic area, level of urbanization, and level of poverty. RESULTS: From 2019 to 2020, the overall firearm homicide rate increased 34.6%, from 4.6 to 6.1 per 100,000 persons. The largest increases occurred among non-Hispanic Black or African American males aged 10-44 years and non-Hispanic American Indian or Alaska Native (AI/AN) males aged 25-44 years. Rates of firearm homicide were lowest and increased least at the lowest poverty level and were higher and showed larger increases at higher poverty levels. The overall firearm suicide rate remained relatively unchanged from 2019 to 2020 (7.9 to 8.1); however, in some populations, including AI/AN males aged 10-44 years, rates did increase. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: During the COVID-19 pandemic, the firearm homicide rate in the United States reached its highest level since 1994, with substantial increases among several population subgroups. These increases have widened disparities in rates by race and ethnicity and poverty level. Several increases in firearm suicide rates were also observed. Implementation of comprehensive strategies employing proven approaches that address underlying economic, physical, and social conditions contributing to the risks for violence and suicide is urgently needed to reduce these rates and disparities.

A quantitative characterization of the spatial distribution of brain metastases from breast cancer and respective molecular subtypes.

PURPOSE: Brain metastases (BM) remain a significant cause of morbidity and mortality in breast cancer (BC) patients. Specific factors promoting the process of BM and predilection for selected neuro-anatomical regions remain unknown, yet may have major implications for prevention or treatment. Anatomical spatial distributions of BM from BC suggest a predominance of metastases in the hindbrain and cerebellum. Systematic approaches to quantifying BM location or location-based analyses based on molecular subtypes, however, remain largely unavailable. METHODS: We analyzed stereotactic Cartesian coordinates derived from 134 patients undergoing gamma- knife radiosurgery (GKRS) for treatment of 407 breast cancer BMs to quantitatively study BM spatial distribution along principal component axes and by intrinsic molecular subtype (ER, PR, Herceptin). We used kernel density estimators (KDE) to highlight clustering and distribution regions in the brain, and we used the metric of mutual information (MI) to tease out subtle differences in the BM distributions associated with different molecular subtypes of BC. BM location maps according to vascular and anatomical distributions using Cartesian coordinates to aid in systematic classification of tumor locations were additionally developed. RESULTS: We corroborated that BC BMs show a consistent propensity to arise posteriorly and caudally, and that Her2+ tumors are relatively more likely to arise medially rather than laterally. To compare the distributions among varying BC molecular subtypes, the mutual information metric reveal that the ER-PR-Her2+ and ER-PR-Her2- subtypes show the smallest amount of mutual information and are most molecularly distinct. The kernel density contour plots show a propensity for triple negative BC to arise in more superiorly or cranially situated BMs. CONCLUSIONS: We present a novel and shareable workflow for characterizing and comparing spatial distributions of BM which may aid in identifying therapeutic or diagnostic targets and interactions with the tumor microenvironment. Further characterization of these patterns with larger multi-institutional data-sets may have major impacts on treatment or management of cancer patients.

Using the Centers for Disease Control and Prevention's National Syndromic Surveillance Program Data to Monitor Trends in US Emergency Department Visits for Firearm Injuries, 2018 to 2019.

STUDY OBJECTIVE: We describe trends in emergency department (ED) visits for initial firearm injury encounters in the United States. METHODS: Using data from the Centers for Disease Control and Prevention's National Syndromic Surveillance Program, we analyzed monthly and yearly trends in ED visit rates involving a firearm injury (calculated as the number of firearm injury-related ED visits divided by the total number of ED visits for each month and multiplied by 100,000) by sex-specific age group and US region from 2018 to 2019 and conducted Joinpoint regression to detect trend significance. RESULTS: Among approximately 215 million ED visits captured in the National Syndromic Surveillance Program from January 2018 to December 2019, 132,767 involved a firearm injury (61.6 per 100,000 ED visits). Among males, rates of firearm injury-related ED visits significantly increased for all age groups between 15 and 64 years during the study period. Among females, rates of firearm injury-related ED visits significantly increased for all age groups between 15 and 54 years during the study period. By region, rates significantly changed in the northeast, southeast, and southwest for males and females during the study period. CONCLUSION: These analyses highlight a novel data source for monitoring trends in ED visits for firearm injuries. With increased and effective use of state and local syndromic surveillance data, in addition to improvements to firearm injury syndrome definitions by intent, public health professionals could better detect unusual patterns of firearm injuries across the United States for improved prevention and tailored response efforts.

Benign and malignant proliferation in idiopathic nephrotic syndrome: a French cohort study.

BACKGROUND: There seems to be a possible link between nephrotic syndrome (NS) and lymphoproliferative syndrome, but it remains poorly understood. METHODS: This multicentric and retrospective study focuses on children, who developed idiopathic NS and malignant or benign proliferation between 2000 and 2021. RESULTS: Eleven patients were included, with a median age of 4 years. Only one had a steroid-resistant nephrotic syndrome (SRNS). The maintenance therapy before the proliferation was in majority tacrolimus or mycophenolate mofetil (MMF), but three patients did not receive treatments. The proliferation was mainly a Hodgkin's lymphoma (45%) or a lymphoproliferative disease (36%), in a median time after the NS of two years. Viruses were found in seven cases (EBV in five cases and HHV-8 in two). CONCLUSION: The association between proliferative syndrome and idiopathic NS may not be fortuitous, possibly with a common lymphocytic disturbance. Genetic analyses could improve the comprehension of these manifestations in the future. A higher resolution version of the Graphical abstract is available as Supplementary information.

Vital Signs: Prevalence of Multiple Forms of Violence and Increased Health Risk Behaviors and Conditions Among Youths - United States, 2019.

INTRODUCTION: Experiencing violence, especially multiple types of violence, can have a negative impact on youths' development. These experiences increase the risk for future violence and other health problems associated with the leading causes of morbidity and mortality among adolescents and adults. METHODS: Data from the 2019 national Youth Risk Behavior Survey were used to determine the prevalence of high school students' self-reported experiences with physical fighting, being threatened with a weapon, physical dating violence, sexual violence, and bullying. Logistic regression models adjusting for sex, grade, and race/ethnicity were used to test the strength of associations between experiencing multiple forms of violence and 16 self-reported health risk behaviors and conditions. RESULTS: Approximately one half of students (44.3%) experienced at least one type of violence; more than one in seven (15.6%) experienced two or more types during the preceding 12 months. Experiencing multiple types of violence was significantly more prevalent among females than among males and among students identifying as gay, lesbian, or bisexual or not sure of their sexual identity than among heterosexual students. Experiencing violence was significantly associated with higher prevalence of all examined health risks and conditions. Relative to youths with no violence experiences, adjusted health risk and condition prevalence estimates were up to seven times higher among those experiencing two types of violence and up to 21 times higher among those experiencing three or more types of violence. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Many youths experience multiple types of violence, with potentially lifelong health impacts. Violence is preventable using proven approaches that address individual, family, and environmental risks. Prioritizing violence prevention is strategic to promoting adolescent and adult health.

Viscoelastometry for detecting oral anticoagulants.

BACKGROUND: Determination of anticoagulant therapy is of pronounced interest in emergency situations. However, routine tests do not provide sufficient insight. This study was performed to investigate the impact of anticoagulants on the results of viscoelastometric assays using the ClotPro device. METHODS: This prospective, observational study was conducted in patients receiving dabigatran, factor Xa (FXa)-inhibitors, phenprocoumon, low molecular weight heparin (LMWH) or unfractionated heparin (UFH) (local ethics committee approval number: 17-525-4). Healthy volunteers served as controls. Viscoelastometric assays were performed, including the extrinsic test (EX-test), intrinsic test (IN-test) Russel's viper venom test (RVV-test), ecarin test (ECA-test), and the tissue plasminogen activator test (TPA-test). RESULTS: 70 patients and 10 healthy volunteers were recruited. Clotting time in the EX-test (CTEX-test) was significantly prolonged versus controls by dabigatran, FXa inhibitors and phenprocoumon. CTIN-test was prolonged by dabigatran, FXa inhibitors and UFH. Dabigatran, FXa inhibitors and UFH significantly prolonged CTRVV-test in comparison with controls (median 200, 207 and 289 vs 63 s, respectively; all p < 0.0005). Only dabigatran elicited a significant increase in CTECA-test compared to controls (median 307 vs 73 s; p < 0.0001). CTECA-test correlated strongly with dabigatran plasma concentration (measured by anti-IIa activity; r = 0.9970; p < 0.0001) and provided 100% sensitivity and 100% specificity for detecting dabigatran. Plasma concentrations (anti-XA activity) of FXa inhibitors correlated with CTRVV-test (r = 0.7998; p < 0.0001), and CTRVV-test provided 83% sensitivity and 64% specificity for detecting FXa inhibitors. CONCLUSIONS: In emergency situations, ClotPro viscoelastometric assessment of whole-blood samples may help towards determining the presence and type of anticoagulant class that a patient is taking. TRIAL REGISTRATION: German clinical trials database ID: DRKS00015302 .