Clinical Impact of Multiplex Molecular Diagnostic Testing in Children With Acute Gastroenteritis Presenting to an Emergency Department: A Multicenter Prospective Study.

BACKGROUND: Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. METHODS: We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at 5 academic children's hospitals on children presenting to the emergency department with acute gastroenteritis. Caregivers were interviewed on enrollment and 7-10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the clinician's discretion . During the intervention period, multiplex molecular testing was performed on all children, with results available to clinicians. The primary outcome was return visits to a healthcare provider within 10 days of enrollment. RESULTS: Potential pathogens were identified by clinician-ordered tests in 19 of 571 (3.3%) in the pre-intervention period compared with 434 of 586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15%, respectively. In the multivariate model, the intervention was associated with a 21% reduction in the odds of any return visit (odds ratio, 0.79; 95% confidence interval, .70-.90) after adjusting for potential confounders. Appropriate treatment was prescribed in 11.3% compared with 19.6% during the intervention period (P = .22). CONCLUSIONS: Routine molecular multiplex testing for all children who presented to the ED with acute gastroenteritis detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing. Clinical Trials Registration. NCT02248285.

Guidelines on the use of sex and gender in cardiovascular research.

In cardiovascular research, sex and gender have not typically been considered in research design and reporting until recently. This has resulted in clinical research findings from which not only all women, but also gender-diverse individuals have been excluded. The resulting dearth of data has led to a lack of sex- and gender-specific clinical guidelines and raises serious questions about evidence-based care. Basic research has also excluded considerations of sex. Including sex and/or gender as research variables not only has the potential to improve the health of society overall now, but it also provides a foundation of knowledge on which to build future advances. The goal of this guidelines article is to provide advice on best practices to include sex and gender considerations in study design, as well as data collection, analysis, and interpretation to optimally establish rigor and reproducibility needed to inform clinical decision-making and improve outcomes. In cardiovascular physiology, incorporating sex and gender is a necessary component when optimally designing and executing research plans. The guidelines serve as the first guidance on how to include sex and gender in cardiovascular research. We provide here a beginning path toward achieving this goal and improve the ability of the research community to interpret results through a sex and gender lens to enable comparison across studies and laboratories, resulting in better health for all.

Defining the value of medical microbiology consultation.

Medical microbiologists, defined as doctoral-level laboratory directors with subspecialty training in medical microbiology, lead the clinical laboratory operations through activities such as clinical consultations, oversight of diagnostic testing menu, institutional leadership, education, and scholastic activities. However, unlike their clinical colleagues, medical microbiologists are largely unable to bill for clinical consultations performed within the hospital and, therefore, unable to generate relative value units or a similar quantifiable metric. As hospital budgets tighten and justification of staffing becomes a necessity, this may present a challenge to the medical microbiologist attempting to prove their value to the organization. To aid in providing tangible data, the Personnel Standards and Workforce subcommittee of the American Society for Microbiology conducted a multi-center study across seven medical centers to document clinical consultations and their impact. Consults were generated equally from internal (laboratory-based) and external (hospital-based) parties, with the majority directly impacting patient management. Near universal acceptance of the medical microbiologist's recommendation highlights the worth derived from their expertise. External consults required more time commitment from the medical microbiologist than internal consults, although both presented ample opportunity for secondary value, including impact through stewardship, education, clinical guidance, and cost reduction. This study is a description of the content and impact of consultations that underscore the importance of the medical microbiologist as a key member of the healthcare team. IMPORTANCE: Medical microbiologists are invaluable to the clinical microbiology laboratory and the healthcare system as a whole. However, as medical microbiologists do not regularly generate relative value units, capturing and quantifying the value provided is challenging. As hospital budgets tighten, justification of staffing becomes a necessity. To aid in providing tangible data, the Personnel Standards and Workforce subcommittee of the American Society for Microbiology conducted a multi-center study across seven medical centers to document clinical consultations and their impact. To our knowledge, this is the first study to provide detailed evaluation of the consultative value provided by medical microbiologists.

Assessing the Impact of the American Heart Association's Research Portfolio: A Scientific Statement From the American Heart Association.

A task force composed of American Heart Association (AHA) Research Committee members established processes to measure the performance of the AHA's research portfolio and evaluated key outcomes that are fundamental to the overall success of the program. This report reviews progress that the AHA research program has had in achieving its goals relevant to the research programs in the AHA's research portfolio from 2008 to 2017. Comprehensive performance metrics were identified to assess the impact of AHA funding on researchers' career progress and research outcomes. Metrics included bibliometric analysis (ie, tracking of publications and their impact) and career development measures (ie, subsequent grant funding, intellectual property, faculty appointment/promotion, or industry position). Publication rates ranged from ≈0.5 to 4 publications per year, with a strong correlation between number of publications per year and later career stage. The Field-Weighted Citation Index, a metric of bibliometric impact, was between 1.5 and 3.0 for all programs, indicating that AHA awardee publications had a higher citation impact compared with similar publications. To gain insight into the career progression of AHA awardees, a 2-year postaward survey was distributed. Of the Postdoctoral Fellowship recipient respondents, 72% obtained academic research positions, with the remaining working in industry or government research settings; 72% of those in academic positions obtained additional funding. Among respondents who were Beginning Grant-in-Aid and Scientist Development Grant awardees, 45% received academic promotions and 83% obtained additional funding. Measuring performance of the AHA's research portfolio is critical to ensure that its strategic goals are met and to show the AHA's commitment to high-quality, impactful research.

Variation in Treatment of Pediatric Tuberculosis Infection in Different Provider Settings.

OBJECTIVES: To evaluate implementation of rifamycin-based regimens (RBR) for pediatric tuberculosis infection (TBI) treatment among 3 provider settings in a high-incidence county. STUDY DESIGN: A multicenter, retrospective observational study was performed across 3 sites in Los Angeles County: an academic center (AC), a general pediatrics federally qualified health center (FQHC), and department of public health (DPH) tuberculosis clinics. Patients initiated on TBI treatment age 1 months to 17 years between 2018 and 2020 were included. RBRs were defined as regimens: 3 months of weekly rifapentine and isoniazid, 4 months of daily rifampin, and 3 months of daily isoniazid and rifampin. RESULTS: We included 424 patients: 51 from AC, 327 from DPH, and 46 from FQHC. RBR use nearly doubled during the study period (from 43% in 2018 to 82% in 2020; P < .001). FQHC had the shortest time to chest radiograph and treatment initiation; however, AC and DPH were 4 times as likely to prescribe an RBR compared to FQHC (95% CI, 2.1-7.8). AC and DPH had similar completion rates (74%) and were 2.6 times as likely to complete treatment compared to FQHC (95% CI, 1.4-4.9). CONCLUSIONS: The use of RBRs for pediatric TBI varies significantly by clinical setting but is improving over time. Strategies are needed to improve RBR uptake, standardize care, and increase treatment completion, particularly among general pediatricians.

Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis.

BACKGROUND: Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. METHODS: In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review. RESULTS: We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment. CONCLUSIONS: Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, NCT02910037.).

Comparison of Upper Respiratory Viral Load Distributions in Asymptomatic and Symptomatic Children Diagnosed with SARS-CoV-2 Infection in Pediatric Hospital Testing Programs.

The distribution of upper respiratory viral loads (VL) in asymptomatic children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed PCR cycle threshold (Ct) values and estimated VL in infected asymptomatic children diagnosed in nine pediatric hospital testing programs. Records for asymptomatic and symptomatic patients with positive clinical SARS-CoV-2 tests were reviewed. Ct values were (i) adjusted by centering each value around the institutional median Ct value from symptomatic children tested with that assay and (ii) converted to estimated VL (numbers of copies per milliliter) using internal or manufacturer data. Adjusted Ct values and estimated VL for asymptomatic versus symptomatic children (118 asymptomatic versus 197 symptomatic children aged 0 to 4 years, 79 asymptomatic versus 97 symptomatic children aged 5 to 9 years, 69 asymptomatic versus 75 symptomatic children aged 10 to 13 years, 73 asymptomatic versus 109 symptomatic children aged 14 to 17 years) were compared. The median adjusted Ct value for asymptomatic children was 10.3 cycles higher than for symptomatic children (P < 0.0001), and VL were 3 to 4 logs lower than for symptomatic children (P < 0.0001); differences were consistent (P < 0.0001) across all four age brackets. These differences were consistent across all institutions and by sex, ethnicity, and race. Asymptomatic children with diabetes (odds ratio [OR], 6.5; P = 0.01), a recent contact (OR, 2.3; P = 0.02), and testing for surveillance (OR, 2.7; P = 0.005) had higher estimated risks of having a Ct value in the lowest quartile than children without, while an immunocompromised status had no effect. Children with asymptomatic SARS-CoV-2 infection had lower levels of virus in their nasopharynx/oropharynx than symptomatic children, but the timing of infection relative to diagnosis likely impacted levels in asymptomatic children. Caution is recommended when choosing diagnostic tests for screening of asymptomatic children.

Androgens drive microvascular endothelial dysfunction in women with polycystic ovary syndrome: role of the endothelin B receptor.

KEY POINTS: Polycystic ovary syndrome (PCOS) is a complex syndrome with cardiovascular risk factors, including obesity and insulin resistance. PCOS is also associated with high androgens, increases the risk of cardiovascular dysfunction in women. Due to the complexity of PCOS, had it has been challenging to isolate specific causes of the cardiovascular dysfunction. Our measure of cardiovascular dysfunction (endothelial dysfunction) was most profound in lean women with PCOS. The endothelin-1-induced vasodilation in these PCOS subject, was dependent on the ETB R but was not NO-dependent. We also demonstrated oestrogen administration improved endothelial function in lean and obese women with PCOS likely because oestrogen increased NO availability. Our studies indicate a primary role for androgens in cardiovascular dysfunction in PCOS. ABSTRACT: Endothelin-1 (ET-1) is an indicator of endothelial injury and dysfunction and is elevated in women with androgen excess polycystic ovary syndrome (AE-PCOS). The endothelin B receptor (ETB R) subtype mediates vasodilatation, but is blunted in women with PCOS. We hypothesized that androgen drives endothelial dysfunction in AE-PCOS women and oestradiol (EE) administration reverses these effects. We assessed microvascular endothelial function in women with (7 lean and 7 obese) and without AE-PCOS (controls, 6 lean, 7 obese). Only obese AE-PCOS women were insulin resistant (IR). We evaluated cutaneous vascular conductance (%CVCmax ) with laser Doppler flowmetry during low dose intradermal microdialysis ET-1 perfusions (1, 3, 4, 5 and 7 pmol) with either lactated Ringer solution alone, or with ETB R (BQ-788), or nitric oxide (NO) inhibition (l-NAME). Log[ET-1]-%maxCVC dose-response curves demonstrated reduced vasodilatory responses to ET-1 in lean AE-PCOS (logED50 , 0.59 ± 0.08) versus lean controls (logED50 , 0.49 ± 0.09, P < 0.05), but not compared to obese AE-PCOS (logED50 , 0.65 ± 0.09). ETB R inhibition decreased ET-1-induced vasodilatation in AE-PCOS women (logED50 , 0.64 ± 0. 22, P < 0.05). This was mechanistically observed at the cellular level, with ET-1-induced, DAF-FM-measurable endothelial cell NO production, which was abrogated by dihydrotestosterone in an androgen receptor-dependent manner. EE augmented the cutaneous vasodilating response to ET-1(logED50 0.29 ± 0.21, 0.47 ± 0.09, P < 0.05 for lean and obese, respectively). Androgens drive endothelial dysfunction in lean and obese AE-PCOS. We propose that the attenuated ET-1-induced vasodilatation in AE-PCOS is a consequence of androgen receptor-mediated, suppressed ETB R-stimulated NO production, and is reversed with EE.

Engaging Patients in Setting a Patient-Centered Outcomes Research Agenda in Hematopoietic Cell Transplantation.

The goal of patient-centered outcomes research (PCOR) is to help patients and those who care for them make informed decisions about healthcare. However, the clinical research enterprise has not involved patients, caregivers, and other nonproviders routinely in the process of prioritizing, designing, and conducting research in hematopoietic cell transplantation (HCT). To address this need the National Marrow Donor Program/Be The Match engaged patients, caregivers, researchers, and other key stakeholders in a 2-year project with the goal of setting a PCOR agenda for the HCT community. Through a collaborative process we identified 6 major areas of interest: (1) patient, caregiver, and family education and support; (2) emotional, cognitive, and social health; (3) physical health and fatigue; (4) sexual health and relationships; (5) financial burden; and (6) models of survivorship care delivery. We then organized into multistakeholder working groups to identify gaps in knowledge and make priority recommendations for critical research to fill those gaps. Gaps varied by working group, but all noted that a historical lack of consistency in measures use and patient populations made it difficult to compare outcomes across studies and urged investigators to incorporate uniform measures and homogenous patient groups in future research. Some groups advised that additional pre-emptory work is needed before conducting prospective interventional trials, whereas others were ready to proceed with comparative clinical effectiveness research studies. This report presents the results of this major initiative and makes recommendations by working group on priority questions for PCOR in HCT.

Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1ß Production.

OBJECTIVE: The calcium composition of atherosclerotic plaque is thought to be associated with increased risk for cardiovascular events, but whether plaque calcium itself is predictive of worsening clinical outcomes remains highly controversial. Inflammation is likely a key mediator of vascular calcification, but immune signaling mechanisms that promote this process are minimally understood. APPROACH AND RESULTS: Here, we identify Rac2 as a major inflammatory regulator of signaling that directs plaque osteogenesis. In experimental atherogenesis, Rac2 prevented progressive calcification through its suppression of Rac1-dependent macrophage interleukin-1ß (IL-1ß) expression, which in turn is a key driver of vascular smooth muscle cell calcium deposition by its ability to promote osteogenic transcriptional programs. Calcified coronary arteries from patients revealed decreased Rac2 expression but increased IL-1ß expression, and high coronary calcium burden in patients with coronary artery disease was associated with significantly increased serum IL-1ß levels. Moreover, we found that elevated IL-1ß was an independent predictor of cardiovascular death in those subjects with high coronary calcium burden. CONCLUSIONS: Overall, these studies identify a novel Rac2-mediated regulation of macrophage IL-1ß expression, which has the potential to serve as a powerful biomarker and therapeutic target for atherosclerosis.

Metagenomics in pediatrics: using a shotgun approach to diagnose infections.

PURPOSE OF REVIEW: With the advent of novel massively parallel sequencing technologies and bioinformatic processing capabilities, clinical applications of metagenomic studies are rapidly being integrated into medicine. Through this paper, we hope to introduce this powerful new tool to clinicians caring for children. RECENT FINDINGS: Very few studies have looked at metagenomic applications in children. The ability to perform these types of massive sequencing projects was not possible as little as 7 years ago. SUMMARY: Metagenomics is defined as the study of all genetic material within a given sample. Novel sequencing and analysis approaches allow for unbiased assays to identify pathogens missed by targeted sequencing and culture methods. Although not widely available yet, metagenomic studies have been used to diagnose pediatric infections, identify resistance genes in clinical samples, and characterize outbreaks. Although cost and turnaround time have limited its application in clinical laboratories to date, novel platforms and increasing comfort with these techniques continue to push diagnostic metagenomics into clinical pediatric medicine. Much work in this field is yet to be done. That being said, we feel that pediatric clinicians will be using metagenomic techniques in the care of children with increasing frequency in the near future.

Longitudinal study of Staphylococcus aureus colonization and infection in a cohort of swine veterinarians in the United States.

BACKGROUND: People working with pigs are at elevated risk of harboring methicillin resistant S. aureus (MRSA) in their nose, which is attributable to occupational exposure to animals harboring livestock adapted S. aureus. To obtain insight into the biological nature of occupationally related nasal culture positivity, we conducted a longitudinal study of 66 swine veterinarians in the USA. METHODS: The study cohort resided in 15 US states and worked predominantly with swine. Monthly for 18 months, participants self-collected nasal swabs and completed a survey to report recent exposure to pigs and other animals; the occurrence of work related injuries; and any relevant health events such as skin and soft tissue infections or confirmed staphylococcal infections. Nasal swabs were cultured using selective methods to determine the presence of MRSA and methicillin susceptible S. aureus (MSSA), and isolates were characterized by spa typing and MLST. RESULTS: Prevalences of S. aureus (64%, monthly range from 58 to 82%) and MRSA (9.5%; monthly range from 6 to15%) were higher than reported for the US population (30% and 1.5% respectively). Predominant spa types were t034 (ST398, 37%), t002 (ST5, 17%) and t337 (ST9/ST398 13%), a distribution similar to that found in a concurrent study in pigs in the USA. Veterinarians were classified into three groups: Persistent carriers (PC, 52%), Intermittent carriers (IC, 47%) and Non-carriers (NC, 1%). Persistent carriage of a single spa type was observed in 14 (21%) of participants, and paired (first and last) isolates from PC subjects had minor genetic differences. Swabs from PC veterinarians carried higher numbers of S. aureus. Among IC veterinarians, culture positivity was significantly associated with recent contact with pigs. CONCLUSIONS: Exposure to pigs did not lead to prolonged colonization in most subjects, and the higher numbers of S. aureus in PC subjects suggests that unknown host factors may determine the likelihood of prolonged colonization by S. aureus of livestock origin. Exposure to S. aureus and persistent colonization of swine veterinarians was common but rarely associated with S. aureus disease.

The PAR complex controls the spatiotemporal dynamics of F-actin and the MTOC in directionally migrating leukocytes.

Inflammatory cells acquire a polarized phenotype to migrate towards sites of infection or injury. A conserved polarity complex comprising PAR-3, PAR-6 and atypical protein kinase C (aPKC) relays extracellular polarizing cues to control cytoskeletal and signaling networks affecting morphological and functional polarization. However, there is no evidence that myeloid cells use PAR signaling to migrate vectorially in three-dimensional (3D) environments in vivo. Using genetically encoded bioprobes and high-resolution live imaging, we reveal the existence of F-actin oscillations in the trailing edge and constant repositioning of the microtubule organizing center (MTOC) to direct leukocyte migration in wounded medaka fish larvae (Oryzias latipes). Genetic manipulation in live myeloid cells demonstrates that the catalytic activity of aPKC and the regulated interaction with PAR-3 and PAR-6 are required for consistent F-actin oscillations, MTOC perinuclear mobility, aPKC repositioning and wound-directed migration upstream of Rho kinase (also known as ROCK or ROK) activation. We propose that the PAR complex coordinately controls cytoskeletal changes affecting both the generation of traction force and the directionality of leukocyte migration to sites of injury.

Clinical Impact of Laboratory Implementation of Verigene BC-GN Microarray-Based Assay for Detection of Gram-Negative Bacteria in Positive Blood Cultures.

Gram-negative bacteremia is highly fatal, and hospitalizations due to sepsis have been increasing worldwide. Molecular tests that supplement Gram stain results from positive blood cultures provide specific organism information to potentially guide therapy, but more clinical data on their real-world impact are still needed. We retrospectively reviewed cases of Gram-negative bacteremia in hospitalized patients over a 6-month period before (n = 98) and over a 6-month period after (n = 97) the implementation of a microarray-based early identification and resistance marker detection system (Verigene BC-GN; Nanosphere) while antimicrobial stewardship practices remained constant. Patient demographics, time to organism identification, time to effective antimicrobial therapy, and other key clinical parameters were compared. The two groups did not differ statistically with regard to comorbid conditions, sources of bacteremia, or numbers of intensive care unit (ICU) admissions, active use of immunosuppressive therapy, neutropenia, or bacteremia due to multidrug-resistant organisms. The BC-GN panel yielded an identification in 87% of Gram-negative cultures and was accurate in 95/97 (98%) of the cases compared to results using conventional culture. Organism identifications were achieved more quickly post-microarray implementation (mean, 10.9 h versus 37.9 h; P < 0.001). Length of ICU stay, 30-day mortality, and mortality associated with multidrug-resistant organisms were significantly lower in the postintervention group (P < 0.05). More rapid implementation of effective therapy was statistically significant for postintervention cases of extended-spectrum beta-lactamase-producing organisms (P = 0.049) but not overall (P = 0.12). The Verigene BC-GN assay is a valuable addition for the early identification of Gram-negative organisms that cause bloodstream infections and can significantly impact patient care, particularly when resistance markers are detected.

The molecular actions of oestrogen in the regulation of vascular health.

NEW FINDINGS: What is the topic of this review? This review summarizes the beneficial actions of oestrogen on the vasculature, highlighting both molecular mechanisms and functional outcomes. What advances does it highlight? The net effect of oestrogen on the vascular health of women continues to be debated. Recent advances have provided strong evidence for the role of membrane-bound oestrogen receptors in the maintenance of normal endothelial function. On a broader scale, functional outcomes of oestrogen actions on the vasculature may mediate the reduced risk of cardiovascular disease in premenopausal women. The conflicting implications of the large-scale clinical menopausal hormone therapy trials in humans versus the findings of studies on experimental animals underscore the limitations within our understanding of the molecular actions of oestrogen. However, recent research has provided improved insight into the actions of oestrogen on the endothelium and vascular smooth muscle. This review outlines the actions of oestrogen as it contributes to vascular structure, function and health.

Ceramide-activated phosphatase mediates fatty acid-induced endothelial VEGF resistance and impaired angiogenesis.

Endothelial dysfunction, including endothelial hyporesponsiveness to prototypical angiogenic growth factors and eNOS agonists, underlies vascular pathology in many dysmetabolic states. We investigated effects of a saturated free fatty acid, palmitic acid (PA), on endothelial cell responses to VEGF. PA-pretreated endothelial cells had markedly diminished Akt, eNOS, and ERK activation responses to VEGF, despite normal VEGFR2 phosphorylation. PA inhibited VEGF-induced angiogenic cord formation in Matrigel, and PA-treated endothelial cells accumulated early species (C16) ceramide. The serine palmitoyltransferase inhibitor myriocin reversed these defects. Protein phosphatase 2A (PP2A) became more eNOS-associated in PA-treated cells; the PP2A inhibitor okadaic acid reversed PA-induced signaling defects. Mice fed a diet high in saturated fat for 2 to 3 weeks had impaired i) aortic Akt and eNOS phosphorylation to infused VEGF, ii) ear angiogenic responses to intradermal adenoviral-VEGF injection, and iii) vascular flow recovery to hindlimb ischemia as indicated by laser Doppler and αVß3 SPECT imaging. High-fat feeding did not impair VEGF-induced signaling or angiogenic responses in mice with reduced serine palmitoyltransferase expression. Thus, de novo ceramide synthesis is required for these detrimental PA effects. The findings demonstrate an endothelial VEGF resistance mechanism conferred by PA, which comprises ceramide-induced, PP2A-mediated dephosphorylation of critical activation sites on enzymes central to vascular homeostasis and angiogenesis. This study defines potential molecular targets for preservation of endothelial function in metabolic syndrome.

Personal Protective Equipment Use and Handwashing Among Animal Farmers: A Multi-site Assessment.

The goal of this study was to compare and contrast the use of personal protective equipment (PPE) and the practice of handwashing among participants of four studies assessing poultry and swine farms in the midwestern United States and in Thailand. This largely descriptive exercise was designed to assess and compare the frequency of these protective practices among the study populations. There were a total of 1113 surveys analyzed across the four studies. The respondents included workers in direct contact with animals as well as flock owners and veterinarians tending to farms. Handwashing was the most common practice observed among all participants with 42% "always" and 35% "sometimes" washing their hands after contact with the animals. This practice was least common among Minnesota swine workers. Even Thai poultry farmers, who demonstrated the lowest overall PPE use, reported a higher frequency of handwashing. Mask use during animal farming activities ("always" or "sometimes") was least commonly practiced, ranging from 1% in Thailand to 26% among backyard poultry farmers in Minnesota. Minnesota poultry and swine farmers had similar frequencies of mask (26%) and glove use (51% and 49%). All other comparisons differed significantly across the four sites (p-values <0.05). The use of PPE in animal farming differed by study location and is likely related to prevalent norms in the respective regions. Overall, the use of PPE did not appear to be influenced by the particular animal (poultry or swine) being farmed. These findings may prove useful to regulating bodies and farm owners in formulating policy or planning strategies for improving personal hygiene practices in animal farming and preparing for influenza and other potential zoonotic disease outbreaks.

Silver lining in the dark cloud of aneurysm disease.

An ascending aortic aneurysm is a common and very much unwelcome diagnosis that has never been associated with anything positive. We believe, however, that there actually is a silver lining to this disease: aortic root and ascending aortic aneurysms actually protect against atherosclerosis. We have found that patients with ascending aneurysms have both decreased arterial calcification and carotid intima-media thickness, late and early indicators of atherosclerosis, respectively. In addition to these clinical data, we also found data regarding molecular mechanisms, genetic studies, and pharmacologic evidence that corroborate our clinical findings, in particular, evidence regarding matrix metalloproteinases and transforming growth factor-ß pathways. In this article, we lay out the evidence that has been accruing for the protective effect of ascending aneurysms against atherosclerosis.

Infants 1-90 days old hospitalized with human rhinovirus infection.

BACKGROUND: Human rhinovirus (HRV) is a common cause of respiratory illness in children. The impact of HRV infection on 1- to 90-day-old infants is unclear. We hypothesized that HRV infection would be clinically similar to respiratory syncytial virus (RSV) infection in the hospitalized infants. METHODS: We conducted a retrospective study of hospitalized infants, who were 1-90 days old, with HRV or RSV within the Southern California Kaiser Permanente network over a 1-year period (August 2010 to October 2011). RESULTS: We identified 245 hospitalized infants who underwent respiratory virus testing. HRV was found in 52 infants (21%) compared to 79 infants (32%) with RSV (P = 0.008). Infants with HRV infection experienced longer hospital stays compared to those with RSV (median length of stay 4 days vs. 3 days, P = 0.009) and had fewer short hospital stays ≤3 days (P = 0.029). There was a trend in infants with HRV infection to be younger (P = 0.071) and have more fevers (P = 0.052). CONCLUSIONS: Recent advances in diagnostics allow for identification of a broad range of viral pathogens in infants. Compared to RSV, HRV was associated with longer hospital stays. Additional studies and improved, more specific testing, methods are needed to further define the effects of HRV infection in infants 1-90 days old.