Epidemiological, clinical, outcome and antibiotic susceptibility differences between PVL positive and PVL negative Staphylococcus aureus infections in Western Australia: A case control study

Background: Panton Valentine Leukocidin (PVL) has been associated with invasive Staphylococcus aureus soft tissue and pneumonic infections. Methods: From September 2007 to January 2009 at Royal Perth Hospital we tested for the PVL gene in S. aureus isolates from an invasive site, a suspected PVL-related soft tissue infection and all MRSA isolates. We could access medical records for 141 PVL positive (PVL + ve) infections and compared these to a control group comprised of 148 PVL negative (PVL-ve) infections. Results: In the PVL + ve group 62 isolates were MRSA (48 were ST93-MRSA-IV) and 79 isolates were methicillin-sensitive S. aureus, and in the PVL-ve group 56 were MRSA (50 were WA-MRSA strains) and 92 were methicillin-sensitive S. aureus. We found the presence of PVL to be significantly associated with younger age, aboriginality, intravenous drug use, community acquisition, shorter length of hospital stay and lower mortality at 1 year. Overall PVL + ve infections more often required surgical intervention (73.0% versus 44.6%, p < 0.001) and were less often polymicrobial (8.5% versus 41.2%, p < 0.001). PVL + ve isolates were more often susceptible to clindamycin (87.9% versus 73.0%, p = 0.002). Conclusions: This study demonstrates that PVL + ve infections are associated with a distinct clinical picture, predominantly pyogenic skin and soft tissue infections often requiring surgery, disproportionately affecting patients who are younger, indigenous or with fewer health-care risk factors

Selection of the solvent and extraction conditions for maximum recovery of antioxidant phenolic compounds from coffee silverskin

The extraction of antioxidant phenolic compounds from coffee silverskin (CS) was studied. Firstly, the effect of different solvents (methanol, ethanol, acetone, and distilled water) on the production of antioxidant extracts was evaluated. All the extracts showed antioxidant activity (FRAP and DPPH assays), but those obtained with methanol and ethanol had significantly higher (p < 0.05) DPPH inhibition than the remaining ones. Due to the lower toxicity, ethanol was selected as extraction solvent, and further experiments were performed in order to define the solvent concentration, solvent/solid ratio, and time to maximize the extraction results. The best condition to produce an extract with high content of phenolic compounds (13 mg gallic acid equivalents/g CS) and antioxidant activity [DPPH = 18.24 μmol Trolox equivalents/g CS and FRAP = 0.83 mmol Fe(II)/g CS] was achieved when using 60 % ethanol in a ratio of 35 ml/g CS, during 30 min at 60–65 °C.This work was supported by the Portuguese Foundation for Science and Technology (FCT). The authors gratefully acknowledge Teresa Conde, student of Biological Engineering, for the help and interest in this work

High-resolution measurements of face-to-face contact patterns in a primary school

Little quantitative information is available on the mixing patterns of children in school environments. Describing and understanding contacts between children at school would help quantify the transmission opportunities of respiratory infections and identify situations within schools where the risk of transmission is higher. We report on measurements carried out in a French school (6-12 years children), where we collected data on the time-resolved face-to-face proximity of children and teachers using a proximity-sensing infrastructure based on radio frequency identification devices. Data on face-to-face interactions were collected on October 1st and 2nd, 2009. We recorded 77,602 contact events between 242 individuals. Each child has on average 323 contacts per day with 47 other children, leading to an average daily interaction time of 176 minutes. Most contacts are brief, but long contacts are also observed. Contacts occur mostly within each class, and each child spends on average three times more time in contact with classmates than with children of other classes. We describe the temporal evolution of the contact network and the trajectories followed by the children in the school, which constrain the contact patterns. We determine an exposure matrix aimed at informing mathematical models. This matrix exhibits a class and age structure which is very different from the homogeneous mixing hypothesis. The observed properties of the contact patterns between school children are relevant for modeling the propagation of diseases and for evaluating control measures. We discuss public health implications related to the management of schools in case of epidemics and pandemics. Our results can help define a prioritization of control measures based on preventive measures, case isolation, classes and school closures, that could reduce the disruption to education during epidemics

Mortality risk after COVID-19 vaccination: A self-controlled case series study

Background Although previous studies found no-increased mortality risk after COVID-19 vaccination, residual confounding bias might have impacted the findings. Using a modified self-controlled case series (SCCS) design, we assessed the risk of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes after primary series COVID-19 vaccination. Methods We analyzed all deaths between December 14, 2020, and August 11, 2021, among individuals from eight Vaccine Safety Datalink sites. Demographic characteristics of deaths in recipients of COVID-19 vaccines and unvaccinated individuals were reported. We conducted SCCS analyses by vaccine type and death outcomes and reported relative incidences (RI). The observation period for death spanned from the dates of emergency use authorization to the end of the study period (August 11, 2021) without censoring the observation period upon death. We pre-specified a primary risk interval of 28-day and a secondary risk interval of 14-day after each vaccination dose. Adjusting for seasonality in mortality analyses is crucial because death rates vary over time. Deaths among unvaccinated individuals were included in SCCS analyses to account for seasonality by incorporating calendar month in the models. Results For Pfizer-BioNTech (BNT162b2), RIs of non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes were below 1 and 95 % confidence intervals (CIs) excluded 1 across both doses and both risk intervals. For Moderna (mRNA-1273), RI point estimates of all outcomes were below 1, although the 95 % CIs of two RI estimates included 1: cardiac-related (RI = 0.78, 95 % CI, 0.58-1.04) and non-COVID-19 cardiac-related mortality (RI = 0.80, 95 % CI, 0.60-1.08) 14 days after the second dose in individuals without pre-existing cancer and heart disease. For Janssen (Ad26.COV2.S), RIs of four cardiac-related death outcomes ranged from 0.94 to 0.98 for the 14-day risk interval, and 0.68 to 0.72 for the 28-day risk interval and 95 % CIs included 1. Conclusion Using a modified SCCS design and adjusting for temporal trends, no-increased risk was found for non-COVID-19 mortality, all-cause mortality, and four cardiac-related death outcomes among recipients of the three COVID-19 vaccines used in the US

Diffusion tensor imaging of frontal lobe white matter tracts in schizophrenia

We acquired diffusion tensor and structural MRI images on 103 patients with schizophrenia and 41 age-matched normal controls. The vector data was used to trace tracts from a region of interest in the anterior limb of the internal capsule to the prefrontal cortex. Patients with schizophrenia had tract paths that were significantly shorter in length from the center of internal capsule to prefrontal white matter. These tracts, the anterior thalamic radiations, are important in frontal-striatal-thalamic pathways. These results are consistent with findings of smaller size of the anterior limb of the internal capsule in patients with schizophrenia, diffusion tensor anisotropy decreases in frontal white matter in schizophrenia and hypothesized disruption of the frontal-striatal-thalamic pathway system

Instrumental Variable Estimation of the Causal Effect of Plasma 25-Hydroxy-Vitamin D on Colorectal Cancer Risk: A Mendelian Randomization Analysis

Vitamin D deficiency has been associated with several common diseases, including cancer and is being investigated as a possible risk factor for these conditions. We reported the striking prevalence of vitamin D deficiency in Scotland. Previous epidemiological studies have reported an association between low dietary vitamin D and colorectal cancer (CRC). Using a case-control study design, we tested the association between plasma 25-hydroxy-vitamin D (25-OHD) and CRC (2,001 cases, 2,237 controls). To determine whether plasma 25-OHD levels are causally linked to CRC risk, we applied the control function instrumental variable (IV) method of the Mendelian randomization (MR) approach using four single nucleotide polymorphisms (rs2282679, rs12785878, rs10741657, rs6013897) previously shown to be associated with plasma 25-OHD. Low plasma 25-OHD levels were associated with CRC risk in the crude model (odds ratio (OR): 0.76, 95% Confidence Interval (CI): 0.71, 0.81, p: 1.4×10−14) and after adjusting for age, sex and other confounding factors. Using an allele score that combined all four SNPs as the IV, the estimated causal effect was OR 1.16 (95% CI 0.60, 2.23), whilst it was 0.94 (95% CI 0.46, 1.91) and 0.93 (0.53, 1.63) when using an upstream (rs12785878, rs10741657) and a downstream allele score (rs2282679, rs6013897), respectively. 25-OHD levels were inversely associated with CRC risk, in agreement with recent meta-analyses. The fact that this finding was not replicated when the MR approach was employed might be due to weak instruments, giving low power to demonstrate an effect (<0.35). The prevalence and degree of vitamin D deficiency amongst individuals living in northerly latitudes is of considerable importance because of its relationship to disease. To elucidate the effect of vitamin D on CRC cancer risk, additional large studies of vitamin D and CRC risk are required and/or the application of alternative methods that are less sensitive to weak instrument restrictions

Community-associated Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis among HIV Patients: A cohort study

<p>Abstract</p> <p>Background</p> <p>HIV patients are at increased risk of development of infections and infection-associated poor health outcomes. We aimed to 1) assess the prevalence of USA300 community-associated methicillin-resistant <it>Staphylococcus aureus </it>(CA-MRSA) among HIV-infected patients with <it>S. aureus </it>bloodstream infections and. 2) determine risk factors for infective endocarditis and in-hospital mortality among patients in this population.</p> <p>Methods</p> <p>All adult HIV-infected patients with documented <it>S. aureus </it>bacteremia admitted to the University of Maryland Medical Center between January 1, 2003 and December 31, 2005 were included. CA-MRSA was defined as a USA300 MRSA isolate with the MBQBLO spa-type motif and positive for both the arginine catabolic mobile element and Panton-Valentin Leukocidin. Risk factors for <it>S. aureus</it>-associated infective endocarditis and mortality were determined using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Potential risk factors included demographic variables, comorbid illnesses, and intravenous drug use.</p> <p>Results</p> <p>Among 131 episodes of <it>S. aureus </it>bacteremia, 85 (66%) were MRSA of which 47 (54%) were CA-MRSA. Sixty-three patients (48%) developed endocarditis and 10 patients (8%) died in the hospital on the index admission Patients with CA-MRSA were significantly more likely to develop endocarditis (OR = 2.73, 95% CI = 1.30, 5.71). No other variables including comorbid conditions, current receipt of antiretroviral therapy, pre-culture severity of illness, or CD4 count were significantly associated with endocarditis and none were associated with in-hospital mortality.</p> <p>Conclusions</p> <p>CA-MRSA was significantly associated with an increased incidence of endocarditis in this cohort of HIV patients with MRSA bacteremia. In populations such as these, in which the prevalence of intravenous drug use and probability of endocarditis are both high, efforts must be made for early detection, which may improve treatment outcomes.</p

Genome-Wide Analysis of Histone H3 Lysine9 Modifications in Human Mesenchymal Stem Cell Osteogenic Differentiation

Mesenchymal stem cells (MSCs) possess self-renewal and multi-lineage differentiation potentials. It has been established that epigenetic mechanisms such as histone modifications could be critical for determining the fate of stem cells. In this study, full human genome promoter microarrays and expression microarrays were used to explore the roles of histone modifications (H3K9Ac and H3K9Me2) upon the induction of MSC osteogenic differentiation. Our results revealed that the enrichment of H3K9Ac was decreased globally at the gene promoters, whereas the number of promoters enriched with H3K9Me2 was increased evidently upon osteogenic induction. By a combined analysis of data from both ChIP-on-chip and expression microarrays, a number of differentially expressed genes regulated by H3K9Ac and/or H3K9Me2 were identified, implicating their roles in several biological events, such as cell cycle withdraw and cytoskeleton reconstruction that were essential to differentiation process. In addition, our results showed that the vitamin D receptor played a trans-repression role via alternations of H3K9Ac and H3K9Me2 upon MSC osteogenic differentiation. Data from this study suggested that gene activation and silencing controlled by changes of H3K9Ac and H3K9Me2, respectively, were crucial to MSC osteogenic differentiation