Ambient noise and neonatal hemodynamics - An observational cross-sectional study

Background: Previous studies reported numerous adverse effects of noise in the newborns such as increase in the heart rate (HR) and respiratory frequency and drop in the oxygen saturation. Objective: The objective of this study was to study the effect of ambient noise levels in neonatal intensive care unit (NICU) on the hemodynamics of neonates. Materials and Methods: This was a hospital-based cross-sectional observational study which aimed at assessing the ambient noise levels in the NICU with a digital decibel meter and its effect on HR, respiratory rate (RR), and oxygen saturation. A total of 105 neonates (both preterm and term) having stable cardiorespiratory status were enrolled in the study. Results: The mean noise level recorded in the NICU was 56.2 dB. The lowest noise level was recorded at 8 am, that is, 46 dB while the highest recorded level was at 2 pm, that is, 65 dB in different areas of the NICU. There was a statistically significant increase in the HR in relation to the noise levels at all times (p<0.0001). The RR also showed a significant rise in relation to the increase in noise level (p<0.0001 at 2 pm with maximum noise level). The oxygen saturation showed a negative correlation and a statistically significant drop at 2 pm when maximum noise level was recorded (p<0.0001). Changing shifts and more number of healthcare personnel were important factors contributing to increased noise levels at 2 pm. Conclusion: Noise levels of >56 dB affected the hemodynamics of the newborn. The maximum increase in the mean HR, RR, and drop in saturation was observed at 2 pm. Staff sensitization and attitude change are needed to decrease the noise pollution in NICU

C-Reactive protein and risk of ESRD: results from the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)

Background: To better understand a potential association of elevated C-reactive protein (CRP) level with progression of chronic kidney disease (CKD), we examined the relationship of CRP level with the development of end-stage renal disease (ESRD) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Study Design Post hoc analysis of a randomized controlled trial. Setting & Participants: 4,038 patients with type 2 diabetes, CKD, and anemia in TREAT. Predictor: Baseline serum CRP concentrations. Outcomes: The primary outcome was development of ESRD; secondary outcomes included doubling of serum creatinine level, a composite of ESRD/serum creatinine doubling, and a composite of death or ESRD. Measurements: We fit unadjusted and adjusted Cox regression models to test the association of baseline CRP level with time to the development of the outcomes of interest. Results: Mean age of participants was 67 years, 43% were men, and 64% were white. Approximately half (48%) the patients had CRP levels > 3.0 mg/L; 668 patients developed ESRD, and 1,270 developed the composite outcome of death or ESRD. Compared with patients with baseline CRP levels ≤ 3.0 mg/L, those with moderately/markedly elevated CRP levels (≥6.9 mg/L; 24% of patients) had a higher adjusted risk for ESRD (HR, 1.32; 95% CI, 1.07-1.63) and the composite outcome of death or ESRD (HR, 1.41; 95% CI, 1.21-1.64). Although nonsignificant, similar trends were noted in competing-risk models. Limitations: Results may not be generalizable to nondiabetic CKD or diabetic CKD in the absence of anemia. Conclusions: Elevated baseline CRP levels are common in type 2 diabetic patients with anemia and CKD and are associated with the future development of ESRD and the composite of death or ESRD

The limits of social class in explaining ethnic gaps in educational attainment

This paper reports an analysis of the educational attainment and progress between age 11 and age 14 of over 14,500 students from the nationally representative Longitudinal Study of Young People in England (LSYPE). The mean attainment gap in national tests at age 14 between White British and several ethnic minority groups were large, more than three times the size of the gender gap, but at the same time only about one-third of the size of the social class gap. Socio-economic variables could account for the attainment gaps for Black African, Pakistani and Bangladeshi students, but not for Black Caribbean students. Further controls for parental and student attitudes, expectations and behaviours indicated minority ethnic groups were on average more advantaged on these measures than White British students, but this was not reflected proportionately in their levels of attainment. Black Caribbean students were distinctive as the only group making less progress than White British students between age 11 and 14 and this could not be accounted for by any of the measured contextual variables. Possible explanations for the White British-Black Caribbean gap are considered

Human cyclin T1 expression ameliorates a T-cell-specific transcriptional limitation for HIV in transgenic rats, but is not sufficient for a spreading infection of prototypic R5 HIV-1 strains ex vivo

<p>Abstract</p> <p>Background</p> <p>Cells derived from native rodents have limits at distinct steps of HIV replication. Rat primary CD4 T-cells, but not macrophages, display a profound transcriptional deficit that is ameliorated by transient trans-complementation with the human Tat-interacting protein Cyclin T1 (hCycT1).</p> <p>Results</p> <p>Here, we generated transgenic rats that selectively express hCycT1 in CD4 T-cells and macrophages. hCycT1 expression in rat T-cells boosted early HIV gene expression to levels approaching those in infected primary human T-cells. hCycT1 expression was necessary, but not sufficient, to enhance HIV transcription in T-cells from individual transgenic animals, indicating that endogenous cellular factors are critical co-regulators of HIV gene expression in rats. T-cells from hCD4/hCCR5/hCycT1-transgenic rats did not support productive infection of prototypic wild-type R5 HIV-1 strains <it>ex vivo</it>, suggesting one or more significant limitation in the late phase of the replication cycle in this primary rodent cell type. Remarkably, we identify a replication-competent HIV-1 GFP reporter strain (R7/3 YU-2 Env) that displays characteristics of a spreading, primarily cell-to-cell-mediated infection in primary T-cells from hCD4/hCCR5-transgenic rats. Moreover, the replication of this recombinant HIV-1 strain was significantly enhanced by hCycT1 transgenesis. The viral determinants of this so far unique replicative ability are currently unknown.</p> <p>Conclusion</p> <p>Thus, hCycT1 expression is beneficial to <it>de novo </it>HIV infection in a transgenic rat model, but additional genetic manipulations of the host or virus are required to achieve full permissivity.</p

Palifermin for oral mucositis after intensive therapy for hematologic cancers

BACKGROUND: Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no effective treatment. We tested the ability of palifermin (recombinant human keratinocyte growth factor) to decrease oral mucosal injury induced by cytotoxic therapy. METHODS: This double-blind study compared the effect of palifermin with that of a placebo on the development of oral mucositis in 212 patients with hematologic cancers; 106 patients received palifermin (60 microg per kilogram of body weight per day) and 106 received a placebo intravenously for three consecutive days immediately before the initiation of conditioning therapy (fractionated total-body irradiation plus high-dose chemotherapy) and after autologous hematopoietic stem-cell transplantation. Oral mucositis was evaluated daily for 28 days after transplantation. RESULTS: The incidence of oral mucositis of World Health Organization (WHO) grade 3 or 4 was 63 percent in the palifermin group and 98 percent in the placebo group (P\u3c0.001). Among patients with this degree of mucositis, the median duration of mucositis was 6 days (range, 1 to 22) in the palifermin group and 9 days (range, 1 to 27) in the placebo group. Among all patients, regardless of the occurrence of mucositis, the median duration of oral mucositis of WHO grade 3 or 4 was 3 days (range, 0 to 22) in the palifermin group and 9 days (range, 0 to 27) in the placebo group (P\u3c0.001). As compared with placebo, palifermin was associated with significant reductions in the incidence of grade 4 oral mucositis (20 percent vs. 62 percent, P\u3c0.001), patient-reported soreness of the mouth and throat (area-under-the-curve score, 29.0 [range, 0 to 98] vs. 46.8 [range, 0 to 110]; P\u3c0.001), the use of opioid analgesics (median, 212 mg of morphine equivalents [range, 0 to 9418] vs. 535 mg of morphine equivalents [range, 0 to 9418], P\u3c0.001), and the incidence of use of total parenteral nutrition (31 percent vs. 55 percent, P\u3c0.001). Adverse events, mainly rash, pruritus, erythema, mouth and tongue disorders, and taste alteration, were mild to moderate in severity and were transient. CONCLUSIONS: Palifermin reduced the duration and severity of oral mucositis after intensive chemotherapy and radiotherapy for hematologic cancers

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

Nucleic Acid, Antibody, and Virus Culture Methods to Detect Xenotropic MLV-Related Virus in Human Blood Samples

The MLV-related retrovirus, XMRV, was recently identified and reported to be associated with both prostate cancer and chronic fatigue syndrome. At the National Cancer Institute-Frederick, MD (NCI-Frederick), we developed highly sensitive methods to detect XMRV nucleic acids, antibodies, and replication competent virus. Analysis of XMRV-spiked samples and/or specimens from two pigtail macaques experimentally inoculated with 22Rv1 cell-derived XMRV confirmed the ability of the assays used to detect XMRV RNA and DNA, and culture isolatable virus when present, along with XMRV reactive antibody responses. Using these assays, we did not detect evidence of XMRV in blood samples (N = 134) or prostate specimens (N = 19) from two independent cohorts of patients with prostate cancer. Previous studies detected XMRV in prostate tissues. In the present study, we primarily investigated the levels of XMRV in blood plasma samples collected from patients with prostate cancer. These results demonstrate that while XMRV-related assays developed at the NCI-Frederick can readily measure XMRV nucleic acids, antibodies, and replication competent virus, no evidence of XMRV was found in the blood of patients with prostate cancer

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue