Lymphotoxins and cytomegalovirus cooperatively induce interferon-beta, establishing host-virus détente

Tumor necrosis factor (TNF)-related cytokines regulate cell death and survival and provide strong selective pressures for viruses, such as cytomegalovirus (CMV), to evolve counterstrategies in order to persist in immune-competent hosts. Signaling by the lymphotoxin (LT)-β receptor or TNF receptor-1, but not Fas or TRAIL receptors, inhibits the cytopathicity and replication of human CMV by a nonapoptotic, reversible process that requires nuclear factor κB (NF-κB)-dependent induction of interferon-β (IFN-β). Efficient induction of IFN-β requires virus infection and LT signaling, demonstrating the need for both host and viral factors in the curtailment of viral replication without cellular elimination. LTα-deficient mice and LTβR-Fc transgenic mice were profoundly susceptible to murine CMV infection. Together, these results reveal an essential and conserved role for LTs in establishing host defense to CMV

Utility of surveillance blood cultures in patients undergoing hematopoietic stem cell transplantation

Background Surveillance blood cultures are often obtained in hematopoietic stem cell transplant (HSCT) patients for detection of bloodstream infection. The major aims of this retrospective cohort study were to determine the utility of the practice of obtaining surveillance blood cultures from asymptomatic patients during the first 100 post-transplant days and to determine if obtaining more than one positive blood culture helps in the diagnosis of bloodstream infection. Methods We conducted a 17-month retrospective analysis of all blood cultures obtained for patients admitted to the hospital for HSCT from January 2010 to June 2011. Each patient’s clinical course, vital signs, diagnostic testing, treatment, and response to treatment were reviewed. The association between number of positive blood cultures and the final diagnosis was analyzed. Results Blood culture results for 205 patients were reviewed. Cultures obtained when symptoms of infection were present (clinical cultures) accounted for 1,033 culture sets, whereas 2,474 culture sets were classified as surveillance cultures (no symptoms of infection were present). The total number of positive blood cultures was 185 sets (5.3% of cultures obtained) and accounted for 84 positive culture episodes. Incidence of infection in autologous, related allogeneic and unrelated allogeneic transplants was 8.3%, 20.0%, and 28.6% respectively. Coagulase-negative staphylococci were the most common organisms isolated. Based on our application of predefined criteria there were 29 infections and 55 episodes of positive blood cultures that were not infections. None of the patients who developed infection were diagnosed by surveillance blood cultures. None of the uninfected patients with positive blood cultures showed any clinical changes after receiving antibiotics. There was a significant difference between the incidence of BSI in the first and second 50-day periods post-HSCT. There was no association between the number of positive blood cultures and the final diagnosis. Conclusion Surveillance blood cultures in patients who have undergone HSCT do not identify bloodstream infections. The number of positive blood cultures was not helpful in determining which patients had infection. Patients are at higher risk of infection in the first 50 days post-transplant period

Portal Vein Thrombosis after Restorative Proctocolectomy for Familial Adenomatous Polyposis and Sigmoid Cancer

Postoperative portal vein thrombosis (PVT) is rare, but has been described after various open as well as minimal access abdominal operations, especially splenectomy and colorectal surgical procedures. We report the case of a 39-year-old female who underwent restorative proctocolectomy and ileal pouch-anal anastomosis for familial adenomatous polyposis with sigmoid cancer. She presented 14 days later with vague upper abdominal pain, nausea, vomiting and high output stoma. Doppler ultrasonography confirmed PVT and therefore anticoagulant therapy was started. Her condition improved dramatically and she underwent closure of ileostomy after finishing adjuvant chemotherapy. She remained well at 3-year follow-up with good pouch function and no local or distant recurrence. A high index of suspicion is essential for early diagnosis and prompt treatment of postoperative PVT after restorative proctocolectomy. Early anticoagulation is essential to avoid subsequent complications

American Cochlear Implant Alliance Task Force guidelines for clinical assessment and management of adult cochlear implantation for single-sided deafness

The indications for cochlear implantation have expanded to include individuals with profound sensorineural hearing loss in the impaired ear and normal hearing (NH) in the contralateral ear, known as single-sided deafness (SSD). There are additional considerations for the clinical assessment and management of adult cochlear implant candidates and recipients with SSD as compared to conventional cochlear implant candidates with bilateral moderate to profound sensorineural hearing loss. The present report reviews the current evidence relevant to the assessment and management of adults with SSD. A systematic review was also conducted on published studies that investigated outcomes of cochlear implant use on measures of speech recognition in quiet and noise, sound source localization, tinnitus perception, and quality of life for this patient population. Expert consensus and systematic review of the current literature were combined to provide guidance for the clinical assessment and management of adults with SSD

Pharmacy education and practice in 13 middle eastern countries

The Arab world has influenced the art and science of pharmacy for centuries. Pharmacy education and practice is continuing to evolve in the Arabic-speaking traditional Middle East countries, although relatively little information has been published in the English press. Our goal was to providea high-level synopsis of conditions in this region. We selected 13 countries for review. Information was obtained by reviewing the available published literature and individual university and program web sites, as well as contacting with program or country representatives. Seventy-eight active pharmacy schools in 12 countries were identified. At least 14,000 students (over 75% from Egypt) are admitted into baccalaureate degree programs every year. The 5-year baccalaureate degree remains the first professional degree to practice. While changes in pharmacy education have been relatively rapid over the past decade, the advancement of pharmacy practice, particularly in the private sector, appears to be slower. Hospital pharmacists often possess an advanced degree and tend to have a higher level of practice compared to that of community pharmacists. Despite the adversities that face academics and practitioners alike, there is a strong desire to advance the science and practice of pharmacy in the Middle East

Prevalence and determinants of anemia among women of reproductive age in Thatta Pakistan: Findings from a cross-sectional study

Background: Anemia is a major public health concern among women of reproductive age leading to high maternal mortality in low- and middle-income countries. Of the prior studies conducted in Pakistan, most focused on large urban areas and did not explore the determinants of anemia among women of reproductive age (WRA) across socio-demographic, dietary, reproductive, and biological domains. Thus, we aimed to study the prevalence and determinants of anemia among WRA in rural Pakistan.Methods: We conducted a cross-sectional study in the Thatta district of Pakistan from September 2018 to January 2019 and enrolled 150 non-pregnant, married women. Data collectors administered a structured questionnaire to collect sociodemographic, reproductive and dietary data from women, who also provided stool and blood samples. We classified all WRA as anemic if their hemoglobin was \u3c12.0 g/dl. We performed logistic regression analysis to calculate adjusted odds ratios (aOR) and their respective 95% CIs to assess the determinants of anemia.Results: In our study, 61.3% of the enrolled women were anemic. In the multivariable analysis, we found that factors such as serum iron levels of less than 50 μg/dl (aOR: 7.17; 95% CI (2.94, 17.47)), history of breastfeeding (aOR: 2.43; 95% CI (1.04, 5.72)), living in a katcha house (aOR: 6.61; 95% CI (2.21, 19.87)), no consumption of meat (aOR: 4.18; 95% CI (1.66, 9.96)) were significantly associated with anemia among WRA. A history of more than one abortion (aOR: 0.06; 95% CI (0.01, 0.33) appeared protective for its association with anemia.Conclusion: Our findings demonstrate a high burden of anemia and its complex determinants among WRA in rural Pakistan. A combination of nutritional and educational strategies should be designed to encourage rural women to consume iron-rich foods in their diet with an access to adequate food. Breastfeeding women should be encouraged to consume extra calories with sufficient intake of the food to continue exclusive breastfeeding and reserve the iron stores through amenorrhea to prevent themselves from becoming anemic

Back Reaction And Local Cosmological Expansion Rate

We calculate the back reaction of cosmological perturbations on a general relativistic variable which measures the local expansion rate of the Universe. Specifically, we consider a cosmological model in which matter is described by a single field. We analyze back reaction both in a matter dominated Universe and in a phase of scalar field-driven chaotic inflation. In both cases, we find that the leading infrared terms contributing to the back reaction vanish when the local expansion rate is measured at a fixed value of the matter field which is used as a clock, whereas they do not appear to vanish if the expansion rate is evaluated at a fixed value of the background time. We discuss possible implications for more realistic models with a more complicated matter sector.Comment: 7 pages, No figure

Exploiting Parallel R in the Cloud with SPRINT

BACKGROUND: Advances in DNA Microarray devices and next-generation massively parallel DNA sequencing platforms have led to an exponential growth in data availability but the arising opportunities require adequate computing resources. High Performance Computing (HPC) in the Cloud offers an affordable way of meeting this need. OBJECTIVES: Bioconductor, a popular tool for high-throughput genomic data analysis, is distributed as add-on modules for the R statistical programming language but R has no native capabilities for exploiting multi-processor architectures. SPRINT is an R package that enables easy access to HPC for genomics researchers. This paper investigates: setting up and running SPRINT-enabled genomic analyses on Amazon’s Elastic Compute Cloud (EC2), the advantages of submitting applications to EC2 from different parts of the world and, if resource underutilization can improve application performance. METHODS: The SPRINT parallel implementations of correlation, permutation testing, partitioning around medoids and the multi-purpose papply have been benchmarked on data sets of various size on Amazon EC2. Jobs have been submitted from both the UK and Thailand to investigate monetary differences. RESULTS: It is possible to obtain good, scalable performance but the level of improvement is dependent upon the nature of algorithm. Resource underutilization can further improve the time to result. End-user’s location impacts on costs due to factors such as local taxation. Conclusions: Although not designed to satisfy HPC requirements, Amazon EC2 and cloud computing in general provides an interesting alternative and provides new possibilities for smaller organisations with limited funds

Oncogenic role of connective tissue growth factor is associated with canonical TGF-β cascade in colorectal cancer

TGF-β signaling pathways promote tumour development and control several downstream genes such as CTGF and MMPs. This study aimed to investigate the association between CTGF and MMP-1 mRNA expressions with clinicopathological status and survival rate in colorectal cancer patients. We investigated expression levels of CTGF and MMP-1 genes in paraffin-embedded tumours and adjacent normal tissue blocks (ADJ) by Real Time-PCR. Then, the expression of Smad2 and Smad4 proteins in the TGF-β canonical pathway was evaluated by immunohistochemistry. Finally, the correlation between CTGF, MMP-1, and the canonical TGF-β-signalling pathway with the clinicopathological features was investigated. Expression levels of MMP-1and CTGF were higher in tumours compared with adjacent normal tissues. Overexpression levels of MMP-1 and CTGF were associated with lymph node metastasis, distant metastasis, tumour histopathological grading, advanced stage, and poor survival (p 0.05). Additionally, a significant association between the upregulation of MMP-1 and tumour location was noted. Upregulation of Smad2 and Smad4 proteins were also significantly correlated with lymph node metastasis, distant metastasis, advanced stage, and poor survival (p 0.0001). This study showed that canonical TGF-β signalling regulates both CTGF and MMP-1 expression and CRC progression. Moreover, TGF-β signalling and its downstream genes could be used as novel biomarkers and novel approaches for targeted therapy in CRC

Whole blood gene expression profiling of neonates with confirmed bacterial sepsis

peer-reviewedNeonatal infection remains a primary cause of infant morbidity and mortality worldwide and yet our understanding of how human neonates respond to infection remains incomplete. Changes in host gene expression in response to infection may occur in any part of the body, with the continuous interaction between blood and tissues allowing blood cells to act as biosensors for the changes. In this study we have used whole blood transcriptome profiling to systematically identify signatures and the pathway biology underlying the pathogenesis of neonatal infection. Blood samples were collected from neonates at the first clinical signs of suspected sepsis alongside age matched healthy control subjects. Here we report a detailed description of the study design, including clinical data collected, experimental methods used and data analysis workflows and which correspond with data in Gene Expression Omnibus (GEO) data sets (GSE25504). Our data set has allowed identification of a patient invariant 52-gene classifier that predicts bacterial infection with high accuracy and lays the foundation for advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis