Prevalence of methicillin-resistant Staphylococcus aureus nasal carriage among hospitalised patients with tuberculosis in rural KwaZulu-Natal

Background. There is little information regarding the presence and characteristics of methicillin-resistant Staphylococcus aureus (MRSA), an important nosocomial pathogen, in rural African hospitals. Objectives. To determine the prevalence of MRSA colonisation in patients admitted to a rural hospital with tuberculosis (TB) in an endemic HIV area and to describe transmission dynamics and resistance patterns among MRSA isolates. Methods. A prospective prevalence survey in the adult TB wards of the Church of Scotland Hospital, a provincial government district hospital in Tugela Ferry, KwaZulu-Natal. Patients were eligible if over the age of 15 and admitted to the TB wards between 15 November and 15 December 2008. Nasal swabs were cultured within 24 hours of admission and repeated at hospital-day 14 or upon discharge. Susceptibility testing was performed with standard disk diffusion. Demographic and clinical information was extracted from medical charts. Results. Of 52 patients with an admission nasal swab, 11 (21%) were positive for MRSA. An additional 4 (10%) of patients with negative admission swabs were positive for MRSA on repeat testing. MRSA carriage on admission was more common among patients with previous hospitalisation, and among HIV-infected patients was significantly associated with lower CD4 counts (p=0.03). All MRSA isolates were resistant to cotrimoxazole, and 74% were resistant to ≥5 classes of antibiotics; all retained susceptibility to vancomycin. Conclusions. A high prevalence of multidrug-resistant MRSA nasal carriage was found. Studies are needed to validate nosocomial acquisition and to evaluate the impact of MRSA on morbidity and mortality among TB patients in similar settings

Detailed protein sequence alignment based on Spectral Similarity Score (SSS)

BACKGROUND: The chemical property and biological function of a protein is a direct consequence of its primary structure. Several algorithms have been developed which determine alignment and similarity of primary protein sequences. However, character based similarity cannot provide insight into the structural aspects of a protein. We present a method based on spectral similarity to compare subsequences of amino acids that behave similarly but are not aligned well by considering amino acids as mere characters. This approach finds a similarity score between sequences based on any given attribute, like hydrophobicity of amino acids, on the basis of spectral information after partial conversion to the frequency domain. RESULTS: Distance matrices of various branches of the human kinome, that is the full complement of human kinases, were developed that matched the phylogenetic tree of the human kinome establishing the efficacy of the global alignment of the algorithm. PKCd and PKCe kinases share close biological properties and structural similarities but do not give high scores with character based alignments. Detailed comparison established close similarities between subsequences that do not have any significant character identity. We compared their known 3D structures to establish that the algorithm is able to pick subsequences that are not considered similar by character based matching algorithms but share structural similarities. Similarly many subsequences with low character identity were picked between xyna-theau and xyna-clotm F/10 xylanases. Comparison of 3D structures of the subsequences confirmed the claim of similarity in structure. CONCLUSION: An algorithm is developed which is inspired by successful application of spectral similarity applied to music sequences. The method captures subsequences that do not align by traditional character based alignment tools but give rise to similar secondary and tertiary structures. The Spectral Similarity Score (SSS) is an extension to the conventional similarity methods and results indicate that it holds a strong potential for analysis of various biological sequences and structural variations in proteins

Standardized high-throughput evaluation of cell-based compound screens

<p>Abstract</p> <p>Background</p> <p>High-throughput screening of pharmaceutical compound activity in tissue culture experiments requires time-consuming repeated analysis of the large amounts of data generated. Automation of the evaluation procedure and assessment of measurement accuracy can save time and improve the comparability of results.</p> <p>Results</p> <p>We present a tool for simultaneous evaluation of an arbitrary number of compound screens including a standardized statistical validation. It is provided as a novel R package with a Tcl/Tk-based GUI for convenient use in the lab and runs on usual platforms like Linux, Windows and Mac OS. In a compound screen of lung cancer cells, the tool was successfully and efficiently applied for data analysis.</p> <p>Conclusion</p> <p>The package provides an efficient and intuitive platform for automatic evaluation of compound screens, improving the performance and standardization of data analysis.</p

Let me Google that for you:a time series analysis of seasonality in internet search trends for terms related to foot and ankle pain

BACKGROUND: The analysis of internet search traffic may present the opportunity to gain insights into general trends and patterns in information seeking behaviour related to medical conditions at a population level. For prevalent and widespread problems such as foot and ankle pain, this information has the potential to improve our understanding of seasonality and trends within these conditions and their treatments, and may act as a useful proxy for their true incidence/prevalence characteristics. This study aimed to explore seasonal effects, general trends and relative popularity of internet search terms related to foot and ankle pain over the past decade. METHODS: We used the Google Trends tool to obtain relative search engine traffic for terms relating to foot and ankle pain and common treatments from Google search and affiliated pages for major northern and southern hemisphere English speaking nations. Analysis of overall trends and seasonality including summer/winter differences was carried out on these terms. RESULTS: Searches relating to general foot pain were on average 3.4 times more common than those relating to ankle pain, and twice as common as searches relating to heel pain. Distinct seasonal effects were seen in the northern hemisphere, with large increases in search volumes in the summer months compared to winter for foot (p = 0.004, 95 % CI [22.2–32.1]), ankle (p = 0.0078, 95 % CI [20.9–35.5]), and heel pain (p = 0.004, 95 % CI [29.1–45.6]). These seasonal effects were reflected by data from Australia, with the exception of ankle pain. Annual seasonal effects for treatment options were limited to terms related to foot surgery and ankle orthoses (p = 0.031, 95 % CI [3.5–20.9]; p = 0.004, 95 % CI [7.6–25.2] respectively), again increasing in the summer months. CONCLUSIONS: A number of general trends and annual seasonal effects were found in time series internet search data for terms relating to foot and ankle pain. This data may provide insights into these conditions at population levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13047-015-0074-9) contains supplementary material, which is available to authorized users

Quantum whistling in superfluid 4He

Fundamental considerations predict that macroscopic quantum systems such as superfluids and the electrons in superconductors will exhibit oscillatory motion when pushed through a small constriction. Here we report the observation of these oscillations between two reservoirs of superfluid 4He partitioned by an array of nanometer-sized apertures. They obey the Josephson frequency equation and are coherent amongst all the apertures. This discovery at the relatively high temperature of 2K (2000 times higher than related phenomena in 3He) may pave the way for a new class of practical rotation sensors of unprecedented precision.Comment: 6 pages, 3 figures, to be published in Natur

Genotype-phenotype correlates of infantile-onset developmental & epileptic encephalopathy syndromes in South India: A single centre experience

INTRODUCTION: A paucity of literature exists on genotype- phenotype correlates of 'unknown-etiology' infantile-onset developmental-epileptic encephalopathies (DEE) from India. The primary objective was to explore the yield of genetic testing in identifying potential disease causing variants in electro-clinical phenotypes of DEE METHODS: An observational hospital-based study was undertaken on children with unexplained refractory seizure-onset ≤12 months age and developmental delay, whose families consented and underwent genetic testing during a three year time period (2016-2018) by next-generation sequencing (NGS) or multiplex ligand protein amplification. Yield was considered based on demonstration of pathogenic/likely pathogenic variants only and variants of unknown significance (VUS) were documented. RESULTS: Pathogenic/likely pathogenic variants were identified in 26 (31.7 %) out of 82 children with DEE. These included those variants responsible for primarily DEE- 21(76.7 %); neuro-metabolic disorders- 3(18.6 %) and chromosomal deletions- 2(4.7 %). Of these patients, early-infantile epilepsy onset ≤ 6 months age was noted in 22(84.6 %). The DEE studied included Ohtahara syndrome associated with STXBP1 and SCN8A variants with yield of 50 % (2/4 tested); early myoclonic encephalopathy (no yield in 2); West syndrome with CDKL5, yield of 13.3 % (2/15 tested); epilepsy of infancy with migrating partial seizures due to CACNA1A and KCNT1 variants, yield of 67 % (2/3 tested); DEE-unclassified with KCNQ2, AP3B2, ZEB2, metabolic variants (SUOX, ALDH7A1, GLDC) and chromosome deletions (chr 1p36, chr2q24.3); yield of 32 % (8/25 tested). Patients with Dravet syndrome/Dravet-like phenotypes (N = 33) had variants in SCN1A (N = 10), SCN1B, CHD2; yield of 36.4 % (12/33 tested; 57.1 % from NGS). Eighteen patients with potential variants (SCN1A, SCN2A, SCN8A, KCNQ2, ALDH7A1 which also included VUS) could be offered targeted therapy. CONCLUSIONS: Our study confirms a good yield of genetic testing in neonatal and infantile-onset DEE provided robust phenotyping of infants is attempted with prognostic and therapeutic implications, particularly relevant to centres with resource constraints

Experiences of refugees and asylum seekers in general practice: a qualitative study

Background: There has been much debate regarding the refugee health situation in the UK. However most of the existing literature fails to take account of the opinions of refugees themselves. This study was established to determine the views of asylum seekers and refugees on their overall experiences in primary care and to suggest improvements to their care. Methods: Qualitative study of adult asylum seekers and refugees who had entered the UK in the last 10 years. The study was set in Barnet Refugee Walk in Service, London. 11 Semi structured interviews were conducted and analysed using framework analysis. Results: Access to GPs may be more difficult for failed asylum seekers and those without support from refugee agencies or family. There may be concerns amongst some in the refugee community regarding the access to and confidentiality of professional interpreters. Most participants stated their preference for GPs who offered advice rather than prescriptions. The stigma associated with refugee status in the UK may have led to some refugees altering their help seeking behaviour. Conclusion: The problem of poor access for those with inadequate support may be improved by better education and support for GPs in how to provide for refugees. Primary Care Trusts could also supply information to newly arrived refugees on how to access services. GPs should be aware that, in some situations, professional interpreters may not always be desired and that instead, it may be advisable to reach a consensus as to who should be used as an interpreter. A better doctor-patient experience resulting from improvements in access and communication may help to reduce the stigma associated with refugee status and lead to more appropriate help seeking behaviour. Given the small nature of our investigation, larger studies need to be conducted to confirm and to quantify these results

External Urethral Sphincter Pressure Measurement: An Accurate Method for the Diagnosis of Detrusor External Sphincter Dyssynergia?

Combined pelvic floor electromyography (EMG) and videocystourethrography (VCUG) during urodynamic investigation are the most acceptable and widely agreed methods for diagnosing detrusor external sphincter dyssynergia (DESD). Theoretically, external urethral sphincter pressure (EUSP) measurement would provide enough information for the diagnosis of DESD and could simplify the urodynamic investigation replacing combined pelvic floor EMG and VCUG. Thus, we evaluated the diagnostic accuracy of EUSP measurement for DESD. PATIENTS #ENTITYSTARTX00026;A consecutive series of 72 patients (36 women, 36 men) with neurogenic lower urinary tract dysfunction able to void spontaneously was prospectively evaluated at a single university spinal cord injury center. Diagnosis of DESD using EUSP measurement (index test) versus combined pelvic floor EMG and VCUG (reference standard) was assessed according to the recommendations of the Standards for Reporting of Diagnostic Accuracy Initiative.Using EUSP measurement (index test) and combined pelvic floor EMG and VCUR (reference standard), DESD was diagnosed in 10 (14%) and in 41 (57%) patients, respectively. More than half of the patients presented discordant diagnosis between the index test and the reference standard. Among 41 patients with DESD diagnosed by combined pelvic floor EMG and VCUR, EUSP measurement identified only 6 patients. EUSP measurement had a sensitivity of 15% (95% CI 5%-25%), specificity of 87% (95% CI 76%-98%), positive predictive value of 60% (95% CI 30%-90%), and negative predictive value of 56% (95% CI 44%-68%) for the diagnosis of DESD.For diagnosis of DESD, EUSP measurement is inaccurate and cannot replace combined pelvic floor EMG and VCUR

Dynamic Carboniferous tropical forests: new views of plant function and potential for physiological forcing of climate

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138385/1/nph14700_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138385/2/nph14700.pd

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV