Policy to practice: impact of GeneXpert MTB/RIF implementation on the TB spectrum of care in Lilongwe, Malawi

While previous research has provided evidence of the diagnostic accuracy of the GeneXpert MTB/RIF (GeneXpert), further information is needed about implementation in the real-world. This study evaluated the impact of the introduction of GeneXpert testing in a tertiary medical center according to the testing algorithm proposed by the National TB Control Program (NTP) guidelines

Toll-like receptor 4 signalling mediates inflammation in skeletal muscle of patients with chronic kidney disease

Background: Inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia but why uremia up-regulates pro-inflammatory cytokines is unknown. Toll-like receptors (TLRs) regulate locally the innate immune responses, but it is unknown whether in chronic kidney disease (CKD) TLR4 muscle signalling is altered. The aim of the study is to investigate whether in CKD muscle, TLRs had abnormal function and may be involved in transcription of pro-inflammatory cytokine. Methods: TLR4, phospho-p65, phospho-ikB\u3b1, tumour necrosis factor (TNF)-\u3b1, phospho p38, Murf 1, and atrogin were studied in skeletal muscle from nondiabetic CKD stage 5 patients (n\u2009=\u200929) and controls (n\u2009=\u200914) by immunohistochemistry, western blot, and RT\u2013PCR. Muscle cell cultures (C2C12) exposed to uremic serum were employed to study TLR4 expression (western blot and RT\u2013PCR) and TLR-driven signalling. TLR4 signalling was abrogated by a small molecule chemical inhibitor or TLR4 siRNA. Phospho AKT and phospho p38 were evaluated by western blot. Results: CKD subjects had elevated TLR4 gene and protein expression. Also expression of NFkB, p38 MAPK and the NFkB-regulated gene TNF-\u3b1 was increased. At multivariate analysis, TLR4 protein content was predicted by eGFR and Subjective Global Assessment, suggesting that the progressive decline in renal function and wasting mediate TLR4 activation. In C2C12, uremic serum increased TLR4 as well as TNF-\u3b1 and down-regulated pAkt. These effects were prevented by blockade of TLR4. Conclusions: CKD promotes muscle inflammation through an up-regulation of TLR4, which may activate downward inflammatory signals such as TNF-\u3b1 and NFkB-regulated genes

Comparison of reactions for the production of 258,257Db: 208Pb(51V,xn) and 209Bi(50Ti,xn)

Excitation functions for the 1n and 2n exit channels of the 208Pb(51V,xn)259-xDb reaction were measured. A maximum cross section of the 1n exit channel of 2070+1100/-760 pb was measured at an excitation energy of 16.0 +- 1.8 MeV. For the 2n exit channel, a maximum cross section of 1660+450/-370 pb was measured at 22.0 +- 1.8 MeV excitation energy. The 1n excitation function for the 209Bi(50Ti,n)258Db reaction was remeasured, resulting in a cross section of 5480+1750/-1370 pb at an excitation energy of 16.0 +- 1.6 MeV, in agreement with previous values [F. P. Hebberger, et al., Eur. Phys. J. A 12, 57 (2001)]. Differences in cross section maxima are discussed in terms of the fusion probability below the barrier

Disinfection by-productinduced diseases and human health risk

This chapter examines the spectrum of health-related diseases associated with exposure to disinfection by-products (DBPs) in disinfected drinking water based on evidences adduced from epidemiological data, experimental animal studies, and other models. Critical evaluation of confounding factors in the design, application, interpretation of results of animal studies, epidemiological evidences, corresponding implications in population health impact assessment was presented. The use of predictors or biomarkers in assessing the overall health implications of the complex mixture of DBPs and why only a few DBPs have been regulated despite emerging evidences of more toxic compounds in the DBPs consortium were highlighted. Specific healthassociated references with contacts with trihalomethanes, haloacetic acids, odorous DBPs, 3-chloro-4(dichloromethyl)-5-hydroxy-2(5H) furanone, chlorite, and bromate were discussed. In conclusion the chapter highlighted differences in sourcing and treatment of water by water utilities in developed and developing countries and recommend more elaborate epidemiologicalstudies in defining the actual health implication of exposure to disinfected water

Effects of beta-hydroxy-beta-methylbutyrate (HMB) on exercise performance and body composition across varying levels of age, sex, and training experience: A review

The leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) has been extensively used as an ergogenic aid; particularly among bodybuilders and strength/power athletes, who use it to promote exercise performance and skeletal muscle hypertrophy. While numerous studies have supported the efficacy of HMB in exercise and clinical conditions, there have been a number of conflicting results. Therefore, the first purpose of this paper will be to provide an in depth and objective analysis of HMB research. Special care is taken to present critical details of each study in an attempt to both examine the effectiveness of HMB as well as explain possible reasons for conflicting results seen in the literature. Within this analysis, moderator variables such as age, training experience, various states of muscle catabolism, and optimal dosages of HMB are discussed. The validity of dependent measurements, clustering of data, and a conflict of interest bias will also be analyzed. A second purpose of this paper is to provide a comprehensive discussion on possible mechanisms, which HMB may operate through. Currently, the most readily discussed mechanism has been attributed to HMB as a precursor to the rate limiting enzyme to cholesterol synthesis HMG-coenzyme A reductase. However, an increase in research has been directed towards possible proteolytic pathways HMB may operate through. Evidence from cachectic cancer studies suggests that HMB may inhibit the ubiquitin-proteasome proteolytic pathway responsible for the specific degradation of intracellular proteins. HMB may also directly stimulate protein synthesis, through an mTOR dependent mechanism. Finally, special care has been taken to provide future research implications

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny

Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein (arp). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles

Two case studies in grammar-based test generation

Grammar-based test generation (GBTG) has seen extensive study and practical use since the 1970s. GBTG was introduced to generate source code for testing compilers from context-free grammars specifying language syntax. More recently, GBTG has been applied to many other testing problems, including the generation of eXtensible Markup Language (XML) documents and the generation of packets for testing communications protocols. Recent research has shown how to integrate covering-array techniques such as pairwise testing into GBTG tools. While the integration offers considerable power to the tester, there are few practical demonstrations in the literature. We present two case studies showing how to use grammars and covering arrays for automated software testing. The first case study exposes HTML injection vulnerabilities in an RSS feed parser. The second case study determines the effectiveness of network firewalls when faced with TCP flag attacks. The case studies illustrate the use of covering arrays in a GBTG context, the use of visualization to understand large test logs, and the issues and tradeoffs in the design of fully automated GBTG test suites