Risk factors for drug resistant tuberculosis in Leicestershire - poor adherence to treatment remains an important cause of resistance

In the light of rising numbers of tuberculosis (TB) cases in the United Kingdom, the problem of anti-tubercular drug resistance remains a significant concern. Drug resistant TB cases are more difficult and costly to treat, and require appropriate treatment and control mechanisms. This matched case control study aimed to investigate risk factors for resistance in Leicestershire, using data for laboratory isolates of Mycobacterium tuberculosis identified from 1993 to 1998. Each case, defined as culture positive laboratory isolates resistant to at least one first-line drug, was matched to four fully sensitive controls on age, sex and ethnic group. Twenty-three cases and 81 controls were included in the analysis. Drug resistance in Leicestershire was found to be associated with poor adherence to treatment (OR 4(.)8, 95% CI 1(.)6-14(.)4, P=0(.)005) and with previous TB (OR 3(.)7, 95% CI 1(.)2-11(.)8, P=0(.)022). These findings emphasize the need to provide support to patients taking treatment in order to maximize adherence

The Reduction of the Permeability of a Lateritic Soil through the Application of Microbially Induced Calcite Precipitation

Lateritic soils are frequently utilised in tropical areas of the developing world as an engineering material in the construction of rural earth roads, usually in the form of engineered natural surface (ENS) roads. The heavy, seasonal rainfalls common to the tropics results in ENS roads becoming quickly saturated with rainwater, and no longer accessible to motorised transportation. Microbially induced calcite precipitation (MICP) has been successfully used as a treatment process to decrease the permeability of clean, cohesionless sands by studies trying to impede the movement of groundwater, and any pollutants they may contain. In order to see if MICP treatment can also reduce the susceptibility of ENS road lateritic soils to rainwater saturation, this study has treated a Brazilian sample extracted from an ENS road in Espirito do Santo, Brazil, using the MICP bacterium Sporosarcina pasteurii contained within a urea-calcium chloride solution inoculum. Investigation, by means of a Rowe cell, of the post-treatment permeability, to untreated control samples, has shown an average decrease in the vertical coefficient of permeability of 83%, from 1.15 × 10-7 m/s for the untreated control samples, to 1.92 × 10-8 m/s in treated samples

Reconstitution of muscle F-actin from Atlantic salmon (Salmo salar L.) with carotenoids – binding characteristics of astaxanthin and canthaxanthin.

The binding of carotenoids to the myofibrillar protein F-actin purified from the white muscle of Atlantic salmon (Salmo salar L.) was studied using in vitro reconstitution. The binding of astaxanthin and canthaxanthin was saturable, and analysis revealed the presence of a single carotenoid-binding site. The dissociation constants (Kd) for actin prepared from 2.5 Kg FW fish were 1.04 ± 0.13 μg carotenoid mg-1 actin and 0.54 ± 0.11 μgmg-1 for astaxanthin and canthaxanthin, respectively. The saturation binding level (Bmax) for astaxanthin was 1.39 ± 0.07 μgmg-1 and 1.04 ± 0.08 μgmg-1 for canthaxanthin. These values were higher for F-actin prepared from organic and small (~0.5 Kg FW) salmon than for non-organic and larger, mature fish. The structural specificity of carotenoid binding revealed a preference for carotenoids that possess a keto group at C-4 on the end-group of the molecule, but the presence of hydroxyl groups at C-3 or C-4 reduced overall binding efficiency. The study suggests that the ability of myofibrillar proteins to bind carotenoids is not a limiting factor governing the deposition of carotenoids in the muscle of salmonids

Appetite suppressants and valvular heart disease - a systematic review

Background Although appetite suppressants have been implicated in the development of valvular heart disease, the exact level of risk is still uncertain. Initial studies suggested that as many as 1 in 3 exposed patients were affected, but subsequent research has yielded substantially different figures. Our objective was to systematically assess the risk of valvular heart disease with appetite suppressants. Methods We accepted studies involving obese patients treated with any of the following appetite suppressants: fenfluramine, dexfenfluramine, and phentermine. Three types of studies were reviewed: controlled and uncontrolled observational studies, and randomized controlled trials. Outcomes of interest were echocardiographically detectable aortic regurgitation of mild or greater severity, or mitral regurgitation of moderate or greater severity. Results Of the 1279 patients evaluated in seven uncontrolled cohort studies, 236 (18%) and 60 (5%) were found to have aortic and mitral regurgitation, respectively. Pooled data from six controlled cohort studies yielded, for aortic regurgitation, a relative risk ratio of 2.32 (95% confidence intervals 1.79 to 3.01, p < 0.00001) and an attributable rate of 4.9%, and for mitral regurgitation, a relative risk ratio of 1.55 (95% confidence intervals 1.06 to 2.25, p = 0.02) with an attributable rate of 1.0%. Only one case of valvular heart disease was detected in 57 randomized controlled trials, but this was judged unrelated to drug therapy. Conclusions The risk of valvular heart disease is significantly increased by the appetite suppressants reviewed here. Nevertheless, when considering all the evidence, valvulopathy is much less common than suggested by the initial, less methodologically rigorous studies

The Effect of Ambient Air Pollution during Early Pregnancy on Fetal Ultrasonic Measurements during Mid-Pregnancy

BACKGROUND: Over the past decade there has been mounting evidence that ambient air pollution during pregnancy influences fetal growth. OBJECTIVES: This study was designed to examine possible associations between fetal ultrasonic measurements collected from 15,623 scans (13–26 weeks gestation) and ambient air pollution during early pregnancy. METHODS: We calculated mothers ’ average monthly exposures over the first 4 months of pregnancy for the following pollutants: particulate matter &lt; 10 µm aerodynamic diameter (PM10), ozone, nitrogen dioxide, and sulfur dioxide. We examined associations with fetal femur length (FL), biparietal diameter (BPD), head circumference (HC), and abdominal circumference (AC). Final analyses included scans from only those women within 2 km of an air pollution monitoring site. We controlled for long-term trend, season, temperature, gestation, mother’s age, socioeconomic status, and fetal sex. RESULTS: A reduction in fetal AC was associated with O3 during days 31–60 [–1.42 mm; 95 % confidence interval (CI), –2.74 to –0.09], SO2 during days 61–90 (–1.67 mm; 95 % CI, –2.94 to –0.40), and PM10 during days 91–120 (–0.78 mm; 95 % CI, –1.49 to –0.08). Other results showed a reduction in BPD (–0.68 mm; 95 % CI, –1.09 to –0.27) associated with SO2 during days 0–30, a reduction in HC (–1.02 mm; 95 % CI, –1.78 to –0.26) associated with PM10 during days 91–120, and a reduction in FL associated with PM10 during days 0–30 (–0.28 mm; 95 % CI, –0.48 to –0.08) and 91–120 (–0.23; 95 % CI, –0.42 to –0.04). CONCLUSION: We found strong effects of ambient air pollution on ultrasound measures. Future research, including more individually detailed data, is needed to confirm our results. KEY WORDS: air pollution, fetal growth, pregnancy, temperature, ultrasound. Environ Health Perspect 116:362–369 (2008). doi:10.1289/ehp.10720 available vi

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

Full Genome Characterization of the Culicoides-Borne Marsupial Orbiviruses: Wallal Virus, Mudjinbarry Virus and Warrego Viruses

Viruses belonging to the species Wallal virus and Warrego virus of the genus Orbivirus were identified as causative agents of blindness in marsupials in Australia during 1994/5. Recent comparisons of nucleotide (nt) and amino acid (aa) sequences have provided a basis for the grouping and classification of orbivirus isolates. However, full-genome sequence data are not available for representatives of all Orbivirus species. We report full-genome sequence data for three additional orbiviruses: Wallal virus (WALV); Mudjinabarry virus (MUDV) and Warrego virus (WARV). Comparisons of conserved polymerase (Pol), sub-core-shell 'T2' and core-surface 'T13' proteins show that these viruses group with other Culicoides borne orbiviruses, clustering with Eubenangee virus (EUBV), another orbivirus infecting marsupials. WARV shares <70% aa identity in all three conserved proteins (Pol, T2 and T13) with other orbiviruses, consistent with its classification within a distinct Orbivirus species. Although WALV and MUDV share <72.86%/67.93% aa/nt identity with other orbiviruses in Pol, T2 and T13, they share >99%/90% aa/nt identities with each other (consistent with membership of the same virus species - Wallal virus). However, WALV and MUDV share <68% aa identity in their larger outer capsid protein VP2(OC1), consistent with membership of different serotypes within the species - WALV-1 and WALV-2 respectively

Primary cilia elongation in response to interleukin-1 mediates the inflammatory response

Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50 % increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA

A Summary of the Inaugural WHO Classification of Pediatric Tumors: Transitioning from the Optical into the Molecular Era

Pediatric tumors are uncommon, yet are the leading cause of cancer-related death in childhood. Tumor types, molecular characteristics, and pathogenesis are unique, often originating from a single genetic driver event. The specific diagnostic challenges of childhood tumors led to the development of the first World Health Organization (WHO) Classification of Pediatric Tumors. The classification is rooted in a multilayered approach, incorporating morphology, IHC, and molecular characteristics. The volume is organized according to organ sites and provides a single, state-of-the-art compendium of pediatric tumor types. A special emphasis was placed on “blastomas,” which variably recapitulate the morphologic maturation of organs from which they originate