Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE)

Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs

The influence of diabetes mellitus on the spectrum of uropathogens and the antimicrobial resistance in elderly adult patients with urinary tract infection

BACKGROUND: The role of Diabetes mellitus (DM) in the etiology and in the antimicrobial resistance of uropathogens in patients with urinary tract infection has not been well clarified. For this reason we have evaluated the spectrum of uropathogens and the profile of antibiotic resistance in both diabetic and non diabetic patients with asymptomatic urinary tract infection (UTI). METHODS: Urinary isolates and their patterns of susceptibility to the antimicrobials were evaluated in 346 diabetics (229 females and 117 males) and 975 non diabetics (679 females and 296 males) who were screened for significant bacteriuria (≥10(5 )CFU/mL urine). The mean age of diabetic and non diabetic patients was respectively 73.7 yrs ± 15 S.D. and 72.7 ± 24 (p = NS). RESULTS: Most of our patients had asymptomatic UTI. The most frequent causative organisms of bacteriuria in females with and without DM were respectively : E. coli 54.1% vs 58.2% (p = NS), Enterococcus spp 8.3% vs 6.5% (p = NS), Pseudomonas spp 3.9 vs 4.7% (p = NS). The most frequent organisms in diabetic and non diabetic males were respectively E. coli 32.5% vs 31.4% (p = NS), Enterococcus spp 9.4% vs 14.5% (p = NS), Pseudomonas spp 8.5% vs 17.2% (p = <0.02). A similar isolation rate of E. coli, Enterococcus spp and Pseudomonas spp was also observed in patients with indwelling bladder catheter with and without DM. No significant differences in resistance rates to ampicillin, nitrofurantoin, cotrimoxazole and ciprofloxacin of E. coli and Enteroccus spp were observed between diabetic and non diabetic patients. CONCLUSION: In our series of patients with asymptomatic UTI (mostly hospital acquired), diabetes mellitus per se does not seem to influence the isolation rate of different uropathogens and their susceptibility patterns to antimicrobials

Trends in all cause and viral liver disease-related hospitalizations in people with hepatitis B or C: a population-based linkage study

<p>Abstract</p> <p>Background</p> <p>Previous studies have reported an excess burden of cancer and mortality in populations with chronic hepatitis B (HBV) or C (HCV), but there are limited data comparing hospitalization rates. In this study, we compared hospitalization rates for all causes and viral liver disease in people notified with HBV or HCV in New South Wales (NSW), Australia.</p> <p>Methods</p> <p>HBV and HCV notifications were linked to their hospital (July 2000-June 2006), HIV and death records. Standardized hospitalization ratios (SHRs) were calculated using rates for the NSW population. Random effects Poisson regression was used to examine temporal trends.</p> <p>Results</p> <p>The SHR for all causes and non alcoholic liver disease was two-fold higher in the HCV cohort compared with the HBV cohort (SHRs 1.4 (95%CI: 1.4-1.4) v 0.6 (95%CI: 0.6-0.6) and 14.0 (95%CI: 12.7-15.4) v 5.4 (95%CI: 4.5-6.4), respectively), whilst the opposite was seen for primary liver cancer (SHRs 16.2 (95%CI: 13.8-19.1) v 29.1 (95%CI: 24.7-34.2)). HIV co-infection doubled the SHR except for primary liver cancer in the HCV/HIV cohort. In HBV and HCV mono-infected cohorts, all cause hospitalization rates declined and primary liver cancer rates increased, whilst rates for non alcoholic liver disease increased by 9% in the HCV cohort but decreased by 14% in the HBV cohort (<it>P </it>< 0.001).</p> <p>Conclusion</p> <p>Hospital-related morbidity overall and for non alcoholic liver disease was considerably higher for HCV than HBV. Improved treatment of advanced HBV-related liver disease may explain why HBV liver-related morbidity declined. In contrast, HCV liver-related morbidity increased and improved treatments, especially for advanced liver disease, and higher levels of treatment uptake are required to reverse this trend.</p

Repeated Assessments of Informed Consent Comprehension among HIV-Infected Participants of a Three-Year Clinical Trial in Botswana

Informed consent (IC) has been an international standard for decades for the ethical conduct of clinical trials. Yet frequently study participants have incomplete understanding of key issues, a problem exacerbated by language barriers or lack of familiarity with research concepts. Few investigators measure participant comprehension of IC, while even fewer conduct interim assessments once a trial is underway.We assessed comprehension of IC using a 20-question true/false quiz administered in 6-month intervals in the context of a placebo-controlled, randomized trial for the prevention of tuberculosis among HIV-infected adults in Botswana (2004-2009). Quizzes were offered in both Setswana and English. To enroll in the TB trial, participants were required to have ≥ 16/20 correct responses. We examined concepts understood and the degree to which understanding changed over three-years. We analyzed 5,555 quizzes from 1,835 participants. The participants' highest education levels were: 28% primary, 59% secondary, 9% tertiary and 7% no formal education. Eighty percent of participants passed the enrollment quiz (Quiz1) on their first attempt and the remainder passed on their second attempt. Those having higher than primary education and those who took the quiz in English were more likely to receive a passing score on their first attempt (adjusted odds ratios and 95% confidence intervals, 3.1 (2.4-4.0) and 1.5 (1.2, 1.9), respectively). The trial's purpose or procedures were understood by 90-100% of participants, while 44-77% understood randomization, placebos, or risks. Participants who failed Quiz1 on their initial attempt were more likely to fail quizzes later in the trial. Pass rates improved with quiz re-administration in subsequent years.Administration of a comprehension quiz at enrollment and during follow-up was feasible in a large, international collaboration and efficiently determined IC comprehension by trial participants. Strategies to improve understanding of concepts like placebos and randomization are needed. Comprehension assessments throughout a study may reinforce key concepts

Diversity of isoprene-degrading bacteria in phyllosphere and soil communities from a high isoprene-emitting environment: a Malaysian oil palm plantation

Background: Isoprene is the most abundantly produced biogenic volatile organic compound (BVOC) on Earth, with annual global emissions almost equal to those of methane. Despite its importance in atmospheric chemistry and climate, little is known about the biological degradation of isoprene in the environment. The largest source of isoprene is terrestrial plants, and oil palms, the cultivation of which is expanding rapidly, are among the highest isoprene-producing trees. Results: DNA stable isotope probing (DNA-SIP) to study the microbial isoprene-degrading community associated with oil palm trees revealed novel genera of isoprene-utilising bacteria including Novosphingobium, Pelomonas, Rhodoblastus, Sphingomonas and Zoogloea in both oil palm soils and on leaves. Amplicon sequencing of isoA genes, which encode the α-subunit of the isoprene monooxygenase (IsoMO), a key enzyme in isoprene metabolism, confirmed that oil palm trees harbour a novel diversity of isoA sequences. In addition, metagenome assembled genomes (MAGs) were reconstructed from oil palm soil and leaf metagenomes and putative isoprene degradation genes were identified. Analysis of unenriched metagenomes showed that isoA-containing bacteria are more abundant in soils than in the oil palm phyllosphere. Conclusion: This study greatly expands the known diversity of bacteria that can metabolise isoprene and contributes to a better understanding of the biological degradation of this important but neglected climate-active gas

Increased Risk of Fragility Fractures among HIV Infected Compared to Uninfected Male Veterans

BACKGROUND: HIV infection has been associated with an increased risk of fragility fracture. We explored whether or not this increased risk persisted in HIV infected and uninfected men when controlling for traditional fragility fracture risk factors. METHODOLOGY/PRINCIPAL FINDINGS: Cox regression models were used to assess the association of HIV infection with the risk for incident hip, vertebral, or upper arm fracture in male Veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC). We calculated adjusted hazard ratios comparing HIV status and controlling for demographics and other established risk factors. The sample consisted of 119,318 men, 33% of whom were HIV infected (34% aged 50 years or older at baseline, and 55% black or Hispanic). Median body mass index (BMI) was lower in HIV infected compared with uninfected men (25 vs. 28 kg/m²; p<0.0001). Unadjusted risk for fracture was higher among HIV infected compared with uninfected men [HR: 1.32 (95% CI: 1.20, 1.47)]. After adjusting for demographics, comorbid disease, smoking and alcohol abuse, HIV infection remained associated with an increased fracture risk [HR: 1.24 (95% CI: 1.11, 1.39)]. However, adjusting for BMI attenuated this association [HR: 1.10 (95% CI: 0.97, 1.25)]. The only HIV-specific factor associated with fragility fracture was current protease inhibitor use [HR: 1.41 (95% CI: 1.16, 1.70)]. CONCLUSIONS/SIGNIFICANCE: HIV infection is associated with fragility fracture risk. This risk is attenuated by BMI

Morphological and Molecular Evolution Are Not Linked in Lamellodiscus (Plathyhelminthes, Monogenea)

Lamellodiscus Johnston & Tiegs 1922 (Monogenea, Diplectanidae) is a genus of common parasites on the gills of sparid fishes. Here we show that this genus is probably undergoing a fast molecular diversification, as reflected by the important genetic variability observed within three molecular markers (partial nuclear 18S rDNA, Internal Transcribed Spacer 1, and mitonchondrial Cytochrome Oxidase I). Using an updated phylogeny of this genus, we show that molecular and morphological evolution are weakly correlated, and that most of the morphologically defined taxonomical units are not consistent with the molecular data. We suggest that Lamellodiscus morphology is probably constrained by strong environmental (host-induced) pressure, and discuss why this result can apply to other taxa. Genetic variability within nuclear 18S and mitochondrial COI genes are compared for several monogenean genera, as this measure may reflect the level of diversification within a genus. Overall our results suggest that cryptic speciation events may occur within Lamellodiscus, and discuss the links between morphological and molecular evolution

Evolution of the eukaryotic ARP2/3 activators of the WASP family: WASP, WAVE, WASH, and WHAMM, and the proposed new family members WAWH and WAML

<p>Abstract</p> <p>Background</p> <p>WASP family proteins stimulate the actin-nucleating activity of the ARP2/3 complex. They include members of the well-known WASP and WAVE/Scar proteins, and the recently identified WASH and WHAMM proteins. WASP family proteins contain family specific N-terminal domains followed by proline-rich regions and C-terminal VCA domains that harbour the ARP2/3-activating regions.</p> <p>Results</p> <p>To reveal the evolution of ARP2/3 activation by WASP family proteins we performed a "holistic" analysis by manually assembling and annotating all homologs in most of the eukaryotic genomes available. We have identified two new families: the WAML proteins (WASP and MIM like), which combine the membrane-deforming and actin bundling functions of the IMD domains with the ARP2/3-activating VCA regions, and the WAWH protein (WASP without WH1 domain) that have been identified in amoebae, Apusozoa, and the anole lizard. Surprisingly, with one exception we did not identify any alternative splice forms for WASP family proteins, which is in strong contrast to other actin-binding proteins like Ena/VASP, MIM, or NHS proteins that share domains with WASP proteins.</p> <p>Conclusions</p> <p>Our analysis showed that the last common ancestor of the eukaryotes must have contained a homolog of WASP, WAVE, and WASH. Specific families have subsequently been lost in many taxa like the WASPs in plants, algae, Stramenopiles, and Euglenozoa, and the WASH proteins in fungi. The WHAMM proteins are metazoa specific and have most probably been invented by the Eumetazoa. The diversity of WASP family proteins has strongly been increased by many species- and taxon-specific gene duplications and multimerisations. All data is freely accessible via <url>http://www.cymobase.org</url>.</p

Testis-specific glyceraldehyde-3-phosphate dehydrogenase: origin and evolution

<p>Abstract</p> <p>Background</p> <p>Glyceraldehyde-3-phosphate dehydrogenase (GAPD) catalyses one of the glycolytic reactions and is also involved in a number of non-glycolytic processes, such as endocytosis, DNA excision repair, and induction of apoptosis. Mammals are known to possess two homologous GAPD isoenzymes: GAPD-1, a well-studied protein found in all somatic cells, and GAPD-2, which is expressed solely in testis. GAPD-2 supplies energy required for the movement of spermatozoa and is tightly bound to the sperm tail cytoskeleton by the additional N-terminal proline-rich domain absent in GAPD-1. In this study we investigate the evolutionary history of GAPD and gain some insights into specialization of GAPD-2 as a testis-specific protein.</p> <p>Results</p> <p>A dataset of GAPD sequences was assembled from public databases and used for phylogeny reconstruction by means of the Bayesian method. Since resolution in some clades of the obtained tree was too low, syntenic analysis was carried out to define the evolutionary history of GAPD more precisely. The performed selection tests showed that selective pressure varies across lineages and isoenzymes, as well as across different regions of the same sequences.</p> <p>Conclusions</p> <p>The obtained results suggest that GAPD-1 and GAPD-2 emerged after duplication during the early evolution of chordates. GAPD-2 was subsequently lost by most lineages except lizards, mammals, as well as cartilaginous and bony fishes. In reptilians and mammals, GAPD-2 specialized to a testis-specific protein and acquired the novel N-terminal proline-rich domain anchoring the protein in the sperm tail cytoskeleton. This domain is likely to have originated by exonization of a microsatellite genomic region. Recognition of the proline-rich domain by cytoskeletal proteins seems to be unspecific. Besides testis, GAPD-2 of lizards was also found in some regenerating tissues, but it lacks the proline-rich domain due to tissue-specific alternative splicing.</p