Insight into hypertrophied hearts: a cardiovascular magnetic resonance study of papillary muscle mass and T1 mapping

AIMS: Left ventricular papillary muscles (LVPM) can appear disproportionately hypertrophied, particularly in Fabry disease (FD) where storage appears detectable by cardiovascular magnetic resonance (CMR) T1 mapping. The aim of the study was to measure LVPM mass in heart diseases with left ventricular hypertrophy (LVH) and to gain insight into the mechanisms of LVPM hypertrophy in FD. METHODS AND RESULTS: Four hundred and seventy-eight cases were retrospectively recruited: 125 FD, 85 hypertrophic cardiomyopathy (HCM), 67 amyloid, 82 aortic stenosis (AS), 40 hypertension, 79 controls. LVPM contribution to LVM was manually contoured on CMR short axis cines. T1 values (septal, LVPM) were measured using ShMOLLI sequences in FD and controls. LVPM contribution to LVM was highest in LVH+ve FD and significantly increased compared to all other LVH+ve groups (FD 13 ± 3%, HCM 10 ± 3%, amyloid 8 ± 2%, AS 7 ± 3%, hypertension 7 ± 2%, controls 7 ± 1%; P < 0.001). LVH+ve HCM also had significantly increased LVPM. In LVH−ve cohorts, only FD had significantly increased LVPM (11 ± 3%; P < 0.001). In FD there was concordant septal and LVPM T1. LVH+ve FD: when septal T1 was low, LVPM T1 was low in 90%. LVH−ve FD: when septal T1 was normal, LVPM T1 was normal in 70% (indicating no detectable storage); when septal T1 was low, 75% had low LVPM T1 (indicating storage). LVPM hypertrophy was similar between the low and normal septal T1 groups (11 ± 3% vs. 10 ± 3%, P = 0.08). CONCLUSION: Disproportionate hypertrophy of LVPMs in LVH+ve hearts occurred in FD and HCM. This phenomenon also occurred in LVH−ve FD. Low T1 was not always present in FD LVPM hypertrophy, implying additional mechanisms activating hypertrophy signalling pathways

Differential diagnosis of tuberculous meningitis from partially-treated pyogenic meningitis by cell ELISA

BACKGROUND: Tuberculous meningitis (TBM) is a major global health problem, and it is sometimes difficult to perform a differential diagnosis of this disease from other diseases, particularly partially-treated pyogenic meningitis (PTPM). In an earlier study, we demonstrated the presence of a 30-kD protein antigen in cerebrospinal fluid (CSF) of TBM patients. We have also shown that lymphocytes from CSF of TBM patients respond differently to this antigen than do those from PTPM patients. The purpose of this study was to develop an assay that can discriminate between TBM and PTPM. METHODS: We developed a cell enzyme-linked immunosorbant assay (Cell ELISA) to quantitatively measure production of antibodies against the 30-kD protein in B cells from CSF of TBM and PTPM patients. RESULTS: The cell ELISA yielded 92% (11/12) sensitivity and 92% (11/12) specificity for the differential diagnosis of TBM from PTPM. CONCLUSION: When induced with the 30-kD protein antigen, B cells derived from CSF of TBM patients respond to IgG production within 24 h while those derived from PTPM patients do not respond

Share of afghanistan populace in hepatitis B and hepatitis C infection's pool: is it worthwhile?

There is a notable dearth of data about Hepatitis B Virus (HBV) and Hepatitis C Virus(HCV) prevalence in Afghanistan. Awareness program and research capacity in the field of hepatitis are very limited in Afghanistan. Number of vulnerabilities and patterns of risk behaviors signal the need to take action now

Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases

We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment

Factors associated with intentions to adhere to colorectal cancer screening follow-up exams

BACKGROUND: To increase adherence rate to recommendations for follow-up after abnormal colorectal cancer (CRC) screening results, factors that inhibit and facilitate follow-up must be identified. The purpose of this study was to identify the factors associated with intention to adhere to CRC screening follow-up exams. METHODS: During a 4-week period in October 2003, this survey was conducted with 426 subjects participating in a community-based CRC screening program in Nagano, Japan. Study measures included intention to adhere to recommendation for clinical follow-up in the event of an abnormal fecal occult blood test (FOBT) result, perceived susceptibility and severity of CRC, perceived benefits and barriers related to undergoing follow-up examination, social support, knowledge of CRC risk factors, health status, previous CRC screening, personality and social demographic characteristics. Univariate and multivariate logistic regression analyses on intention to adhere to recommendations for follow-up were performed. RESULTS: Among the 288 individuals analyzed, approximately 74.7% indicated that they would definitely adhere to recommendations for follow-up. After controlling for age, gender, marital status, education, economic status, trait anxiety, bowel symptoms, family history of CRC, and previous screening FOBT, analyses revealed that lower levels of perceived barriers, higher levers of perceived benefits and knowledge of CRC risk factors were significantly associated with high intention respectively. CONCLUSION: The results of this study suggest that future interventions should focus on reducing modifiable barriers by clarifying misperceptions about follow-up, promoting the acceptance of complete diagnostic evaluations, addressing psychological distress, and making follow-up testing more convenient and accessible. Moreover, educating the public regarding the risk factors of CRC and increasing understanding of the benefits of follow-up is also important

Genetic Affinities within a Large Global Collection of Pathogenic Leptospira: Implications for Strain Identification and Molecular Epidemiology

Leptospirosis is an important zoonosis with widespread human health implications. The non-availability of accurate identification methods for the individualization of different Leptospira for outbreak investigations poses bountiful problems in the disease control arena. We harnessed fluorescent amplified fragment length polymorphism analysis (FAFLP) for Leptospira and investigated its utility in establishing genetic relationships among 271 isolates in the context of species level assignments of our global collection of isolates and strains obtained from a diverse array of hosts. In addition, this method was compared to an in-house multilocus sequence typing (MLST) method based on polymorphisms in three housekeeping genes, the rrs locus and two envelope proteins. Phylogenetic relationships were deduced based on bifurcating Neighbor-joining trees as well as median joining network analyses integrating both the FAFLP data and MLST based haplotypes. The phylogenetic relationships were also reproduced through Bayesian analysis of the multilocus sequence polymorphisms. We found FAFLP to be an important method for outbreak investigation and for clustering of isolates based on their geographical descent rather than by genome species types. The FAFLP method was, however, not able to convey much taxonomical utility sufficient to replace the highly tedious serotyping procedures in vogue. MLST, on the other hand, was found to be highly robust and efficient in identifying ancestral relationships and segregating the outbreak associated strains or otherwise according to their genome species status and, therefore, could unambiguously be applied for investigating phylogenetics of Leptospira in the context of taxonomy as well as gene flow. For instance, MLST was more efficient, as compared to FAFLP method, in clustering strains from the Andaman island of India, with their counterparts from mainland India and Sri Lanka, implying that such strains share genetic relationships and that leptospiral strains might be frequently circulating between the islands and the mainland

Dunno if you've any plans for the future: medical student indirect questioning in simulated oncology interviews

<p>Abstract</p> <p>Background</p> <p>This exploratory study investigated the motives of medical students (N = 63) for using indirect questions of the type <it>I don't know if </it>[you have already heard about chemotherapies], <it>I don't know how </it>[you are], or <it>I don't know what </it>[you do for a living] in simulated patient interviews during a communication skills course.</p> <p>Methods</p> <p><it>I don't know </it>questions (IDK-Qs) were observed during the initial evaluation of students' communication skills; they were systematically identified through video screening and subjected to a qualitative content and discourse analysis considering their context, their content, their intent and their effect on the simulated patients. To evaluate the specificity of medical students' IDK-Qs, the data were compared with a data set of oncologists (N = 31) conducting simulated patient interviews in the context of a Communication Skills Training (CST).</p> <p>Results</p> <p>During the interviews, 41.3% of the students asked 1-6 IDK-Qs. The IDK-Qs were attributed to three content categories: medical/treatment questions (N = 24); lifestyle/psychosocial questions (N = 18); and "inviting questions" questions (N = 11). Most of the IDK-Qs had an exploratory function (46/53), with simulated patients providing detailed responses or asking for more information (36/53). IDK-Qs were rare in the oncologist sample compared to the student sample (5 vs. 53 occurrences).</p> <p>Conclusions</p> <p>IDK-Qs showed a question design difference between medical students and oncologists in simulated patient interviews. Among other reasons for this difference, the possible function of IDK-Qs as a protective linguistic strategy and marker for psychological discomfort is discussed.</p

Dissecting Molecular Differences between Wnt Coreceptors LRP5 and LRP6

Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6) serve as Wnt co-receptors for the canonical β-catenin pathway. While LRP6 is essential for embryogenesis, both LRP5 and LRP6 play critical roles for skeletal remodeling, osteoporosis pathogenesis and cancer formation, making LRP5 and LRP6 key therapeutic targets for cancer and disease treatment. LRP5 and LRP6 each contain in the cytoplasmic domain five conserved PPPSPxS motifs that are pivotal for signaling and serve collectively as phosphorylation-dependent docking sites for the scaffolding protein Axin. However existing data suggest that LRP6 is more effective than LRP5 in transducing the Wnt signal. To understand the molecular basis that accounts for the different signaling activity of LRP5 and LRP6, we generated a series of chimeric receptors via swapping LRP5 and LRP6 cytoplasmic domains, LRP5C and LRP6C, and studied their Wnt signaling activity using biochemical and functional assays. We demonstrate that LRP6C exhibits strong signaling activity while LRP5C is much less active in cells. Recombinant LRP5C and LRP6C upon in vitro phosphorylation exhibit similar Axin-binding capability, suggesting that LRP5 and LRP6 differ in vivo at a step prior to Axin-binding, likely at receiving phosphorylation. We identified between the two most carboxyl PPPSPxS motifs an intervening “gap4” region that appears to account for much of the difference between LRP5C and LRP6C, and showed that alterations in this region are sufficient to enhance LRP5 PPPSPxS phosphorylation and signaling to levels comparable to LRP6 in cells. In addition we provide evidence that binding of phosphorylated LRP5 or LRP6 to Axin is likely direct and does not require the GSK3 kinase as a bridging intermediate as has been proposed. Our studies therefore uncover a new and important molecular tuning mechanism for differential regulation of LRP5 and LRP6 phosphorylation and signaling activity