Mapping carcass and meat quality QTL on Sus Scrofa chromosome 2 in commercial finishing pigs

Quantitative trait loci (QTL) affecting carcass and meat quality located on SSC2 were identified using variance component methods. A large number of traits involved in meat and carcass quality was detected in a commercial crossbred population: 1855 pigs sired by 17 boars from a synthetic line, which where homozygous (A/A) for IGF2. Using combined linkage and linkage disequilibrium mapping (LDLA), several QTL significantly affecting loin muscle mass, ham weight and ham muscles (outer ham and knuckle ham) and meat quality traits, such as Minolta-L* and -b*, ultimate pH and Japanese colour score were detected. These results agreed well with previous QTL-studies involving SSC2. Since our study is carried out on crossbreds, different QTL may be segregating in the parental lines. To address this question, we compared models with a single QTL-variance component with models allowing for separate sire and dam QTL-variance components. The same QTL were identified using a single QTL variance component model compared to a model allowing for separate variances with minor differences with respect to QTL location. However, the variance component method made it possible to detect QTL segregating in the paternal line (e.g. HAMB), the maternal lines (e.g. Ham) or in both (e.g. pHu). Combining association and linkage information among haplotypes improved slightly the significance of the QTL compared to an analysis using linkage information only

UK experience of liver transplantation for erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is characterised by excess production of free protoporphyrin from the bone marrow, most commonly due to deficiency of the enzyme ferrochelatase. Excess protoporphyrin gives rise to the cutaneous photosensitivity characteristic of the disease, and in a minority of patients leads to end-stage liver disease necessitating liver transplantation (LT). There is limited information regarding the timing, impact and long-term outcome of LT in such patients, thus we aimed to identify the indications and outcomes of all transplants performed for EPP in the UK using data from the UK Transplant Registry. Between 1987 and 2009, five patients underwent LT for EPP liver disease. Median follow-up was 60 months, and there were two deaths at 44 and 95 months from causes unrelated to liver disease. The remaining recipients are alive at 22.4 years, 61 months and 55 months after transplant. A high rate of postoperative biliary stricturing requiring multiple biliary interventions was observed. Recurrent EPP-liver disease occurred in 4/5 (80%) of patients but graft failure has not been observed. Given the role of biliary obstruction in inducing EPP-mediated liver damage, we suggest that consideration should be given for construction of a Roux loop at the time of transplant. Thus we demonstrate that although EPP liver transplant recipients have a good long-term survival, comparable to patients undergoing LT for other indications, biliary complications and disease recurrence are almost universal, and bone marrow transplantation should be considered where possible

Randomized double-blind placebo-controlled trial of sublingual immunotherapy in children with house dust mite allergy in primary care: study design and recruitment

Background. For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized double-blind placebo-controlled study was designed to establish the ef

Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling

Tibolone, a tissue-selective compound with a combination of estrogenic, progestagenic, and androgenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. The current study compares the endometrial gene expression profiles after short-term (21 days) treatment with tibolone to the profiles after treatment with estradiol-only (E2) and E2 + medroxyprogesterone acetate (E2 + MPA) in healthy postmenopausal women undergoing hysterectomy for endometrial prolapse. The impact of E2 treatment on endometrial gene expression (799 genes) was much higher than the effect of tibolone (173 genes) or E2 + MPA treatment (174 genes). Furthermore, endometrial gene expression profiles after tibolone treatment show a weak similarity to the profiles after E2 treatment (overlap 72 genes) and even less profile similarity to E2 + MPA treatment (overlap 17 genes). Interestingly, 95 tibolone-specific genes were identified. Translation of profile similarity into biological processes and pathways showed that ER-mediated downstream processes, such as cell cycle and cell proliferation, are not affected by E2 + MPA, slightly by tibolone, but are significantly affected by E2. In conclusion, tibolone treatment results in a tibolone-specific gene expression profile in the human endometrium, which shares only limited resemblance to E2 and even less resemblance to E2 + MPA induced profiles

Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al

Health and literacy in first- and second-generation Moroccan Berber women in the Netherlands: Ill literacy?

AIM: The present study was aimed at investigating the role of literacy and generation in the self-reported general health status of Moroccan Berber speaking women in the Netherlands. METHOD: Fifty women in our sample (N = 75) were first generation women, from which group 25 were literates and 25 illiterates. Another group of 25 literate women belonged to the second generation. The three groups were matched for demographic characteristics. Questionnaires were administered reflecting all concepts under study. We hypothesized that, within the first generation, illiterates compared with literates would report worse health. Our second hypothesis was that literates of the first generation compared with those of the second generation would have a similar health condition. RESULTS: After controlling for age, having a job, and having an employed partner, the first generation literates compared with the illiterates of the first generation indeed reported significantly better health. Additionally, we did not find any differences in health condition between both literate groups, even after controlling for age, number of children, and marital status. Health complaints that were most frequently reported by both groups, concerned pain in shoulders, back and head. CONCLUSIONS: Our results underline the importance of offering immigrants optimal access to opportunities and facilities that can improve their literacy and reading ability

The Amsterdam Studies of Acute Psychiatry - II (ASAP-II): a comparative study of psychiatric intensive care units in the Netherlands

Background The number of patients in whom mental illness progresses to stages in which acute, and often forced treatment is warranted, is on the increase across Europe. As a consequence, more patients are involuntarily admitted to Psychiatric Intensive Care Units (PICU). From several studies and reports it has become evident that important dissimilarities exist between PICU's. The current study seeks to describe organisational as well as clinical and patient related factors across ten PICU's in and outside the Amsterdam region, adjusted for or stratified by level of urbanization. Method/Design This paper describes the design of the Amsterdam Studies of Acute Psychiatry II (ASAP-II). This study is a prospective observational cohort study comparing PICU's in and outside the Amsterdam region on various patient characteristics, treatment aspects and recovery related variables. Dissimilarities were measured by means of collecting standardized forms which were filled out in the framework of care as usual, by means of questionnaires filled out by mental health care professionals and by means of extracting data from patient files for every consecutive patient admitted at participating PICU's during a specific time period. Urbanization levels for every PICU were calculated conform procedures as proposed by the Dutch Central Bureau for Statistics (CBS). Discussion The current study may provide a deeper understanding of the differences between psychiatric intensive care units that can be used to promote best practice and benchmarking procedures, and thus improve the standard of care

Cardiac regeneration: different cells same goal

Cardiovascular diseases are the leading cause of mortality, morbidity, hospitalization and impaired quality of life. In most, if not all, pathologic cardiac ischemia ensues triggering a succession of events leading to massive death of cardiomyocytes, fibroblast and extracellular matrix accumulation, cardiomyocyte hypertrophy which culminates in heart failure and eventually death. Though current pharmacological treatment is able to delay the succession of events and as a consequence the development of heart failure, the only currently available and effective treatment of end-stage heart failure is heart transplantation. However, donor heart availability and immunorejection upon transplantation seriously limit the applicability. Cardiac regeneration could provide a solution, making real a dream of both scientist and clinician in the previous century and ending an ongoing challenge for this century. In this review, we present a basic overview of the various cell types that have been used in both the clinical and research setting with respect to myocardial differentiation

Transcranial Doppler ultrasonography predicts cardiovascular events after TIA

<p>Abstract</p> <p>Background</p> <p>Transient ischemic attack (TIA) patients are at high vascular risk. We assessed the value of extracranial (ECD) and transcranial (TCD) Doppler and duplex ultrasonography to predict clinical outcome after TIA.</p> <p>Methods</p> <p>176 consecutive TIA patients admitted to the Stroke Unit were recruited in the study. All patients received diffusion-weighted imaging, standardized ECD and TCD. At a median follow-up of 27 months, new vascular events were recorded.</p> <p>Results</p> <p>22 (13.8%) patients experienced an ischemic stroke or TIA, 5 (3.1%) a myocardial infarction or acute coronary syndrome, and 5 (3.1%) underwent arterial revascularization. ECD revealed extracranial ≥ 50% stenosis or occlusions in 34 (19.3%) patients, TCD showed intracranial stenosis in 15 (9.2%) and collateral flow patterns due to extracranial stenosis in 5 (3.1%) cases. Multivariate analysis identified these abnormal ECD and TCD findings as predictors of new cerebral ischemic events (ECD: hazard ratio (HR) 4.30, 95% confidence interval (CI) 1.75 to 10.57, P = 0.01; TCD: HR 4.73, 95% CI 1.86 to 12.04, P = 0.01). Abnormal TCD findings were also predictive of cardiovascular ischemic events (HR 18.51, 95% CI 3.49 to 98.24, P = 0.001).</p> <p>Conclusion</p> <p>TIA patients with abnormal TCD findings are at high risk to develop further cerebral and cardiovascular ischemic events.</p