Exome sequencing and genome-wide linkage analysis in 17 families illustrate the complex contribution of TTN truncating variants to dilated cardiomyopathy.

BACKGROUND- Familial dilated cardiomyopathy (DCM) is a genetically heterogeneous disease with >30 known genes. TTN truncating variants were recently implicated in a candidate gene study to cause 25% of familial and 18% of sporadic DCM cases. METHODS AND RESULTS- We used an unbiased genome-wide approach using both linkage analysis and variant filtering across the exome sequences of 48 individuals affected with DCM from 17 families to identify genetic cause.

Discordant hepatitis C serological testing in Australia and the implications for organ transplant programs.

Background: Discordant and equivocal hepatitis C (HCV) serology testing is problematic for making decisions regarding deceased organ donor (DOD) transplant allocation based on allograft infection status.

Objectives: This study aimed to analyse the prevalence and follow-up testing of discordant HCV tested patients from an Australian population at increased risk of HCV infection, with prevalence modelling for the Australian DOD population.

Study Design: De-identified patient discordant HCV serology results (primary chemiluminescent microparticle immunoassay and secondary Bio-Rad MonoLisa HCV Ag/Ab Ultra assay) were retrospectively identified in a general referral laboratory between May 2008 and August 2011.

Effects of dose and route of administration of genistein on isoflavone concentrations in post-weaned and gestating sows.

Phytoestrogens could be a useful tool in swine husbandry practices because of their structural and functional similarities to estradiol. The goal of this study was to compare various routes and doses of administration of the phytoestrogen genistein in sows of two different physiological statuses. Circulating concentrations of isoflavones, estradiol and IGF-I were determined.

Pharmacokinetics and excretion of 14C-bendamustine in patients with relapsed or refractory malignancy.

Background: Bendamustine is an alkylating agent with clinical activity against a variety of hematologic malignancies and solid tumors. To assess the roles of renal and hepatic drug elimination pathways in the excretion and metabolism of bendamustine, a mass balance study was performed in patients with relapsed or refractory malignancies.

Methods: A single 60-minute intravenous dose of 120 mg/m(2), 80-95 μCi (14)C-bendamustine hydrochloride was administered to six patients, followed by collection of blood, urine, and fecal samples at specified time points up to day 8 or until the radioactivity of the 24-hour urine and fecal collections was below 1% of the administered dose (whichever was longer).

Clinical Practice Guideline Development Manual, Third Edition: a quality-driven approach for translating evidence into action.

Background: Guidelines translate best evidence into best practice. A well-crafted guideline promotes quality by reducing health care variations, improving diagnostic accuracy, promoting effective therapy, and discouraging ineffective-or potentially harmful-interventions. Despite a plethora of published guidelines, methodology is often poorly defined and varies greatly within and among organizations.

Functional gene differences in soil microbial communities from conventional, low-input, and organic farmlands.

Various agriculture management practices may have distinct influences on soil microbial communities and their ecological functions. In this study, we utilized GeoChip, a high-throughput microarray-based technique containing approximately 28,000 probes for genes involved in nitrogen (N)/carbon (C)/sulfur (S)/phosphorus (P) cycles and other processes, to evaluate the potential functions of soil microbial communities under conventional (CT), low-input (LI), and organic (ORG) management systems at an agricultural research site in Michigan. Compared to CT, a high diversity of functional genes was observed in LI.

Improving diagnosis of primary cytomegalovirus infection in pregnant women using immunoblots.

Human cytomegalovirus (CMV) is the most common infectious cause of mental disability in newborns of developed countries. Transmission of CMV from mother to baby is more frequent in maternal primary infection, although CMV reactivation causes more congenital infections overall. Current diagnostic tests for distinguishing primary and reactivation CMV have problems with interpretation and immunoblots may assist with diagnosis.

Novel common and rare genetic determinants of paraoxonase activity: FTO, SERPINA12, and ITGAL.

HDL-associated paraoxonase 1 (PON1) activity is associated with cardiovascular and other human diseases. As the role of genetic variants outside of the PON gene cluster on PON1 activity is unknown, we sought to identify common and rare variants in such loci. We typed 33,057 variants on the CVD chip in 1,362 subjects to test for their effects on adjusted-PON1 activity.

Excellent outcomes of simultaneous pancreas kidney transplantation in patients from rural and urban Australia: a national service experience.

Background: Simultaneous pancreas and kidney (SPK) transplantation is performed to restore normoglycemia and renal function in patients with type 1 diabetes mellitus and end-stage renal failure. The National Pancreas Transplant Unit (NPTU) in Sydney provides a service to a population spread across 7.4 million km.

Pharmacist intervention in cardiac rehabilitation: a randomized controlled trial.

Purpose: We aimed to determine to what extent a telephone-based pharmacist intervention would (a) be utilized by individuals not attending a traditional cardiac rehabilitation (CR) program and (b) facilitate adherence to cardiovascular medications.

Methods: We conducted a randomized, controlled open-label trial among patients eligible for CR in Saskatoon, Canada. Patients were invited to participate in telephone-based CR, regardless of participation in the formal program.

Use of barrier protection for sexual activity among women who have sex with women.

Objective: To assess the frequency and associations of barrier protection use during sexual activity in a population of women who have sex with women (WSW).

Methods: WSW were invited to participate in an international internet-based survey. Information regarding ethnodemographics, sexual health, and barrier use during sexual activities was collected.

Mechanism of repair of 5'-topoisomerase II-DNA adducts by mammalian tyrosyl-DNA phosphodiesterase 2.

The topoisomerase II (topo II) DNA incision-and-ligation cycle can be poisoned (for example following treatment with cancer chemotherapeutics) to generate cytotoxic DNA double-strand breaks (DSBs) with topo II covalently conjugated to DNA. Tyrosyl-DNA phosphodiesterase 2 (Tdp2) protects genomic integrity by reversing 5'-phosphotyrosyl-linked topo II-DNA adducts. Here, X-ray structures of mouse Tdp2-DNA complexes reveal that Tdp2 β-2-helix-β DNA damage-binding 'grasp', helical 'cap' and DNA lesion-binding elements fuse to form an elongated protein-DNA conjugate substrate-interaction groove.

Case report and evaluation of the frequency of the prozone phenomenon in syphilis serology - an infrequent but important laboratory phenomenon.

Background: Treponema pallidum specific serology generally remains reactive for life. Therefore, the diagnosis of syphilis reinfection relies on clinical assessment and nontreponemal (reagin) serologic testing. The prozone phenomenon can lead to a falsely nonreactive rapid plasma reagin (RPR) assay result.

Arrhythmias in Fabry cardiomyopathy.

Background: Prior studies suggest that the incidence of ventricular arrhythmias is high in patients with Fabry cardiomyopathy. This study evaluated the incidence of significant arrhythmias in a series of patients with Fabry cardiomyopathy.

Hypothesis: Arrhythmias are important causes of morbidity and mortality in Fabry Cardiomyopathy.

Significance of isolated reactive treponemal chemiluminescence immunoassay results.

Background: Isolated reactive serum treponemal chemiluminescence immunoassay (CIA) specimens cause clinical uncertainty.

Methods: Sera were screened by CIA, and reactive samples underwent reflex testing with rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and fluorescent treponemal antibody absorption (FTA Abs) assays. Samples reactive only on the CIA were deemed "isolated" reactive CIA samples.

Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5.

Background: Familial dyskinesia with facial myokymia (FDFM) is an autosomal dominant disorder that is exacerbated by anxiety. In a 5-generation family of German ancestry, we previously mapped FDFM to chromosome band 3p21-3q21. The 72.

An abundance of small exoplanets around stars with a wide range of metallicities.

The abundance of heavy elements (metallicity) in the photospheres of stars similar to the Sun provides a 'fossil' record of the chemical composition of the initial protoplanetary disk. Metal-rich stars are much more likely to harbour gas giant planets, supporting the model that planets form by accumulation of dust and ice particles. Recent ground-based surveys suggest that this correlation is weakened for Neptunian-sized planets.

On the extent and nature of nucleus-annulus integration.

Study Design: Mechanical and microstructural assessment of nucleus-annulus integration.

Objective: To investigate the existence of structural integration between the nucleus and the inner annulus.

Summary Of Background Data: The nucleus is often viewed as a hydrostatically functioning entity that is largely separate from its surroundings.

A cohort study comparing cardiovascular risk factors in rural Maori, urban Maori and non-Maori communities in New Zealand.

Objectives: To understand health disparities in cardiovascular disease (CVD) in the indigenous Māori of New Zealand, diagnosed and undiagnosed CVD risk factors were compared in rural Māori in an area remote from health services with urban Māori and non-Māori in a city well served with health services.

Design: Prospective cohort study.

Setting: Hauora Manawa is a cohort study of diagnosed and previously undiagnosed CVD, diabetes and risk factors, based on random selection from electoral rolls of the rural Wairoa District and Christchurch City, New Zealand.

On how nucleus-endplate integration is achieved at the fibrillar level in the ovine lumbar disc.

The intervertebral disc nucleus has traditionally been viewed as a largely unstructured amorphous gel having little obvious integration with the cartilaginous endplates (CEPs). However, recent work by the present authors has provided clear evidence of structural cohesion across the nucleus-endplate junction via a distinctive microanatomical feature termed insertion nodes. The aim of this study was to explore the nature of these insertion nodes at the fibrillar level.

Metabolite profiling of bendamustine in urine of cancer patients after administration of [14C]bendamustine.

Bendamustine is an alkylating agent consisting of a mechlorethamine derivative, a benzimidazole group, and a butyric acid substituent. A human mass balance study showed that bendamustine is extensively metabolized and subsequently excreted in urine. However, limited information is available on the metabolite profile of bendamustine in human urine.