ddpcr: an R package and web application for analysis of droplet digital PCR data.

Droplet digital polymerase chain reaction (ddPCR) is a novel platform for exact quantification of DNA which holds great promise in clinical diagnostics. It is increasingly popular due to its digital nature, which provides more accurate quantification and higher sensitivity than traditional real-time PCR. However, clinical adoption has been slowed in part by the lack of software tools available for analyzing ddPCR data.

The Mediterranean Diet and Cognitive Function among Healthy Older Adults in a 6-Month Randomised Controlled Trial: The MedLey Study.

Evidence from a limited number of randomised controlled intervention trials (RCTs) have shown that a Mediterranean dietary pattern may reduce the risk of cognitive decline and enhance cognitive function among healthy older adults. However, there are currently no data in non-Mediterranean older adult populations. The present study aimed to address this gap by examining the effect of a Mediterranean dietary pattern (MedDiet) for six months on aspects of cognitive function in a randomised controlled intervention trial (the MedLey study) that extended for a duration of 18 months.

Intravitreal implantation of TPP1-transduced stem cells delays retinal degeneration in canine CLN2 neuronal ceroid lipofuscinosis.

The CLN2 form of neuronal ceroid lipofuscinosis is a neurodegenerative disease that results from mutations in the TPP1 gene. Affected children exhibit progressive declines in most neurological functions including vision. Functional declines are accompanied by progressive brain and retinal atrophy.

Phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate in dogs with naturally occurring malignant tumors.

OBJECTIVE To conduct a phase I-II clinical trial of hyaluronan-cisplatin nanoconjugate (HA-Pt) in dogs with naturally occurring malignant tumors. ANIMALS 18 healthy rats, 9 healthy mice, and 16 dogs with cancer. PROCEDURES HA-Pt was prepared and tested by inductively coupled plasma mass spectrometry; DNA-platinum adduct formation and antiproliferation effects of cisplatin and HA-Pt were compared in vitro.

A One Health overview, facilitating advances in comparative medicine and translational research.

A1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N.

Blinatumomab: Bridging the Gap in Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia.

Adult patients with acute lymphoblastic leukemia who relapse after frontline therapy have extremely poor outcomes despite advances in chemotherapy and hematopoietic stem cell transplantation. Blinatumomab is a first-in-class bispecific T-cell engager that links T cells to tumor cells leading to T-cell activation and tumor cell lysis. In December 2014, the Food and Drug Administration approved blinatumomab for treatment of relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia.

Compounding risk: An examination of associations between spirituality/religiosity, drinking motives, and alcohol-related ambivalence among heavy drinking young adults.

Objectives: The present study assessed combinations of spirituality/religiosity (S/R), a known protective factor against heavy drinking, with drinking motives, and alcohol-related ambivalence to better understand how these factors interrelate and are associated with drinking and alcohol-related problems.

Methods: Participants were 241 heavy drinking undergraduate students (81.74% female; Mage=23.

Cerebrovascular and cognitive benefits of high-oleic peanut consumption in healthy overweight middle-aged adults.

Objective: Peanuts contain bioactive nutrients beneficial for vascular function. This study investigated whether consumption of unsalted peanuts (with skins) would enhance cerebrovascular perfusion and cognitive performance.

Method: In a randomized crossover trial, 61 volunteers (29 males/32 females, 65 ± 7 years, BMI 31 ± 4 kg/m) consumed their habitual diet ± high-oleic peanuts (56-84 g/day), each for 12 weeks.

The Sur1-Trpm4 channel regulates NOS2 transcription in TLR4-activated microglia.

Background: Harmful effects of activated microglia are due, in part, to the formation of peroxynitrite radicals, which is attributable to the upregulation of inducible nitric oxide (NO) synthase (NOS2). Because NOS2 expression is determined by Ca(2+)-sensitive calcineurin (CN) dephosphorylating nuclear factor of activated T cells (NFAT), and because Sur1-Trpm4 channels are crucial for regulating Ca(2+) influx, we hypothesized that, in activated microglia, Sur1-Trpm4 channels play a central role in regulating CN/NFAT and downstream target genes such as Nos2.

Methods: We studied microglia in vivo and in primary culture from adult rats, and from wild type, Abcc8-/- and Trpm4-/- mice, and immortalized N9 microglia, following activation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS), using in situ hybridization, immunohistochemistry, co-immunoprecipitation, immunoblot, qPCR, patch clamp electrophysiology, calcium imaging, the Griess assay, and chromatin immunoprecipitation.

Integrative veterinary medical education and consensus guidelines for an integrative veterinary medicine curriculum within veterinary colleges.

Integrative veterinary medicine (IVM) describes the combination of complementary and alternative therapies with conventional care and is guided by the best available evidence. Veterinarians frequently encounter questions about complementary and alternative veterinary medicine (CAVM) in practice, and the general public has demonstrated increased interest in these areas for both human and animal health. Consequently, veterinary students should receive adequate exposure to the principles, theories, and current knowledge supporting or refuting such techniques.

The Mediterranean diet and age-related cognitive functioning: A systematic review of study findings and neuropsychological assessment methodology.

Objectives: The primary aims of this review were to identify studies investigating the association between the MedDiet pattern and age-related cognitive function, to determine the current status of knowledge, and to ascertain whether a lack of standardization with the operationalization of age-related cognitive function and differences in the chosen neuropsychological assessment methodology impacted on the results and findings.

Methods: The systematic review protocol for this paper was carried out following the statement and general principles of PRISMA and the UK Centre for Reviews and Dissemination (CRD).

Results: A systematic search of electronic databases yielded two cross-sectional studies, two cross-sectional/prospective studies, and 11 prospective studies for inclusion.

Hyaluronan-Lysine Cisplatin Drug Carrier for Treatment of Localized Cancers: Pharmacokinetics, Tolerability, and Efficacy in Rodents and Canines.

The purpose of this study was to develop a safe and efficacious drug delivery platform for sustained release of cisplatin after locoregional administration. We successfully synthesized hyaluronan-cisplatin nanoconjugates (HA-Lys-Pt) using an N-Ac-lysine linker, which formed a thermodynamically stable five-membered ring with the platinum. The conjugate was characterized for release kinetics, in vitro anti-proliferative activity, degradability, impurity content, formation of Pt-DNA adducts, pharmacokinetics, tolerability in rodents and canines, and for efficacy in rodents.

Liver Surface Nodularity Quantification from Routine CT Images as a Biomarker for Detection and Evaluation of Cirrhosis.

Purpose To determine the accuracy, reproducibility, and intra- and interobserver agreement of a computer-based quantitative method to measure liver surface nodularity (LSN) from routine computed tomographic (CT) images as a biomarker for detection and evaluation of cirrhosis. Materials and Methods For this institutional review board-approved HIPAA-compliant retrospective study, adult patients with healthy livers (n = 24) or various stages of hepatitis C virus-induced chronic liver disease (n = 70) with routine nonenhanced and portal venous phase contrast agent-enhanced liver CT imaging with thick-section (5.0 mm) and thin-section (1.

Antibiotic resistance: challenges and successes in respiratory infection.

European Respiratory Society Congress, Amsterdam, 26-30 September 2015, and CHEST 2015, Montréal, Canada, 24-28 October 2015 With approximately 50,000 deaths in the US and EU attributed to antibacterial resistance each year, together with several million days of hospital care [1], the need to address resistance mechanisms and find new targets for novel antibiotics has never been greater. At the annual congresses of the European Respiratory Society and the American College of Chest Physicians, presenters reported advances in understanding of the mechanisms of antibiotic resistance and how these may be overcome. The latest clinical trial data on antibiotic treatment for hospital- and community-acquired pneumonia, including the potential for novel nebulized forms of therapy, were also discussed.

God, Can I Tell You Something? The Effect of Religious Coping on the Relationship between Anxiety Over Emotional Expression, Anxiety, and Depressive Symptoms.

The current study investigated whether religious coping would moderate the association between ambivalence over emotional expression (AEE) and depressive symptoms and anxiety symptoms such that the positive relationship between AEE and depressive symptoms and anxiety symptoms would be weaker among those higher in religious coping. Three-hundred and fifty-two undergraduates ( age=23.51 years, =6.

Overcoming treatment challenges in myelofibrosis and polycythemia vera: the role of ruxolitinib.

Myelofibrosis (MF) and polycythemia vera (PV) are BCR-ABL1-negative myeloproliferative neoplasms associated with somatic hematopoietic stem cell mutations leading to over activation of JAK-STAT signaling. MF and PV are pathogenically related and share specific clinical features such as splenomegaly and constitutional symptoms. The MF phenotype is dominated by the effects of progressive bone marrow fibrosis resulting in shortened survival.

Evaluation of Alcohol-Related Personalized Normative Feedback With and Without an Injunctive Message.

Objective: Personalized normative feedback (PNF) has been used extensively to reduce alcohol consumption, particularly among heavy drinkers. However, the majority of PNF studies have used only descriptive norms (real or perceived pervasiveness of a given behavior). The purpose of the current study was to explore the efficacy of PNF both with and without an injunctive message indicating approval or disapproval based on the participants' standing relative to other students' drinking levels.

Prevention of cervical cancer: journey to develop the first human papillomavirus virus-like particle vaccine and the next generation vaccine.

In 2006, the first human papillomavirus (HPV) virus-like particle (VLP) vaccine was licensed. Gardasil(®), the quadrivalent HPV 6, 11, 16 and 18 recombinant VLP vaccine (4vHPV), developed by Merck demonstrated remarkable efficacy in prevention of important clinical pre-cursors to cervical cancer and genital warts. The vaccine was designed to protect against HPV 16 and 18 that cause ∼70% of cervical cancers and HPV 6 and 11 that cause ∼90% of genital warts.

Institutional Animal Care and Use Committee Considerations for the Use of Wildlife in Research and Education.

Ethical and effective oversight of the use of wildlife species in research and education requires consideration of issues and methods not relevant to work with traditional laboratory or domesticated animals, just as the effective oversight of biomedical research requires consideration of issues and methods not germane to wildlife research. Institutional Animal Care and Use Committees or other institutional review committees can meet their responsibilities in these disparate types of animal activities only by using resources tailored to the animals and situations encountered. Here we review the issues and the resources that facilitate effective oversight of such activities in the wildlife research arena available to researchers, institutional review committees, regulatory bodies, and accrediting bodies.

Introduction to Insights Gained from Wildlife Research in the Context of Global Anthropogenic Change.

The language and subject matter offered in this issue of the ILAR Journal represent a departure from standard discourse on research animal welfare. Although the overall character of such a departure will become evident, the contributions herein reinforce and expand upon the shared, established tenets of research animal welfare. Through the work and experience of contributing wildlife research professionals, this issue of the ILAR Journal offers a diverse consortium of wildlife topics ranging from policy to conservation to disease investigation, all against the backdrop of the complexities of effective compliance and oversight when the research subjects are wild.

Radiotherapy-induced skin reactions: assessment and management.

Patients undergoing radiotherapy often experience a skin reaction to their treatment. In an attempt to assist clinicians in the recognition and care of these radiotherapy-induced skin reactions, an assessment and management tool has been designed for use. This patient-focused assessment tool has been distributed across the counties that the authors' trust serves.

Population Density, Poor Sanitation, and Enteric Infections in Nueva Santa Rosa, Guatemala.

Poor sanitation could pose greater risk for enteric pathogen transmission at higher human population densities because of greater potential for pathogens to infect new hosts through environmentally mediated and person-to-person transmission. We hypothesized that incidence and prevalence of diarrhea, enteric protozoans, and soil-transmitted helminth infections would be higher in high-population-density areas compared with low-population-density areas, and that poor sanitation would pose greater risk for these enteric infections at high density compared with low density. We tested our hypotheses using 6 years of clinic-based diarrhea surveillance (2007-2013) including 4,360 geolocated diarrhea cases tested for 13 pathogens and a 2010 cross-sectional survey that measured environmental exposures from 204 households (920 people) and tested 701 stool specimens for enteric parasites.

Quantitative Detection and Resolution of BRAF V600 Status in Colorectal Cancer Using Droplet Digital PCR and a Novel Wild-Type Negative Assay.

A need exists for robust and cost-effective assays to detect a single or small set of actionable point mutations, or a complete set of clinically informative mutant alleles. Knowledge of these mutations can be used to alert the clinician to a rare mutation that might necessitate more aggressive clinical monitoring or a personalized course of treatment. An example is BRAF, a (proto)oncogene susceptible to either common or rare mutations in codon V600 and adjacent codons.

Intradialytic Hypertension / Hypotension and Mortality in San Juan, Puerto Rico.

End Stage Renal Disease patients undergo profound hemodynamic changes during hemodialysis treatments which are now recognized as a marker for increased risk of morbidity and mortality. Development of intradialytic hypotension or hypertension are a common clinical problem in this population with an incidence of up to 20%. We performed a retrospective review of 49 Hispanic patients receiving ambulatory hemodialysis during a period of 6 months to ascertain the development of aforementioned intradialytic events.