Inhibitors of ORAI1 Prevent Cytosolic Calcium-Associated Injury of Human Pancreatic Acinar Cells and Acute Pancreatitis in 3 Mouse Models.

Background & Aims: Sustained activation of the cytosolic calcium concentration induces injury to pancreatic acinar cells and necrosis. The calcium release-activated calcium modulator ORAI1 is the most abundant Ca(2+) entry channel in pancreatic acinar cells; it sustains calcium overload in mice exposed to toxins that induce pancreatitis. We investigated the roles of ORAI1 in pancreatic acinar cell injury and the development of acute pancreatitis in mice.

Lung nodule detection by microdose CT versus chest radiography (standard and dual-energy subtracted).

Objective: The purpose of this study was to investigate the feasibility of microdose CT using a comparable dose as for conventional chest radiographs in two planes including dual-energy subtraction for lung nodule assessment.

Materials And Methods: We investigated 65 chest phantoms with 141 lung nodules, using an anthropomorphic chest phantom with artificial lung nodules. Microdose CT parameters were 80 kV and 6 mAs, with pitch of 2.

Development of the first urinary reproductive hormone ranges referenced to independently determined ovulation day.

Background: Urinary hormone level analysis provides valuable fertility status information; however, previous studies have not referenced levels to the ovulation day, or have used outdated methods. This study aimed to produce reproductive hormone ranges referenced to ovulation day determined by ultrasound.

Methods: Women aged 18-40 years (no reported infertility) collected daily urine samples for one complete menstrual cycle.

Multiple vascular and enteric fistulas into an anal pouch.

We present a case of an 87-year-old female who presented 3 months following an emergency Hartmann's procedure for perforated diverticulum with per rectum bleed. She was found to have a false aneurysm in the iliac artery communicating with her rectal stump. This was treated successfully with intravascular coiling; however, she re-presented 2 years later complaining of passing stool per rectum and decreased colostomy output.

Susceptibility to Verticillium longisporum is linked to monoterpene production by TPS23/27 in Arabidopsis.

The fungus Verticillium longisporum is a soil-borne plant pathogen of increasing economic importance, and information on plant responses to it is limited. To identify the genes and components involved in the early stages of infection, transcripts in roots of V. longisporum-challenged Arabidopsis Col-0 and the susceptible NON-RACE SPECIFIC DISEASE RESISTANCE 1 (ndr1-1) mutant were compared using ATH1 gene chips.

STAT activation status differentiates leukemogenic from non-leukemogenic stem cells in AML and is suppressed by arsenic in t(6;9)-positive AML.

Acute myeloid leukemia (AML) is characterized by an aberrant self-renewal of hematopoietic stem cells (HSC) and a block in differentiation. The major therapeutic challenge is the characterization of the leukemic stem cell as a target for the eradication of the disease. Until now the biology of AML-associated fusion proteins (AAFPs), such as the t(15;17)-PML/RARα, t(8;21)-RUNX1/RUNX1T1 and t(6;9)-DEK/NUP214, all able to induce AML in mice, was investigated in different models and genetic backgrounds, not directly comparable to each other.

Effects of model-based iterative reconstruction on image quality for low-dose computed tomographic angiography of the thoracic aorta in a Swine model.

Purpose: The aim of the study was to assess the image quality of multi-detector-row computed tomography (CT) angiographic images of the thoracic aorta reconstructed with filtered back projection (FBP), adaptive statistical iterative reconstruction, and model-based iterative reconstruction (MBIR) at different kVp and mA settings.

Methods: A healthy 56.1-kg Yorkshire pig underwent sequential arterial CT angiograms on a 64-slice multi-detector-row CT scanner (Discovery CT 750HD; GE Healthcare Inc, Milwaukee, Wis) at progressively lower kVp and mA settings.

Phenotypic features of patients with schizophrenia carrying de novo gene mutations: a pilot study.

Genome-wide scans have revealed a significant role for de novo copy number variants (CNVs) and Single Nucleotide variants (SNVs) in the genetic architecture of schizophrenia. The present study attempts to parse schizophrenia based on the presence of such de novo mutations and attempts genotype-phenotype correlation. We examined phenotypic variables across three broad categories: clinical presentation, premorbid function, disease course and functional outcome and compared them in individuals with schizophrenia carrying either a de novo CNV, a de novo SNV, or no de novo mutation.

Orphan drugs: expensive yet necessary.

Whether the prices of certain orphan treatments are justified is highly controversial. One argument is that such therapies should not be funded through the public purse or private health plans because a patient with a rare disease requires more than their 'fair share' of a limited health care budget. Orphan medications can also be denied because they fare poorly in the cost-effectiveness assessments of drugs.

Characterizing search, recognition, and decision in the detection of lung nodules on CT scans: elucidation with eye tracking.

Purpose: To determine the effectiveness of radiologists' search, recognition, and acceptance of lung nodules on computed tomographic (CT) images by using eye tracking.

Materials And Methods: This study was performed with a protocol approved by the institutional review board. All study subjects provided informed consent, and all private health information was protected in accordance with HIPAA.

Tin doping speeds up hole transfer during light-driven water oxidation at hematite photoanodes.

Numerous studies have shown that the performance of hematite photoanodes for light-driven water splitting is improved substantially by doping with various metals, including tin. Although the enhanced performance has commonly been attributed to bulk effects such as increased conductivity, recent studies have noted an impact of doping on the efficiency of the interfacial transfer of holes involved in the oxygen evolution reaction. However, the methods used were not able to elucidate the origin of this improved efficiency, which could originate from passivation of surface electron-hole recombination or catalysis of the oxygen evolution reaction.

Impact of sperm cell source on the results of intracytoplasmic sperm injection.

Purpose: There is an ongoing debate whether the source of sperm cells, the etiology or the extent of male factor infertility has influence on the outcome of ICSI cycles.

Methods: The results of intracytoplasmic sperm injection (ICSI) according to the source of spermatozoa in patients with severe male factor infertility were compared in a retrospective study: 249 couples underwent a total of 337 fresh ICSI cycles with the use of fresh motile testicular or fresh motile ejaculated spermatozoa.

Results: For all variables, there were no statistically significant differences in the ICSI results between both groups.

Communication satisfaction of professional nurses working in public hospitals.

Aim: This study aimed to establish and describe the level of communication satisfaction that professional nurses experience in selected public hospitals in the City of Johannesburg, South Africa.

Background: The success of any organisation depends on the effectiveness of its communication systems and the interaction between staff members.

Method: Data were collected by means of questionnaires, based on the Communication Satisfaction Questionnaire (CSQ), from a sample of 265 professional nurses from different categories, chosen using a disproportionate random stratified sampling method.

Suction against resistance: a new breathing technique to significantly improve the blood flow ratio of the superior and inferior vena cava.

Objectives: Optimal contrast within the pulmonary artery is achieved by the maximum amount of contrast-enhanced blood flowing through the superior vena cava (SVC), while minimum amounts of non-contrasted blood should originate from the inferior vena cava (IVC). This study aims to clarify whether "suction against resistance" might optimise this ratio.

Methods: Phase-contrast pulse sequences on a 1.

5-Lipoxygenase is a candidate target for therapeutic management of stem cell-like cells in acute myeloid leukemia.

Nonsteroidal anti-inflammatory drugs such as sulindac inhibit Wnt signaling, which is critical to maintain cancer stem cell-like cells (CSC), but they also suppress the activity of 5-lipoxygenase (5-LO) at clinically feasible concentrations. Recently, 5-LO was shown to be critical to maintain CSC in a model of chronic myeloid leukemia. For these reasons, we hypothesized that 5-LO may offer a therapeutic target to improve the management of acute myeloid leukemia (AML), an aggressive disease driven by CSCs.

Measuring diffusion limitation with a perfusion-limited gas--hyperpolarized 129Xe gas-transfer spectroscopy in patients with idiopathic pulmonary fibrosis.

Although xenon is classically taught to be a "perfusion-limited" gas, (129)Xe in its hyperpolarized (HP) form, when detected by magnetic resonance (MR), can probe diffusion limitation. Inhaled HP (129)Xe diffuses across the pulmonary blood-gas barrier, and, depending on its tissue environment, shifts its resonant frequency relative to the gas-phase reference (0 ppm) by 198 ppm in tissue/plasma barrier and 217 ppm in red blood cells (RBCs). In this work, we hypothesized that in patients with idiopathic pulmonary fibrosis (IPF), the ratio of (129)Xe spectroscopic signal in the RBCs vs.

Loss-of-function variants in schizophrenia risk and SETD1A as a candidate susceptibility gene.

Loss-of-function (LOF) (i.e., nonsense, splice site, and frameshift) variants that lead to disruption of gene function are likely to contribute to the etiology of neuropsychiatric disorders.

Prolonged mydriasis after inadvertent topical administration of the calcium channel antagonist amlodipine: implications for glaucoma drug development.

Context: Calcium channel inhibitors are being investigated as potential therapeutic adjuncts to reduce painful ciliary muscle spasm and control intraocular pressure in glaucoma. Relatively little is known about the effect of topical administration of calcium channel blockers in humans.

Objective: (1) To describe prolonged fixed pupil dilation resulting from exposure to topical amlodipine (2) to review the evidence that links calcium channel blockers with mydriasis and (3) to discuss the implications for glaucoma pharmacotherapy.

Comparison of the cancer gene targeting and biochemical selectivities of all targeted kinase inhibitors approved for clinical use.

The anti-proliferative activities of all twenty-five targeted kinase inhibitor drugs that are in clinical use were measured in two large assay panels: (1) a panel of proliferation assays of forty-four human cancer cell lines from diverse tumour tissue origins; and (2) a panel of more than 300 kinase enzyme activity assays. This study provides a head-on comparison of all kinase inhibitor drugs in use (status Nov. 2013), and for six of these drugs, the first kinome profiling data in the public domain.

RabGAP22 is required for defense to the vascular pathogen Verticillium longisporum and contributes to stomata immunity.

Verticillium longisporum is a soil-borne pathogen with a preference for plants within the family Brassicaceae. Following invasion of the roots, the fungus proliferates in the plant vascular system leading to stunted plant growth, chlorosis and premature senescence. RabGTPases have been demonstrated to play a crucial role in regulating multiple responses in plants.

Limits on use of health economic assessments for rare diseases.

Funding of expensive treatments for rare (orphan) diseases is contentious. These agents fare poorly on 'efficiency' or health economic measures, such as the quality-adjusted life years, because of high cost and frequently poor gains in quality of life and survival. We show that cost-effectiveness assessments are flawed, and have only a limited role to play in reimbursement decisions for orphan drugs and beyond.

Optimal dose levels in screening chest CT for unimpaired detection and volumetry of lung nodules, with and without computer assisted detection at minimal patient radiation.

Objectives: The aim of this phantom study was to minimize the radiation dose by finding the best combination of low tube current and low voltage that would result in accurate volume measurements when compared to standard CT imaging without significantly decreasing the sensitivity of detecting lung nodules both with and without the assistance of CAD.

Methods: An anthropomorphic chest phantom containing artificial solid and ground glass nodules (GGNs, 5-12 mm) was examined with a 64-row multi-detector CT scanner with three tube currents of 100, 50 and 25 mAs in combination with three tube voltages of 120, 100 and 80 kVp. This resulted in eight different protocols that were then compared to standard CT sensitivity (100 mAs/120 kVp).

Scan statistic-based analysis of exome sequencing data identifies FAN1 at 15q13.3 as a susceptibility gene for schizophrenia and autism.

We used a family-based cluster detection approach designed to localize significant rare disease-risk variants clusters within a region of interest to systematically search for schizophrenia (SCZ) susceptibility genes within 49 genomic loci previously implicated by de novo copy number variants. Using two independent whole-exome sequencing family datasets and a follow-up autism spectrum disorder (ASD) case/control whole-exome sequencing dataset, we identified variants in one gene, Fanconi-associated nuclease 1 (FAN1), as being associated with both SCZ and ASD. FAN1 is located in a region on chromosome 15q13.

Bone mineral density at diagnosis determines fracture rate in children with acute lymphoblastic leukemia treated according to the DCOG-ALL9 protocol.

Purpose: To elucidate incidence and risk factors of bone mineral density and fracture risk in children with Acute Lymphoblastic Leukemia (ALL).

Methods: Prospectively, cumulative fracture incidence, calculated from diagnosis until one year after cessation of treatment, was assessed in 672 patients. This fracture incidence was compared between subgroups of treatment stratification and age subgroups (Log-Rank test).