Pharmacokinetics and Tolerability of Intravenous Sildenafil in Two Subjects with Child-Turcotte-Pugh Class C Cirrhosis and Renal Dysfunction.

Phosphodiesterase-5 (PDE-5) inhibitors have been used successfully in patients with cirrhosis to treat porto-pulmonary hypertension. Additionally, in cirrhosis, PDE-5 inhibitors can potentially improve portal hypertension and renal hemodynamics. No pharmacokinetics and tolerability studies of intravenous (IV) sildenafil have been conducted in Child-Turcotte-Pugh (CTP) class C cirrhosis and renal dysfunction.

(18)F-Fluorocholine PET-CT enables minimal invasive parathyroidectomy in patients with negative sestamibi SPECT-CT and ultrasound: A case report.

Introduction: Primary hyperparathyroidism is a common endocrine disorder for which the primary treatment is surgery. For minimal invasive parathyroidectomy adequate pre-operative imaging is essential. Conventional imaging is often inconclusive.

Synthesis and evaluation of thymidine kinase 1-targeting carboranyl pyrimidine nucleoside analogs for boron neutron capture therapy of cancer.

A library of sixteen 2nd generation amino- and amido-substituted carboranyl pyrimidine nucleoside analogs, designed as substrates and inhibitors of thymidine kinase 1 (TK1) for potential use in boron neutron capture therapy (BNCT) of cancer, was synthesized and evaluated in enzyme kinetic-, enzyme inhibition-, metabolomic-, and biodistribution studies. One of these 2nd generation carboranyl pyrimidine nucleoside analogs (YB18A [3]), having an amino group directly attached to a meta-carborane cage tethered via ethylene spacer to the 3-position of thymidine, was approximately 3-4 times superior as a substrate and inhibitor of hTK1 than N5-2OH (2), a 1st generation carboranyl pyrimidine nucleoside analog. Both 2 and 3 appeared to be 5'-monophosphorylated in TK1(+) RG2 cells, both in vitro and in vivo.

Gadolinium nanoparticles and contrast agent as radiation sensitizers.

The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist(®) in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.

Perioperative Bundle Decreases Postoperative Hepatic Surgery Infections.

Background: Postoperative infections are a costly and morbid complication. The introduction of perioperative infection prevention bundles have decreased surgical site infections (SSIs) in patients undergoing colorectal and pancreatic surgery.

Aim: The purpose of this study was to determine if the implementation of a perioperative bundle would reduce postoperative infectious complications in patients undergoing hepatic surgery.

Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murine T-cell responses.

V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a negative immune-checkpoint protein that suppresses T-cell responses. To determine whether VISTA synergizes with another immune-checkpoint, programmed death 1 (PD-1), this study characterizes the immune responses in VISTA-deficient, PD-1-deficient (KO) mice and VISTA/PD-1 double KO mice. Chronic inflammation and spontaneous activation of T cells were observed in both single KO mice, demonstrating their nonredundancy.

Nodal lymph flow quantified with afferent vessel input function allows differentiation between normal and cancer-bearing nodes.

Morbidity and complexity involved in lymph node staging via surgical resection and biopsy could ideally be improved using node assay techniques that are non-invasive. While visible blue dyes are often used to locate the sentinel lymph nodes from draining lymphatic vessels near a tumor, they do not provide an in situ metric to evaluate presence of cancer. In this study, the transport kinetics of methylene blue were analyzed to determine the potential for better in situ information about metastatic involvement in the nodes.

A Pilot Study of Ultrasound-Guided Cryoablation of Invasive Ductal Carcinomas up to 15 mm With MRI Follow-Up and Subsequent Surgical Resection.

Objective: The purpose of this study was to evaluate the effectiveness of ultrasound-guided cryoablation in treating small invasive ductal carcinoma and to assess the role of contrast-enhanced (CE) MRI in determining the outcome of cryoablation.

Subjects And Methods: Twenty consecutive participants with invasive ductal carcinomas up to 15 mm, with limited or no ductal carcinoma in situ (DCIS), underwent ultrasound-guided cryoablation. Preablation mammography, ultrasound, and CE-MRI were performed to assess eligibility.

Molecular dyes used for surgical specimen margin orientation allow for intraoperative optical assessment during breast conserving surgery.

A variety of optical techniques utilizing near-infrared (NIR) light are being proposed for intraoperative breast tumor margin assessment. However, immediately following a lumpectomy excision, the margins are inked, which preserves the orientation of the specimen but prevents optical interrogation of the tissue margins. Here, a workflow is proposed that allows for both NIR optical assessment following full specimen marking using molecular dyes which have negligible absorption and scattering in the NIR.

Radiologist compliance with California CT dose reporting requirements: a single-center review of pediatric chest CT.

Objective: Effective July 1, 2012, CT dose reporting became mandatory in California. We sought to assess radiologist compliance with this legislation and to determine areas for improvement.

Materials And Methods: We retrospectively reviewed reports from all chest CT examinations performed at our institution from July 1, 2012, through June 30, 2013, for errors in documentation of volume CT dose index (CTDIvol), dose-length product (DLP), and phantom size.

Completely stereocontrolled aldol reaction of chiral β-amino acids.

A general protocol to independently access stereoisomerically pure β'-hydroxy-β-amino acid derivatives that is based on dibutylboron triflate-mediated aldol reaction of suitably protected β-amino acids bearing chiral oxazolidinone auxiliary is reported. The method smoothly afforded syn-aldol (α,β'-syn) products in pure form and excellent isolated yield. Both α,β-syn and α,β-anti isomers are readily accessible solely through the choice of the oxazolidinone chirality.

Diminished impact of ethnicity as a risk factor for chronic kidney disease in the current HIV treatment era.

Background: Chronic kidney disease (CKD) is an important comorbidity during human immunodeficiency virus (HIV) infection. Historically, HIV-associated nephropathy has been the predominant cause of CKD and has primarily been observed in people of African ancestry. This study aims to investigate the role of ethnicity in relation to CKD risk in recent years.

The PI3K/mTOR dual inhibitor P7170 demonstrates potent activity against endocrine-sensitive and endocrine-resistant ER+ breast cancer.

Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway has been implicated in anti-estrogen resistance in breast cancer. We tested the therapeutic potential of the novel PI3K/mTOR dual inhibitor P7170 in a panel of anti-estrogen-sensitive and anti-estrogen-resistant models of ER+ breast cancer. Estrogen receptor-positive (ER+) breast cancer cells were treated ±P7170.

Benign phyllodes tumor of the breast recurring as a malignant phyllodes tumor and spindle cell metaplastic carcinoma.

We report a unique case of a 59-year-old woman diagnosed with a benign phyllodes tumor (PT), which recurred twice in the same location over a 7-year period: first as a malignant PT and then as a malignant PT with coexisting spindle cell metaplastic breast carcinoma (MBC). The MBC was differentiated from the malignant PT by expression of cytokeratins (CKs) AE1/AE3, CK MNF-116, CK 5/6, and p63. Somatic mutation analysis using a next-generation sequencing platform revealed a shared mutation in F-box and WD repeat domain containing 7, a tumor suppressor gene that encodes a ubiquitin ligase-associated protein, in the original benign PT and the first recurrent malignant PT.

Microscopic lymph node tumor burden quantified by macroscopic dual-tracer molecular imaging.

Lymph node biopsy is employed in many cancer surgeries to identify metastatic disease and to determine cancer stage, yet morbidity and diagnostic delays associated with lymph node biopsy could be avoided if noninvasive imaging of nodal involvement were reliable. Molecular imaging has potential in this regard; however, variable delivery and nonspecific uptake of imaging tracers have made conventional approaches ineffective clinically. Here we present a method of correcting for nonspecific uptake with injection of a second untargeted tracer that allows for quantification of tumor burden in lymph nodes.

Shorter waitlist times and improved graft survivals are observed in patients who accept hepatitis C virus+ renal allografts.

Background: There is a paucity of data regarding long-term renal graft survival in hepatitis C virus positive (HCV+) patients. We analyzed our institution's experience with HCV+ renal transplantation and factors contributing to subsequent renal graft failure.

Methods: We analyzed 1,679 adult, deceased donor, single-organ renal transplants occurring between 2000 and 2012.

Inhibiting CARD11 translation during BCR activation by targeting the eIF4A RNA helicase.

Human diffuse large B-cell lymphomas (DLBCLs) often aberrantly express oncogenes that generally contain complex secondary structures in their 5' untranslated region (UTR). Oncogenes with complex 5'UTRs require enhanced eIF4A RNA helicase activity for translation. PDCD4 inhibits eIF4A, and PDCD4 knockout mice have a high penetrance for B-cell lymphomas.

Preventing rapid repeat pregnancy and promoting positive parenting among young mothers in foster care.

Young mothers in foster care face considerable challenges above and beyond that of their non-foster care peers. Child welfare workers have few resources to guide them in the selection of evidence-informed programs, models, and strategies that address the unique risk factors and needs of youth in foster care who are at risk for rapid repeat pregnancy and inadequate parenting practices. Workers need knowledge of the evidence about which programs are most likely to improve key health and well-being outcomes.

Tumoricidal activity of low-energy 160-KV versus 6-MV X-rays against platinum-sensitized F98 glioma cells.

The purposes of this study were (i) to investigate the differences in effects between 160-kV low-energy and 6-MV high-energy X-rays, both by computational analysis and in vitro studies; (ii) to determine the effects of each on platinum-sensitized F98 rat glioma and murine B16 melanoma cells; and (iii) to describe the in vitro cytotoxicity and in vivo toxicity of a Pt(II) terpyridine platinum (Typ-Pt) complex. Simulations were performed using the Monte Carlo code Geant4 to determine enhancement in absorption of low- versus high-energy X-rays by Pt and to determine dose enhancement factors (DEFs) for a Pt-sensitized tumor phantom. In vitro studies were carried out using Typ-Pt and again with carboplatin due to the unexpected in vivo toxicity of Typ-Pt.

Pseudohypernatremia and pseudohyponatremia: a linear correction.

Background: Serum sodium is commonly measured by direct potentiometry (DNa), in blood gas panels, or indirect potentiometry (INa), in metabolic panels run on chemistry analyzers. Abnormal values of the serum non-water fraction interfere with INa, with low values causing pseudohypernatremia (INa > DNa) and high values causing pseudohyponatremia (INa < DNa). Previous attempts to derive a linear correction for the difference between INa and DNa (ΔNa) arising from non-water bias--using serum total protein (TP) or albumin (ALB) to represent the non-water fraction--have yielded inconsistent results, possibly owing to differences in sample inclusion criteria, analytic platforms and statistical approach.

Real-time electrical impedance variations in women with and without breast cancer.

The chaotic vascular network surrounding malignant tumors leads to pulsatile blood flow patterns that differ from those in benign regions of the breast. This study aimed to determine if high-speed electrical impedance tomography (EIT) is able to detect conductivity changes associated with cyclic blood-volume changes and to gauge the potential of using these signatures to differentiate malignant from benign regions within the breast. EIT imaging of pulsating latex membranes submerged in saline baths provided initial validation of its use for tracking temporally varying conductivities.