A Sensitive Peptide Nucleic Acid Probe Assay for Detection of BRAF V600 Mutations in Melanoma.

Mutated v-Raf murine sarcoma viral oncogene homolog B (BRAF) is an important biomarker for the prediction of therapeutic efficacy of several anticancer drugs. The detection of BRAF mutation faces two challenges: Firstly, there are multiple types of mutations, and secondly, tumor samples usually contain various amounts of wild-type, normal tissues. Here, we describe a newly established method for sensitive detection of multiple types of BRAF V600 mutations in excess wild-type background.

Visual Performance after Bilateral Implantation of a Four-Haptic Diffractive Toric Multifocal Intraocular Lens in High Myopes.

Background. The vision with diffractive toric multifocal intraocular lenses after cataract surgery in long eyes has not been studied previously. Objectives.

Schedules for Pneumococcal Vaccination of Preterm Infants: An RCT.

Background And Objective: Premature infants have a higher risk of invasive pneumococcal disease and are more likely to have lower vaccine responses compared with term infants. Increasingly, immunization schedules are including a reduced, 2-dose, pneumococcal conjugate vaccine priming schedule. Our goal was to assess the immunogenicity of 3 commonly used 13-valent pneumococcal conjugate vaccine (PCV13) priming schedules in premature infants and their response to a 12-month booster dose.

A comparison of immunohistochemical and molecular methods used for analyzing the BRAF V600E gene mutation in malignant melanoma in Taiwan.

Aims: The BRAF V600 mutation has been shown to be clinically meaningful in terms of both the prognosis and sensitivity of BRAF inhibitors in patients with metastatic melanoma. Recently, a BRAF V600E mutation-specific antibody, VE1, was generated for the detection of tumors bearing BRAF V600E mutations. To determine the clinical value of immunohistochemical testing, we compared the prevalence of mutant BRAF detected by VE1 with direct sequencing results.

Rationale and design of the randomized evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) Study.

Background: Despite the availability of effective therapies, most gout patients achieve suboptimal treatment outcomes. Current best practices suggest gradual dose-escalation of urate lowering therapy and serial serum urate (sUA) measurement to achieve sUA<6.0mg/dl.

The TRPA1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1.

Objective: Transient receptor potential ankyrin-1 (TRPA1) and transient receptor potential vanilloid-1 (TRPV1) are calcium (Ca)-permeable ion channels mostly known as pain receptors in sensory neurons. However, growing evidence suggests their crucial involvement in the pathogenesis of IBD. We explored the possible contribution of TRPA1 and TRPV1 to T-cell-mediated colitis.

Diagnostic accuracy of methicillin-resistant Staphylococcus aureus nasal colonization to predict methicillin-resistant S aureus soft tissue infections.

Nasal methicillin-resistant Staphylococcus aureus (MRSA) testing at admission to the hospital was found to have a positive likelihood ratio of 8.5 and a negative likelihood ratio of 0.41 for predicting MRSA soft tissue infections.

The Real-World Effectiveness and Safety of Vedolizumab for Moderate-Severe Crohn's Disease: Results From the US VICTORY Consortium.

Objectives: We assessed the real-world effectiveness and safety of vedolizumab (VDZ) in moderate-severe Crohn's disease (CD).

Methods: Retrospective cohort study of seven medical centers, from May 2014 to December 2015. Adults with moderate-severe CD treated with VDZ, with follow-up after initiation of therapy, were included.

TLG-S criteria are superior to both EORTC and PERCIST for predicting outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib.

Purpose: In this retrospective review of prospectively collected data, we sought to investigate whether early FDG-PET assessment of treatment response based on total lesion glycolysis measured using a systemic approach (TLG-S) would be superior to either local assessment with EORTC (European Organization for Research and Treatment of Cancer) criteria or single-lesion assessment with PERCIST (PET Response Criteria in Solid Tumors) for predicting clinical outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. We also examined the effect of bone flares on tumor response evaluation by single-lesion assessment with PERCIST in patients with metastatic bone lesions.

Methods: We performed a retrospective review of prospectively collected data from 23 patients with metastatic lung adenocarcinoma treated with erlotinib.

Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism.

To sustain their proliferation, cancer cells overcome negative-acting signals that restrain their growth and promote senescence and cell death. Renalase (RNLS) is a secreted flavoprotein that functions as a survival factor after ischemic and toxic injury, signaling through the plasma calcium channel PMCA4b to activate the PI3K/AKT and MAPK pathways. We show that RNLS expression is increased markedly in primary melanomas and CD163(+) tumor-associated macrophages (TAM).

Feasibility of Proton Beam Therapy for Ocular Melanoma Using a Novel 3D Treatment Planning Technique.

Purpose: We evaluated sparing of normal structures using 3-dimensional (3D) treatment planning for proton therapy of ocular melanomas.

Methods And Materials: We evaluated 26 consecutive patients with choroidal melanomas on a prospective registry. Ophthalmologic work-up included fundoscopic photographs, fluorescein angiography, ultrasonographic evaluation of tumor dimensions, and magnetic resonance imaging of orbits.

Comparison of refractive and visual outcomes with centration points 80% and 100% from pupil center toward the coaxially sighted corneal light reflex.

Purpose: To compare the refractive and visual outcomes between 2 ablation centration points, 80% and 100% from the pupil center toward the coaxially sighted corneal light reflex.

Setting: Hong Kong Sanatorium and Hospital, Hong Kong, China.

Design: Retrospective comparative study.

The Microtubule-Associated Protein Lis1 Regulates T Lymphocyte Homeostasis and Differentiation.

The microtubule-associated protein lissencephaly 1 (Lis1) is a key regulator of cell division during stem cell renewal and differentiation. In this study, we examined the role of Lis1 in T lymphocyte homeostasis and fate diversification in response to microbial infection. T cell-specific deletion of Lis1 resulted in depletion of the peripheral CD4(+) and CD8(+) T lymphocyte pool owing to a loss of homeostatic, cytokine-induced proliferation.

Visual Functioning and Health-related Quality-of-Life are Compromised in Patients with Uveitis.

Purpose: To assess the vision-related (VR) and health-related (HR) quality-of-life (QoL) of patients with uveitis.

Methods: In total, 60 patients with uveitis, 81 patients with diabetic retinopathy (DR), and 70 healthy subjects completed the National Eye Institute Visual Functioning Questionnaire and the Medical Outcome Study 36-Item Short Form.

Results: Patients with uveitis reported lower HR- and VR-QoL than healthy subjects (p<0.

A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients.

Aims: This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus.

Methods: Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin.

The Association of Ursodeoxycholic Acid Use With Colorectal Cancer Risk: A Nationwide Cohort Study.

Data from preclinical studies suggest that ursodeoxycholic acid (UDCA) has a chemopreventive effect on colorectal cancer (CRC) development, but no large observational study has examined this possibility. The aim of this study was to investigate the association of UDCA use with CRC risk in a nationwide population-based cohort. This nationwide population-based cohort study used data from the Taiwan National Health Insurance Research Database for the period from 2000 through 2010.

Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer.

An essential feature of cancer is dysregulation of cell senescence and death. Renalase, a recently discovered secreted flavoprotein, provides cytoprotection against ischemic and toxic cellular injury by signaling through the PI3K-AKT and MAPK pathways. Here we show that renalase expression is increased in pancreatic cancer tissue and that it functions as a growth factor.

Clinical characteristics and outcomes of veterans hospitalised with purulent soft tissue infections with and without systemic signs of infection.

Objective To describe the frequency of systemic inflammatory response syndrome (SIRS) criteria in a cohort of patients hospitalised with purulent soft tissue infections and to determine their impact on clinical characteristics, microbiology and outcomes. Methods Retrospective cohort study of adults hospitalised at the West Haven Veteran's Hospital with purulent soft tissue infections between 1 October 2008 and 30 September 2013. Results A total of 173 patients were included with purulent soft tissue infections; 60 patients had no SIRS, 48 had one SIRS and 65 had ≥ 2 SIRS.

Downregulation of 26S proteasome catalytic activity promotes epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) endows carcinoma cells with phenotypic plasticity that can facilitate the formation of cancer stem cells (CSCs) and contribute to the metastatic cascade. While there is substantial support for the role of EMT in driving cancer cell dissemination, less is known about the intracellular molecular mechanisms that govern formation of CSCs via EMT. Here we show that β2 and β5 proteasome subunit activity is downregulated during EMT in immortalized human mammary epithelial cells.

Promoter polymorphism at the tumour necrosis factor/lymphotoxin-alpha locus is associated with type of diabetes but not with susceptibility to sight-threatening diabetic retinopathy.

Aim: To investigate, in a large cohort of 2494 individuals with diabetes mellitus, whether functional single nucleotide polymorphisms in the promoter region of tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA) genes are associated with type of diabetes or presence of diabetic retinopathy.

Methods: A total of 334 type 1 diabetes and 999 type 2 diabetes participants with sight-threatening diabetic retinopathy, and 260 type 1 diabetes and 901 type 2 diabetes participants with no diabetic retinopathy or minimal non-proliferative diabetic retinopathy, were genotyped for two single nucleotide polymorphisms (rs1800629 and rs361525).

Results: The A allele of rs1800629 was associated with type 1 diabetes (p < 0.

Regulation of Asymmetric Division by Atypical Protein Kinase C Influences Early Specification of CD8(+) T Lymphocyte Fates.

Naïve CD8(+) T lymphocytes responding to microbial pathogens give rise to effector T cells that provide acute defense and memory T cells that provide long-lived immunity. Upon activation, CD8(+) T lymphocytes can undergo asymmetric division, unequally distributing factors to the nascent daughter cells that influence their eventual fate towards the effector or memory lineages. Individual loss of either atypical protein kinase C (aPKC) isoform, PKCζ or PKCλ/ι, partially impairs asymmetric divisions and increases CD8(+) T lymphocyte differentiation toward a long-lived effector fate at the expense of memory T cell formation.

Preoperative Pelvic Floor Muscle Exercise and Postprostatectomy Incontinence: A Systematic Review and Meta-analysis.

Context: Preoperative pelvic floor muscle exercise (PFME) is often prescribed to reduce the severity of postprostatectomy incontinence.

Objective: Systematic review and meta-analysis of evidence regarding the effect of preoperative PFME on postoperative urinary incontinence following radical prostatectomy.

Evidence Acquisition: A systematic search was performed of the Cochrane Library, Medline, Embase, and all potential articles from references in relevant articles on 4 October 2014.