Endovaginal ultrasound-assisted pain mapping in endometriosis and chronic pelvic pain.

The objective of this study was to determine if the combination of tenderness-guided endovaginal ultrasound and digital pelvic exam (i.e. EVUS-assisted exam) for preoperative pain mapping, in cases without nodules or endometriomas, increases sensitivity/specificity for laparoscopic findings.

Vibration-assisted crystallization improves organic/dielectric interface in organic thin-film transistors.

Solution processability of organic semiconductors allows high-throughput fabrication on arbitrary substrates at low-cost, but the films often exhibit low performance. Here, we report on a new method for device fabrication, vibration assisted crystallization (VAC) that produces superior films, which approach the fundamental performance limits shown in corresponding single-crystal measurements.

Identification of stage-specific breast markers using quantitative proteomics.

Matched healthy and diseased tissues from breast cancer patients were analyzed by quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive ductal carcinoma (four patients), we identified protein alterations that correlated with breast cancer progression. Three 8-plex iTRAQ experiments generated an average of 826 protein identifications, of which 402 were common.

Targeted interventions for patellofemoral pain syndrome (TIPPS): classification of clinical subgroups.

Introduction: Patellofemoral pain (PFP) can cause significant pain leading to limitations in societal participation and physical activity. An international expert group has highlighted the need for a classification system to allow targeted intervention for patients with PFP; we have developed a work programme systematically investigating this. We have proposed six potential subgroups: hip abductor weakness, quadriceps weakness, patellar hypermobility, patellar hypomobility, pronated foot posture and lower limb biarticular muscle tightness.

Correlations between night eating, sleep quality, and excessive daytime sleepiness in a severely obese UK population.

Objective: The relationships between night eating, poor sleep quality, and obesity-related comorbidity in a severely obese UK clinic population is unknown. We used validated tools to identify prevalence and to explore this relationship.

Methods: Consecutive consenting clinic attendees completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Score (ESS), and Night Eating Questionnaire (NEQ) to identify sleep quality, excessive daytime sleepiness (EDS) (a surrogate marker for suspected obstructive sleep apnea [OSA]), and night eating, respectively.

Training emergency services' dispatchers to recognise stroke: an interrupted time-series analysis.

Background: Stroke is a time-dependent medical emergency in which early presentation to specialist care reduces death and dependency. Up to 70% of all stroke patients obtain first medical contact from the Emergency Medical Services (EMS). Identifying 'true stroke' from an EMS call is challenging, with over 50% of strokes being misclassified.

Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies.

Human epidermal growth factor receptor 2 (HER2; ERBB2) amplification and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations often co-occur in breast cancer. Aberrant activation of the phosphatidylinositol 3-kinase (PI3K) pathway has been shown to correlate with a diminished response to HER2-directed therapies. We generated a mouse model of HER2-overexpressing (HER2(+)), PIK3CA(H1047R)-mutant breast cancer.

An antibody that locks HER3 in the inactive conformation inhibits tumor growth driven by HER2 or neuregulin.

HER2/HER3 dimerization resulting from overexpression of HER2 or neuregulin (NRG1) in cancer leads to HER3-mediated oncogenic activation of phosphoinositide 3-kinase (PI3K) signaling. Although ligand-blocking HER3 antibodies inhibit NRG1-driven tumor growth, they are ineffective against HER2-driven tumor growth because HER2 activates HER3 in a ligand-independent manner. In this study, we describe a novel HER3 monoclonal antibody (LJM716) that can neutralize multiple modes of HER3 activation, making it a superior candidate for clinical translation as a therapeutic candidate.

Combination of antibody that inhibits ligand-independent HER3 dimerization and a p110α inhibitor potently blocks PI3K signaling and growth of HER2+ breast cancers.

We examined the effects of LJM716, an HER3 (ERBB3) neutralizing antibody that inhibits ligand-induced and ligand-independent HER3 dimerization, as a single agent and in combination with BYL719, an ATP competitive p110α-specific inhibitor, against HER2-overexpressing breast and gastric cancers. Treatment with LJM716 reduced HER2-HER3 and HER3-p85 dimers, P-HER3 and P-AKT, both in vitro and in vivo. Treatment with LJM716 alone markedly reduced growth of BT474 xenografts.

An audit to determine if vitamin b12 supplementation is necessary after sleeve gastrectomy.

Abstract: Sleeve gastrectomy has increased in popularity over the last five years and it is likely to supersede gastric banding. Nevertheless, it is unclear whether vitamin B12 supplementation is required after surgery. The aim of this short report is to identify any vitamin B12 deficiency and highlight the necessity of post laparoscopic sleeve gastrectomy vitamin B12 monitoring.

Retinoic acid expression associates with enhanced IL-22 production by γδ T cells and innate lymphoid cells and attenuation of intestinal inflammation.

Retinoic acid (RA), a vitamin A metabolite, modulates mucosal T helper cell responses. Here we examined the role of RA in regulating IL-22 production by γδ T cells and innate lymphoid cells in intestinal inflammation. RA significantly enhanced IL-22 production by γδ T cells stimulated in vitro with IL-1β or IL-18 and IL-23.

History of power sources in endoscopic surgery.

The history of energy sources used in surgery is inextricably linked to the history of electricity. Milestones include identification of safe electrical waveforms that can be used in the human body, patient isolation to prevent alternate-site burns, bipolar energy sources to negate capacitance injuries, laser energy, and the combination vessel sealing devices commonly used today. Engineering efforts to eliminate many of the hazards of electrosurgery are critical to how we practice modern gynecologic surgery.

Relative contribution of Th1 and Th17 cells in adaptive immunity to Bordetella pertussis: towards the rational design of an improved acellular pertussis vaccine.

Whooping cough caused by Bordetella pertussis is a re-emerging infectious disease despite the introduction of safer acellular pertussis vaccines (Pa). One explanation for this is that Pa are less protective than the more reactogenic whole cell pertussis vaccines (Pw) that they replaced. Although Pa induce potent antibody responses, and protection has been found to be associated with high concentrations of circulating IgG against vaccine antigens, it has not been firmly established that host protection induced with this vaccine is mediated solely by humoral immunity.

Development of a multi-biomarker disease activity test for rheumatoid arthritis.

Background: Disease activity measurement is a key component of rheumatoid arthritis (RA) management. Biomarkers that capture the complex and heterogeneous biology of RA have the potential to complement clinical disease activity assessment.

Objectives: To develop a multi-biomarker disease activity (MBDA) test for rheumatoid arthritis.

The effects of experience on the inter-reliability of osteopaths to detect changes in posterior superior iliac spine levels using a hidden heel wedge.

Background: The use of palpation to diagnose musculoskeletal dysfunction is commonly taught within osteopathy and other manual therapies. However the clinical tests used to detect sacroiliac joint dysfunction have not shown good reliability.

Objectives: To investigate the inter-examiner reliability of osteopaths to detect asymmetries of the posterior superior iliac spine (PSIS), and to determine if inter-examiner reliability was affected by the level of practitioner experience.

The evolution of minimally invasive bariatric surgery.

Background: Obesity is a pandemic associated with significant morbidity and mortality. This historical article charts the progress of successful strategies that have been used to tackle weight loss from dietary modifications to the development of surgical interventions that have subsequently evolved. It also provides a précis of the reported outcome data following minimally invasive bariatric procedures.

Understanding the Density Functional Dependence of DFT-Calculated Electronic Couplings in Organic Semiconductors.

We present an analysis of the magnitude of density functional theory (DFT)-calculated intermolecular electronic couplings (transfer integrals) in organic semiconductors to give insight into the impact that the choice of functional has on the value of this parameter, which is particularly important in the context of charge transport. The major factor determining the magnitude of the calculated transfer integrals is the amount of nonlocal Hartree-Fock (HF) exchange within a given functional, with the transfer integrals increasing by up to a factor of 2 when going from 0 to 100% HF exchange for a series of conventional functionals. We underline that these variations in the transfer integrals are in fact to be expected, with the computed transfer integrals evolving linearly with the amount of HF exchange.

Night eating syndrome: implications for severe obesity.

Night eating syndrome (NES) was first identified in 1955 by Stunkard, a psychiatrist specialising in eating disorders (ED). Over the last 20 years considerable progress has been made in defining NES as a significant clinical entity in its own right and it has now been accepted for inclusion in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) due for publication in 2013. NES is considered a dysfunction of circadian rhythm with a disassociation between eating and sleeping.

UK Breastfeeding Helpline support: An investigation of influences upon satisfaction.

Background: Helpline services have become an increasingly popular mode of providing community access to information and expert information and advice in the health and welfare sector. This paper reports on data collected from 908 callers to UK-based breastfeeding helplines.

Methods: A mixed methods design was adopted utilising a structured interview schedule to elicit callers experiences of the help and support received.

Dual blockade of HER2 in HER2-overexpressing tumor cells does not completely eliminate HER3 function.

Purpose: Dual blockade of HER2 with trastuzumab and lapatinib or with pertuzumab is a superior treatment approach compared with single-agent HER2 inhibitors. However, many HER2-overexpressing breast cancers still escape from this combinatorial approach. Inhibition of HER2 and downstream phosphoinositide 3-kinase (PI3K)/AKT causes a transcriptional and posttranslational upregulation of HER3 which, in turn, counteracts the antitumor action of the HER2-directed therapies.

Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-survivin axis and are sensitive to PI3K inhibitors.

The antibody trastuzumab is approved for treatment of patients with HER2 (ERBB2)-overexpressing breast cancer. A significant fraction of these tumors are either intrinsically resistant or acquire resistance rendering the drug ineffective. The development of resistance has been attributed to failure of the antibody to inhibit phosphoinositide 3-kinase (PI3K), which is activated by the HER2 network.

Postal and face-to-face administration of stroke outcome measures: can mixed modes be used?

Background And Purpose: Different modes of administration are used to collect stroke outcomes, even within the same study, potentially leading to different results. We investigated the effect of administration mode (postal questionnaire; face-to-face interview) on self-reports of activities of daily living and mood.

Methods: The study was nested within a poststroke motivational interviewing trial.

Proteomic profiling of breast tissue collagens and site-specific characterization of hydroxyproline residues of collagen alpha-1-(I).

In a quantitative proteomics-based breast cancer study of complementary normal and tumor biopsies, 22 collagen isoforms were detected by LC-MALDI TOF/TOF MS. By applying proline oxidation, representing hydroxyproline, in database search parameters a substantial increase in assigned MS/MS was achieved, boosting the average (three experiments) number of peptides from 306 to 8126 for collagen alpha-1(I). The plethora of peptide identities for alpha-1(I) was disproportionate with full length protein sequence coverage which only increased from 28.

Illustrating problems faced by stroke researchers: a review of cluster-randomized controlled trials.

The cluster-randomized controlled trial is a design increasingly used in prevention and health care evaluation studies and is highly relevant to stroke research. However, there are methodological issues that make it complex to implement. These are not always fully appreciated, with reviews continuing to reveal deficiencies.