The cytoskeletal motor proteins Dynein and MyoV direct apical transport of Crumbs.

Crumbs (Crb in Drosophila; CRB1-3 in mammals) is a transmembrane determinant of epithelial cell polarity and a regulator of Hippo signalling. Crb is normally localized to apical cell-cell contacts, just above adherens junctions, but how apical trafficking of Crb is regulated in epithelial cells remains unclear. We use the Drosophila follicular epithelium to demonstrate that polarized trafficking of Crb is mediated by transport along microtubules by the motor protein Dynein and along actin filaments by the motor protein Myosin-V (MyoV). Blocking transport of Crb-containing vesicles by Dynein or MyoV leads to accumulation of Crb within Rab11 endosomes, rather than apical delivery. The final steps of Crb delivery and stabilisation at the plasma membrane requires the exocyst complex and three apical FERM domain proteins - Merlin, Moesin and Expanded - whose simultaneous loss disrupts apical localization of Crb. Accordingly, a knock-in deletion of the Crb FERM-binding motif (FBM) also impairs apical localization. Finally, overexpression of Crb challenges this system, creating a sensitized background to identify components involved in cytoskeletal polarization, apical membrane trafficking and stabilisation of Crb at the apical domain.

Inactivation of the gene encoding the cationic antimicrobial peptide resistance factor MprF increases biofilm formation but reduces invasiveness of Listeria monocytogenes.

AIMS: To understand the genetics involved in surface attachment and biofilm formation of Listeria monocytogenes. METHODS AND RESULTS: An in vitro screen of a Himar1 transposon library of L. monocytogenes strain 15G01 identified three transposants that produced significantly different biofilm levels when compared to the wild-type strain; two mutants exhibited enhanced biofilm formation and one produced less biofilm biomass than the wild-type. The mutant 15G01 mprF::Himar1, which had a transposon insertion in the mprF gene, was selected for further analysis. The mutant produced a more densely populated biofilm on solid surfaces such as stainless steel and polystyrene, as determined using scanning electron and light microscopy. The 15G01 mprF::Himar1 mutant remained viable in biofilms, but showed an increase in sensitivity to the cationic antimicrobial gallidermin. The mutant also displayed reduced invasiveness in CaCo-2 intestinal cells, suggesting virulence properties are compromised by the inactivation of mprF. CONCLUSIONS: Biofilm formation and gallidermin resistance of L. monocytogenes is influenced by mprF, but this trait is associated with a compromise in invasiveness. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of pathogenic microorganisms in the food processing environment can cause a significant problem, especially when these microorganisms are established as biofilms. This study shows that the inactivation of the mprF gene results in enhanced biofilm formation and abiotic surface attachment of L. monocytogenes.

Sonographers' self-reported visualization of normal postmenopausal ovaries on transvaginal ultrasound is not reliable: results of expert review of archived images from UKCTOCS.

OBJECTIVE: In the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), self-reported visualization rate (VR) of the ovaries by the sonographer on annual transvaginal sonographic (TVS) examinations was a key quality control (QC) metric. The objective of this study was to assess self-reported VR using expert review of a random sample of archived images of TVS examinations from UKCTOCS, and then to develop software for measuring VR automatically. METHODS: A single expert reviewed images archived from 1000 TVS examinations selected randomly from 68 931 TVS scans performed in UKCTOCS between 2008 and 2011 with ovaries reported as 'seen and normal'. Software was developed to identify the exact images used by the sonographer to measure the ovaries. This was achieved by measuring caliper dimensions in the image and matching them to those recorded by the sonographer. A logistic regression classifier to determine visualization was trained and validated using ovarian dimensions and visualization data reported by the expert. RESULTS: The expert reviewer confirmed visualization of both ovaries (VR-Both) in 50.2% (502/1000) of the examinations. The software identified the measurement image in 534 exams, which were split 2:1:1 providing training, validation and test data. Classifier mean accuracy on validation data was 70.9% (95% CI, 70.0-71.8%). Analysis of test data (133 exams) provided a sensitivity of 90.5% (95% CI, 80.9-95.8%) and specificity of 47.5% (95% CI, 34.5-60.8%) in detecting expert confirmed visualization of both ovaries. CONCLUSIONS: Our results suggest that, in a significant proportion of TVS annual screens, the sonographers may have mistaken other structures for normal ovaries. It is uncertain whether or not this affected the sensitivity and stage at detection of ovarian cancer in the ultrasound arm of UKCTOCS, but we conclude that QC metrics based on self-reported visualization of normal ovaries are unreliable. The classifier shows some potential for addressing this problem, though further research is needed. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Inhibition of foodborne bacteria by antibacterial coatings printed onto food packaging films.

Films containing antibacterial compounds could be used for packaging perishable foods such as fresh fish and meat for sea freighting over long distances. However, existing commercialised options (films with nanosilver zeolites or wasabi extract) are only permitted for food contact in certain regions and films containing alternative antibacterial ingredients are required e.g. for exports to Europe. Certain non-volatile phenolic plant extracts have shown promising antibacterial activity against a wide range of foodborne bacteria in in vitro assays and when integrated in coatings for perishable foods such as fish and meat. Extracts rich in gallotannins tend to show stronger antibacterial effects than other phenols such as flavonoids. Such extracts could be coated onto commercial barrier films by means of flexographic printing-a more industrially feasible option than rod coating or solvent casting typically used in antibacterial coating research. The goal of the present work was to investigate the antibacterial effect of printed latex coatings containing extracts rich in gallotannins and other types of phenolic compounds against 16 common spoilage and pathogenic bacteria of fish and meat. The largest zones of inhibition in disk diffusion assays were obtained with plastic films with coatings containing tannic acid alone, followed by tannic acid with phenolic-rich extracts of feijoa skin or mango seed. Significant inhibition was seen for all bacteria. This study shows that coatings with gallotannins as the main active ingredient can be printed onto commercial barrier films to control the bacteria that limit the shelf-life of fresh fish and meat.

Quality assurance and its impact on ovarian visualization rates in the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

OBJECTIVE: To describe the quality assurance (QA) processes and their impact on visualization of postmenopausal ovaries in the ultrasound arm of a multicenter screening trial for ovarian cancer. METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 50 639 women aged 50-74 years were randomized to the ultrasound arm and underwent annual transvaginal ultrasound (TVS) examinations. QA processes were developed during the course of the trial and included regular monitoring of the visualization rate (VR) of the right ovary. Non-subjective factors identified previously as impacting on VR of the right ovary were included in a generalized estimating equation model for binary outcomes to enable comparison of observed vs adjusted VR between individual sonographers who had undertaken > 1000 scans during the trial and comparison between centers. Observed and adjusted VRs of sonographers and centers were ranked according to the highest VR. Analysis of annual VRs of sonographers and those of the included centers was undertaken. RESULTS: Between June 2001 and December 2010, 48 230 of 50 639 women attended one of 13 centers for a total of 270 035 annual TVS scans. One or both ovaries were seen in 228 145 (84.5%) TVS scans. The right ovary was seen on 196 426 (72.7%) of the scans. For the 78 sonographers included in the model, the median difference between observed and adjusted VR was -0.7% (range, -7.9 to 5.9%) and the median change in VR rank after adjustment was 3 (range, 0-18). For the 13 centers, the median difference between observed and adjusted VR was -0.5% (range, -2.2 to 1%), with no change in ranking after adjustment. The median adjusted VR was 73% (interquartile range (IQR), 65-82%) for sonographers and 74.7% (IQR, 67.1-79.0%) for centers. Despite the increasing age of the women being scanned, there was a steady decrease in the number of sonographers with VR < 60% (21.4% in 2002 vs 2.0% in 2010) and an increase in sonographers with VR > 80% (14.3% in 2002 vs 40.8% in 2010). The median VR of the centers increased from 65.5% (range, 55.7-81.0%) in 2001 to 80.3% (range, 74.5-90.9%) in 2010. CONCLUSIONS: A robust QA program can improve visualization of postmenopausal ovaries and is an essential component of ultrasound-based ovarian cancer screening trials. While VR should be adjusted for non-subjective factors that impact on ovarian visualization, subjective factors are likely to be the largest contributors to differences in VR.

Prevalence, characteristics and ecology of Vibrio vulnificus found in New Zealand shellfish.

AIMS: In New Zealand, there have been no known cases of foodborne diseases linked to Vibrio vulnificus and shellfish consumption, but two cases of wound infection have been reported. We evaluated the distribution, the effect of environmental parameters, the pheno-genotypic profile and the growth characteristics of strains isolated from shellfish. METHODS AND RESULTS: Vibrio vulnificus was present in 13·6% of Pacific oysters and not found in any dredge oyster or Greenshell(™) mussel samples. Eleven isolates belonged to biotype 1 while nine appeared to be variants of biotype 1. Nineteen isolates were genotype E (type A) and just one was genotype C (type B). Some isolates were more resistant to high salt concentrations (>30‰) than others, but not different from ATCC 27562. CONCLUSIONS: Vibrio vulnificus were low in numbers, mostly belonging to genotype E, 16S rRNA type A and biotype 1. No relationship or adaptability to high salinity was observed, but seawater temperature was a strong predictor of bacterial numbers in shellfish. SIGNIFICANCE AND IMPACT OF THE STUDY: We report, for the first time, the characterization of V. vulnificus isolated from New Zealand shellfish and its long-term distribution and prevalence. This information will help the authorities on risk assessments.

Lipolytic Markers, Insulin and Resting Fat Oxidation are Associated with Maximal Fat Oxidation.

The maximal capacity to oxidize fat during exercise (MFO) is associated with 24-h fat balance and insulin sensitivity. Understanding factors that influence MFO could have implications for metabolic health. We investigated relationships between selected plasma metabolites, hormones and overnight-fasted resting fat oxidation rates (Resting), with MFO. Resting fat oxidation and MFO was measured in 57 men with blood collected at rest and during exercise. Plasma glycerol (R=0.39, P=0.033), non-esterified fatty acids (NEFA: R=0.27, P=0.030) and insulin (R=- 0.36, P=0.007) measured at MFO correlated with MFO; only glycerol remained correlated when controlled for resting concentrations (R=0.36, P=0.008). The change in glycerol from rest to MFO correlated with exercise-induced fat oxidation (R=0.32, P=0.012). V˙O 2max correlated with resting fat oxidation (R=0.44, P=0.001) and MFO (R=0.52, P<0.001). Resting fat oxidation correlated with MFO (R=0.55, P<0.001); this remained when controlled for V˙O 2max (R=0.41, P=0.001). This study reports weak-to-moderate, albeit significant, relationships between plasma lipolytic markers, insulin and resting overnight-fasted fat oxidation with MFO and shows the plasma glycerol response to uniquely reflect exercise-induced fat oxidation. V˙O 2max correlates with fat oxidation but the relationship can be dissociated. Interventions to increase fat oxidation for optimal metabolic health would benefit from, but are not reliant on, increases in V˙O 2max.

Long-term study of Vibrio parahaemolyticus prevalence and distribution in New Zealand shellfish.

The food-borne pathogen Vibrio parahaemolyticus has been reported as being present in New Zealand (NZ) seawaters, but there have been no reported outbreaks of food-borne infection from commercially grown NZ seafood. Our study determined the current incidence of V. parahaemolyticus in NZ oysters and Greenshell mussels and the prevalence of V. parahaemolyticus tdh and trh strains. Pacific (235) and dredge (21) oyster samples and mussel samples (55) were obtained from commercial shellfish-growing areas between December 2009 and June 2012. Total V. parahaemolyticus numbers and the presence of pathogenic genes tdh and trh were determined using the FDA most-probable-number (MPN) method and confirmed using PCR analysis. In samples from the North Island of NZ, V. parahaemolyticus was detected in 81% of Pacific oysters and 34% of mussel samples, while the numbers of V. parahaemolyticus tdh and trh strains were low, with just 3/215 Pacific oyster samples carrying the tdh gene. V. parahaemolyticus organisms carrying tdh and trh were not detected in South Island samples, and V. parahaemolyticus was detected in just 1/21 dredge oyster and 2/16 mussel samples. Numbers of V. parahaemolyticus organisms increased when seawater temperatures were high, the season when most commercial shellfish-growing areas are not harvested. The numbers of V. parahaemolyticus organisms in samples exceeded 1,000 MPN/g only when the seawater temperatures exceeded 19°C, so this environmental parameter could be used as a trigger warning of potential hazard. There is some evidence that the total V. parahaemolyticus numbers increased compared with those reported from a previous 1981 to 1984 study, but the analytical methods differed significantly.

Task-specific neural adaptations to isoinertial resistance training.

This study aimed to delineate the contribution of adaptations in agonist, antagonist, and stabilizer muscle activation to changes in isometric and isoinertial lifting strength after short-term isoinertial resistance training (RT). Following familiarization, 45 men (23.2 ± 2.8 years) performed maximal isometric and isoinertial strength tests of the elbow flexors of their dominant arms before and after 3 weeks of isoinertial RT. During these tasks, surface electromyography (EMG) amplitude was recorded from the agonist (biceps brachii short and long heads), antagonist (triceps brachii lateral head), and stabilizer (anterior deltoid, pectoralis major) muscles and normalized to either Mmax (agonists) or to maximum EMG during relevant reference tasks (antagonist, stabilizers). After training, there was more than a twofold greater increase in training task-specific isoinertial than isometric strength (17% vs 7%). There were also task-specific adaptations in agonist EMG, with greater increases during the isoinertial than isometric strength task [analysis of variance (ANOVA), training × task, P = 0.005]. A novel finding of this study was that training increased stabilizer muscle activation during all the elbow flexion strength tasks (P < 0.001), although these were not task-specific training effects. RT elicited specific neural adaptations to the training task that appeared to explain the greater increase in isoinertial than isometric strength.

Hybrid responsive hydrogel carriers for oral delivery of low molecular weight therapeutic agents.

Hydrogels have been influential in the development of controlled release systems for a wide variety of therapeutic agents. These materials are attractive as carriers for transmucosal and intracellular drug delivery because of their inherent biocompatibility, tunable physicochemical properties, basic synthesis, and ability to be physiologically responsive. Due to their hydrophilic nature, hydrogel-based carrier systems are not always the best systems for delivery of small molecular weight, hydrophobic therapeutic agents. In this work, versatile hydrogel-based carriers composed of copolymers of methyl methacrylate (MMA) and acrylic acid (AA) were designed and synthesized to create formulations for oral delivery of small molecular weight therapeutic agents. Through practical material selection and careful design of copolymer composition and molecular architecture, we engineered systems capable of responding to physiological changes, with tunable physicochemical properties that are optimized to load, protect, and deliver their payloads to their intended site of action. The synthesized carriers' ability to respond to changes in pH, to load and release small molecular weight drugs, and biocompatibility were investigated. Our results suggest these hydrophilic networks have great potential for controlled delivery of small-molecular weight, hydrophobic and hydrophilic agents.

Systemic targeted therapy for her2-positive early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline.

BACKGROUND: This systematic review addresses the question "What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)-positive breast cancer?" METHODS: The medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major guideline organizations were also searched. RESULTS: Sixty publications relevant to the targeted therapy portion of the systematic review were identified. In four major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31, North Central Cancer Treatment Group N9831, and Breast Cancer International Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1 year compared with 1 year) was evaluated, with mixed results for dfs: one trial showed superiority (finher), one trial could not demonstrate noninferiority (phare), another trial showed equivalent results (E 2198), and one trial is still ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year) showed no improvement in dfs or os and a higher rate of cardiac events. Newer her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are still being evaluated in both adjuvant and neoadjuvant trials, either by direct comparison with trastuzumab alone or combined with trastuzumab. In the neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in combination with another anti-her2 agent (lapatinib, pertuzumab) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response. In the adjuvant setting, lapatinib alone or in combination with trastuzumab, compared with trastuzumab alone (altto) or with placebo (teach), was not superior in dfs. The results of the completed aphinity trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab, are highly anticipated. Ongoing trials are evaluating trastuzumab as a single agent without adjuvant chemotherapy (respect) and in patients with low her2 expression (National Surgical Adjuvant Breast and Bowel Project B-47). CONCLUSIONS: Taking into consideration disease characteristics and patient preference, 1 year of trastuzumab should be offered to all patients with her2-positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function should be regularly assessed in this patient population.

Locoregional therapy of locally advanced breast cancer: a clinical practice guideline.

QUESTIONS: In female patients with locally advanced breast cancer (labc) and good response to neoadjuvant chemotherapy (nact), including endocrine therapy, what is the role of breast-conserving surgery (bcs) compared with mastectomy?In female patients with labc, is radiotherapy (rt) indicated for those who have undergone mastectomy?does locoregional rt, compared with breast or chest wall rt alone, result in a higher survival rate and lower recurrence rates?is rt indicated for those achieving a pathologic complete response (pcr) to nact?In female patients with labc who receive nact, is the most appropriate axillary staging procedure sentinel lymph node biopsy (slnb) or axillary dissection? Is slnb indicated before nact rather than at the time of surgery?How should female patients with labc that does not respond to initial nact be treated? METHODS: This guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care (pebc) and the Breast Cancer Disease Site Group (dsg). A systematic review was prepared based on literature searches conducted using the medline and embase databases for the period 1996 to December 11, 2013. Guidelines were located from that search and from the Web sites of major guideline organizations. The working group drafted recommendations based on the systemic review. The systematic review and recommendations were then circulated to the Breast Cancer dsg and the pebc Report Approval Panel for internal review; the revised document underwent external review. The full three-part evidence series can be found on the Cancer Care Ontario Web site. RECOMMENDATIONS: For most patients with labc, modified radical mastectomy should be considered the standard of care. For some patients with noninflammatory labc, bcs can be considered on a case-by-case basis when the surgeon deems that the disease can be fully resected and the patient expresses a strong preference for breast preservation.For patients with labc, rt after mastectomy is recommended.It is recommended that, after bcs or mastectomy, patients with labc receive locoregional rt encompassing the breast or chest wall and local node-bearing areas.It is recommended that postoperative rt remain the standard of care for patients with labc who achieve pcr to nact.It is recommended that axillary dissection remain the standard of care for axillary staging in labc, with the judicious use of slnb in patients who are advised of the limitations of the current data.Although slnb either before or after nact is technically feasible, the data are insufficient to make any recommendation about the optimal timing of slnb with respect to nact. Limited data suggest higher sentinel lymph node identification rates and lower false negative identification rates when slnb is conducted before nact; however, those data must be balanced against the requirement for two operations if slnb is not performed at the time of resection of the main tumour.It is recommended that patients receiving neoadjuvant anthracycline-taxane-based therapy (or other sequential regimens) whose tumours do not respond to the initial agent or agents, or who experience disease progression, be expedited to the next agent or agents of the regimen.For patients who, in the opinion of the treating physician, fail to respond or progress on first-line nact, several therapeutic options can be considered, including second-line chemotherapy, hormonal therapy (if appropriate), rt, or immediate surgery (if technically feasible). Treatment should be individualized through discussion at a multidisciplinary case conference, considering tumour characteristics, patient factors and preferences, and risk of adverse effects.It is recommended that prospective randomized clinical trials be designed for patients with labc who fail to respond to nact so that more definitive treatment recommendations can be developed.

Optimal systemic therapy for early breast cancer in women: a clinical practice guideline.

The Breast Cancer Disease Site Group of Cancer Care Ontario identified the need for new guidelines for the adjuvant systemic therapy of early-stage breast cancer. The specific question to be addressed was "What is the optimal adjuvant systemic therapy for female patients with early-stage operable breast cancer, when patient and disease factors are considered?" A systematic review was prepared based on literature searches conducted using the medline and embase databases for the period January 2008 to March 5, 2012, and updated to May 12, 2014. Guidelines were located from that search, from the Standards and Guidelines Evidence directory of cancer guidelines, and from the Web sites of major guideline organizations. The literature located was subdivided into the broad categories of chemotherapy, hormonal therapy, and therapy targeted to her2 (human epidermal growth factor receptor 2). Although several of the systemic therapies discussed in this guideline can be considered in the neoadjuvant setting, the review focused on trials with rates of disease-free and overall survival as endpoints and thus excluded several trials that used pathologic complete response as a primary endpoint. Based on the systematic review, the working group drafted recommendations on the use of chemotherapy, hormonal therapy, and targeted therapy; based on their professional experience, they also drafted recommendations on patient and disease characteristics and recurrence risk. The literature review and draft recommendations were circulated to a consensus panel of medical oncologists who had expertise in breast cancer and who represented the regions of Ontario. Items without initial consensus were discussed at an in-person consensus meeting held in Toronto, November 23, 2012. The final recommendations are those for which consensus was reached before or at the meeting. Some of the key evidence was revised after the updated literature search. Evidence reviews for systemic chemotherapy, endocrine therapy, and targeted therapy for her2-positive disease are reported in separate articles in this supplement. The full three-part 1-21 evidence-based series, including complete details of the development and consensus processes, can be found on the Cancer Care Ontario Web site at https://www.cancercare.on.ca/toolbox/qualityguidelines/diseasesite/breast-ebs.

Adjuvant chemotherapy for early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline.

BACKGROUND: The Program in Evidence-Based Care (pebc) of Cancer Care Ontario recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question "What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?" The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2 (her2)-directed therapy. METHODS: For the systematic review, the medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were "breast cancer" and "systemic therapy" (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (rcts), guidelines, systematic reviews, and meta-analyses. RESULTS: Several hundred documents that met the inclusion criteria were retrieved. The Early Breast Cancer Trialists' Collaborative Group meta-analyses encompassed many of the rcts found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. Chemotherapy was reviewed mainly in three classes: anti-metabolite-based regimens (for example, cyclophosphamide-methotrexate-5-fluorouracil), anthracyclines, and taxane-based regimens. In general, single-agent chemotherapy is not recommended for the adjuvant treatment of breast cancer in any patient population. Anthracycline-taxane-based polychemotherapy regimens are, overall, considered superior to earlier-generation regimens and have the most significant impact on patient survival outcomes. Regimens with varying anthracycline and taxane doses and schedules are options; in general, paclitaxel given every 3 weeks is inferior. Evidence does not support the use of bevacizumab in the adjuvant setting; other systemic therapy agents such as metformin and vaccines remain investigatory. Adjuvant bisphosphonates for menopausal women will be discussed in later work. CONCLUSIONS: The results of this systematic review constitute a comprehensive compilation of the high-level evidence that is the basis for the 2014 pebc guideline on systemic therapy for early breast cancer. Use of cytotoxic chemotherapy is presented here; the results addressing endocrine therapy and her2-targeted treatment, and the final clinical practice recommendations, are published separately in this supplement.

Adjuvant endocrine therapy for early breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline.

BACKGROUND: Cancer Care Ontario's Program in Evidence-Based Care (pebc) recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question "What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?" The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and her2 (human epidermal growth factor receptor 2)-targeted therapy. METHODS: For the systematic review, the literature in the medline and embase databases was searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were "breast cancer" and "systemic therapy" (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (rcts), guidelines, systematic reviews, and meta-analyses. RESULTS: Several hundred documents that met the inclusion criteria were retrieved. Meta-analyses from the Early Breast Cancer Trialists' Collaborative Group encompassed many of the rcts found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. SUMMARY: The results of the systematic review constitute a comprehensive compilation of high-level evidence, which was the basis for the 2014 pebc guideline on systemic therapy for early breast cancer. The review of the evidence for systemic endocrine therapy (adjuvant tamoxifen, aromatase inhibitors, and ovarian ablation and suppression) is presented here; the evidence for chemotherapy and her2-targeted treatment-and the final clinical practice recommendations-are presented separately in this supplement.

Human herpes virus-8 infections among subjects with human immunodeficiency virus infection and normal healthy individuals in India.

Human herpes virus-8 (HHV-8) is etiologically associated with Kaposi's sarcoma. There is insufficient information on the epidemiology of HHV-8 infection from India. Blood samples from 87 human immunodeficiency virus (HIV)-infected individuals and 84 normal healthy blood donors were tested for the HHV-8 IgG antibodies. Further, a total of 309 whole blood samples from treatment-naïve HIV-1-infected individuals and from 70 normal healthy individuals were also collected and tested for HHV-8 DNA. The seroprevalence of HHV-8 was 4.7% in the South Indian population. There was no significant difference in the seroprevalence of HHV-8 in the HIV-infected and uninfected patients. None of the 379 samples tested were positive for HHV-8 DNA. Our study revealed a very low exposure of the South Indian patient population to HHV-8 and multicentric epidemiological studies are needed to understand the prevalence of HHV-8 in different regions of India and to confirm any gender-specific differences in seroprevalence.

Factors affecting visualization of postmenopausal ovaries: descriptive study from the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

OBJECTIVE: Transvaginal sonography (TVS) is core to any ovarian cancer screening strategy. General-population screening involves older postmenopausal women in whom ovarian visualization is difficult because of decreasing ovarian size and lack of follicular activity. We report on factors affecting the visualization of postmenopausal ovaries in the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). METHODS: The UKCTOCS is a randomized controlled trial of 202 638 postmenopausal women with 50 639 women in the ultrasound scan arm. TVS is the primary screening modality in the ultrasound scan arm. Age, education, ethnicity, body mass index (BMI), previous pelvic surgery, lifestyle and reproductive factors, and a personal/family history of cancer were assessed for their effects on ovarian visualization at the initial TVS. RESULTS: Between 11 June 2001 and 18 August 2007, 43 867 women underwent TVS. The median age and BMI of the women were 60.6 (interquartile range (IQR), 9.9) years and 25.7 (IQR, 5.8), respectively. The right ovary was visualized in 29 297 (66.8%) and the left ovary was visualized in 28 726 (65.5%). Visualization of ovaries decreased with previous hysterectomy (odds ratio (OR) = 0.534; 95% CI, 0.504-0.567), previous tubal ligation (OR = 0.895; 95% CI, 0.852-0.940), increasing age (OR = 0.953; 95% CI, 0.950-0.956), unilateral oophorectomy (OR = 0.224; 95% CI, 0.186-0.269) and being overweight (OR = 0.918; 95% CI, 0.876-0.962) or obese (OR = 0.715; 95% CI, 0.677-0.755). Increased visualization was observed with a history of infertility (OR = 1.134; 95% CI, 1.005-1.279) and increasing age (in years) at menopause (OR = 1.005; 95% CI, 1.001-1.009). CONCLUSIONS: Several factors affect the visualization of postmenopausal ovaries. Their impact needs to be taken into consideration when developing quality assurance for ovarian ultrasound scanning or comparing study results as their prevalence may differ between populations.

Acceptance of transvaginal sonography by postmenopausal women participating in the United Kingdom Collaborative Trial of Ovarian Cancer Screening.

OBJECTIVE: To assess pain and overall experience of transvaginal sonography (TVS) in asymptomatic postmenopausal women. METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50 639 postmenopausal women were randomized to undergo annual TVS at 13 trial centers in England, Wales and Northern Ireland. Together with the appointment letter for their annual scan, a random sample of 150 women per center was sent a detailed 48-item postal questionnaire regarding the screening experience. It included a specific question about pain using a score of 0-5, where 5 was severe pain and 3 was discomfort. To assess factors that might affect a woman's reported pain experience, the pain score was regressed on age, hormone replacement therapy use, body mass index, a history of hysterectomy, prolonged scanning time, ovarian visualization, scan result, sonographer's visualization rates and opinion of the women regarding the sonographer who performed the scan. RESULTS: Between 7 July and 9 September 2009, 1950 randomly chosen women (150 per regional center) were sent the questionnaire. Of the 800 (41.0%) who returned the questionnaire, 651 could be linked to their TVS appointment. One-hundred and fifty-two (23.3%) women reported pain/discomfort (score 3-5) during TVS and 473 (72.7%) reported no discomfort (score 0-2). Only 23 (3.5%) women reported experiencing moderate/severe pain. Increasing discomfort/pain was independently associated with a history of hysterectomy and participant's reporting of prolonged scan time. Women who experienced pain on TVS were less compliant (odds ratio = 0.87) with the following year's scan compared with those who did not experience pain. CONCLUSIONS: The majority of postmenopausal women found TVS acceptable. Pain influenced compliance and correlated with women's perception of increased scanning time and previous hysterectomy.

An extension of the Coconut Cream Agar method to screen Penicillium citrinum isolates for citrinin production.

A simple and rapid screening method was developed for the detection of citrinin in fungal cultures using Coconut Cream Agar (CCA) described previously for detecting aflatoxin and ochratoxin A. Fifteen isolates of Penicillium citrinum were inoculated onto CCA and incubated at 25 and 30°C for 10 days. All isolates produced a distinct yellow green fluorescence on CCA when the reverse side of the agar plates were viewed under long wavelength UV light. Detection was optimal at 25°C after four to 5 days of incubation. Isolates positive by the CCA method also tested positive for citrinin production by the TLC agar plug method after growth on CCA, Czapek yeast extract agar and yeast extract sucrose agar. Control cultures were negative by both methods, indicating that the CCA Petri dish method was suitable for screening cultures for citrinin production.