Multiple human herpesvirus-8 infection

In Malawian patients with Kaposi sarcoma (KS) and their relatives, we investigated nucleotide-sequence variation in human herpesvirus-8 (HHV-8) subgenomic DNA, amplified from oral and blood samples by use of polymerase chain reaction. Twenty-four people had amplifiable HHV-8 DNA in >1 sample; 9 (38%) were seropositive for human immunodeficiency virus type 1, 21 (88%) were anti-HHV-8-seropositive, and 7 (29%) had KS. Sequence variation was sought in 3 loci of the HHV-8 genome: the internal repeat domain of open-reading frame (ORF) 73, the KS330 segment of ORF 26, and variable region 1 of ORF K1. Significant intraperson/intersample and intrasample sequence polymorphisms were observed in 14 people (60%). For 3 patients with KS, intraperson genotypic differences, arising from nucleotide sequence variations in ORFs 26 and K1, were found in blood and oral samples. For 2 other patients with KS and for 9 people without KS, intraperson genotypic and subgenotypic differences, originating predominantly from ORF K1, were found in oral samples; for the 2 patients with KS and for 4 individuals without KS, intrasample carriage of distinct ORF K1 sequences also were discernible. Our findings imply HHV-8 superinfection

von Willebrand factor/ADAMTS13 ratio at presentation of acute ischemic brain injury is predictive of outcome

Acute ischemic stroke (IS) and transient ischemic attack (TIA) are associated with raised von Willebrand factor (VWF) and decreased ADAMTS13 activity (ADAMTS13Ac). Their impact on mortality and morbidity is unclear. We conducted a prospective investigation of the VWF-ADAMTS13 axis in 292 adults (acute IS, n = 103; TIA, n = 80; controls, n = 109) serially from presentation until >6 weeks. The National Institutes of Health Stroke Score (NIHSS) and modified Rankin scale (mRS) were used to assess stroke severity. Presenting median VWF antigen (VWF:Ag)/ADAMTS13Ac ratios were: IS, 2.42 (range, 0.78-9.53); TIA, 1.89 (range, 0.41-8.14); and controls, 1.69 (range, 0.25-15.63). Longitudinally, the median VWF:Ag/ADAMTS13Ac ratio decreased (IS, 2.42 to 1.66; P = .0008; TIA, 1.89 to 0.65; P 2.6 predicted mortality (odds ratio, 6.33; range, 2.22-18.1). Those with a VWF:Ag/ADAMTS13Ac ratio in the highest quartile (>3.091) had 31% increased risk mortality. VWF:Ag/ADAMTS13Ac ratio at presentation of ischemic brain injury was associated with higher mRS (P = .021) and NIHSS scores (P = .029) at follow-up. Thrombolysis resulted in prompt reduction of the VWF:Ag/ADAMTS13Ac ratio and significant improvement in mRS on follow-up. A raised VWF:Ag/ADAMTS13Ac ratio at presentation of acute IS or TIA is associated with increased mortality and poorer functional outcome. A ratio of 2.6 seems to differentiate outcome. Prompt reduction in the ratio in thrombolysed patients was associated with decreased mortality and morbidity. The VWF:Ag/ADAMTS13Ac ratio is a biomarker for the acute impact of an ischemic event and longer-term outcome

A case of sigmoid endometriosis difficult to differentiate from colon cancer

BACKGROUND: Although endometriosis with sigmoid serosal involvement is not uncommon in women of childbearing age, the mucosal involvement is rare and differential diagnosis from colon cancer may be difficult due to the lack of pathognomonic symptoms and the poor diagnostic yield of colonoscopy and colonic biopsies. CASE PRESENTATION: We present a case of a young woman with sigmoid endometriosis, in which the initial diagnostic workup suggested colon cancer. Histologic evidence, obtained from a second colonoscopy, along with pelvic ultrasound findings led to the final diagnosis of intestinal endometriosis which was confirmed by laparoscopy. CONCLUSION: Colonic endometriosis is often a diagnostic challenge and should be considered in young women with symptoms from the lower gastrointestinal tract

Androgen secreting steroid cell tumor of the ovary in a young lactating women with acute onset of severe hyperandrogenism: a case report and review of literature

<p>Abstract</p> <p>Introduction</p> <p>Steroid cell tumors of the ovary account for less than 0.1% of all ovarian tumors <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> and these tumours may present at any age in association with interesting presentations related to the hormonal activity and virilizing properties of tumor. Hayes and Scully <abbrgrp><abbr bid="B2">2</abbr></abbrgrp> reported 63 cases in patients ranging from 2 to 80 years of age. The subtype, not otherwise specified, is associated with androgenic changes in approximately one half of patients with this tumour <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. In a series of 63 cases from Massachusetts General Hospital, 94% of the tumors were found to be unilateral and 28.6% were malignant <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>. As most of these tumors are diagnosed at an early stage and do not recur or metastasize, little is known about their response to therapies such as chemotherapy or radiation <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>.</p> <p>Case Presentation</p> <p>We present the case of a 22-year old lactating woman who presented with four months of amenorrhea associated with signs of virilization. Clinical and diagnostic evaluation revealed a right adenexal mass and elevated serum levels of testosterone and she was diagnosed as having a stage 1A androgen secreting steroid cell tumor. In view of the early stage of the disease, she underwent right salpingo-oopherectomy. Histopathological examination and immunohistochemistry confirmed the diagnosis. Two months after surgery she regained normal menses and showed regression of the androgenic changes.</p> <p>Conclusion</p> <p>Surgery remains the mainstay of the treatment of gonadotrophin receptor positive steroid cell tumors although medical therapy using Gonadotrophin Releasing Hormone [GnRH analogues has been tried recently in recurrent or inoperable cases. There is no described effective chemotherapy or radiotherapy for this condition.</p

Effectiveness of YouRAction, an Intervention to Promote Adolescent Physical Activity Using Personal and Environmental Feedback: A Cluster RCT

Background: In this study the one and six months effects of the computer-tailored YouRAction (targeting individual level determinants) and YouRAction+e (targeting in addition perceived environmental determinants) on compliance with the moderate-to-vigorous physical activity (MVPA) guideline and weight status are examined. In addition the use and appreciation of both interventions are studied. Methods: A three-armed cluster randomized trial was conducted in 2009-2010 with measurements at baseline, one and six months post intervention. School classes were assigned to one of the study arms (YouRaction, YouRAction+e and Generic Information (GI) control group). MVPA was derived from self-reports at baseline, one and six months post intervention. Body Mass Index and waist circumference were measured at baseline and six months post intervention in a random sub-sample of the population. Use of the interventions was measured by webserver logs and appreciation by self-reports. Multilevel regression analyses were conducted to study the effects of the intervention against the GI control group. ANOVA's and chi-square tests were used to describe differences in use and appreciation between study arms. Results: There were no statistically significant intervention effects on compliance with the MVPA guideline, overweight or WC. Access to the full intervention was significantly lower for YouRAction (24.0%) and YouRAction+e (21.7%) compared to the GI (54.4%). Conclusion: This study could not demonstrate that the YouRAction and YouRAction+e interventions were effective in promoting MVPA or improve anthropometric outcomes among adolescents, compared to generic information. Insufficient use and exposure to the intervention content may be an explanation for the lack of effects

Testing foundations of quantum mechanics with photons

The foundational ideas of quantum mechanics continue to give rise to counterintuitive theories and physical effects that are in conflict with a classical description of Nature. Experiments with light at the single photon level have historically been at the forefront of tests of fundamental quantum theory and new developments in photonics engineering continue to enable new experiments. Here we review recent photonic experiments to test two foundational themes in quantum mechanics: wave-particle duality, central to recent complementarity and delayed-choice experiments; and Bell nonlocality where recent theoretical and technological advances have allowed all controversial loopholes to be separately addressed in different photonics experiments.Comment: 10 pages, 5 figures, published as a Nature Physics Insight review articl

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Role of BRCA gene dysfunction in breast and ovarian cancer predisposition

Tumor suppressor genes that perform apparently generic cellular functions nonetheless cause tissue-specific syndromes in the human population when they are mutated in the germline. The two major hereditary breast/ovarian cancer predisposition genes, BRCA1 and BRCA2, appear to participate in a common pathway that is involved in the control of homologous recombination and in the maintenance of genomic integrity. How might such functions translate into the specific suppression of cancers of the breast and ovarian epithelia? Recent advances in the study of BRCA1 and BRCA2, discussed herein, have provided new opportunities to address this question

Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer remains the leading cause of death from gynaecological malignancy. More than 60% of the patients are presenting the disease in stage III or IV. In spite of combination of chemotherapy and surgery the prognosis stays poor for therapy regimen.</p> <p>Methods</p> <p>The leaves of a plant endemic to Australia, <it>Calomeria amaranthoides</it>, were extracted and then fractionated by column chromatography. <it>In vitro </it>cytotoxicity tests were performed with fractions of the plant extract and later with an isolated compound on ovarian cancer cell lines, as well as normal fibroblasts at concentrations of 1-100 μg/mL (crude extract) and 1-10 μg/mL (compound). Cytotoxicity was measured after 24, 48 and 72 hours by using a non-fluorescent substrate, Alamar blue.</p> <p><it>In vivo </it>cytotoxicity was tested on ascites, developed in the abdomen of nude mice after inoculation with human OVCAR₃cells intraperitoneally. The rate of change in abdomen size for the mice was determined by linear regression and statistically evaluated for significance by the unpaired t test.</p> <p>Results</p> <p>Two compounds were isolated by chromatographic fractionation and identified by ¹H-NMR, ¹³C-NMR and mass spectrometry analyses, EPD, an α-methylene sesquiterpene lactone of the eremophilanolide subtype, and EPA, an α-methylene carboxylic acid.</p> <p>Cytotoxicity of EPD for normal fibroblasts at all time points IC₅₀was greater than 10 μg/mL, whereas, for OVCAR₃cells at 48 hours IC₅₀was 5.3 μg/mL (95% confidence interval 4.3 to 6.5 μg/mL).</p> <p>Both, the crude plant extract as well as EPD killed the cancer cells at a final concentration of 10 μg/mL and 5 μg/mL respectively, while in normal cells only 20% cell killing effect was observed. EPA had no cytotoxic effects.</p> <p>Changes in abdomen size for control versus Cisplatin treated mice were significantly different, P = 0.023, as were control versus EPD treated mice, P = 0.025, whereas, EPD versus Cisplatin treated mice were not significantly different, P = 0.13.</p> <p>Conclusions</p> <p>For the first time both crude plant extract from <it>Calomeria amaranthoides </it>and EPD have been shown to have potent anti-cancer effects against ovarian cancer.</p