Passive sampling and benchmarking to rank HOC levels in the aquatic environment

The identification and prioritisation of water bodies presenting elevated levels of anthropogenic chemicals is a key aspect of environmental monitoring programmes. Albeit this is challenging owing to geographical scales, choice of indicator aquatic species used for chemical monitoring, and inherent need for an understanding of contaminant fate and distribution in the environment. Here, we propose an innovative methodology for identifying and ranking water bodies according to their levels of hydrophobic organic contaminants (HOCs) in water. This is based on a unique passive sampling dataset acquired over a 10-year period with silicone rubber exposures in surface water bodies across Europe. We show with these data that, far from point sources of contamination, levels of hexachlorobenzene (HCB) and pentachlorobenzene (PeCB) in water approach equilibrium with atmospheric concentrations near the air/water surface. This results in a relatively constant ratio of their concentrations in the water phase. This, in turn, allows us to (i) identify sites of contamination with either of the two chemicals when the HCB/PeCB ratio deviates from theory and (ii) define benchmark levels of other HOCs in surface water against those of HCB and/or PeCB. For two polychlorinated biphenyls (congener 28 and 52) used as model chemicals, differences in contamination levels between the more contaminated and pristine sites are wider than differences in HCB and PeCB concentrations endorsing the benchmarking procedure

Neuropathic pain associated with first metatarsophalangeal joint osteoarthritis: frequency and associated factors.

OBJECTIVE: To determine whether neuropathic pain is a feature of first metatarsophalangeal (MTP) joint osteoarthritis (OA). METHODS: Ninety-eight participants (mean age 57.4 years, standard deviation 10.3) with symptomatic radiographic first MTP joint OA completed the painDETECT questionnaire (PDQ), which incorporates nine questions regarding the intensity and quality of pain. The likelihood of neuropathic pain was determined using established cut-points of the PDQ. Participants with unlikely neuropathic pain were then compared to those with possible/likely neuropathic pain in relation to age, sex, general health (Short Form [SF] 12), psychological wellbeing (Depression, Anxiety and Stress Scale), pain characteristics (self-efficacy, duration, and severity), foot health (Foot Health Status Questionnaire [FHSQ]), first MTP dorsiflexion range of motion and radiographic severity. Effect sizes (Cohen's d) were also calculated. RESULTS: Thirty (31%) participants had possible/likely neuropathic pain (possible n=19, [19.4%], likely n=11 [11.2%]). The most common neuropathic symptoms were sensitivity to pressure (56%), sudden pain attacks/electric shocks (36%) and burning (25%). Compared to those with unlikely neuropathic pain, those with possible/likely neuropathic pain were significantly older (d=0.59, p=0.010), had worse SF12 physical (d=1.10, p<0.001), pain self-efficacy (d=0.98, p<0.001), FHSQ pain (d=0.98, p<0.001) and FHSQ function (d=0.82, p<0.001) scores, and had higher pain severity at rest (d=1.01, p<0.001). CONCLUSION: A significant proportion of individuals with first MTP joint OA report symptoms suggestive of neuropathic pain, which may partly explain the suboptimal responses to commonly used treatments for this condition. Screening for neuropathic pain may assist in the selection of targeted interventions and improve clinical outcomes

Shoe-stiffening inserts for first metatarsophalangeal joint osteoarthritis (the SIMPLE trial): study protocol for a randomised controlled trial

BACKGROUND: This article describes the design of a parallel-group, participant- and assessor-blinded randomised controlled trial comparing the effectiveness of shoe-stiffening inserts versus sham shoe insert(s) for reducing pain associated with first metatarsophalangeal joint (MTPJ) osteoarthritis (OA). METHODS: Ninety participants with first MTPJ OA will be randomised to receive full-length shoe-stiffening insert(s) (Carbon Fibre Spring Plate, Paris Orthotics, Vancouver, BC, Canada) plus rehabilitation therapy or sham shoe insert(s) plus rehabilitation therapy. Outcome measures will be obtained at baseline, 4, 12, 24 and 52 weeks; the primary endpoint for assessing effectiveness being 12 weeks. The primary outcome measure will be the foot pain domain of the Foot Health Status Questionnaire (FHSQ). Secondary outcome measures will include the function domain of the FHSQ, severity of first MTPJ pain (using a 100-mm Visual Analogue Scale), global change in symptoms (using a 15-point Likert scale), health status (using the Short-Form-12® Version 2.0 and EuroQol (EQ-5D-5L™) questionnaires), use of rescue medication and co-interventions, self-reported adverse events and physical activity levels (using the Incidental and Planned Activity Questionnaire). Data will be analysed using the intention-to-treat principle. Economic analysis (cost-effectiveness and cost-utility) will also be performed. In addition, the kinematic effects of the interventions will be examined at 1 week using a three-dimensional motion analysis system and multisegment foot model. DISCUSSION: This study will determine whether shoe-stiffening inserts are a cost-effective intervention for relieving pain associated with first MTPJ OA. The biomechanical analysis will provide useful insights into the mechanism of action of the shoe-stiffening inserts. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, identifier: ACTRN12616000552482 . Registered on 28 April 2016

Reproducibility of fetal heart volume by 3D-sonography using the XI VOCAL method

<p>Abstract</p> <p>Background</p> <p>To assess the reliability of fetal heart volume measurement by three-dimensional sonography (3DUS) using the eXtended Imaging Virtual Organ Computer-aided AnaLysis (XI VOCAL) method.</p> <p>Methods</p> <p>This reliability study enrolled 30 pregnant women with singleton healthy pregnancies between 19 and 34 weeks of gestation. All volume acquirements were performed with a convex volumetric transducer (C3-7ED) coupled to an Accuvix XQ sonography device (Medison, Korea). The XI VOCAL 10 planes was the method of choice for volumetric measurement. 3D datasets were analyzed by two observers (EQSB and HJFM); fetal heart volume was measured twice by the first and once by the second observer to calculate intra and interobserver reproducibility. Statistical analysis used pareated Student's t test (p) and calculated Intraclass correlation coefficients (ICC). Bland-Altman plots were also constructed.</p> <p>Results</p> <p>We observed an excellent intra- and interobserver reliability for fetal cardiac volume assessed by XI VOCAL. For the intraobserver the ICC was 0.998 (95% CI: 0.997; 0.999), with mean of differences of 0.12 cm³(95% limits of agreement: -0.84; +0.84; p = 0.130). For interobserver the ICC was 0.899 (95%CI: 0.996; 0.998), mean of differences 0.05 cm³(95% limits of agreement: -0.84; +0.84; p = 0.175).</p> <p>Conclusion</p> <p>Fetal cardiac volume assessed by 3DUS using XI VOCAL method is highly reproducible between 19 to 34 gestational weeks.</p

Transfusion of red cells in hematopoietic stem cell transplantation (TRIST): study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Insight regarding transfusion practices in Hematopoietic Stem cell Transplantation (HSCT) are lacking and the impact of red cell transfusion in this high risk group on outcomes following HSCT are not well appreciated. Red blood cell transfusion can be life-saving, however, liberal use of transfusion in critically ill patients failed to demonstrate significant clinical benefit. A large number of other observational studies have also demonstrated an association between red blood cell transfusions and increased morbidity such as infections and multi organ failure as well as increased mortality. The role of red cell transfusion on the clinical outcomes observed in patients undergoing HSCT remains poorly understood and a prospective randomized study of transfusion is required to gain insight and knowledge on best transfusion practices in this high risk population.</p> <p>Methods</p> <p>This report describes the design and methodological issues of a randomized pilot study evaluating red cell transfusion triggers in the setting of Hematopoietic Stem Cell Transplantation. This study has been funded by a peer review grant from the Canadian Blood Services and is registered on Clinicaltrials.gov NCT01237639.</p> <p>Results</p> <p>In 3 Canadian centres, 100 patients undergoing Hematopoietic Stem Cell Transplantation will be randomized to either a restrictive (target hemoglobin of 70-90 g/L) or liberal (target hemoglobin of 90-110 g/L) red cell transfusion strategy, based daily hemoglobin values up to 100 days post-transplant. The study will stratify participants by centre and type of transplant. The primary goal is to demonstrate study feasibility and we will collect clinical outcomes on 1) Transfusion Requirements, 2) Transplant Related Mortality, 3) Maximum grade of acute Graft versus Host Disease, 4) Veno-occlusive Disease, 5) Serious Infections, 6) Bearman Toxicity Score, 7) Bleeding, 8) Quality of Life, 9) Number of Hospitalizations and 10) Number of Intensive Care Unit (ICU) Admissions.</p> <p>Conclusion</p> <p>Upon completion, this pilot trial will provide preliminary insight into red cell transfusion practice and its influence in hematopoietic stem cell transplant outcomes. The results of this trial will inform the conduct of a larger study.</p

DNA topoisomerases participate in fragility of the oncogene RET

Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

A global analysis of the comparability of winter chill models for fruit and nut trees

Many fruit and nut trees must fulfill a chilling requirement to break their winter dormancy and resume normal growth in spring. Several models exist for quantifying winter chill, and growers and researchers often tacitly assume that the choice of model is not important and estimates of species chilling requirements are valid across growing regions. To test this assumption, Safe Winter Chill (the amount of winter chill that is exceeded in 90% of years) was calculated for 5,078 weather stations around the world, using the Dynamic Model [in Chill Portions (CP)], the Chilling Hours (CH) Model and the Utah Model [Utah Chill Units (UCU)]. Distributions of the ratios between different winter chill metrics were mapped on a global scale. These ratios should be constant if the models were strictly proportional. Ratios between winter chill metrics varied substantially, with the CH/CP ratio ranging between 0 and 34, the UCU/CP ratio between −155 and +20 and the UCU/CH ratio between −10 and +5. The models are thus not proportional, and chilling requirements determined in a given location may not be valid elsewhere. The Utah Model produced negative winter chill totals in many Subtropical regions, where it does not seem to be useful. Mean annual temperature and daily temperature range influenced all winter chill ratios, but explained only between 12 and 27% of the variation. Data on chilling requirements should always be amended with information on the location and experimental conditions of the study in which they were determined, ideally including site-specific conversion factors between winter chill models. This would greatly facilitate the transfer of such information across growing regions, and help prepare growers for the impact of climate change