Freezing and chemical preservatives alter the stable isotope values of carbon and nitrogen of the Asiatic clam (Corbicula fluminea)

We tested the impacts of most common sample preservation methods used for aquatic sample materials on the stable isotope ratios of carbon and nitrogen in clams, a typical baseline indicator organism for many aquatic food web studies utilising stable isotope analysis (SIA). In addition to common chemical preservatives ethanol and formalin, we also assessed the potential impacts of freezing on δ¹³C and δ¹⁵N values and compared the preserved samples against freshly dried and analysed samples. All preservation methods, including freezing, had significant impacts on δ¹³C and δ¹⁵N values and the effects in general were greater on the carbon isotope values (1.3-2.2% difference) than on the nitrogen isotope values (0.9-1.0% difference). However, the impacts produced by the preservation were rather consistent within each method during the whole 1 year experiment allowing these to be accounted for, if clams are intended for use in retrospective stable isotope studies

Unstructured treatment interruption: an important risk factor for arterial stiffness in adult Malawian patients with antiretroviral treatment

OBJECTIVE: The aim of the study was to evaluate the impact of unstructured antiretroviral treatment (ART) interruption on arterial stiffness in adult Malawians who are on ART for at least 35 years. DESIGN: The number of treatment interruption events for at least 60 days during ART treatment was quantified in patients for at least 35 years using retrospective routinely collected clinic data. Treatment interruption data were linked to patient carotid-femoral pulse wave velocity (PWV); PWV more than 10 m/s was set as the threshold for clinically significant cardiovascular disease risk. METHODS: PWV was measured in patients (on ART >= 18 months), during routine ART clinic visits in Blantyre, Malawi, between November 2014 and July 2015. Multivariable linear regression was used to estimate the change in PWV m/s associated with treatment interruption. Multivariable logistic regression was used to estimate risk of PWV more than 10 m/s. All models were controlled for demographic and cardiometabolic risk factors. RESULTS: In 220 patients (median age 45 years, range 37–80 years), 86 (37.4%) patients had at least one treatment interruption event. Median length of treatment interruption events was 75 days (range 31 days to 8 years). Overall, 31 (14%) patients had a PWV more than 10 m/s. In multivariable analysis, we found a 0.2 increase in PWV m/s per treatment interruption event (0.2, 95% confidence interval 0.1–0.4) and a two-fold increased risk of PWV more than 10 m/s per treatment interruption event (adjusted odds ratio 2.2, 95% confidence interval 1.2–4.0). CONCLUSIONS: Treatment interruption in patients with ART for at least 35 years is a common and important risk factor for arterial stiffness. Therefore, the link between treatment interruption and cardiovascular disease in this setting in which traditional risks factors are less prevalent needs to be explored further

Moderate-to-vigorous physical activity modifies the relationship between sedentary time and sarcopenia: the Tromsø Study 2015–2016

Background: Sarcopenia is an age-related muscle disease primarily characterized by reductions in muscle strength that increases the risk of falls, fractures, cognitive impairment, and mortality. Exercise is currently preferred in prevention and treatment, but it is unknown how different habitual physical activity and sedentary behaviour patterns associate with sarcopenia status. The purpose of the present study was to compare associations of these patterns with probable sarcopenia in older adults. Methods: In 3653 community-dwelling participants (51% women) aged 60–84 years from the seventh survey of the Tromsø Study, we assessed objective physical activity and sedentary behaviour collected over 8 days (ActiGraph wGT3X-BT Accelerometer), grip strength (Jamar+ Digital Dynamometer), five-repetition chair stands, and self-reported disease. We combined tertiles of sedentary (SED) time and moderate-to-vigorous physical activity (MVPA) to create nine different activity profiles (SEDHIGH, SEDMOD, and SEDLOW combined with MVPAHIGH, MVPAMOD, or MVPALOW). Multiple logistic regression models were used to examine how these profiles associated with probable sarcopenia, defined by low handgrip strength and/or slow chair stands time according to the revised European Working Group on Sarcopenia in Older People criteria. Results: Probable sarcopenia was present in 227 (6.2%) participants. Men with probable sarcopenia had on average 35.3 min more SED time and 20 min less MVPA compared with participants without sarcopenia (P HIGH–MVPALOW reference activity profile (714.2 min SED/day and 10.4 min MVPA/day), the SEDHIGH–MVPAMOD profile (697.1 min SED/day and 31.5 min MVPA/day) had significantly lower odds ratio (OR) for probable sarcopenia (OR 0.17, 95% confidence interval [CI] 0.08–0.35), while the SEDLOW–MVPALOW profile (482.9 min SED/day and 11.0 min MVPA/day) did not (OR 0.72, 95% CI 0.47–1.11). These findings were not influenced by age, sex, smoking, or self-reported diseases, and higher levels of MVPA did not further decrease ORs for probable sarcopenia. Conclusions: Older adults who achieve moderate amounts of MVPA have reduced odds for probable sarcopenia, even when they have high sedentary time. Those with low sedentary time did not have reduced odds for probable sarcopenia when they also had low amounts of MVPA. These findings need confirmation in longitudinal studies but suggest that interventions for preventing sarcopenia should prioritize increasing MVPA over reducing sedentary behaviour

Species' geographic distributions through time: Playing catchup with changing climates

This is the author's accepted manuscript.Species’ ranges are often treated as a rather fixed characteristic, rather than a fluid, ever-changing manifestation of their ecological requirements and dispersal abilities. Paleontologists generally have had a more flexible point of view on this issue than neontologists, but each perspective can improve by appreciating the other. Here, we provide an overview of paleontological and neontological perspectives on species’ geographic distributions, focusing on what can be learned about historical variations in distributions. The cross-disciplinary view, we hope, offers some novel perspectives on species-level biogeography

Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions

Challenges of one-year longitudinal follow-up of a prospective, observational cohort study using an anonymised database:Recommendations for trainee research collaboratives

Background: trainee research collaboratives (TRCs) have pioneered high quality, prospective ‘snap-shot’ surgical cohort studies in the UK. Outcomes After Kidney injury in Surgery (OAKS) was the first TRC cohort study to attempt to collect one-year follow-up data. The aims of this study were to evaluate one-year follow-up and data completion rates, and to identify factors associated with improved follow-up rates. Methods: in this multicentre study, patients undergoing major gastrointestinal surgery were prospectively identified and followed up at one-year following surgery for six clinical outcomes. The primary outcome for this report was the follow-up rate for mortality at 1 year. The secondary outcome was the data completeness rate in those patients who were followed-up. An electronic survey was disseminated to investigators to identify strategies associated with improved follow-up. Results: of the 173 centres that collected baseline data, 126 centres registered to participate in one-year follow-up. Overall 62.3% (3482/5585) of patients were followed-up at 1 year; in centres registered to collect one-year outcomes, the follow-up rate was 82.6% (3482/4213). There were no differences in sex, comorbidity, operative urgency, or 7-day postoperative AKI rate between patients who were lost to follow-up and those who were successfully followed-up. In centres registered to collect one-year follow-up outcomes, overall data completeness was 83.1%, with 57.9% (73/126) of centres having ≥95% data completeness. Factors associated with increased likelihood of achieving ≥95% data completeness were total number of patients to be followed-up (77.4% in centres with < 15 patients, 59.0% with 15–29 patients, 51.4% with 30–59 patients, and 36.8% with > 60 patients, p = 0.030), and central versus local storage of patient identifiers (72.5% vs 48.0%, respectively, p = 0.006). Conclusions: TRC methodology can be used to follow-up patients identified in prospective cohort studies at one-year. Follow-up rates are maximized by central storage of patient identifiers

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

Male reproductive health and environmental xenoestrogens

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.Supported by EU Contract BMH4-CT96-0314