Assessing the impacts of livestock production on biodiversity in rangeland ecosystems

Biodiversity in rangelands is decreasing, due to intense utilization for livestock production and conversion of rangeland into cropland; yet the outlook of rangeland biodiversity has not been considered in view of future global demand for food. Here we assess the impact of future livestock production on the global rangelands area and their biodiversity. First we formalized existing knowledge about livestock grazing impacts on biodiversity, expressed in mean species abundance (MSA) of the original rangeland native species assemblages, through metaanalysis of peer-reviewed literature. MSA values, ranging from 1 in natural rangelands to 0.3 in man-made grasslands, were entered in the IMAGE-GLOBIO model. This model was used to assess the impact of change in food demand and livestock production on future rangeland biodiversity. The model revealed remarkable regional variation in impact on rangeland area and MSA between two agricultural production scenarios. The area of used rangelands slightly increases globally between 2000 and 2050 in the baseline scenario and reduces under a scenario of enhanced uptake of resource-efficient production technologies increasing production [high levels of agricultural knowledge, science, and technology (high-AKST)], particularly in Africa. Both scenarios suggest a global decrease in MSA for rangelands until 2050. The contribution of livestock grazing to MSA loss is, however, expected to diminish after 2030, in particular in Africa under the high-AKST scenario. Policies fostering agricultural intensification can reduce the overall pressure on rangeland biodiversity, but additional measures, addressing factors such as climate change and infrastructural development, are necessary to totally halt biodiversity loss.     

Community Influences on Married Men’s Uptake of HIV Testing in Eight African Countries

Despite efforts to increase HIV testing in the African region, the proportion of men who report ever having been tested for HIV remains low. Research has focused on individual level determinants of women’s testing however little is known about factors associated with men’s testing behavior. This analysis investigates community influences on HIV testing among men ages 15–54, using Demographic and Health Survey (DHS) data from Chad, Ghana, Malawi, Nigeria, Tanzania, Uganda, Zambia, and Zimbabwe. Multilevel models were fitted in each country for the outcome of ever receiving an HIV test. After controlling for individual and household level factors, community level factors of demographics, economics, and behavior and knowledge remain significantly associated with HIV testing among men. The results of this analysis highlight the need to recognize the impact of community influences on men’s HIV test seeking behavior, and to harness these community factors in the design of programs aimed at encouraging the uptake of HIV testing among men in Africa.     

Unraveling toxicological mechanisms and predicting toxicity classes with gene dysregulation networks

The use of genes for distinguishing classes of toxicity has become well established. In this paper we combine the reconstruction of a gene dysregulation network (GDN) with a classifier to assign unseen compounds to their appropriate class. Gene pairs in the GDN are dysregulated in the sense that they are linked by a common expression pattern in one class and differ in this pattern in another class. The classifier gives a quantitative measure on this difference by its prediction accuracy. As an in‐depth example, gene pairs were selected that were dysregulated between skin cells treated with either sensitizers or irritants. Pairs with known and novel markers were found such as HMOX1 and ZFAND2A, ATF3 and PPP1R15A, OXSR1 and HSPA1B, ZFP36 and MAFF. The resulting GDN proved biologically valid as it was well‐connected and enriched in known interactions, processes and common regulatory motifs for pairs. Classification accuracy was improved when compared with conventional classifiers. As the dysregulated patterns for heat shock responding genes proved to be distinct from those of other stress genes, we were able to formulate the hypothesis that heat shock genes play a specific role in sensitization, apart from other stress genes. In conclusion, our combined approach creates added value for classification‐based toxicogenomics by obtaining novel, well‐distinguishing and biologically interesting measures, suitable for the formulation of hypotheses on functional relationships between genes and their relevance for toxicity class differences. Copyright © 2012 John Wiley & Sons, Ltd.     

Predicting In Vivo Efficacy of Therapeutic Bacteriophages Used To Treat Pulmonary Infections

The potential of bacteriophage therapy to treat infections caused by antibiotic-resistant bacteria has now been well established using various animal models. While numerous newly isolated bacteriophages have been claimed to be potential therapeutic candidates on the basis of in vitro observations, the parameters used to guide their choice among billions of available bacteriophages are still not clearly defined. We made use of a mouse lung infection model and a bioluminescent strain of Pseudomonas aeruginosa to compare the activities in vitro and in vivo of a set of nine different bacteriophages (PAK_P1, PAK_P2, PAK_P3, PAK_P4, PAK_P5, CHA_P1, LBL3, LUZ19, and PhiKZ). For seven bacteriophages, a good correlation was found between in vitro and in vivo activity. While the remaining two bacteriophages were active in vitro, they were not sufficiently active in vivo under similar conditions to rescue infected animals. Based on the bioluminescence recorded at 2 and 8 h postinfection, we also define for the first time a reliable index to predict treatment efficacy. Our results showed that the bacteriophages isolated directly on the targeted host were the most efficient in vivo, supporting a personalized approach favoring an optimal treatment.     

Pharmacokinetics of First-Line Tuberculosis Drugs in Tanzanian Patients

East Africa has a high tuberculosis (TB) incidence and mortality, yet there are very limited data on exposure to TB drugs in patients from this region. We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling. In 20 adult TB patients, plasma concentrations were determined just before and at 1, 2, 3, 4, 6, 8, 10, and 24 h after observed drug intake with food to estimate the areas under the curve from 0 to 24 h (AUC_0–24) and peak plasma concentrations (C_max) of isoniazid, rifampin, pyrazinamide, and ethambutol. Acetylator status for isoniazid was assessed phenotypically using the isoniazid elimination half-life and the acetylisoniazid/isoniazid metabolic ratio at 3 h postdose. The geometric mean AUC_0–24s were as follows: isoniazid, 11.0 h · mg/liter; rifampin, 39.9 h · mg/liter; pyrazinamide, 344 h · mg/liter; and ethambutol, 20.2 h · mg/liter. The C_max was below the reference range for isoniazid in 10/19 patients and for rifampin in 7/20 patients. In none of the patients were the C_maxs for pyrazinamide and ethambutol below the reference range. Elimination half-life and metabolic ratio of isoniazid gave discordant phenotyping results in only 2/19 patients. A substantial proportion of patients had an isoniazid and/or rifampin C_max below the reference range. Intake of TB drugs with food may partly explain these low drug levels, but such a drug intake reflects common practice. The finding of low TB drug concentrations is concerning because low concentrations have been associated with worse treatment outcome in several other studies.     

Similar risk of complete revision for infection with single-dose versus multiple-dose antibiotic prophylaxis in primary arthroplasty of the hip and knee: results of an observational cohort study in the Dutch Arthroplasty Register in 242,179 patients

Background and purpose — The optimal type and duration of antibiotic prophylaxis for primary arthroplasty of the hip and knee are subject to debate. We compared the risk of complete revision (obtained by a 1- or 2-stage procedure) for periprosthetic joint infection (PJI) after primary total hip or knee arthroplasty between patients receiving a single dose of prophylactic antibiotics and patients receiving multiple doses of antibiotics for prevention of PJI.Patients and methods — A cohort of 130,712 primary total hip and 111,467 knee arthroplasties performed between 2011 and 2015 in the Netherlands was analyzed. We linked data from the Dutch arthroplasty register to a survey collected across all Dutch institutions on hospital-level antibiotic prophylaxis policy. We used restricted cubic spline Poisson models adjusted for hospital clustering to compare the risk of revision for infection according to type and duration of antibiotic prophylaxis received.Results — For total hip arthroplasties, the rates of revision for infection were 31/10,000 person-years (95% CI 28–35), 39 (25–59), and 23 (15–34) in the groups that received multiple doses of cefazolin, multiple doses of cefuroxime, and a single dose of cefazolin, respectively. The rates for knee arthroplasties were 27/10,000 person-years (95% CI 24–31), 40 (24–62), and 24 (16–36). Similar risk of complete revision for infection among antibiotic prophylaxis regimens was found when adjusting for confounders.Interpretation — In a large observational cohort we found no apparent association between the type or duration of antibiotic prophylaxis and the risk of complete revision for infection. This does question whether there is any advantage to the use of prolonged antibiotic prophylaxis beyond a single dose.

Annually around 1 million patients receive a total hip or total knee prosthesis in the United States and over 190,000 hip and knee replacements are performed in England and Wales (Maradit et al. 2015, National Joint Registry for England and Wales 2018). The incidences of prosthetic replacement of the hip and knee are expected to increase (Kurtz et al. 2014). Prosthetic joint infection (PJI) following total hip or knee arthroplasty and the treatment thereof are catastrophic for patients and pose tremendous costs to healthcare systems (Poultsides et al. 2010, Zmistowski et al. 2013, Moore et al. 2015). Perioperative antibiotic prophylaxis remains an effective method of reducing the risk of PJI (Illingworth et al. 2013, Thornley et al. 2015). The type and duration of antibiotic prophylaxis are subject to debate.Both single-dose and multiple-dose antibiotic prophylaxis regimens have been advocated with comparable results (Thornley et al. 2015, Tan et al. 2019). The recommendations provided by the Second International Consensus Meeting of the MusculoSkeletal Infection Society (MSIS) and the European Bone and Joint Infection Society (EBJIS) advise that antibiotic prophylaxis should be administered 30–60 minutes before incision and discontinued within 24 hours after surgery (Hansen et al. 2014, Parvizi and Gehrke 2018). Large variation in prophylaxis regimens has been observed in the United Kingdom (Hickson et al. 2015). The Dutch national orthopedic association advises administration of antibiotic prophylaxis using a first- or second-generation cephalosporin starting 30–60 minutes preoperatively and discontinuing the antibiotic prophylaxis within 24 hours (Swierstra et al. 2009, Nederlandse Orthopaedische Vereniging 2018). The World Health Organization and, in the USA, the Centers for Disease Control and Prevention (CDC) recommend against the use of postoperative continuation of antibiotic prophylaxis and advocate for a single dose of antibiotics delivered preoperatively (Berrios-Torres et al. 2017). This recommendation is vehemently challenged by the American Association of Hip and Knee Surgeons and the International Consensus Meeting, which encourage their members to proceed with the current common practice of multiple-dose antibiotic prophylaxis protocols until more evidence is available (Yates 2018).We compared the risk of complete revision for infection in the 1st year following primary hip and knee arthroplasty according to the perioperatively administered antibiotic prophylaxis regimen by using data from the Dutch Arthroplasty Register (LROI).     

Coincident plasma ACTH and corticosterone time series: Comparisons between young and old rats

Senescence is accompanied by a reduced ability to respond to a variety of physical and behavioral stressors. A sizable literature has been devoted to the interplay between hypothalamic-pituitary-adrenocortical axis dysfunction and senescence; yet, the precise interactions remain an enigma. Adrenocorticotropic hormone (ACTH) is secreted in pulsatile bursts generating complex signals in the plasma compartment that must be “read” by adrenocortical cells in order to initiate appropriate secretory responses. We have previously demonstrated subtle differences between young and old rats in the pattern of fluctuations in plasma ACTH concentrations over time, despite no difference in mean levels. The present work addressed the physiological significance of these differences in the plasma ACTH signal by analyzing the corresponding plasma corticosterone concentration time series and the relationship between these two hormones over time. Time series of integrated 10-min ACTH and corticosterone concentrations were collected over 4 h at the time of diurnal activation and analyzed in the time and frequency domains. The time of onset of the diurnal surge occurred 20 min later in old rats, and the ratio of corticosterone to ACTH was less at the time of onset and peak of the diurnal surge. Corticosterone levels were lower in old rats and mean ACTH and corticosterone levels were correlated in young but not old rats, as were maximum levels of the two hormones. Cross-correlation of ACTH and corticosterone time series and comparison of spectra were consistent with smoother fluctuations in plasma corticosterone in old animals with less variability at time scales less than 55 min. We conclude that age may be associated with a delay in diurnal activation of the HPA axis, a loss of sensitivity of adrenal corticosterone secretion to plasma ACTH levels, and a relative loss of high frequency variability in the corticosterone signal, as seen in many physiological systems with age.     

Risk Factors for Thromboembolic Complications in Inflammatory Bowel Disease: The Role of Hyperhomocysteinaemia

Inflammatory bowel disease (IBD) is associated with an increased risk for thromboembolic events. Aim of this study was to examine the relationship of hyperhomocysteinemia and thrombosis in IBD patients and to assess the role of this factor in addition to other known prothrombotic abnormalities. IBD patients with a history of thrombosis (n = 22) and sex-, age-, and diagnosis-matched IBD controls (n = 23) were studied. Homocysteine (tHcy) was assessed before and after methionine loading. Plasma levels of protein C, protein S, antithrombin III, and fibrinogen and the presence of anticardiolipin and antiphospholipid antibodies were determined and genetic testing for factor V Leiden and the prothrombin gene mutation was performed. Results showed that fasting homocysteine levels in IBD patients with a history of arterial or venous thrombosis tended to be higher than in IBD controls, although not significantly. The increase in homocysteine levels after methionine loading was significantly higher in IBD patients in the arterial thrombosis group than in IBD controls (40.9 ± 17.7 vs. 27.2 ± 9.9 M; P < 0.05). Among the other prothrombotic factors, only factor V Leiden was significantly associated with a history of venous thrombosis (20 vs. 0%). At least one risk factor was found in 64% of the IBD patients with previous thromboembolic complications. We conclude that there is an association between hyperhomocysteinemia and a history of arterial thrombosis in IBD patients. We confirm the high prevalence of factor V Leiden in IBD patients with a history of venous thrombosis. In the majority of IBD patients with previous thromboembolic complications, at least one prothrombotic risk factor is detected.