Dictyocaulus viviparus bulk tank milk seropositivity is correlated with meteorological variables

Control of infections with Dictyocaulus viviparus is difficult due to its volatile epidemiology. In the absence of predictive models, ‘vigilance and treatment’ is today’s mainstay for control. In order to evaluate the potential of predictive model development to support a more preventative approach, this longitudinal study aimed at understanding the influence of weather factors on D. viviparus bulk tank milk antibody ELISA results. Bulk tank milk samples were analysed with a Major Sperm Protein-based ELISA (expressed as an optical density ratio) twice monthly on 717 Flemish dairy farms during the grazing season (April–October) in 2018. Meteorological data of the sampled farms were obtained at 1 km spatial scale using the ALARO-SURFEX climate model. A mixed effects model showed that the bulk tank milk optical density ratio was significantly associated with the month of sampling, evapotranspiration, temperature and its quadratic term, the number of hot days and the number of rainy days in the 7–8 weeks prior to sampling. There were significant farm effects involved. The model’s accuracy to predict bulk tank milk optical density ratio infection status was 80%, while optical density ratios were generally overestimated by 38%. Inclusion of the previous (2-week-old) optical density ratio values increased accuracy to 86% and reduced the mean square error. We conclude that meteorological parameters have a predictive value for bulk tank milk optical density ratio results, while further research should evaluate model improvements through the addition of herd management factors as well as confirm the predictive power through external validation in additional farms and years.     

Fracture prevention in COPD patients; a clinical 5-step approach

Although osteoporosis and its related fractures are common in patients with COPD, patients at high risk of fracture are poorly identified, and consequently, undertreated. Since there are no fracture prevention guidelines available that focus on COPD patients, we developed a clinical approach to improve the identification and treatment of COPD patients at high risk of fracture. We organised a round-table discussion with 8 clinical experts in the field of COPD and fracture prevention in the Netherlands in December 2013. The clinical experts presented a review of the literature on COPD, osteoporosis and fracture prevention. Based on the Dutch fracture prevention guideline, they developed a 5-step clinical approach for fracture prevention in COPD. Thereby, they took into account both classical risk factors for fracture (low body mass index, older age, personal and family history of fracture, immobility, smoking, alcohol intake, use of glucocorticoids and increased fall risk) and COPD-specific risk factors for fracture (severe airflow obstruction, pulmonary exacerbations and oxygen therapy). Severe COPD (defined as postbronchodilator FEV₁ < 50% predicted) was added as COPD-specific risk factor to the list of classical risk factors for fracture. The 5-step clinical approach starts with case finding using clinical risk factors, followed by risk evaluation (dual energy X-ray absorptiometry and imaging of the spine), differential diagnosis, treatment and follow-up. This systematic clinical approach, which is evidence-based and easy-to-use in daily practice by pulmonologists, should contribute to optimise fracture prevention in COPD patients at high risk of fracture.     

A Dutch Approach to the European Directive on Integrated Pollution Prevention and Control: Using Life-Cycle Assessment for the Integrated Assessment of Technologies

In light of the European Directive on Integrated Pollution Prevention and Control (IPPC Directive), traditional environmental regulation can be improved using the framework of industrial ecology. The objective of the IPPC Directive is to achieve a high level of protection of the environment as a whole (Article 1) by applying the best available techniques (BAT). In essence, the IPPC Directive obliges member states of the European Union to include considerations such as resources, energy, waste, and multimedia emissions when permitting industrial installations. This is a marked contrast to traditional environmental regulation that focuses on individual media of an individual site. In order to take all considerations into account, an integrated assessment of technologies is needed, for which a standard method is currently lacking.
In this article, a systematic approach is introduced for the integrated assessment of IPPC technologies using life-cycle assessment (LCA), a form of environmental assessment that can be broadened to an overall assessment of environmental, economic, and social aspects. This systematic approach has proven to be successful for the environmental assessment of the described cases. It is suggested here that weighting can be omitted for the evaluation of IPPC technologies. Leaving the weighting step to competent authorities of member states and allowing them to consider local issues provides maximum opportunity for the subsidiarity and flexibility principles of the IPPC Directive.     

Harnessing host immune responses to preneoplasia: promise and challenges

Preneoplastic lesions are more common than clinical cancer and define a population at increased risk for the development of malignancy. Recent studies suggest that the immune system has the capacity to recognize these lesions, and enrichment of preneoplasia-specific immune effectors can be detected in the tumor bed of some preneoplastic lesions such as monoclonal gammopathies. Here, I discuss the promise and challenges of harnessing the immune response against preneoplasia. Approaches to boost the natural host response to these lesions may have a major impact on reducing net cancer burden.     

Antiarrhythmic Mechanisms of n-3 PUFA and the Results of the GISSI-Prevenzione Trial

The purpose of this paper is twofold: on the one hand, to confirm the positive results on n-3 PUFA from the overall results Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GlSSI)-Prevenzione trial; on the other, to summarize and describe how the results of an important trial can help generate hypotheses either on mechanisms of action or on differential results in particular subgroups of patients, as well as test the pathophysiological hypotheses that have accompanied in the years the story of the hypothesized mechanisms of action of a drug. GISSI-Prevenzione was conceived as a pragmatic population trial on patients with recent myocardial infarction and it was conducted in the framework of the Italian public health system. In GISSI-Prevenzione, 11,323 patients were enrolled in a clinical trial aimed at testing the effectiveness of n-3 polyunsaturated fatty acids (PUFA) and vitamin E. Patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term n-3 PUFA at 1 g daily, but not vitamin E at 300 mg daily, was beneficial for death and for combined death, non-fatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall (−20%), cardiovascular (−30%), and sudden death (−45%). At variance from the orientation of a scientific scenario largely dominated by the “cholesterol-heart hypothesis”, GISSI-Prevenzione results indicate n-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico (GISSI) Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO), Italy. Istituto di Ricerche Farmacologiche Mario Negri - Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy *The names of GISSI-Prevenzione Investigators are reported in Lancet 1999; 354:447–55. (40)     

Proanthocyanidin exposure to B6C3F1 mice significantly attenuates dimethylnitrosamine-induced liver tumor induction and mortality by differentially modulating programmed and unprogrammed cell deaths

Proanthocyanidins are of current interest as chemopreventive agents. The potential of the pre-, post- and co-exposure of proanthocyanidin-rich grape seed extract (GSPE) in preventing, reducing and/or delaying dimethylnitrosamine (N-nitrosodimethylamine, DMN)-induced liver tumorigenesis, carcinogenesis and mortality in male B6C3F1 mice was determined. Animals were divided into six groups: I—control, II—GSPE alone, III—DMN alone, IV—GSPE + DMN, V—DMN exposure (3 months) followed by GSPE diet (9 months) and VI—GSPE diet (3 months) + DMN (3 months) + control diet (6 months). DMN exposure (0–8 weeks: 5 mg/kg; 8–12 weeks: 10 mg/kg, i.p.) was limited to a total period of 3 months. GSPE was incorporated in laboratory chow (ADI: 100 mg/kg b.w.). Animals were sacrificed at 3 month intervals, and serum chemistry, liver histopathology, integrity of hepatic genomic DNA, antioxidant status, and rates of apoptotic and necrotic cell deaths were determined. DMN-induced liver tumor formation (85%) and animal lethality (38%) were powerfully antagonized by co-administration of GSPE + DMN (tumor positive: 45%; death: 11%). More than 75% of the DMN-treated animals had numerous tumors (five or more), which were significantly reduced in the GSPE + DMN group (35%). GSPE also negatively influenced other protocols specifically designed to test initiation and progression phases. Thus, GSPE was instrumental in modulating metabolic cascades and regulated orchestration of cell death processes involved during the multistage tumorigenic process. These results unraveled that long-term exposure to proanthocyanidin-rich grape seed extract may serve as a potent barrier to all three stages of DMN-induced liver carcinogenesis and tumorigenesis by selectively altering oxidative stress, genomic integrity and cell death patterns in vivo.     

Biotechnological advances in the diagnosis of avian coccidiosis and the analysis of genetic variation in Eimeria

Coccidiosis is an intestinal disease of chickens caused by various species of protozoan parasites within the genus Eimeria. This disease has a major economic impact to growers and to the poultry industry world-wide. The diagnosis and genetic characterization of the different species of Eimeria are central to the prevention, surveillance and control of coccidiosis, particularly now given the major problems with wide-spread resistance of Eimeria species against anticoccidial drugs (coccidiostats) and the residue problems associated with these compounds. While traditional methods have had major limitations in the specific diagnosis of coccidiosis, there have been significant advances in the development of molecular-diagnostic tools. The present article provides a background on coccidiosis, reviews the main molecular methods which have been used and describes recent advances in the establishment of polymerase chain reaction (PCR)-coupled electrophoretic approaches for the specific diagnosis of coccidiosis as well as the genetic characterization of species of Eimeria. These biotechnological advances are considered to represent a significant step toward the improved prevention and control of this important disease of poultry.     

Extremely low penetrance of deafness associated with the mitochondrial 12S rRNA mutation in 16 Chinese families: implication for early detection and prevention of deafness

Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here the clinical, genetic, and molecular characterization of 16 Chinese pedigrees (a total of 246 matrilineal relatives) with aminoglycoside-induced impairment. Clinical evaluation revealed the variable phenotype of hearing impairment including audiometric configuration in these subjects, although these subjects share some common features: being bilateral and sensorineural hearing impairment. Strikingly, these Chinese pedigrees exhibited extremely low penetrance of hearing loss, ranging from 4% to 18%, with an average of 8%. In particular, nineteen of 246 matrilineal relatives in these pedigrees had aminoglycoside-induced hearing loss. Mutational analysis of the mtDNA in these pedigrees showed the presence of homoplasmic 12S rRNA A1555G mutation, which has been associated with hearing impairment in many families worldwide. The extremely low penetrance of hearing loss in these Chinese families carrying the A1555G mutation strongly supports the notion that the A1555G mutation itself is not sufficient to produce the clinical phenotype. Children carrying the A1555G mutation are susceptible to the exposure of aminoglycosides, thereby inducing or worsening hearing impairment, as in the case of these Chinese families. Using those genetic and molecular approaches, we are able to diagnose whether children carry the ototoxic mtDNA mutation. Therefore, these data have been providing valuable information and technology to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside therapy, and eventually to decrease the incidence of deafness.     

Informative Dorfman screening

Since the early 1940s, group testing (pooled testing) has been used to reduce costs in a variety of applications, including infectious disease screening, drug discovery, and genetics. In such applications, the goal is often to classify individuals as positive or negative using initial group testing results and the subsequent process of decoding of positive pools. Many decoding algorithms have been proposed, but most fail to acknowledge, and to further exploit, the heterogeneous nature of the individuals being screened. In this article, we use individuals' risk probabilities to formulate new informative decoding algorithms that implement Dorfman retesting in a heterogeneous population. We introduce the concept of "thresholding" to classify individuals as "high" or "low risk," so that separate, risk-specific algorithms may be used, while simultaneously identifying pool sizes that minimize the expected number of tests. When compared to competing algorithms which treat the population as homogeneous, we show that significant gains in testing efficiency can be realized with virtually no loss in screening accuracy. An important additional benefit is that our new procedures are easy to implement. We apply our methods to chlamydia and gonorrhea data collected recently in Nebraska as part of the Infertility Prevention Project.     

微生态制剂预防儿科ICU抗生素相关性腹泻的临床观察

目的 探讨在儿科ICU住院患儿中应用微生态制剂预防抗生素相关性腹泻的效果。方法 对符合研究的580例入住PICU的患儿,随机分为预防组和对照组,预防组在常规治疗基础上加用微生态制剂（金双歧）常规剂量口服或经鼻饲管给药直至出院,观察2组之间发生抗生素相关性腹泻的差异显著性。结果 580例分为预防组286例,对照组294例,腹泻预防组的发生率为5.24%,对照组的发生率为12.93%,预防组的发生率较对照组低（P＜0.05）。结论 儿科ICU住院患儿常规加用微生态制剂可以很好地预防抗生素相关性腹泻。其机制认为与微生态制剂具有保持肠道微生态平衡、提高局部和全身的免疫功能有关。