Moving towards the immunodiagnosis of staphylococcal intramammary infections

Bovine mastitis is the primary disease of dairy cattle that has a great impact on the dairy industry. It is estimated that worldwide economic losses due to mastitis range between US$82 and US$131 per cow/year. A fast and efficient diagnosis of the disease remains a major bottleneck that directly influences the speed with which treatment decisions and management are undertaken. Microbiological culture remains the gold standard in the identification of bacteria that cause mastitis, but the method has inherent limitations, such as a delay in obtaining results and cost, and requires special care during the collection and processing of the sample. For this reason, multiple groups have devoted efforts to develop alternative methods that, preferably, can be easily accomplished in the field. The specificity of the antigen–antibody reaction has enabled the emergence of major diagnostic methods used in clinical practice, such as immunoassays, which have significant advantages in terms of speed, sensitivity, specificity, and portability. Commercially, immunodiagnostics have been used in the detection of various diseases in cattle. However, in several cases, only a presumptive diagnosis can be made, which requires confirmation using culture-based methods. This review discusses the immunological-based assays developed since the 1990s for the detection of Staphylococcus aureus, which is considered the primary pathogen of contagious bovine mastitis. Although no ideal antigens ensure the accurate performance of tests and the costs need to be reduced to allow for good market competitiveness, immunoassays, particularly lateral flow immunoassay and immunoagglutination, have emerged as promising tests to be used in the field.     

Tackling nasal symptoms in athletes: Moving towards personalized medicine

Adequate nasal breathing is indispensable for athletes, and nasal symptoms have been shown to interfere with their subjective feeling of comfortable breathing and quality of life. Nasal symptoms are caused by either structural abnormalities or mucosal pathology. Structural pathologies are managed differently from mucosal disease, and therefore, adequate diagnosis is of utmost importance in athletes in order to choose the correct treatment option for the individual. Literature suggests that nasal symptoms are more prevalent in athletes compared to the general population and certain sports environments might even trigger the development of symptoms. Given the high demands of respiratory function in athletes, insight into triggering factors is of high importance for disease prevention. Also, it has been suggested that athletes are more neglectful to their symptoms and hence remain undertreated, meaning that special attention should be paid to education of athletes and their caregivers. This review aims at giving an overview of nasal physiology in exercise as well as the possible types of nasal pathology. Additionally, diagnostic and treatment options are discussed and we focus on unmet needs for the management and prevention of these symptoms in athletes within the concept of precision medicine.     

Predictors of ovarian response: progress towards individualized treatment in ovulation induction and ovarian stimulation

Ovarian stimulation is applied in the clinic to restore mono-ovulatory cycles in anovulatory women (ovulation induction) or to induce the development of multiple dominant follicles for assisted reproduction. Ovarian response is the endocrine and follicular reaction of the ovaries to stimulation. Achieving an appropriate ovarian response to anti-estrogens or exogenous gonadotrophins is central to ovulation induction and ovarian stimulation protocols. However, achieving an adequate response, without cycle cancellation or adverse events related to under- or over-stimulation, is complicated by high intra- and inter-individual variability. To predict each patient's ovarian response to medication for ovarian stimulation and to individualize the starting dose of exogenous gonadotrophin or the need for exogenous luteinizing hormone, various clinical, endocrine, ovarian ultrasonographic and genetic characteristics have been explored. Some of these features have been incorporated into prediction models. In this review, the methodology behind predictive factors and prediction models and their potential clinical applicability across ovulation induction and ovarian stimulation are explored.     

Understanding alternative splicing of Cav1.2 calcium channels for a new approach towards individualized medicine

Calcium channel blockers (CCBs) are widely used to treat cardiovascular diseases such as hypertension, angina pectoris, hypertrophic cardiomyopathy, and supraventricular tachycardia. CCBs selectively inhibit the inward flow of calcium ions through voltage-gated calcium channels, particularly Ca_v1.2, that are expressed in the cardiovascular system. Changes to the molecular structure of Ca_v1.2 channels could affect sensitivity of the channels to blockade by CCBs. Recently, extensive alternative splicing was found in Ca_v1.2 channels that generated wide phenotypic variations. Cardiac and smooth muscles express slightly different, but functionally important Ca_v1.2 splice variants. Alternative splicing could also modulate the gating properties of the channels and giving rise to different responses to inhibition by CCBs. Importantly, alternative splicing of Ca_v1.2 channels may play an important role to influence the outcome of many cardiovascular disorders. Therefore, the understanding of how alternative splicing impacts Ca_v1.2 channels pharmacology in various diseases and different organs may provide the possibility for individualized therapy with minimal side effects.     

Establishment of organoid models for pancreatic ductal adenocarcinoma and screening of individualized therapy strategy

Background : Patients with pancreatic ductal adenocarcinoma(PDAC) who undergo surgical resection and receive effective chemotherapy have the best chance for longterm survival. Unfortunately, because of the heterogeneity of pancreatic cancer, it is difficult to find a personalized treatment strategy for patients. Organoids are ideal preclinical models for personalized medicine. Therefore, we explore the cultivation conditions and construction methods of PDAC organoid models to screen the individu...     

Life events in bipolar disorder: towards more specific models

This article reviews the evidence concerning life events as a predictor of symptoms within bipolar disorder. First, key methodological issues in this area are described, and criteria used for including studies in this review are defined. Then findings that negative life events predict worse outcomes within bipolar disorder are reviewed. Beyond general studies on relapse, it is important to differentiate predictors of depression from predictors of mania. When severe negative life events occur, they appear to trigger increases in bipolar depression. Nonetheless, many depressions are unrelated to negative life events and appear to be triggered by other variables. The strongest evidence suggests that negative life events do not trigger mania, except perhaps in certain contexts. Retrospective findings for schedule-disrupting life events as a trigger for manic symptoms await further assessment within a longitudinal study. Life events involving goal attainment do appear to trigger manic symptoms. Overall, it is time to differentiate among specific types of life events, as these different forms of events point towards mechanisms linking stressors with symptom expression. These mechanisms provide clues into ways to integrate the social environment with biological vulnerability (see [Monroe, S.M., & Johnson, S.L. (1990)). the dimensions of life stress and the specificity of disorder. Journal of Applied Social Psychology, 20, 167-1694; Harris, T.O. (1991). Life stress and illness: the question of specificity. Annals of Behavioral Medicine, 13, 211-219]).     

Animal models of intellectual disability: towards a translational approach

Intellectual disability is a prevalent form of cognitive impairment, affecting 2-3% of the general population. It is a daunting societal problem characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social and practical adaptive skills. Intellectual disability is a clinically important disorder for which the etiology and pathogenesis are still poorly understood. Moreover, although tremendous progress has been made, pharmacological intervention is still currently non-existent and therapeutic strategies remain limited. Studies in humans have a very limited capacity to explain basic mechanisms of this condition. In this sense, animal models have been invaluable in intellectual disability investigation. Certainly, a great deal of the knowledge that has improved our understanding of several pathologies has derived from appropriate animal models. Moreover, to improve human health, scientific discoveries must be translated into practical applications. Translational research specifically aims at taking basic scientific discoveries and best practices to benefit the lives of people in our communities. In this context, the challenge that basic science research needs to meet is to make use of a comparative approach to benefit the most from what each animal model can tell us. Intellectual disability results from many different genetic and environmental insults. Taken together, the present review will describe several animal models of potential intellectual disability risk factors.     

3D打印个体化骨盆假体多孔结构物理性能检测方法研究

目的提出针对三维(3D)打印个体化骨盆假体多孔结构部分物理性能的检测方法并通过实验验证方法的可行性。方法设计3D打印个体化骨盆假体多孔结构孔径、丝径、孔隙率和抗压强度的检测方法。使用3D打印个体化骨盆假体样品和同等工艺制造的致密样件、多孔样件,对其各个项目分别进行了验证实验,并对实验结果进行了分析。结果根据文中提出的检测方法,测得实验样品的平均孔径为464.95μm,平均丝径为601.13μm,平均孔隙率为62.47%,平均抗压强度为48.0 MPa。结论提出了针对3D打印个体化骨盆假体多孔结构多项物理性能的检测方法,验证实验表明方法可行性,并且重复操作性良好,具有较高的应用价值。     

Stress and psychosis: towards the development of new models of investigation

The experience of stress is commonly implicated in the onset and maintenance of psychotic disorders such as schizophrenia. Previous studies that have addressed this relationship have had mixed results and serious methodological flaws associated with study design are common. One central limitation is the over-reliance on the experience of life events as a measure of the experience of stress. Research in the general stress literature suggest that attention also needs to be paid to the experience of other types of stressful events (such as 'hassles') as well as qualitative appraisals of events to fully understand the relationship between stressful experiences and mental health problems such as psychosis. Investigation of the experiences of stress by young people who are identified as being at heightened risk of developing a psychotic disorder would also result in a more complete understanding of the relationship between the experience of stress and the onset of psychotic disorder.     

Analytical models for multi-slice helical CT performance parameters

One of the most recent technological advancements in computed tomography (CT) is the introduction of multi-slice CT (MSCT). When combined with the helical scan mode, MSCT offers significant improvements in volume coverage, isotropic spatial resolution, and contrast utilization. Although experimental studies have been conducted on MSCT performance, there is a lack of theoretical analysis on the slice sensitivity profile (SSP) and noise performance. In this paper, we derive several closed-form expressions, for linear interpolation based helical reconstruction algorithms, to characterize these performance parameters under different detector configurations and acquisition modes. Following the common practice, the expressions are explicitly described for regions near the iso-center, although the same approach can be used to describe system performances away from the iso-center. These models are validated against phantom experiments.     

Rasch models of aphasic performance on syntactic comprehension tests

Responses of 42 people with aphasia to 11 sentence types in enactment and sentence-picture matching tasks were characterized using Rasch models that varied in the inclusion of the factors of task, sentence type, and patient group. The best fitting models required the factors of task and patient group but not sentence type. The results provide evidence that aphasic syntactic comprehension is best accounted for by models that include different estimates of patient ability in different tasks and different difficulty of all sentences in different groups of patients, but that do not include different estimates of patient ability for different types of sentences.     

Rasch models of aphasic performance on syntactic comprehension tests

Responses of 42 people with aphasia to 11 sentence types in enactment and sentence–picture matching tasks were characterized using Rasch models that varied in the inclusion of the factors of task, sentence type, and patient group. The best fitting models required the factors of task and patient group but not sentence type. The results provide evidence that aphasic syntactic comprehension is best accounted for by models that include different estimates of patient ability in different tasks and different difficulty of all sentences in different groups of patients, but that do not include different estimates of patient ability for different types of sentences.     

Reporting performance of prognostic models in cancer: a review

Background  

Appropriate choice and use of prognostic models in clinical practice require the use of good methods for both model development, and for developing prognostic indices and risk groups from the models. In order to assess reliability and generalizability for use, models need to have been validated and measures of model performance reported. We reviewed published articles to assess the methods and reporting used to develop and evaluate performance of prognostic indices and risk groups from prognostic models.     

Advances in individualized and regenerative medicine

Molecular and cell biology have resulted in major advances in our understanding of disease pathogenesis as well as in novel strategies for the diagnosis, therapy and prevention of human diseases. Based on modern molecular, genetic and biochemical methodologies it is on the one hand possible to identify for example disease-related point mutations and single nucleotide polymorphisms. On the other hand, using high throughput array and other technologies, it is for example possible to simultaneously analyze thousands of genes or gene products (RNA and proteins), resulting in an individual gene or gene expression profile (‘signature’). Such data increasingly allow to define the individual disposition for a given disease and to predict disease prognosis as well as the efficacy of therapeutic strategies in the individual patient (‘individualized medicine’). At the same time, the basic discoveries in cell biology, including embryonic and adult stem cells, induced pluripotent stem cells, genetically modified cells and others, have moved regenerative medicine into the center of biomedical research worldwide with a major translational impact on tissue engineering as well as transplantation medicine. All these aspects have greatly contributed to the recent advances in regenerative medicine and the development novel concepts for the treatment of many human diseases, including liver diseases.