南充市自发性脑出血发病与气温的相关性及滞后效应

目的分析南充市自发性脑出血（sICH）发病与气温的相关性及滞后关系。 方法收集南充市全市范围内二级以上医院2014年1月至2018年12月收治的sICH患者病例资料及同期气温数据，利用Spearman等级相关法确定最佳温度指标，将其组建分布滞后非线性模型，评估其与sICH日发病风险的暴露-剂量反应关系，分层分析各温度节点在性别及年龄组别的滞后-剂量反应关系。 结果共收集sICH患者资料13 952例。Spearman相关性分析揭示sICH日发病人数与日均气温呈非线性负相关（r=-0.324，P<0.05）。分布滞后非线性模型分析结果表明极低温和低温当天sICH的相对危险度为1.68（1.35~2.08）及1.47（1.24~1.72），危害效应最大，其随着滞后天数增加而减弱，极低温滞后1~2 d，低温持续滞后1~10 d。低龄组（18~60岁）在极低温、低温下滞后2 d，高龄组（>60岁）在极低温下滞后10 d，低温下滞后24 d。不同性别组在极低温、低温下滞后效应趋势一致，随滞后天数增加风险下降。 结论低温增加sICH发病风险，早期呈明显急性影响，且具有滞后效应，老年人对低温反应更加滞后。     

Bayesian bent‐cable growth mixture tobit models for longitudinal data with skewness and detection limit: application to AIDS studies

This paper presents a new Bayesian methodology for identifying a transition period for the development of drug resistance to antiretroviral drug or therapy in HIV/AIDS studies or other related fields. Estimation of such a transition period requires an availability of longitudinal data where growth trajectories of a response variable tend to exhibit a gradual change from a declining trend to an increasing trend rather than an abrupt change. We assess this clinically important feature of the longitudinal HIV/AIDS data using the bent‐cable framework within a growth mixture Tobit model. To account for heterogeneity of drug resistance among subjects, the parameters of the bent‐cable growth mixture Tobit model are also allowed to differ by subgroups (subpopulations) of patients classified into latent classes on the basis of trajectories of observed viral load data with skewness and left‐censoring. The proposed methods are illustrated using real data from an AIDS clinical study. Copyright © 2016 John Wiley & Sons, Ltd.     

Increased bladder permeability in interstitial cystitis/painful bladder syndrome

The definition of interstitial cystitis (IC) has evolved over the years from being a well-defined entity characterized by diagnostic lesion (Hunner’s ulcer) in the urothelium to a clinical diagnosis by exclusion [painful bladder syndrome (PBS)]. Although the etiology is unknown, a central theme has been an association with increased permeability of the bladder. This article reviews the evidence for increased permeability being important to the symptoms of interstitial cystitis/painful bladder syndrome (IC/PBS) and in treating the disorder. Recent work showing cross-communication among visceral organs is also reviewed to provide a basis for understanding IC/PBS as a systemic disorder of a complex, interconnected system consisting of the bladder, bowel and other organs, nerves, cytokine-responding cells and the nervous system.     

Obesity exacerbates imiquimod‐induced psoriasis‐like epidermal hyperplasia and interleukin‐17 and interleukin‐22 production in mice

Psoriasis is a chronic inflammatory skin disorder that is accompanied by an imbalance between the proliferation and differentiation of keratinocytes. A number of studies have suggested an association between obesity and severe psoriasis; however, it remains to be clarified whether obesity exacerbates psoriasis. To address this unsolved question, we induced psoriasiform dermatitis in mouse models for obesity. We found that obesity exaggerated the severity of psoriasiform dermatitis induced by topical application of the Toll‐like receptor (TLR) 7 agonist, imiquimod. Ear swelling and epidermal hyperplasia were more prominent in the obese mice than in the control mice. When compared to imiquimod‐treated control mice, imiquimod‐treated obese mice expressed higher levels of psoriasis mediators, interleukin‐17A (IL‐17A) and IL‐22 in the skin. Food intake restriction partially abrogated enhanced ear swelling and cytokine overproduction in obese mice. Furthermore, the obesity environment and imiquimod treatment synergistically induced an IL‐17A downstream molecule, regenerating islet‐derived 3γ (Reg3γ), which is a critical molecule for psoriatic epidermal hyperplasia. Palmitic acid, one of the fatty acids released by subcutaneous adipocytes, increased the expression of REG3A (a human homologue of mouse Reg3γ) in both the HaCaT keratinocyte cell line and normal human keratinocytes. Taken together, these results strongly suggest that obesity exacerbates psoriasiform dermatitis in mice by upregulating IL‐17A, IL‐22 and Reg3γ.     

Goal‐directed behaviors in patients with schizophrenia: Concept relevance and updated model

Goal‐directed behaviors are formulated to pursue a given objective by constructing a plan and selecting actions that lead to the intended goal, either immediately or over an extended period. This concept is important to the study of human behavior because of its involvement in the majority of complex or novel situations that an individual may encounter, regardless of the cognitive, affective, or social abilities required. In this paper, we aim to demonstrate the relevance of goal‐directed behaviors to our understanding of the cognitive deficits and other symptoms associated with schizophrenia. A systematic analysis of this relation may allow us to develop integrative hypotheses regarding positive, negative, and disorganized symptoms of schizophrenia rather than consider them to be distinct issues. In this article, we review previous studies of goal‐directed actions in patients with schizophrenia in order to clarify the relevant concepts and provide a theoretical basis for the integration of existing results. Based on available theoretical models and data, we propose an updated model to facilitate further investigation of schizophrenia‐related impairments in goal‐directed behaviors.     

Use of Monoclonal Antibodies in the Sensitive Detection and Neutralization of Botulinum Neurotoxin Serotype B

Botulinum neurotoxins (BoNT) are some of nature’s most potent toxins. Due to potential food contamination, and bioterrorism concerns, the development of detection reagents, therapeutics and countermeasures are of urgent interest. Recently, we have developed a sensitive electrochemiluminescent (ECL) immunoassay for BoNT/B, using monoclonal antibodies (mAbs) MCS6-27 and anti-BoNT/B rabbit polyclonal antibodies as the capture and detector. The ECL assay detected as little as 1 pg/mL BoNT/B in the buffer matrix, surpassing the detection sensitivities of the gold standard mouse bioassays. The ECL assay also allowed detection of BoNT/B in sera matrices of up to 100% sera with negligible matrix effects. This highly-sensitive assay allowed the determination of the biological half-lives of BoNT/B holotoxin in vivo. We further tested the toxin neutralization potential of our monoclonal antibodies using the mouse systemic and oral intoxication models. A combination of mAbs protected mice in both pre- and post-exposure models to lethal doses of BoNT/B. MAbs were capable of increasing survival of animals when administered even 10 h post-intoxication in an oral model, suggesting a likely time for BoNT/B complexes to reach the blood stream. More sensitive detection assays and treatments against BoNT intoxication will greatly enhance efforts to combat botulism.     

Spatial clustering of “measured” and “unmeasured” risk factors for HIV infections in hyper-endemic communities in KwaZulu-Natal,South Africa: results from geoadditive models

Sub-Saharan Africa contains more than 60% of all HIV infections worldwide. HIV prevalence was currently estimated to be at least 15% in KwaZulu-Natal and the epidemic is described as hyper-endemic. Knowledge of spatial clustering of risk factors which are linked to new HIV infections is important for prioritizing areas to change the trajectory of the epidemic. Geoadditive models were used to investigate spatial characteristics of the risk factors from two clinical trial units (Umkomaas and Botha's Hill) in the province of KwaZulu-Natal, South Africa. Study population was a cohort of women who screened and enrolled in an HIV prevention biomedical intervention trial. The results suggest high HIV incidence rates (5.8 and 8 per 100 person-year). Considerable spatial variations in behavioural factors within a relatively small geographical region, low level of education, early age at sexual debut, higher number of sexual partners, not being married/cohabitating with a sexual partner and sexual activity in exchange for money, gift and drugs were all determined to be clustered in certain regions; they were accounted for 25% (Umkomaas) and 65% (Botha's Hill) of the excess new HIV infections in two clinical trial units. Results from our study highlighted existence of significant spatial heterogeneity in “measured” and “unmeasured” risk factors in a relatively small region. As the HIV funding has been declining, identifying, targeting and reaching the most-at-risk individuals will likely play a significant role in developing the most efficient and cost-effective prevention programmes and subsequently will change the trajectory of the epidemic.     

Taxonomic Characterization and Secondary Metabolite Profiling of Aspergillus Section Aspergillus Contaminating Feeds and Feedstuffs

Xerophilic fungal species of the genus Aspergillus are economically highly relevant due to their ability to grow on low water activity substrates causing spoilage of stored goods and animal feeds. These fungi can synthesize a variety of secondary metabolites, many of which show animal toxicity, creating a health risk for food production animals and to humans as final consumers, respectively. Animal feeds used for rabbit, chinchilla and rainbow trout production in Argentina were analysed for the presence of xerophilic Aspergillus section Aspergillus species. High isolation frequencies (>60%) were detected in all the studied rabbit and chinchilla feeds, while the rainbow trout feeds showed lower fungal charge (25%). These section Aspergillus contaminations comprised predominantly five taxa. Twenty isolates were subjected to taxonomic characterization using both ascospore SEM micromorphology and two independent DNA loci sequencing. The secondary metabolite profiles of the isolates were determined qualitatively by HPLC-MS. All the isolates produced neoechinulin A, 17 isolates were positive for cladosporin and echinulin, and 18 were positive for neoechinulin B. Physcion and preechinulin were detected in a minor proportion of the isolates. This is the first report describing the detailed species composition and the secondary metabolite profiles of Aspergillus section Aspergillus contaminating animal feeds.     

Development and function of tissue resident macrophages in mice

Macrophages are important for tissue development, homeostasis as well as immune response upon injury or infection. For a long time they were only seen as one uniform group of phagocytes with a common origin and similar functions. However, this view has been challenged in the last decade and revealed a complex diversity of tissue resident macrophages. Here, we want to present the current view on macrophage development and tissue specification and we will discuss differences as well as common patterns between heterogeneous macrophage subpopulations.     

Animal models to evaluate anti‐atherosclerotic drugs

Atherosclerosis is a multifactorial condition characterized by endothelial injury, fatty streak deposition, and stiffening of the blood vessels. The pathogenesis is complex and mediated by adhesion molecules, inflammatory cells, and smooth muscle cells. Statins have been the major drugs in treating hypercholesterolemia for the past two decades despite little efficacy. There is an urgent need for new drugs that can replace statins or combined with statins. The preclinical studies evaluating atherosclerosis require an ideal animal model which resembles the disease condition, but there is no single animal model which mimics the disease. The animal models used are rabbits, rats, mice, hamsters, mini pigs, etc. Each animal model has its own advantages and disadvantages. The method of induction of atherosclerosis includes diet, chemical induction, mechanically induced injuries, and genetically manipulated animal models. This review mainly focuses on the various animal models, method of induction, the advantages, disadvantages, and the current perspectives with regard to preclinical studies on atherosclerosis.