Origins of Psychiatric Hospitalization in Medieval Spain

Specification of the earliest institution devoted primarily to the treatment of the mentally ill in the Western World remains elusive. Uncertainty arises from limited documentation and gradual evolution of most candidate sites from hospices for the poor, foreign, or homeless, or as clinical centers for the care of a range of persons with general medical and psychiatric disorders. Plausible candidates identified in the late fourteenth and early fifteenth centuries include Bethlem Asylum in London. Much less often considered are two centers in medieval Spain: the Moorish Maristan at Granada (1365) and the Christian Hospital of Our Lady Mary for Lunatics, the Insane and Innocents at Valencia (1409). Since the early Spanish sites are not well known, we have summarized available information concerning their foundation, facilities, theories and practices, as arising from the cultural and political background of the times and regions.     

Well-being in clozapine-treated schizophrenia patients: The significance of positive symptoms

ObjectivesWell-being perception is seldom explored in schizophrenia patients. Recurrent limitations, such as the questionable applicability of gold standard definitions of health and well-being, and fewer tools available to assess well-being, are pronounced in this subpopulation. This cross-sectional study sought to explore potential clinical factors that may predict subjective well-being scores in chronic schizophrenia patients (N = 142) receiving clozapine treatment.MethodsThe Short Warwick–Edinburgh Mental Well-being Scale (SWEMWBS) was used to measure well-being. We correlated SWEMWBS scores and 27 clinically recognized factors, spanning socio-demographics, symptom severity scores, physical health diagnosis, clozapine side effects, habits and prescribed medication. Factors with a p < 0.2 correlation were included as a predictors in a linear regression model.ResultsTen factors were included in the linear regression model, however only positive symptom severity was a significant predictor of SWEMWBS score (p < 0.0001).ConclusionsWe suggest that greater levels of clinical attention given to positive symptoms compared with other symptoms and aspects of well-being, during biomedical treatment for chronic schizophrenia, may partially explain the finding that only positive symptoms significantly predicted patient perceptions of low well-being.     

Andrology: Studies on the development of diluents for the transportation and storage of human semen at ambient temperature

Storage of human semen samples at ambient temperature for 24h resulted in a significant loss of sperm motility from a mean45.1±1.8% to 13.8±1.1% (n = 148). This motilityloss was associated with a significant increase in the osmolalityof the seminal plasma and the induction of peroxidative damageto the spermatozoa. Both of these detrimental changes couldbe prevented by diluting the original semen sample 1:1 witha citrate-egg yolk buffer (CYB). In the presence of this extenderall aspects of semen quality were efficiently preserved for24 h, including sperm movement, penetration of a cervical mucussubstitute, the acrosome reaction and sperm-oocyte fusion. CYBextension also permitted the use of chemiluminescent tests ofleukocyte contamination to be performed on semen samples storedfor 24 h at ambient temperatures. As a preservation medium,CYB was found to be superior to alternative formulations lackingcitrate and storage at ambient temperatures was preferable to4°C. Significant improvements in motility retention werealso observed when CYB was supplemented with pentoxifylline,although this treatment significantly stimulated peroxidativedamage in the spermatozoa. However, if the pentoxifylline wascombined with antioxidants then this collateral peroxidativedamage could be reduced and the performance of CYB significantlyenhanced. These results have implications for the design ofdiluents permitting the long-term storage and transportationof human semen samples at ambient temperatures.     

偏倚风险评估系列:(九)如何应用偏倚风险评估的结果

本文为偏倚风险评估系列讲座的最后一节,主要讨论偏倚风险评估结果的应用。偏倚风险评估是证据质量评估中关键的一环,能为循证决策提供重要的参考依据。偏倚风险评估结果可以用于单个研究的偏倚风险诊断,其结果可影响系统综述中对于原始研究的纳入排除和数据的分析。此外,本文重点讨论偏倚风险评估的结果如何应用到推荐分级的评价、制订与评估（GRADE）的整体证据质量评价,包括证据质量评价中的原则以及注意事项。     

偏倚风险评估系列:(六)诊断试验

本讲座详细介绍了诊断试验准确性研究的偏倚评估工具（QUADAS-2）的主要内容,同时阐述了QUADAS-2的开发过程及与第一版QUADAS工具的区别,并举例说明QUADAS-2的使用方法和注意事项。QUADAS-2相比第一版QUADAS工具有巨大改进,例如QUADAS-2删除了QUADAS中易混淆的条目内容,仅通过对重叠度最小的4个关键领域（Domain）的描述和对每个领域内信号问题的回答完成偏倚风险和适用性两个核心方面的评价,最后得出原始研究每个领域的偏倚风险和适用性为高（High）、低（Low）或不清楚（Unclear）的结论,而不再是给出原始研究质量评价的总分,这与Cochrane干预措施系统综述中偏倚风险的评估一致。同时,QUADAS-2还可以应用于金标准中包括随访但不涉及预后问题的原始研究的偏倚风险评价。虽然开展QUADAS-2评价需要花费更多时间,但这对于诊断准确性研究的偏倚风险评价非常重要。QUADAS-2研究组后续还将在比较多种待评价诊断试验的原始研究中应用QUADAS-2进行偏倚风险评估,使用者可持续关注其进展,同时也可在线反馈使用体验或提供改进建议。     

Genomic evidence that the live Chlamydia abortus vaccine strain 1B is not attenuated and has the potential to cause disease

BackgroundThe live, temperature-attenuated vaccine strain 1B of Chlamydia abortus, the aetiological agent of ovine enzootic abortion (OEA), has been implicated in cases of vaccine breakdown. The aim of this study was to understand the nature of this attenuation through sequencing of the vaccine parent strain (AB7) and the derived mutant strains 1B and 1H, as well as to clarify the role of the vaccine strain in causing disease through comparative whole genome analysis.MethodsWhole genome sequencing was performed on: vaccine parent strain AB7; N-methyl-N′-nitro-N-nitrosoguanidine (NTG)-induced temperature attenuated mutant strain 1B grown from the commercial live vaccines Cevac Chlamydia and Enzovax; strain 1H a reverted NTG mutant; and 5 strains isolated from cases of OEA originating from animals from the original vaccine safety trial (2 strains) or from vaccinated ewes or ewes exposed to vaccinated animals (3 strains).ResultsWe confirmed that AB7 is in a different lineage from the reference strain S26/3. The genome of vaccine strain 1B contains ten single nucleotide polymorphisms (SNPs) created by the NTG treatment, which are identical to those found in strain 1H. The strains from OEA cases also cluster phylogenetically very tightly with these vaccine strains.ConclusionsThe results show that C. abortus vaccine strain 1B has an identical genome sequence to the non-attenuated “reverted mutant” strain 1H. Thus, the protection of the 1B vaccine is unlikely to be due to the NTG induced SNPs and is more likely caused by the administration of high doses of C. abortus elementary bodies that stimulate protective immunity. Vaccine-identical strains were also isolated from cases of disease, as well as strains which had acquired 1–3 SNPs, including an animal that had not been vaccinated with either of the commercial live OEA vaccines, indicating that the 1B vaccine strain may be circulating and causing disease.     

An ontology-based comparative anatomy information system

Introduction

This paper describes the design, implementation, and potential use of a comparative anatomy information system (CAIS) for querying on similarities and differences between homologous anatomical structures across species, the knowledge base it operates upon, the method it uses for determining the answers to the queries, and the user interface it employs to present the results. The relevant informatics contributions of our work include (1) the development and application of the structural difference method, a formalism for symbolically representing anatomical similarities and differences across species; (2) the design of the structure of a mapping between the anatomical models of two different species and its application to information about specific structures in humans, mice, and rats; and (3) the design of the internal syntax and semantics of the query language. These contributions provide the foundation for the development of a working system that allows users to submit queries about the similarities and differences between mouse, rat, and human anatomy; delivers result sets that describe those similarities and differences in symbolic terms; and serves as a prototype for the extension of the knowledge base to any number of species. Additionally, we expanded the domain knowledge by identifying medically relevant structural questions for the human, the mouse, and the rat, and made an initial foray into the validation of the application and its content by means of user questionnaires, software testing, and other feedback.

Methods

The anatomical structures of the species to be compared, as well as the mappings between species, are modeled on templates from the Foundational Model of Anatomy knowledge base, and compared using graph-matching techniques. A graphical user interface allows users to issue queries that retrieve information concerning similarities and differences between structures in the species being examined. Queries from diverse information sources, including domain experts, peer-reviewed articles, and reference books, have been used to test the system and to illustrate its potential use in comparative anatomy studies.

Results

157 test queries were submitted to the CAIS system, and all of them were correctly answered. The interface was evaluated in terms of clarity and ease of use. This testing determined that the application works well, and is fairly intuitive to use, but users want to see more clarification of the meaning of the different types of possible queries. Some of the interface issues will naturally be resolved as we refine our conceptual model to deal with partial and complex homologies in the content.

Conclusions

The CAIS system and its associated methods are expected to be useful to biologists and translational medicine researchers. Possible applications range from supporting theoretical work in clarifying and modeling ontogenetic, physiological, pathological, and evolutionary transformations, to concrete techniques for improving the analysis of genotype-phenotype relationships among various animal models in support of a wide array of clinical and scientific initiatives.     

Neuropsychological Attention Skills and Related Behaviours in Adults with Tuberous Sclerosis Complex

Tuberous sclerosis complex (TSC) is a genetic disorder associated with mTOR over-activation and disruption of MAPK, PI3K and AMPK signalling. Children with TSC have significant deficits on neuropsychological attention tasks, particularly dual tasking. Here we investigated attentional skills and related behaviours in daily life in normally intelligent adults with TSC and matched controls using the Test of Everyday Attention for Children (TEA-Ch) and the Attention-Deficit Scales for Adults (ADSA). No group differences were demonstrated on selective or sustained attention tasks carried out alone. However, adults with TSC performed significantly worse when these tasks were combined in a cross-modal dual task condition. On the ADSA the TSC group had significantly worse scores on several subscales (attention/concentration, behaviour/disorganization, academic and emotional behaviours) compared to controls and these correlated with dual task performance, indicating a clear impact of dual task deficits on attention-related behaviours in daily life. The presence or absence of epilepsy did not influence dual task performance or attention-deficits in daily life. Taken together with similar findings in children, results suggest that dual task difficulties are a core feature of the neuropsychological phenotype of TSC.