From degeneration to genetic susceptibility,from eugenics to genethics,from Bezugsziffer to LOD score: the history of psychiatric genetics

Reviewing the history of psychiatric genetics is a difficult task, since—in contrast to genetic research into most other disorders—it cannot simply be done by chronologically listing methodological achievements and major findings. Instead, it necessitates a comprehensive assessment of how the aetiological concept of mental disorders has developed since as early as the world of ancient Greece. Furthermore, it has to touch upon the sensitive issue of the eugenic movement that was closely linked to the study of heredity in mental disorders in the first half of the 20th century and, in Nazi Germany, led to the systematic mass murder of psychiatric patients. Finally, reviewing the scientific dimensions, history of psychiatric genetics is at the same time a walk through the history of complex genetics in general. In our review, we try to pay tribute to this complexity. We argue that psychiatric genetics has not only propelled our understanding of mental disorders but has significantly benefited genetic research into other complex disorders through the development of methodologically robust approaches (e.g., systematic phenotype characterisation, methods to control for ascertainment biases, age-correction). Given the recent reasons for new optimism, i.e., the identification of susceptibility genes for psychiatric phenotypes, a continued methodologically sound approach is needed more than ever to guarantee robust results. Finally, psychiatric genetic research should never again be performed in an environment void of ethical standards.     

Urologie und Sexualwissenschaft in Berlin 1880–1933

The connections between urology and sexology are often not obvious today. At the end of the 19th century both specialties developed in parallel especially in Berlin and had a fruitful relationship. Urologic journals and books were an ideal forum for publication especially for sexologists.     

The Nobel Prize and otolaryngology: ‘Papa Gunnar’s’ promotion of his peers Gustav Killian and Themistocles Gluck

Objectives: This study is part of a larger project investigating the enactment of excellence in medicine, with a focus on the Nobel Prize. It takes a closer look at two promising candidates for the Prize in the 1920s and 1930s, Gustav Killian and Themistocles Gluck, and aims at reconstructing their Nobel careers as well as taking Gunnar Holmgren’s role as a nominator and evaluator behind the curtains into account.

Method: Besides the files collected at the Nobel Archive, the paper is based on a review of scientific publications and ergo-biographical sketches.

Results: An analysis of Nobel Prize nominations and evaluations offer a unique perspective to study aspects of the history of otolaryngology.

Conclusion: Using original files in the archive of the Nobel committee for physiology or medicine in Sweden, this historical vignette explores judgments of scientific innovation and performance in the history of otolaryngology during the first half of the 20th century. This study shows that Gunnar Holmgren, the founder of Acta Oto-Laryngologica in 1918, repeatedly put forward scholars within the field as prime contenders for the award.     

Patient education in Parkinson's disease: Formative evaluation of a standardized programme in seven European countries

OBJECTIVE: To evaluate a newly developed education programme for Parkinson's disease (PD) patients. METHODS: The programme consisted of eight sessions and aimed at improving knowledge and skills related to self-monitoring, health promotion, stress management, depression, anxiety, social competence, and social support, all with special reference to PD. The programme was formatively evaluated in seven European countries (Spain, Finland, Italy, The Netherlands, United Kingdom, Estonia, Germany) with 151 patients diagnosed with idiopathic PD. The evaluation included patients' ratings of the comprehensibility and feasibility of the programme as well as mood ratings before and after each session. Patients also completed questionnaires at the beginning and end of the programme to explore possible changes in disease-related psychosocial problems, quality of life, and depression. RESULTS: The programme was feasible to run, and patients were able to understand its elements. Patients reported mood elevations following individual sessions and reduced disease-related psychosocial problems after completing the programme. There were no substantial differences in results between cultures. CONCLUSION: Patient education appears to have potential as a useful and feasible intervention, complementing medical treatment in PD. PRACTICE IMPLICATIONS: The present programme will soon be available in seven European languages and can be tested in different health care systems.     

Evaluating Mediterranean diet and risk of chronic disease in cohort studies: an umbrella review of meta-analyses

Several meta-analyses have been published summarizing the associations of the Mediterranean diet (MedDiet) with chronic diseases. We evaluated the quality and credibility of evidence from these meta-analyses as well as characterized the different indices used to define MedDiet and re-calculated the associations with the different indices identified. We conducted an umbrella review of meta-analyses on cohort studies evaluating the association of the MedDiet with type 2 diabetes, cardiovascular disease, cancer and cognitive-related diseases. We used the AMSTAR (A MeaSurement Tool to Assess systematic Reviews) checklist to evaluate the methodological quality of the meta-analyses, and the NutriGrade scoring system to evaluate the credibility of evidence. We also identified different indices used to define MedDiet; tests for subgroup differences were performed to compare the associations with the different indices when at least 2 studies were available for different definitions. Fourteen publications were identified and within them 27 meta-analyses which were based on 70 primary studies. Almost all meta-analyses reported inverse associations between MedDiet and risk of chronic disease, but the credibility of evidence was rated low to moderate. Moreover, substantial heterogeneity was observed on the use of the indices assessing adherence to the MedDiet, but two indices were the most used ones [Trichopoulou MedDiet (tMedDiet) and alternative MedDiet (aMedDiet)]. Overall, we observed little difference in risk associations comparing different MedDiet indices in the subgroup meta-analyses. Future prospective cohort studies are advised to use more homogenous definitions of the MedDiet to improve the comparability across meta-analyses.     

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency with inadvertent caries in infants

BACKGROUND: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare systemic disease that is associated with early tooth decay. CASE REPORT: This report describes the case of a 3-year-old boy suffering from LCHADD. At the time of referral, extensive carious lesions of the subject's maxillary dentition necessitated the surgical removal of eight teeth. Preventive treatment for LCHADD involves a regular oral intake of glucose that is vital for the survival of the affected individual. In young infants, the glucose solution needs to be administered as often as every 3 h in order to prevent hypoglycaemia, leading to a local environment similar to that experienced in nursing bottle syndrome. While nursing bottle syndrome can be resolved by eliminating the sugar substrate and curtailing the feeding sessions, these alternatives are not available in cases of LCHADD. CONCLUSION: This report highlights this rare disease and emphasizes its dire consequences for the dentition. Prophylactic recommendations for high-risk children are reviewed. Familiarity with LCHADD allows this high-risk group of patients to be identified, and thus, ensures diligent prophylactic action.     

Triple (GGTA1, CMAH,B2M) modified pigs expressing an SLA class Ilow phenotype—Effects on immune status and susceptibility to human immune responses

Porcine xenografts lacking swine leukocyte antigen (SLA) class I are thought to be protected from human T cell responses. We have previously shown that SLA class I deficiency can be achieved in pigs by CRISPR/Cas9‐mediated deletion of β₂‐microglobulin (B2M). Here, we characterized another line of genetically modified pigs in which targeting of the B2M locus did not result in complete absence of B2M and SLA class I but rather in significantly reduced expression levels of both molecules. Residual SLA class I was functionally inert, because no proper differentiation of the CD8⁺ T cell subset was observed in B2M^low pigs. Cells from B2M^low pigs were less capable in triggering proliferation of human peripheral blood mononuclear cells in vitro, which was mainly due to the nonresponsiveness of CD8⁺ T cells. Nevertheless, cytotoxic effector cells developing from unaffected cell populations (eg, CD4⁺ T cells, natural killer cells) lysed targets from both SLA class I⁺ wildtype and SLA class I^low pigs with similar efficiency. These data indicate that the absence of SLA class I is an effective approach to prevent the activation of human CD8⁺ T cells during the induction phase of an anti‐xenograft response. However, cytotoxic activity of cells during the effector phase cannot be controlled by this approach.