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Abstract:Introduction: A new Swiss teaching aid – "Sport without Borders: People with Psychiatric disorders" – was published at the end of 2020 and then evaluated six months later. The main question of the present qualitative evaluation was to what extent different aspects of the three macro levels – design, content, and applicability of the teaching material – are assessed as appropriate by the current trainers of the voluntary exercise and sports groups for people with psychiatric disorders. Methods: For this purpose, eight (N=8) semi-structured interviews (maximum variation sampling) were conducted in spring 2021 with the trainers of various sports groups for people with psychiatric disorders in Switzerland. The recorded interviews were subsequently transcribed and analysed with nVivo according to Thematic Analysis. Results: The interviewees rated the teaching material as very successful and necessary in all aspects (design, content, and applicability of the teaching material). Regarding applicability of the teaching material, the interviewees mentioned the potential for development and expansion of sports groups, and mentioned interesting possible applications and needs. Discussion & Conclusion: The results show that the current trainers of voluntary exercise and sports groups for people with psychiatric disorders are generally very satisfied with the teaching material. Compared to the existing literature in the context of physical activity and psychiatry, the current teaching material has significant language differences (e.g., avoiding lengthy and complicated sentences, minimum of academic terms) and is strongly oriented to the mass sports (lay)-coaches with none or low (para)-medical or academic background. [ABSTRACT FROM AUTHOR]

Background: The rising global population of older persons with chronic conditions demands new primary care models. Advanced practice nurses (APNs) can help meet that need. In Switzerland, APNs have only recently been introduced in primary care and little is known about their daily practice. This study aims to describe APNs' activities and general roles at four sites with multi-professional primary care practices in the Swiss cantons of Bern and Solothurn. Methods: To study the practices of APNs at the study sites, we adopted a social constructivist perspective, lending methods from ethnographic field research. We interviewed, observed and accompanied participants over five months, generating rich data on their daily practices. The analysis followed Braun and Clarke's six-step thematic analysis process. Results: The APNs' daily practices cover three main themes. Their core activities are working with expanded clinical skills and being on-site specialists for patients and their relatives. These practices are surrounded by net activities, i.e., taking care of patients in tandem with the physicians and regular visits in residential long-term care facilities. The outer activity layer consists of cohesive activities, with which APNs anchor and facilitate their role and catalyze further development of the care model. APNs tailor their expanded medical knowledge and nursing practice to maximize the value they provide in patient care. Conclusions: This study extends our knowledge of APNs' daily practice within a Swiss multi-professional primary care practice. Our results indicate competencies that need to be integrated in APN education and point out the high potential of APN integration in such primary care practices. [ABSTRACT FROM AUTHOR]

The discrepancy between the observed concentration of ice nucleating particles (INPs) and the ice crystal number concentration (ICNC) remains unresolved and limits our understanding of ice formation and, hence, precipitation amount, location and intensity. Enhanced ice formation through secondary ice production (SIP) could account for this discrepancy. Here, in a region over the eastern Swiss Alps, we perform sensitivity studies of additional simulated SIP processes on precipitation formation and surface precipitation intensity. The SIP processes considered include rime splintering, droplet shattering during freezing and breakup through ice–graupel collisions. We simulated the passage of a cold front at Gotschnagrat, a peak at 2281 m a.s.l. (above sea level), on 7 March 2019 with the Consortium for Small-scale Modeling (COSMO), at a 1 km horizontal grid spacing, as part of the RACLETS (Role of Aerosols and CLouds Enhanced by Topography and Snow) field campaign in the Davos region in Switzerland. The largest simulated difference in the ICNC at the surface originated from the breakup simulations. Indeed, breakup caused a 1 to 3 orders of magnitude increase in the ICNC compared to SIP from rime splintering or without SIP processes in the control simulation. The ICNCs from the collisional breakup simulations at Gotschnagrat were in best agreement with the ICNCs measured on a gondola near the surface. However, these simulations were not able to reproduce the ice crystal habits near the surface. Enhanced ICNCs from collisional breakup reduced localized regions of higher precipitation and, thereby, improved the model performance in terms of surface precipitation over the domain. [ABSTRACT FROM AUTHOR]

Background: Beliefs about the helpfulness of interventions are influencing the individual help-seeking behavior in case of mental illnesses. It is important to identify these beliefs as professional helpers are asked to consider them in their treatment recommendations.Objective: Assessing lay proposals for an appropriate treatment of mental illnesses.Methods: We conducted a representative opinion survey in Switzerland. Eighteen treatment proposals were presented with respect to a vignette either depicting schizophrenia or depression. Respondents were asked to indicate the proposals considered to be helpful for treatment and those considered to be harmful, respectively.Results: 'Psychologist,' 'general practitioner,' 'fresh air, and 'psychiatrist' were mostly proposed as being helpful. Among several psychiatric treatment approaches 'psychotherapy' was favored, while psychopharmacological treatment and electroconvulsive therapy were only proposed by less than one-fourth of the interviewees. Especially psychotropic drugs were considered to be harmful. Treatment by a psychiatrist was regarded as being more helpful for schizophrenic individuals than for depressive persons. For a person experiencing a life crisis, treatment by a psychiatrist and psychological treatment were viewed as being harmful, and non-medical interventions were preferred. However, for persons thought to be mentally ill, psychiatric and psychopharmacological treatments were recommended.Conclusion: Mental health professionals are regarded as being helpful although their treatment methods are seen as being less helpful. A clear distinction is made between lay proposals for depression and schizophrenia. However, the perception of whether a condition is considered to be an illness or a life crisis has significantly more influence on lay treatment proposals than the cited diagnosis in the vignette. [ABSTRACT FROM AUTHOR]

Background: Patients with a psychiatric illness have a higher prevalence of physical diseases and thus a higher morbidity and mortality. Aim: The main aim was to investigate where patients with co-occurring physical diseases and mental disorders (psychotic spectrum or mood) in the health and social service system are identified most frequently before admission into psychiatry. The second aim was to compare the differences in the treatment routes taken by the patients before entry into psychiatric services in all the participating countries (Denmark, Germany, Japan, Nigeria and Switzerland). Methodology: On admission to a psychiatric service, patients diagnosed with schizophrenia, schizotypal or delusional disorders (International Classification of Diseases-10 (ICD-10) group F2) or mood (affective) disorders (ICD-10 group F3) and a co-morbid physical condition (cardiovascular disease, diabetes mellitus and overweight) were asked with which institutions or persons they had been in contact with in the previous 6 months. Results: Patients from Denmark, Germany and Switzerland with mental disorders had almost the same contact pattern. Their primary contact was to public or private psychiatry, with a contact percentage of 46%–91%; in addition, general practice was a common contact, with a margin of 41%–93%. Similar tendencies are seen in Japan despite the small sample size. With regard to general practice, this is also the case with Nigerian patients. However, religious guidance or healing was rarely sought by patients in Europe and Japan, while in Nigeria about 80% of patients with mental disorders had contacted this type of service. Conclusion: Promoting prophylactic work between psychiatry and the general practice sector may be beneficial in diminishing physical conditions such as cardiovascular disease, diabetes mellitus and overweight in patients with mental disorders in European countries and Japan. In Nigeria (a low-to-middle-income country), religious guides or healers, along with general practitioners, are the most frequently contacted, and they therefore seem to be the most obvious partner to collaborate with. [ABSTRACT FROM AUTHOR]

Background: Physical comorbidities and substance use are commonly reported in patients with mental disorders.Aim: To examine somatic comorbidity in patients with substance use disorders (SUD) compared to patients with mental disorders but no SUD.Methods: Lifetime prevalence data on mental and physical health status were collected from inpatients in 12 mental health care facilities in five different countries. Differences in somatic comorbidity were examined by means of logistic regression analysis controlling for age and gender.Results: Of 2,338 patients, 447 (19%) had a primary or secondary SUD diagnosis. In comparison to patients with other mental disorders, patients with SUD had a higher prevalence of infectious and digestive diseases but a lower prevalence of endocrine, nutritional and metabolic disorders. Patterns of physical comorbidities differed according to type of substance used (alcohol use – cardiovascular; tobacco use – respiratory, neoplasms; cannabinoid use – injuries; opioid use – infectious, digestive; benzodiazepine use – endocrine, nutritional, metabolic; stimulants – urogenital).Conclusions: SUD are related to specific somatic health risks while some of our findings point to potentially protective effects. The widespread prescription of benzodiazepines requires research on physical health effects. Early detection of SUD and their integration into programmes targeting physical comorbidity should be a priority in organizing mental health care. [ABSTRACT FROM AUTHOR]

The article reports a study to examine the incidence of cardiovascular diseases (CVD), diabetes (DM) and obesity in schizophrenia and depression in various geographical areas to analyze the transcultural differences among them. The results revealed that incidence of obesity, CVD and DM were higher in schizophrenia spectrum disorders and affective disorders. It is concluded that cultural background is an important factor in dealing with lifestyle diseases among people with mental illnesses.

Objective: To describe the suicide rates of psychiatric in-patients in the canton of Zurich for the period 1992–2004, and to determine putative risk factors. Method: The data were derived from the psychiatric case register of the canton Zurich. The analyses were based on person-years calculations and standardised mortality ratios. Additional information was assessed via case records. Results: During the 13-year period the standardised mortality ratio was 48.9. The risk of suicide was particularly high in patients with personality and affective disorders. Most suicides occurred during regular leave periods, despite the fact that clinical assessment had indicated there was no suicide risk for the patient. Conclusion: The suicide risk of in-patients is distinctly higher than in the general population. A better assessment of suicide risk before regular leave periods could lead to a decrease of suicides in in-patient settings, as well as a more rigorous treatment of borderline cases, and of affective and psychotic symptoms. [ABSTRACT FROM AUTHOR]

Objective: Little is known in our own as well as in other cultures about the knowledge and prejudices mental health professionals have about mental illness and those affected. We therefore: 1) assessed mental health literacy and general attitudes towards people with mental illness in a sample of Brazilian mental health professionals; 2) compared the outcomes among the different professional groups; and 3) compared the data with a sample of Swiss mental health professionals. Methods: A questionnaire used to assess knowledge and attitudes towards the mentally ill among mental health professionals in Switzerland was translated into Portuguese. Mental health professionals were presented a case vignette describing a person suffering from a major depression as well as related treatment proposals. Furthermore, general attitudes towards people with mental illness were assessed. Results: Both samples had equal scores for social acceptance. Brazilian mental health professionals displayed a more positive attitude towards community psychiatry whereas the Swiss sample showed more stigmatization and social distance, and a more positive attitude towards psychopharmacology. Recognition of the case vignette was significantly better in Brazil than in Switzerland (94.7% versus 71%). Mental health professionals in Brazil were more conservative/medically orientated in their treatment propositions whereas professionals from Switzerland also proposed social interventions and alternative treatment strategies. Conclusions: There are some major differences in attitudes towards people with mental illness between mental health professionals in Switzerland and Brazil. With respect to therapeutic interventions, the different healthcare systems as well as the cultural differences seem to have an impact. [ABSTRACT FROM AUTHOR]

Abstract: There is controversy over whether the incidence rates of schizophrenia and psychotic disorders have changed in recent decades. To detect deviations from trends in incidence, we analysed admission data of patients with an ICD-8/9/10 diagnosis of psychotic disorders in the Canton Zurich / Switzerland, for the period 1977–2005. The data was derived from the central psychiatric register of the Canton Zurich. Ex-post forecasting with ARIMA (Autoregressive Integrated Moving Average) models was used to assess departures from existing trends. In addition, age-period-cohort analysis was applied to determine hidden birth cohort effects. First admission rates of patients with psychotic disorders were constant in men and showed a downward trend in women. However, the rates in the youngest age groups showed a strong increase in the second half of the 1990''s. The trend reversal among the youngest age groups coincides with the increased use of cannabis among young Swiss in the 1990''s. [Copyright &y& Elsevier]

Background.Many patients with psychological or physical problems are interested in non-medical approaches. The reasons for the growing popularity of complementary and alternative medicine (CAM) are not well understood considering that evidence of the effectiveness of conventional therapies is greater than ever before. We have examined data from the Zurich Study to determine trends and predictors of CAM use in Switzerland.Method.The Zurich Study is a longitudinal community study that was started in 1979 with a sample of 591 participants born in 1958 and 1959. In 1999, the last of six interview waves with face-to-face interviews was conducted. CAM use was analyzed with data from interviews in 1993 and 1999. Polytomous logistic regression analysis focused on the personal, demographic and sociocultural background of CAM users.Results.CAM use in the last 12 months was reported by 21·9% of the participants in 1993 and by 29·5% in 1999. CAM use among those exhibiting either physical or psychological problems was in the ratio of two to one. There was a trend from alternative variants of CAM (homeopathy) to complementary ones (massage, osteopathy, acupuncture). The vast majority of CAM use was in addition to conventional therapies. Predictors of CAM use were, among others, attribution of physical complaints to stress and other psychological variables, very low education level in parents, and lacking political interest.Conclusions.Besides the sociocultural background, characteristics such as the psychological attribution style play an important role in CAM use. CAM use in Switzerland is mainly of a complementary rather than an alternative nature. [ABSTRACT FROM AUTHOR]

At the end of the 19th century, male suicide rates in Switzerland were as high as the respective rates in recent decades, whereas female suicide rates were distinctly lower. An age–period–cohort analysis was performed to provide more information about the genderspecific changes over the last century. Suicide mortality has been reported in Switzerland since 1876 when the standardised registration of mortality data began. The analysed data cover the period 1881–2000. The statistical analyses were based on log–linear models and data aggregated by 10–year age–intervals and 10–year periodintervals. The results indicate similar age and period effects in males and females. The estimates representing age–specific risk increase steadily with age, with intermediate plateaus in the 20s and the 50s. The period–specific estimates follow the economic cycles. The birth cohort effects are stronger in males and weaker in females. In the males' estimates, there is a peak in cohorts born around 1840 and a low in cohorts born some 60–100 years later. The estimates increased again in generations born after World War II. In females, the birth cohort estimates are low in cohorts born in the first half of the 19th century and increase until the first half of the 20th century. Birth cohort effects remain an intriguing topic in epidemiology of suicide. A better understanding of birth cohort effects might open new doors to suicide prevention. [ABSTRACT FROM AUTHOR]

Background: Migration has become a major political and social concern in West European societies.Methods: A case-control method was used to analyse the utilisation of inpatient mental health services by immigrants from a catchment area in Switzerland over a 7-year period.Results: Compared to natives, immigrants had fewer psychiatric hospitalisations, but more emergency and compulsory admissions. During inpatient treatment, they received less psycho-, ergo- and physiotherapy. Other therapies as well as compulsory measures were at comparable rates, as was the frequency of irregular discharge. They spent shorter periods as inpatients and the rate of psychiatric readmissions was significantly lower. Comparison of different countries of origin revealed that only patients from West and North Europe were comparable to natives regarding type of referral, inpatient treatment, and longitudinal measures of service utilisation. Even after accounting for effects of social class, immigrants from South Europe, former Yugoslavia, Turkey, East Europe and more distant countries spent significantly shorter time in inpatient treatment, compared to Swiss control patients.Conclusions: Results of this study clearly point to an underutilisation of inpatient facilities among immigrants with mental disorders, and to disadvantages in psychiatric inpatient care. This, however, does not pertain to all foreign patients to the same extent: inequalities of mental health service use are particularly pronounced in immigrants from more distant countries. [ABSTRACT FROM AUTHOR]

Background: Attitudes towards antipsychotic medication play an important part in the treatment for schizophrenia and related disorders. We aimed measuring general practitioners' attitudes to antipsychotic drugs and their adverse side effects and comparing these with the attitudes of the general population. Methods: Analysis and comparison of two representative samples, one comprising 100 General Practitioners (GPs), the other 791 individuals randomly selected from the general population. The setting was the German speaking cantons of Switzerland. Results: General practitioners have significantly more positive attitudes towards anti-psychotic drugs than the general public. They reject widespread prejudices about the use of anti-psychotic medication significantly more than the general population. In particular the risk of dependency was assessed as 'low' by GP's (80%), in contrast to only 18% of the general population sample. In no instance did a majority of the GPs advise not tolerating any of the 10 possible adverse effects presented in this study. This is in marked contrast to the general population sample, where a majority recommended discontinuation for movement disorder (63%), strong tremor (59%), risk of dependency (55%) and feelings of unrest (54%). Conclusion: As well as effective management of side-effects being a vital aspect of patient and carer education, prescribing doctors need to be aware that their mentally ill patients are likely to be confronted with extremely negative public attitudes towards antipsychotic medication and with strong pressures to stop taking their medication in the event of side-effects. [ABSTRACT FROM AUTHOR]

Background: Recent research has corroborated the notion that seasonality in suicide is more heterogeneous and less consistent than postulated by former scholars. This work investigates the smoothing out of suicide seasonality in Switzerland between the late 19th and the end of the 20th century. It includes analyses by region and by suicide method. Methods: Monthly suicide frequencies in Switzerland are available for the period 1876-2000. Data on canton/region are available for the periods 1901-1920 and 1969-2000, and data on suicide method for the periods 1881-1920 and 1969-2000. Analyses focusing on the overall change rely on data aggregated by quinquennia. The Edwards' test and the peak-low ratio were used in univariate analyses of seasonality. Putative determinants of the peak-low ratio were examined using regression analysis with cantonal data. Results: The decrease of seasonal effects in suicide applies to a period of more than 100 years in Switzerland. Big differences of seasonal effects have existed all the time with regard to specific methods and to specific regions. No seasonality was apparent in poisoning, and in Geneva and Basle City, respectively. However, the seasonal effects have been most impressive in drowning and hanging suicides, and in rural Catholic regions. In regression analysis, the decline in suicide seasonality is associated with the decline in the agricultural work force. Conclusions: The smoothing out of suicide seasonality in Switzerland has been a continuous long term process, which probably started by the end of 19th century. Seasonal effects in suicide will probably fade away in most regions of Switzerland and in most suicide methods. This process is in parallel with the disappearance of the traditional rural society. [ABSTRACT FROM AUTHOR]

Background: General practitioners (GPs) have an important role in the care of patients with chronic schizophrenia and of those in the early phases of this disorder.Aims: To obtain information about the number of patients in the early and chronic stages of schizophrenia seen in general practice; the needs and attitudes of GPs, their diagnostic knowledge concerning early phases of schizophrenia and their knowledge and practice concerning treatment of patients with first-episode and multi-episode schizophrenia.Method: A postal survey was conducted among randomly selected GPs in Switzerland.Results: A total of 1089 GPs responded to the survey. Early psychosis had a low prevalence in general practice, and GPs expressed a wish for specialised, low-threshold referral services. Diagnostic and treatment knowledge showed inconsistencies. Most GPs said they would treat first-episode schizophrenia with antipsychotics, but only a third recommended maintenance treatment after a first episode of schizophrenia that would conform with international recommendations.Conclusions: Easily accessible, low-threshold referral services are pivotal in supporting GPs in the management and treatment of emerging schizophrenia in primary healthcare patients. [ABSTRACT FROM AUTHOR]

Objective: Assessing lay beliefs about causes of depressive behaviour and analysing the influence of labelling and demographic factors on causal attributions. Method: In Switzerland we conducted a representative telephone survey with 873 interviewees. A vignette depicting a man with depression satisfying the Diagnostic and Statistical Manual (DSM)-III-R criteria was presented. Content analysis of up to three answers about assumed causes was conducted. Results: For more than half the respondents (56.6%) difficulties within the family or the partnership are causal for depression. Occupational stress is the second most-mentioned cause (32.7%), whereas unspecified further stress is in third place (19.9%). Traumatic events (17.9%), depressive disorder (14.1%) and further unspecified illnesses (11.6%) follow. Few correlations were found between causal attributions, labelling and demographic factors. Conclusion: The respective causal attributions are mainly independent of demographic factors, thus generalizable for the population. The attributions are shaped primarily by psychosocial ideas about aetiology. Nevertheless, one-third of the interviewees holds biological or disease-related beliefs about causes of depression. The respective illness models cannot be neglected in the therapeutic relationship. [ABSTRACT FROM AUTHOR]

Objective: Assessing the public attitude to compulsory admission of mentally ill in Switzerland and analyzing the influence of demographic, psychological, and sociological factors. Method: We conducted a representative telephone survey with 1737 interviewees. In a logistic regression analysis compulsory admission was used as the dependent variable. Results: More than 70% of the respondents display a positive attitude to compulsory admission. Education, negative stereotypes, and living in the French speaking part of Switzerland are predictors for accepting compulsory admission whereas older age, extreme political opinion, and rigid personality traits show an inverse effect. Negative emotions, anomie, social distance, and contact to mentally ill have no significant influence. Conclusion: The mostly positive attitude to compulsory admission suggests that the public trust in psychiatry to deal with the assigned responsibility. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. In this nationwide prospective study we wanted to verify the trend of increasing diabetes incidence data from our earlier retrospective analysis of the military registry of Swiss men. Subjects and methods. The data collection of newly diagnosed children in Switzerland at an age younger than 15 years started in 1991. The countrywide survey used a small questionnaire which was sent back to the study centre. The questionnaire was anonymous and contained: hospital of diagnosis, initials, sex, birth date, date of diagnosis, residence, country of citizenship, and responsible physician. General data on the population were taken from publications of the Swiss Federal Statistical Office. Results. A total of 941 children below the age of 15 years with newly diagnosed Type I (insulin-dependent) diabetes mellitus were collected (434 girls, 507 boys). The incidence in children aged 0 to 14 years rose significantly between 1991 and 1999 with a yearly average increase of 5.1 %. In the age group 0 to 4 years a more than four-fold increase in incidence from 2.4/100 000 per year to 10.5/100 000 per year (p = 0.0002) was recorded, whereas the age-specific incidence in the 5 to 9-year-old and 10 to 14-year-old children did not change during the data collection period. The incidence was significantly higher in boys than in girls, whereas no difference was found between rural and urban populations. Conclusion/interpretation. The incidence of Type I diabetes is rising in children living in Switzerland but only the youngest age group of under 5 years of age is affected showing a large annual average increase of 23.8 %. [Diabetologia (2001) 44: 286–289] [ABSTRACT FROM AUTHOR]

Objective: To examine the precision and completeness of information in medical records for evaluating the appropriateness of operative indications for lumbar disc surgery. Design: Retrospective review of records. Setting: University department of neurosurgery, Switzerland. Subjects: 100 patients. Interventions: None. Main outcome measures: Proportion of pre-defined, detailed appropriateness criteria present in the records. Proportion of cases that could unequivocally be classified as to the appropriateness of the indication for operation. Results: The criteria were present and precise for 52 of the items (range 9-90); present but imprecise for 38 of the items, and absent for 10. Because of this imprecision, the appropriateness of only 7 of the operative indications could be unequivocally assessed retrospectively. Conclusion: Medical records are of limited use in assessing the appropriate management of care. The process of care should therefore be evaluated prospectively. [ABSTRACT FROM AUTHOR]

Information about several papers discussed during the 2nd International Zurich Conference on Clinical and Social Psychiatry held on September 6-8, 200 in Zurich, Switzerland regarding affective disorder is presented. Topics include the diagnostic challenges of schizoaffective disorders, medical comorbidity and aetiology of depressive illness. The conference featured several participants including A. Marneros, W. Greil, and D. Goldberg.

Abstract: The influence of water-extractable organic matter from 6 Opalinus Clay (OPA) samples from Mont Terri and Benken (Switzerland) on the sorption of Ni(II), Eu(III) and Th(IV) has been measured using an ion exchange technique. OPA is considered to be one of the potential host rocks for the deep geological disposal of high-level and long-lived intermediate-level radioactive waste in Switzerland. Within the range of estimated uncertainties, no significant differences in sorption were observed in most cases as compared with suitable synthetic waters devoid of organic C. Only in certain individual cases were slight reductions in sorption (less than a factor of 5) for Eu(III) and Ni(II) found. The results of accompanying laser fluorescence spectroscopy experiments did not show any influence of the extracts on Cm(III) speciation. This would suggest that the reduction of sorption occasionally observed in the ion exchange experiments is probably not caused by the formation of complexes between the radionuclides and the organic matter in the extracts, but is rather due to an underestimation of systematic uncertainties. From these findings, and from UV–VIS spectroscopic characterisation of the organic matter in the extracts, it can be concluded that only a negligible fraction of the organic matter present may be in the form of humic or fulvic acids. It is consequently justified to put aside overly conservative assumptions with respect to the complexing behaviour of the organic matter used towards the metal ions investigated and their chemical analogues. In view of the site-specific character of the present study, these conclusions may not be arbitrarily applied to other geological formations considered as possible host rocks for the disposal of radioactive waste. [Copyright &y& Elsevier]

Type 1 diabetes is caused by autoimmune-mediated β cell destruction leading to insulin deficiency. The histone deacetylase SIRT1 plays an essential role in modulating several age-related diseases. Here we describe a family carrying a mutation in the SIRT1 gene, in which all five affected members developed an autoimmune disorder: four developed type 1 diabetes, and one developed ulcerative colitis. Initially, a 26-year-old man was diagnosed with the typical features of type 1 diabetes, including lean body mass, autoantibodies, T cell reactivity to β cell antigens, and a rapid dependence on insulin. Direct and exome sequencing identified the presence of a T-to-C exchange in exon 1 of SIRT1, corresponding to a leucine-to-proline mutation at residue 107. Expression of SIRT1-L107P in insulin-producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines. These observations identify a role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aims/hypothesis: Loss of pancreatic beta cells is the crucial event in the development of type 1 diabetes. It is the result of an imbalance between autoimmune destruction and insufficient regeneration of islet cells. To study the role of islet cell regeneration in the pathogenesis of type 1 diabetes, we focused on PAX4, a paired homeodomain transcriptional repressor that is involved in islet cell growth., Methods: The study included 379 diabetic children and 1,070 controls from two distinct populations, and a cohort of children who had not developed type 1 diabetes, despite the presence of islet cell antibodies. Genomic DNA analysis of PAX4 was carried out via direct sequencing of PCR-amplified fragments and allelic discrimination. We compared the transrepression potential of the PAX4 variants in betaTC3 cells and analysed their influence on beta cell growth., Results: The type 1 diabetic subjects are different from the normal individuals in terms of the genotype distribution of the A1168C single nucleotide polymorphism in PAX4. The C/C genotype is frequent among type 1 diabetic children (73%) and rare among the control population (32%). Conversely, the A/C genotype is prevalent among control subjects (62%) and antibody-positive children without type 1 diabetes (73.6%), but uncommon among subjects with type 1 diabetes (17.5%). The combination of PAX4A and PAX4C is functionally more active than PAX4C alone (the "diabetic" variant). Beta cells expressing PAX4A and PAX4C efficiently proliferate when stimulated with glucose, whereas cells expressing the PAX4C variant alone do not., Conclusions/interpretation: We have identified a link between beta cell regenerative capacity and susceptibility to type 1 diabetes. This finding could explain the fact that not all of the individuals who develop autoimmunity against beta cells actually contract the disease. The C/C genotype of the A1168C polymorphism in PAX4 can be viewed as a predisposition marker that can help to detect individuals prone to develop type 1 diabetes.

Newborn screening for congenital adrenal hyperplasia (CAH) is justified by the sometimes difficult clinical diagnosis and the risks associated with missed diagnosis, particularly the life-threatening salt-wasting crisis. In Switzerland, nationwide screening for CAH by measuring 17-hydroxyprogesterone levels in dried blood spots was introduced in 1992. At the Zurich University Children's Hospital, 50% of the population of Switzerland is screened. The aim of the study was to evaluate the efficiency of the Zurich screening program. Between January 1, 1993, and May 31, 2001, 333,221 newborns were screened for CAH. Thirty-one newborns had CAH (incidence, 1 in 10,749); 30 were detected through screening (sensitivity, 97%). A recall for suspected CAH was performed in only 60 cases, corresponding to a very low recall rate (0.0018%). In 30 recalls CAH was confirmed (positive predictive value, 50%; specificity, 99.99%). Fifteen of 31 patients profited from screening, as CAH had not been recognized clinically. The timely availability of screening results made therapy possible within the first week of life in most cases and helped in preventing salt-wasting crisis in all patients. With a sensitivity of 97%, a specificity of 99.99%, and a positive predictive value of 50%, the Zurich neonatal screening program for CAH can be considered highly reliable.