Filling data gaps in long-term solar UV monitoring by statistical imputation methods.

Knowledge of long-term time trends of solar ultraviolet (UV) radiation on ground level is of high scientific interest. For this purpose, precise measurements over a long time are necessary. One of the challenges solar UV monitoring faces is the permanent and gap-free data collection over several decades. Data gaps hamper the formation and comparison of monthly or annual means, and, in the worst case, lead to incorrect conclusions in further data evaluation and trend analysis of UV data. For estimating data to fill gaps in long-term UV data series (daily radiant exposure and highest daily irradiance), we developed three statistical imputation methods: a model-based imputation, considering actual local solar radiation conditions using predictors correlated to the local UV values in an empirical model; an average-based imputation based on a statistical approach of averaging available local UV measurement data without predictors; and a mixture of these two imputation methods. A detailed validation demonstrates the superiority of the model-based imputation method. The combined method can be considered the best one in practice. Furthermore, it has been shown that the model-based imputation method can be used as an useful tool to identify systematic errors at and between calibration steps in long-term erythemal UV data series.

CLN7/MFSD8 may be an important factor for SARS-CoV-2 cell entry.

The SARS-CoV-2 virus has triggered a worldwide pandemic. According to the BioGrid database, CLN7 (MFSD8) is thought to interact with several viral proteins. The aim of this work was to investigate a possible involvement of CLN7 in the infection process. Experiments on a CLN7-deficient HEK293T cell line exhibited a 90% reduced viral load compared to wild-type cells. This observation may be linked to the finding that CLN7 ko cells have a significantly reduced GM1 content in their cell membrane. GM1 is found highly enriched in lipid rafts, which are thought to play an important role in SARS-CoV-2 infection. In contrast, overexpression of CLN7 led to an increase in viral load. This study provides evidence that CLN7 is involved in SARS-CoV-2 infection. This makes it a potential pharmacological target for drug development against COVID-19. Furthermore, it provides insights into the physiological function of CLN7 where still only little is known about.

Autoantibodies to Vasoregulative G-Protein-Coupled Receptors Correlate with Symptom Severity, Autonomic Dysfunction and Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an acquired complex disease with patients suffering from the cardinal symptoms of fatigue, post-exertional malaise (PEM), cognitive impairment, pain and autonomous dysfunction. ME/CFS is triggered by an infection in the majority of patients. Initial evidence for a potential role of natural regulatory autoantibodies (AAB) to beta-adrenergic (AdR) and muscarinic acetylcholine receptors (M-AChR) in ME/CFS patients comes from a few studies. METHODS: Here, we analyzed the correlations of symptom severity with levels of AAB to vasoregulative AdR, AChR and Endothelin-1 type A and B (ETA/B) and Angiotensin II type 1 (AT1) receptor in a Berlin cohort of ME/CFS patients (n = 116) by ELISA. The severity of disease, symptoms and autonomic dysfunction were assessed by questionnaires. RESULTS: We found levels of most AABs significantly correlated with key symptoms of fatigue and muscle pain in patients with infection-triggered onset. The severity of cognitive impairment correlated with AT1-R- and ETA-R-AAB and severity of gastrointestinal symptoms with alpha1/2-AdR-AAB. In contrast, the patients with non-infection-triggered ME/CFS showed fewer and other correlations. CONCLUSION: Correlations of specific AAB against G-protein-coupled receptors (GPCR) with symptoms provide evidence for a role of these AAB or respective receptor pathways in disease pathomechanism.

Multi-pass probing for high-sensitivity tomographic interferometry.

Optical probing is an indispensable tool in research and development. In fact, it has always been the most natural way for humankind to explore nature. However, objects consisting of transparent materials with a refractive index close to unity, such as low-density gas jets, are a typical example of samples that often reach the sensitivity limits of optical probing techniques. We introduce an advanced optical probing method employing multiple passes of the probe through the object to increase phase sensitivity, and relay-imaging of the object between individual passes to preserve spatial resolution. An interferometer with four-passes was set up and the concept was validated by tomographic characterization of low-density supersonic gas jets. The results show an evident increase of sensitivity, which allows for the accurate quantitation of fine features such as a shock formed by an obstacle or a barrel shock on the jet boundary in low ambient gas pressures. Despite its limitations in temporal resolution, this novel method has demonstrated an increase in phase sensitivity in transmission, however, it can also be employed to boost the absorption or polarization contrast of weakly interacting objects in both transmission and reflection setups, thus, upgrading the sensitivity of various optical characterization methods.

Delineating the Association Between Soluble CD26 and Autoantibodies Against G-Protein Coupled Receptors, Immunological and Cardiovascular Parameters Identifies Distinct Patterns in Post-Infectious vs. Non-Infection-Triggered Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Soluble cluster of differentiation 26 (sCD26) has a wide range of enzymatic functions affecting immunological, metabolic and vascular regulation. Diminished sCD26 concentrations have been reported in various autoimmune diseases and also in Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). Here we re-evaluate sCD26 as a diagnostic marker and perform a comprehensive correlation analysis of sCD26 concentrations with clinical and paraclinical parameters in ME/CFS patients. Though this study did find significantly lower concentrations of sCD26 only in the female cohort and could not confirm diagnostic suitability, results from correlation analyses provide striking pathomechanistic insights. In patients with infection-triggered onset, the associations of low sCD26 with elevated autoantibodies (AAB) against alpha1 adrenergic (AR) and M3 muscarinic acetylcholine receptors (mAChR) point to a pathomechanism of infection-triggered autoimmune-mediated vascular and immunological dysregulation. sCD26 concentrations in infection-triggered ME/CFS were found to be associated with activated T cells, liver enzymes, creatin kinase (CK) and lactate dehydrogenase (LDH) and inversely with Interleukin-1 beta (IL-1b). Most associations are in line with the known effects of sCD26/DPP-4 inhibition. Remarkably, in non-infection-triggered ME/CFS lower sCD26 in patients with higher heart rate after orthostatic challenge and postural orthostatic tachycardia syndrome (POTS) suggest an association with orthostatic regulation. These findings provide evidence that the key enzyme sCD26 is linked to immunological alterations in infection-triggered ME/CFS and delineate a different pathomechanism in the non-infectious ME/CFS subset.

The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps.

Neutrophil extracellular traps (NETs) are structures consisting of chromatin and antimicrobial molecules that are released by neutrophils during a form of regulated cell death called NETosis. NETs trap invading pathogens, promote coagulation, and activate myeloid cells to produce type I interferons (IFNs), proinflammatory cytokines that regulate the immune system. Here, we showed that macrophages and other myeloid cells phagocytosed NETs. Once in phagosomes, NETs translocated to the cytosol, where the DNA backbones of these structures activated the innate immune sensor cyclic GMP-AMP synthase (cGAS) and induced type I IFN production. The NET-associated serine protease neutrophil elastase (NE) mediated the activation of this pathway. We showed that NET induction in mice treated with the lectin concanavalin A, a model of autoimmune hepatitis, resulted in cGAS-dependent stimulation of an IFN response, suggesting that NETs activated cGAS in vivo. Thus, our findings suggest that cGAS is a sensor of NETs, mediating immune cell activation during infection.

Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset.

Single nucleotide polymorphisms (SNP) in various genes have been described to be associated with susceptibility to autoimmune disease. In this study, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients and controls were genotyped for five immune gene SNPs in tyrosine phosphatase non-receptor type 22 (PTPN22, rs2476601), cytotoxic T-lymphocyte-associated protein 4 (CTLA4, rs3087243), tumor necrosis factor (TNF, rs1800629 and rs1799724), and interferon regulatory factor 5 (IRF5, rs3807306), which are among the most important risk variants for autoimmune diseases. Analysis of 305 ME/CFS patients and 201 healthy controls showed significant associations of the PTPN22 rs2476601 and CTLA4 rs3087243 autoimmunity-risk alleles with ME/CFS. The associations were only found in ME/CFS patients, who reported an acute onset of disease with an infection (PTPN22 rs2476601: OR 1.63, CI 1.04-2.55, p = 0.016; CTLA4 rs3087243: OR 1.53, CI 1.17-2.03, p = 0.001), but not in ME/CFS patients without infection-triggered onset (PTPN22 rs2476601: OR 1.09, CI 0.56-2.14, p = 0.398; CTLA4 rs3087243: OR 0.89, CI 0.61-1.30, p = 0.268). This finding provides evidence that autoimmunity might play a role in ME/CFS with an infection-triggered onset. Both genes play a key role in regulating B and T cell activation.

Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome.

AIMS: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystem disease. Evidence for disturbed vascular regulation comes from various studies showing cerebral hypoperfusion and orthostatic intolerance. The peripheral endothelial dysfunction (ED) has not been sufficiently investigated in patients with ME/CFS. The aim of the present study was to examine peripheral endothelial function in patients with ME/CFS. METHODS AND RESULTS: Thirty-five patients [median age 40 (range 18-70) years, mean body mass index 23.8 ± 4.2 kg/m2 , 31% male] with ME/CFS were studied for peripheral endothelial function assessed by peripheral arterial tonometry (EndoPAT2000). Clinical diagnosis of ME/CFS was based on Canadian Criteria. Nine of these patients with elevated antibodies against ß2-adrenergic receptor underwent immunoadsorption, and endothelial function was measured at baseline and 3, 6, and 12 months follow-up. ED was defined by reactive hyperaemia index ≤1.81. Twenty healthy subjects of similar age and body mass index were used as a control group. Peripheral ED was found in 18 of 35 patients (51%) with ME/CFS and in 4 healthy subjects (20%, P < 0.05). Patients with ED, in contrast to patients with normal endothelial function, reported more severe disease according to Bell score (31 ± 12 vs. 40 ± 16, P = 0.04), as well as more severe fatigue-related symptoms (8.62 ± 0.87 vs. 7.75 ± 1.40, P = 0.04) including a higher demand for breaks [9.0 (interquartile range 7.0-10.0) vs. 7.5 (interquartile range 6.0-9.25), P = 0.04]. Peripheral ED showed correlations with more severe immune-associated symptoms (r = -0.41, P = 0.026), such as sore throat (r = -0.38, P = 0.038) and painful lymph nodes (r = -0.37, P = 0.042), as well as more severe disease according to Bell score (r = 0.41, P = 0.008) and symptom score (r = -0.59, P = 0.005). There were no differences between the patient group with ED and the patient group with normal endothelial function regarding demographic, metabolic, and laboratory parameters. Further, there was no difference in soluble vascular cell adhesion molecule and soluble intercellular adhesion molecule levels. At baseline, peripheral ED was observed in six patients who underwent immunoadsorption. After 12 months, endothelial function had improved in five of these six patients (reactive hyperaemia index 1.58 ± 0.15 vs. 2.02 ± 0.46, P = 0.06). CONCLUSIONS: Peripheral ED is frequent in patients with ME/CFS and associated with disease severity and severity of immune symptoms. As ED is a risk factor for cardiovascular disease, it is important to elucidate if peripheral ED is associated with increased cardiovascular morbidity and mortality in ME/CFS.

[UV radiation in Germany: influences of ozone depletion and climate change and measures to protect the population]. / UV-Strahlung in Deutschland: Einflüsse des Ozonabbaus und des Klimawandels sowie Maßnahmen zum Schutz der Bevölkerung.

Ultraviolet radiation (UV radiation) can lead to numerous skin and eye diseases, both immediately and later in life. The most serious consequence is skin cancer. The risk of skin cancer increases, among other things, with increasing UV irradiance and/or with increasing outdoor exposure times. Due to the fact that UV radiation is carcinogenic, protection of the population against harmful UV exposure is an important radiation protection and health objective.In Germany, ozone depletion and climate change can also influence the UV irradiance and outdoor exposure times to such an extent that the UV exposure of the population and thus the skin cancer risk can increase. This is why protection against harmful UV exposure is even more important. Since ozone depletion and climate change can further increase the UV exposure of humans, protection against high UV exposure is even more important. A country's adaptation strategies to the health consequences of ozone depletion and climate change should therefore also include strategies to reduce UV exposure.In this review, the health effects of UV radiation and the risk factors for UV-related skin cancer are first presented. The measurement of UV irradiance and exposure in Germany is explained. The effects of ozone depletion and climate change on UV exposure are then described and measures to protect the population are presented.

Effectiveness of Eye Movement Desensitization and Reprocessing in German Armed Forces Soldiers With Post-Traumatic Stress Disorder Under Routine Inpatient Care Conditions.

BACKGROUND: Post-traumatic stress disorder (PTSD) is one of the more commonly occurring mental disorders following potentially traumatizing events soldiers may encounter when deployed abroad. One of the first-line recommended treatment options is eye movement desensitization and reprocessing (EMDR). The number of studies assessing the effectiveness of EMDR in German soldiers under routine conditions is currently almost nil. METHODS: A retrospective, quasi-experimental effectiveness study on EMDR in an inpatient setting is presented using a prepost design. The study compares symptom reduction in soldiers (N = 78) with a wait-list (N = 18). Effect sizes of EMDR were measured for PTSD, symptoms of depression, and general mental health. RESULTS: Effect size for EMDR treatment of PTSD was d = 0.77; 95% confidence interval (CI): 0.51 to 1.36, for symptoms of depression d = 0.99; 95% CI: 0.31 to 1.36, and for general psychiatric symptoms d = 0.53; 95% CI: 0.17 to 1.21. The effects resulting from EMDR treatment were somewhat weaker than those reported in comparable studies in civilians. CONCLUSION: EMDR therapy is an effective treatment to reduce symptoms of PTSD and depression. However, in the military context it needs to be complemented by treatment options that specifically address further conditions perpetuating the disorders.

Influence of focal point properties on energy transfer and plasma evolution during laser ignition process with a passively q-switched laser.

Miniaturized passively q-switched laser ignition systems are a promising alternative to conventional ignition sources to ensure a reliable ignition under difficult conditions. In this study the influences of focal point properties on energy transfer from laser to plasma as well as plasma formation and propagation are investigated as the first steps of the laser induced ignition process. Maximum fluence and fluence volume are introduced to characterize focal point properties for varying laser pulse energies and focusing configurations. The results show that the transferred laser energy increases with increasing maximum fluence. During laser emission plasma propagates along the beam path of the focused laser beam. Rising maximum fluence results in increased plasma volume, but expansion saturates when fluence volume reaches its maximum.

Extracellular Iron is a Modulator of the Differentiation of Osteoclast Lineage Cells.

Osteoclasts originate from the hematopoietic stem cell and share a differentiation pathway with the cells of the monocyte/macrophage lineages. Development and activation of osteoclasts, and as a consequence regulation of bone resorption, depend on two growth factors: macrophage colony-stimulating factor and receptor activator of NF-κB ligand. Furthermore, cell development and activity are modulated by a microenvironment composed of cytokines and growth factors and of the extracellular matrix. Membrane transporters are a means for cells to interact with their environment. Within this study, the expression of proteins regulating cellular iron homeostasis in osteoclast-like cells grown from bone marrow-derived progenitors was compared to the expression of this set of proteins by monocyte/macrophage lineage cells. In differentiating osteoclasts, levels of transcripts encoding transferrin receptor 1 and divalent metal transporter 1 (Slc11A2) were increased, while levels of transcripts encoding ferroportin (Slc40A1) and natural resistance-associated macrophage protein 1 (Slc11A1) were decreased. Supplementation of the culture media with exogenous iron led to an increase in the proliferation of osteoclast progenitor cells and to the expression of a macrophage-like phenotype, while the development of osteoclasts was reduced. Upon transfer of mature OC onto a CaP substrate, iron depletion of the medium with the Fe(3+)-chelator Deferoxamine Mesylate decreased CaP dissolution by ~30 %, which could be restored by addition of exogenous iron. During the 24 h of the assay, no effects were observed on total TRAP activity. The data demonstrate transcriptional regulation of the components of cellular iron transporters during OC development and suggests that iron homeostasis may contribute to fine-tuning of the RANKL-induced OC development.

Can We Use Tree Rings of Black Alder to Reconstruct Lake Levels? A Case Study for the Mecklenburg Lake District, Northeastern Germany.

In this study, we explore the potential to reconstruct lake-level (and groundwater) fluctuations from tree-ring chronologies of black alder (Alnus glutinosa L.) for three study lakes in the Mecklenburg Lake District, northeastern Germany. As gauging records for lakes in this region are generally short, long-term reconstructions of lake-level fluctuations could provide valuable information on past hydrological conditions, which, in turn, are useful to assess dynamics of climate and landscape evolution. We selected black alder as our study species as alder typically thrives as riparian vegetation along lakeshores. For the study lakes, we tested whether a regional signal in lake-level fluctuations and in the growth of alder exists that could be used for long-term regional hydrological reconstructions, but found that local (i.e. site-specific) signals in lake level and tree-ring chronologies prevailed. Hence, we built lake/groundwater-level reconstruction models for the three study lakes individually. Two sets of models were considered based on (1) local tree-ring series of black alder, and (2) site-specific Standardized Precipitation Evapotranspiration Indices (SPEI). Although the SPEI-based models performed statistically well, we critically reflect on the reliability of these reconstructions, as SPEI cannot account for human influence. Tree-ring based reconstruction models, on the other hand, performed poor. Combined, our results suggest that, for our study area, long-term regional reconstructions of lake-level fluctuations that consider both recent and ancient (e.g., archaeological) wood of black alder seem extremely challenging, if not impossible.

Assessment of modulated cytostatic drug resistance by automated γH2AX analysis.

The efficacy of many chemotherapeutic agents relies on the preferential destruction of rapidly dividing cancer cells by inducing various kinds of DNA damage. The most deleterious type of DNA lesions are DNA double-strand breaks (DSB), which can be detected by immunofluorescence staining of phosphorylated histone protein H2AX (γH2AX). Furthermore, γH2AX has been suggested as clinical pharmacodynamic biomarker in chemotherapeutic cancer treatment. A great challenge in treating neoplastic diseases is the varying response behavior among cancer patients. Thus, intrinsic or drug-induced overexpression of efflux pumps often leads to multiple drug resistance (MDR) and treatment failure. In particular, inter-individual differences in expression levels of efflux pumps, such as the permeability glycoprotein (P-gp), were shown to correlate with cancer progression. Several efficient cytostatic drugs, including the DSB-inducing agent etoposide (ETP) are known P-gp substrates. In this respect, modulation of MDR by P-gp inhibitors, like the immunosuppressives cyclosporine A (CsA) and rapamycin (Rapa) have been described. Here, we investigated the application of γH2AX focus assay to monitor the impact of CsA and Rapa on ETP-induced cytotoxicity in human peripheral blood mononuclear cells. Evaluation of γH2AX foci was performed by the automated fluorescence microscopy and interpretation system AKLIDES. Compared to ETP treatment alone, our results revealed a significant rise in γH2AX focus number and percentage of DSB-positive cells after cells have been treated with ETP in the presence of either CsA or Rapa. In contrast, DSB levels of cells incubated with CsA or Rapa alone were comparable to focus number of untreated cells. Our results successfully demonstrated how automated γH2AX analysis can be used as fast and reliable approach to monitor drug resistance and the impact of MDR modulators during treatment with DSB-inducing cytostatics..

Fully automated analysis of chemically induced γH2AX foci in human peripheral blood mononuclear cells by indirect immunofluorescence.

Analysis of phosphorylated histone protein H2AX (γH2AX) foci is currently the most sensitive method to detect DNA double-strand breaks (DSB). This protein modification has the potential to become an individual biomarker of cellular stress, especially in the diagnosis and monitoring of neoplastic diseases. To make γH2AX foci analysis available as a routine screening method, different software approaches for automated immunofluorescence pattern evaluation have recently been developed. In this study, we used novel pattern recognition algorithms on the AKLIDES® platform to automatically analyze immunofluorescence images of γH2AX foci and compared the results with visual assessments. Dose- and time-dependent γH2AX foci formation was investigated in human peripheral blood mononuclear cells (PBMCs) treated with the chemotherapeutic drug etoposide (ETP). Moreover, the AKLIDES system was used to analyze the impact of different immunomodulatory reagents on γH2AX foci formation in PBMCs. Apart from γH2AX foci counting the use of novel pattern recognition algorithms allowed the measurement of their fluorescence intensity and size, as well as the analysis of overlapping γH2AX foci. The comparison of automated and manual foci quantification showed overall a good correlation. After ETP exposure, a clear dose-dependent increase of γH2AX foci formation was evident using the AKLIDES as well as Western blot analysis. Kinetic experiments on PBMCs incubated with 5 µM ETP demonstrated a peak in γH2AX foci formation after 4 to 8 h, while a removal of ETP resulted in a strong reduction of γH2AX foci after 1 to 4 h. In summary, this study demonstrated that the AKLIDES system can be used as an efficient automatic screening tool for γH2AX foci analysis by providing new evaluation features and facilitating the identification of drugs which induce or modulate DNA damage.

Vascularized os pisiform for reinforcement of the lunate in Kienböck's Disease: an average of 12 years of follow-up study.

PURPOSE: Little is known about the long-term results of vascularized bone transplantation for Kienböck's disease. This retrospective study investigated the long-term results of vascularized pisiform transfer. METHODS: We reviewed 23 patients to analyze results after vascularized pisiform transposition to a cored-out lunate for Lichtman stages II and III. Patients with ulnar-minus variance received additional radial shortening. RESULTS: Pain improved in 20 of 23 patients. Range of motion increased significantly relative to preoperative values but was only 80% that of opposite side. Grip power was 84% of the contralateral hand. At follow-up evaluation the mean Disabilities of the Arm, Shoulder, and Hand questionnaire score was 15.3 +/- 17.9 and the mean Cooney score was 82.4 +/- 10.0. Radiologically, out of 20 patients with preoperative x-rays Lichtman stage was unchanged in 11, improved in 3, and progressed in 6 patients. No patient showed radiologic signs of arthritis before surgery. At follow-up evaluation osteoarthritis was found in 7 of 22 patients. The majority of degenerative changes were of low grade and were seen at the radiocarpal joint. CONCLUSIONS: The results show high patient satisfaction and good function after vascularized bone transplantation for Kienböck's disease. In the long term vascularized pisiform transfer prevented lunate collapse in 16 of 22 patients.

Lunate resection and vascularized Os pisiform transfer in Kienböck's Disease: an average of 10 years of follow-up study after Saffar's procedure.

PURPOSE: To investigate the long-term results of lunate replacement by vascularized bone transfer in advanced Kienböck's disease. METHODS: Twenty-one patients were reviewed (mean follow-up period +/- SD, 9.9 +/- 3.5 y) to analyze results after lunate replacement by vascularized pisiform transposition (Saffar's procedure) for Lichtman stages III and IV. RESULTS: Pain was improved in 16 of 21 patients but range of motion did not improve after surgery. Range of motion was reduced to 68% and grip power to 80% of that of the opposite hand. At follow-up evaluation the mean score on the Disabilities of the Arm, Shoulder, and Hand Questionnaire was 22.3 +/- 17.9 and the mean Cooney score was 75.4 +/- 13.2. Radiologically, Lichtman stage persisted in 8, improved in 1, progressed in 8, and could not be evaluated in 3 patients. Two patients had radiologic signs of arthritis before surgery. At follow-up examination osteoarthritis was found in 50% of patients. The majority of degenerative changes were associated with carpal collapse. CONCLUSIONS: The replacement of the lunate by vascularized pisiform transposition maintained preoperative ranges of motion. At follow-up examination both patient satisfaction and wrist function were high. In the long term, however, Saffar's procedure can restore alignment of the carpus only partly and also results in osteoarthritis in half of all patients.

Provision and remuneration of psychotherapeutic services in Switzerland.

OBJECTIVES: To establish the number of psychotherapists with professional backgrounds; psychotherapeutic provision and its cost; change in cost in case of integration of non-medical psychotherapy into the mandatory minimum health care benefit. METHODS: A population-based survey using computer-assisted telephone interviews in a randomly selected sample of medical and non-medical psychotherapists (NMP), stratified by professional status and language regions. RESULTS: 1,633 psychiatrists, 2,332 general practitioners and 2,616 NMP provide psychotherapy in Switzerland. NMP by training: 1,674 (64%) hold a university degree in psychology; 539 (21%) hold a professional school degree in psychology; and 403 (15%) have various backgrounds. In 2000, 146,000 patients utilised 4.52 million hours of medical psychotherapy, which cost CHF 579 million, CHF 396 million of which were reimbursed by mandatory health insurance (MHI). Reimbursement of NMP by MHI would result in additional expenditures of CHF 102-252 million. CONCLUSIONS: NMP provide 46% of psychotherapy which is currently partly reimbursed by the MHI. An integration of NMP into the MHI benefit package would incur additional costs to MHI of CHF 102-252 million.