Do values and political attitudes affect help-seeking? Exploring reported help-seeking for mental health problems in a general population sample using a milieu framework.

AIMS: Help-seeking for mental health problems is facilitated and hindered by several factors at the individual, interpersonal and community level. The most frequently researched factors contributing to differences in help-seeking behaviour are based on classical socio-demographic variables, such as age, gender and education, but explanations for the observed differences are often absent or remain vague. The present study complements traditional approaches in help-seeking research by introducing a milieu approach, focusing on values and political attitudes as a possible explanation for differences in help-seeking for emotional mental health problems. METHODS: A representative cross-sectional survey of N = 3,042 respondents in Germany was conducted through face-to-face interviews about past help-seeking for mental health problems, socio-demographic characteristics and values and political attitudes. RESULTS: Multivariate logistic regression analyses indicated that belonging to a cosmopolitan intellectual milieu group was significantly associated with an increased likelihood of past help-seeking for mental health issues (psychotherapeutic/psychological help-seeking [OR = 2.09, 95% CI: 1.11-3.93, p < 0.05) and primary care (OR = 2.21, 95% CI: 1.15-4.24, p < 0.05]), whereas members of individualist and conservative milieu groups were less likely to report having sought help from a psychotherapist, but not from a general practitioner. Increased odds ratios were also found for a number of socio-demographic variables, such as being aged 26 years and over, a female gender and more than 12 years of formal education. Associations between socio-demographic variables remained significant, and the explained variance of the used models improved considerably when milieu variables were added. CONCLUSIONS: We discuss how milieu-specific patterns were relevant for explaining differences in mental health service use in addition to socio-demographic factors. It seems promising to consider help-seeking from a milieu perspective to improve disparities in access to and the use of psychotherapy as well as to resource allocation.

The rise in acceptance of mental health professionals: help-seeking recommendations of the German public 1990-2020.

AIMS: We will first examine whether seeking help for depression and schizophrenia from mental health professionals is nowadays more accepted among the German public than it used to be 30 years ago. Next, we will explore whether changes in help-seeking preferences between 1990 and 2020 are specific to mental health professions or are part of changes in attitudes to professional help-seeking in general. Finally, we will study whether a temporal relationship does exist between the advent of awareness-raising and anti-stigma campaigns after the turn of the millennium and changes in the acceptance of mental health care. METHODS: In 1990 (n = 2044), 2001 (n = 4005), 2011 (n = 1984) and 2020 (n = 2449) methodologically identical population-based surveys were conducted in Germany. After presentation of an unlabelled case vignette depicting someone with either schizophrenia or depression, we asked about help-seeking recommendations for the person described. RESULTS: The German public's readiness to recommend seeking help from mental health professionals has markedly grown over the past 30 years. In contrast, in the eyes of the public, turning to a general practitioner has become only slightly more, consulting a priest even less advisable than it used to be three decades ago. Seeing a naturopath is seen with markedly less disapproval today compared to 1990, but explicit recommendation of this helping source has not increased correspondingly in. The most pronounced increase in the German public's propensity to recommend seeking help from mental health professionals occurred already in the 1990s, i.e. before efforts to heighten public awareness had started. CONCLUSIONS: Today, the German public is more in favour of mental health professionals than it used to be three decades ago. This seems to be a specific trend, and not to reflecting an increasing propensity towards professional help-seeking in general. Our findings counter the narrative that mental health communication efforts and initiatives have created more favourable attitudes towards mental health care among the public, since the observed changes in attitudes have preceded any campaigns. Instead, we tend to interpret the rise of the popularity of mental health professionals as a reflection of general cultural changes that have taken place over the past decades in Germany, as in other western countries.

A case of fulminant respiratory diphtheria in a 24-year-old Afghan refugee in Austria in May 2022: a case report.

PURPOSE: Raising awareness of respiratory diphtheria and for the importance of early antitoxin administration. METHODS: Report of a case of fulminant, imported respiratory diphtheria in an otherwise healthy 24-year-old Afghan refugee in Austria in May 2022. RESULT: This was the first case of respiratory diphtheria in Austria since 1993. Diphtheria antitoxin was administered at an already progressed disease stage. This delay contributed to a fulminant disease course with multiorgan failure and death. CONCLUSION: In high-income countries with low case numbers, awareness of respiratory diphtheria and for the importance of early antitoxin administration must be raised.

[Escalation and de-escalation concept for intensive care beds in hospitals reserved for COVID-19]. / Eskalations­/Deeskalationskonzept zur COVID-19-bedingten Freihaltung von Intensivkapazitäten an Kliniken.

BACKGROUND: Since the spread of Severe Acute Respiratory Syndrom Corona Virus 2 (SARS-CoV­2) in Germany, intensive care beds have been kept free for patients suffering from Corona Virus Disease (COVID-19). Also, after the number of infections had declined, intensive care beds were kept free prophylactically; however, the percentage of beds reserved for COVID-19 differ in the individual federal states in Germany. The aim of this article is to define a necessary clearance quota of intensive beds for COVID-19 patients in Germany. An escalation and de-escalation scheme was created for rising and falling numbers of infected patients. METHODS: Data from the COVID-19 resource board of the state of Baden-Württemberg, the daily situation report of the Robert Koch Institute (RKI), the register of COVID-19 intensive care beds of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI) as well as the daily report of COVID-19 Baden-Württemberg from April to November 2020 were used for the calculation. RESULTS: At the end of November 2020 approximately 13.5% of intensive care beds in Germany were used by COVID-19 patients. Of all persons tested positive for SARS-CoV­2, 1.5% were admitted to an intensive care unit. The hospitalization rate was 6% and the mean age of infected persons was 43 years. Based on these numbers hospitals are recommended to keep 10% of intensive care beds available for COVID-19 patients in the case of less than 35 new infections/100,000 in the catchment area, 20% should be kept free in case of an advanced warning level of 35 new infections/100,000 inhabitants and 30% for a critical limit of 50 new infections/100,000 inhabitants. Further internal hospital triggers, such as the occupancy of the intensive care beds with COVID-19 patients, should be considered. CONCLUSION: If the number of infections is low a general nationwide retention rate of more than 10% of intensive care beds for COVID-19 patients is not justified. Locally increasing numbers of infections require a local dynamic approach. If the number of infections increases, the free holding capacity should be increased according to a step by step concept in close coordination with the local health authorities and other internal hospital triggers. In order not to overwhelm hospital capacities in the event of local outbreaks, a corresponding relocation concept should be considered at an early stage.

Demonstration of a compact plasma accelerator powered by laser-accelerated electron beams.

Plasma wakefield accelerators are capable of sustaining gigavolt-per-centimeter accelerating fields, surpassing the electric breakdown threshold in state-of-the-art accelerator modules by 3-4 orders of magnitude. Beam-driven wakefields offer particularly attractive conditions for the generation and acceleration of high-quality beams. However, this scheme relies on kilometer-scale accelerators. Here, we report on the demonstration of a millimeter-scale plasma accelerator powered by laser-accelerated electron beams. We showcase the acceleration of electron beams to 128 MeV, consistent with simulations exhibiting accelerating gradients exceeding 100 GV m-1. This miniaturized accelerator is further explored by employing a controlled pair of drive and witness electron bunches, where a fraction of the driver energy is transferred to the accelerated witness through the plasma. Such a hybrid approach allows fundamental studies of beam-driven plasma accelerator concepts at widely accessible high-power laser facilities. It is anticipated to provide compact sources of energetic high-brightness electron beams for quality-demanding applications such as free-electron lasers.

[Managing the pandemic-relocation concept for COVID-19 intensive care patients and non-COVID-19 intensive care patients in Baden-Württemberg]. / Die Pandemie bewältigen ­ Verlegungskonzept von COVID-19-Intensivpatienten und Non-COVID-19-Intensivpatienten in Baden-Württemberg.

BACKGROUND: A sharp rise in COVID-19 infections threatened to lead to a local overload of intensive care units in autumn 2020. To prevent this scenario a nationwide relocation concept was developed. METHODS: For the development of the concept publicly available infection rates of the leading infection authority in Germany were used. Within this concept six medical care regions (clusters) were designed around a center of maximum intensive care (ECMO option) based on the number of intensive care beds per 100,000 inhabitants. The concept describes the management structure including a structural chart, the individual tasks, the organization and the cluster assignment of the clinics. The transfers of intensive care patients within and between the clusters were recorded from 11 December 2020 to 31 January 2021. RESULT: In Germany and Baden-Württemberg, 1.5% of patients newly infected with SARS-CoV­2 required intensive care treatment in mid-December 2020. With a 7-day incidence of 192 new infections in Germany, the hospitalization rate was 10% and 28-35% of the intensive care beds were occupied by COVID-19 patients. Only 16.8% of the intensive care beds were still available, in contrast to 35% in June 2020. The developed relocation concept has been in use in Baden-Württemberg starting from 10 December 2020. From then until 7 February 2021, a median of 24 ± 5/54 intensive care patients were transferred within the individual clusters, in total 154 intensive care patients. Between the clusters, a minimum of 1 and a maximum of 15 (median 12.5) patients were transferred, 21 intensive care patients were transferred to other federal states and 21 intensive care patients were admitted from these states. The total number of intensive care patients transferred was 261. CONCLUSION: If the number of infections with SARS-CoV­2 increases, a nationwide relocation concept for COVID-19 intensive care patients and non-COVID-19 intensive care patients should be installed at an early stage in order not to overwhelm the capacities of hospitals. Supply regions around a leading clinic with maximum intensive care options are to be defined with a central management that organizes the necessary relocations in cooperation with regional and superregional rescue service control centers. With this concept and the intensive care transports carried out, it was possible to effectively prevent the overload of individual clinics with COVID-19 patients in Baden-Württemberg. Due to that an almost unchanged number of patients requiring regular intensive care could be treated.

Nonlinear plasma wavelength scalings in a laser wakefield accelerator.

Laser wakefield acceleration relies on the excitation of a plasma wave due to the ponderomotive force of an intense laser pulse. However, plasma wave trains in the wake of the laser have scarcely been studied directly in experiments. Here we use few-cycle shadowgraphy in conjunction with interferometry to quantify plasma waves excited by the laser within the density range of GeV-scale accelerators, i.e., a few 10^{18}cm^{-3}. While analytical models suggest a clear dependency between the nonlinear plasma wavelength and the peak potential a_{0}, our study shows that the analytical models are only accurate for driver strength a_{0}≲1. Experimental data and systematic particle-in-cell simulations reveal that nonlinear lengthening of the plasma wave train depends not solely on the laser peak intensity but also on the waist of the focal spot.

Higher body mass index is linked to altered hypothalamic microstructure.

Animal studies suggest that obesity-related diets induce structural changes in the hypothalamus, a key brain area involved in energy homeostasis. Whether this translates to humans is however largely unknown. Using a novel multimodal approach with manual segmentation, we here show that a higher body mass index (BMI) selectively predicted higher proton diffusivity within the hypothalamus, indicative of compromised microstructure in the underlying tissue, in a well-characterized population-based cohort (n1 = 338, 48% females, age 21-78 years, BMI 18-43 kg/m²). Results were independent from confounders and confirmed in another independent sample (n2 = 236). In addition, while hypothalamic volume was not associated with obesity, we identified a sexual dimorphism and larger hypothalamic volumes in the left compared to the right hemisphere. Using two large samples of the general population, we showed that a higher BMI specifically relates to altered microstructure in the hypothalamus, independent from confounders such as age, sex and obesity-associated co-morbidities. This points to persisting microstructural changes in a key regulatory area of energy homeostasis occurring with excessive weight. Our findings may help to better understand the pathomechanisms of obesity and other eating-related disorders.

Hypothalamus enlargement in mood disorders.

OBJECTIVE: The purpose of this study was to determine, in vivo, whether the hypothalamus volume is reduced in patients with mood disorders. METHODS: The cross-sectional study included 20 unmedicated (MDDu) and 20 medicated patients with major depressive disorder, 21 patients with bipolar disorder, and 23 controls. Twenty of the controls were matched to the MDDu. Seven Tesla, T1-weighted magnetic resonance images were acquired and processed using methods specifically developed for high-precision volumetry of the hypothalamus. RESULTS: An overall group difference was observed for the left hypothalamus volume corrected for intracranial volume. Planned contrasts identified that the left hypothalamus was approximately 5% larger in each patient group compared with the control group. A paired t-test with the 20 matched pairs of MDDu and controls and without correction for covariates confirmed the larger left hypothalamus volume in MDDu. CONCLUSIONS: Contrary to our expectations, the hypothalamus volume was increased in patients with uni- and bipolar affective disorders. The effect was left-sided and independent of medication status or statistical correction for covariates. Supported by emerging evidence that the stress response may be related to structural and functional asymmetry in the brain, our finding suggests a crucial role of the hypothalamus in mood disorders.

The pro-oxidative drug WF-10 inhibits serial killing by primary human cytotoxic T-cells.

Cytotoxic T-cells (CTLs) play an important role in many immune-mediated inflammatory diseases. Targeting cytotoxicity of CTLs would allow to interfere with immune-mediated tissue destruction. Here we demonstrate that WF-10, a pro-oxidative compound, inhibits CTL-mediated cytotoxicity. WF-10 did not influence early steps of target-cell killing, but impaired the ability of CTLs to detach from the initial target cell and to move to a second target cell. This reduced serial killing was accompanied by stronger enrichment of the adhesion molecule LFA-1 in the cytolytic immune synapse. LFA-1 clustering requires activation of the actin-bundling protein L-plastin and was accordingly diminished in L-plastin knockdown cells. Interestingly, WF-10 likely acts through regulating L-plastin: (I) It induced L-plastin activation through phosphorylation leading to enhanced LFA-1-mediated cell adhesion, and, importantly, (II) WF-10 lost its influence on target-cell killing in L-plastin knockdown cells. Finally, we demonstrate that WF-10 can improve immunosuppression by conventional drugs. Thus, while cyclosporine A alone had no significant effect on cytotoxicity of CTLs, a combination of cyclosporine A and WF-10 blocked target-cell killing synergistically. Together, our findings suggest that WF-10 - either alone or in combination with conventional immunosuppressive drugs - may be efficient to control progression of diseases, in which CTLs are crucially involved.

N(pro) fusion technology: On-column complementation to improve efficiency in biopharmaceutical production.

N(pro) fusion technology, a highly efficient system for overexpression of proteins and peptides in Escherichia coli, was further developed by splitting the autoprotease N(pro) into two fragments to generate a functional complementation system. The size of the expression tag is thus reduced from 168 to 58 amino acids, so by 66%. Upon complementation of the fragments auto-proteolytic activity is restored. This process has been shown for three model proteins of different size, a short 16 aa-peptide, MCP-1, and lysozyme. Moreover, the complementation was still functional after immobilization of the N-terminal fragment to a solid support which enables recycling of the immobilized fragment. This strategy enhances overall productivity of N(pro) Fusion Technology and thus allows more efficient production of recombinant proteins with reduced costs and in higher yields. Overall, the N(pro) complementation system has, depending on the size of the target molecule, potential to increase the productivity up to 4 fold for batch refolding and even more for on-column refolding strategies by the proven possibility of regeneration of the immobilized fragment.

Halogen bonds in organic synthesis and organocatalysis.

In contrast to hydrogen bonding, halogen bonding has so far found very little use in organic synthesis and organocatalysis. Although there are multiple reports on the use of elemental iodine in a wide range of organic reactions, the understanding of the actual mode of activation in these cases is very rudimentary. Recently, first proof-of-principle reactions have been established towards the use of carbon-based halogen-bond donors as activators or organocatalysts. These halogen-based Lewis acids offer more structural variety and potential than elemental iodine itself, and the mode of activation is better understood. Yet, the reported cases still only cover simple benchmark reactions, and there is a clear need for further and more complex applications.

Should varicella-zoster virus culture be eliminated? A comparison of direct immunofluorescence antigen detection, culture, and PCR, with a historical review.

A comparison of direct fluorescent-antibody assay (DFA), culture, and two PCR assays disclosed sensitivities of 87.8%, 46.3%, and 97.6% and 100%, respectively. We reviewed 1,150 results for clinical specimens submitted for DFA and culture and found that only 17 were culture positive/DFA negative. The incremental cost to detect these 17 positives was $3,078/specimen.

ß-catenin-independent WNT signaling in basal-like breast cancer and brain metastasis.

A role of WNT signaling for primary breast cancers of the basal-like subtype and as a predictor of brain metastasis has been described. However, a responsible WNT ligand has not been identified. To further clarify this question, we comparatively investigated 22 human breast cancer brain metastases as well as the highly invasive human breast cancer cell line MDA-MB-231 and the weakly motile MCF-7 as models for the basal-like and the luminal A subtype. WNT5A and B were found overexpressed in MDA-MB-231 cells as compared with MCF-7. This corresponded to reduction of MDA-MB-231 invasiveness by WNT inhibitors, whereas MCF-7 invasion was enhanced by recombinant WNT5B and abolished by WNT and Jun-N-terminal kinase antagonists. Expression and subcellular distribution of ß-catenin remained uninfluenced. Consistently, ß-catenin was not localized in the nuclei of brain metastases while there was strong nuclear c-Jun staining. Similar to MDA-MB-231, metastases showed expression of WNT5A/B and the alternative WNT receptors ROR1 and 2. These findings were validated using external gene expression datasets (Gene Expression Omnibus) of different breast cancer subtypes and brain metastases. Hierarchical cluster analysis yielded a close relation between basal-like cancers and brain metastases. Gene set enrichment analyses confirmed WNT pathway enrichment not only in basal-like primaries but also in cerebral metastases of all subtypes. In conclusion, WNT signaling seems highly relevant for basal-like and other subtypes of breast cancers metastasizing into the brain. ß-catenin-independent WNT signaling, presumably via ROR1-2, plays a major role in this context.

Diffusion-weighted MRI for tumour volume delineation: comparison with morphological MRI.

Diffusion-weighted magnetic resonance imaging (dwMRI) is sensitive to tissue microstructure on the cellular level and may therefore help to define biological tumour subvolumes and add complementary information to morphology-based cancer treatment protocols and therapy monitoring. The purpose of this study was therefore to evaluate the potential of dwMRI as compared with morphological MRI (mMRI) for tumour volume delineation using a nude rat human tumour xenograft model. Sixteen tumour-bearing rats (10 H1299, six FaDu) were examined with mMRI (T2-weighted true fast imaging with steady precession (TrueFISP), T1-weighted fast low angle shot (FLASH), T2-weighted dual echo steady state (DESS)) and echo-planar dwMRI in a clinical scanner at 1.5 T. For each method, we compared tumour volume and intra- and inter-observer variability of tumour outer edge delineation (disregarding intra-tumoural structure) as well as tumour signal-to-noise ratio (SNR) and tumour-to-muscle contrast-to-noise ratio (CNR). Tumours were visualised with significantly higher SNR and CNR in dwMRI. Median tumour volumes as measured by dwMRI (3.5 cm(3)) and mMRI (TrueFISP: 3.3 cm(3); FLASH: 3.3 cm(3); DESS: 3.2 cm(3)) were not significantly different and significantly correlated. Related to partial volume effects, the intra- and inter-observer variability of dwMRI (intra/inter: 12%/12%) was larger than for mMRI (TrueFISP: 4%/4%; FLASH: 5%/5%; DESS: 5%/5%). In conclusion, dwMRI allows tumour delineation with overall volume estimation comparable with mMRI approaches but slightly higher observer variability. Thus, besides tumour outline, it may potentially supplement morphology-based therapy planning and monitoring with additional biological information.

Pyrogen testing of lipidic parenterals with a novel in vitro test--application of the IPT based on cryopreserved human whole blood.

The European Pharmacopoeia has made the testing of small volume parenterals (< 15) obligatory since 2004. This concerns many formulations, e.g. vitamins, steroids and hormones, many of which are applied intramuscularly using a lipidic carrier. Lipopolysaccharides, the best established endotoxins from Gram-negative bacteria, bind strongly to lipophilic substances, which mask them in Limulus amebocyte lysate assays. End-product testing, therefore, can only be carried out in rabbit pyrogen tests. This will lead to a pronounced increase in animal experiments if no alternative procedures become available. We have described a novel in vitro pyrogen test (IPT) based on human whole blood, which has recently been validated in a collaborative study including the European Pharmacopoeia. Here, the utility of the IPT for lipophilic substances and lipid-containing end-products was assessed. For a variety of lipids commonly added to formulations of injectable endproducts, namely peanut oil, sesame oil, miglyol and paraffin, a protocol which allows interference-free testing was established applying the pharmacopoeial criterion of 50 to 200% retrieval of an LPS spike. Furthermore, end-product testing for three sample formulations was possible. In all, a method could be established which allows the determination of given or calculated ELC (endotoxin limit concentrations) according to Pharmacopoeia. It is concluded that monocytes do react to lipid-bound LPS, indicating that immune responses to contaminated endproducts must be anticipated, and that the IPT is suitable for endproduct control of these formulations.

PTH secretion in patients with chronic renal failure assessed by a modified CiCa clamp method: effects of 1-year calcitriol therapy.

BACKGROUND: Secondary hyperparathyroidism (secondary HPT) in patients with chronic renal failure (CRF) is characterized by parathyroid gland hyperplasia and an intrinsic defect in the recognition of parathyroid hormone (PTH) secretion. Conflicting results have been reported regarding the set point for calcium-regulated PTH release and its modification by calcitriol therapy in hemodialysis patients. Additionally, the effect of calcitriol on the calcium/PTH relationship in predialysis CRF patients with early secondary HPT has not been investigated. Our objective in this controlled study was to investigate the calcium/PTH relationship and to determine the calcium set point in patients with early stages of CRF before and after a 1-year treatment with calcitriol and in normal volunteers. METHODS: Nine patients with an early stage of CRF (GFR between 20 and 50 ml/min x 1.73 m2 b.s.) aged 35-77 years and 13 healthy volunteers (HV) aged 26-60, years were included in the study. All participants were investigated by sequential lowering and raising of serum calcium levels comprising the following phases: blood-ionized calcium (Ca2+) was lowered by about 0.2 mmol/l (3 steps), steady-state hypocalcemia of Ca2+ 0.2 mmol/l below the baseline (step 4), stop of the infusion for 5 minutes (step 5), Ca2+ was raised to about 0.2 mmol/l above baseline (steps 6 and 7), and a steady state hypercalcemia of Ca2+ 0.2 mmol/l above baseline (step 8). Ionized calcium and intact PTH (iPTH) were measured at 30 time points during 240 minutes. The calcium set point was determined using the classical 4-parameter model. The CiCa clamp test was performed before and after a 1-year treatment with 0.5 microg of calcitriol thrice weekly. RESULTS: No differences in the set point were observed between HV and CRF patients with early secondary HPT. Four of 9 patients responded to calcitriol treatment with a decrease in basal serum iPTH levels ("responders"). There was no difference between renal function (GFR 18 +/- 6 vs. 17 +/- 8 ml/min x 1.73 m2 b.s.), set point (Ca2+ 1.07 +/- 0.13 vs. 1.07 +/- 0.06 mmol/l) and suppressibility of PTH secretion (PTHmin% 7.3 +/- 1.6 vs. 8.2 +/- 2.9) in responders vs non-responders, nor did these values change after treatment with calcitriol. PTHmin% decreased significantly in the whole group after treatment (10.4 +/- 8.5 vs. 7.8 +/- 2.4). CONCLUSIONS: Although the calcium set point was not different in predialysis CRF patients with early secondary HPT compared to HV, calcitriol treatment improved the calcium-related suppression of PTH secretion (PTHmin%).

[Tourette's syndrome - a review]. / Das Tourette-Syndrom Eine Ubersicht.

Tourette's syndrome (TS) is a neuropsychiatric disorder characterised by the occurrence of chronic motor and vocal tics that usually begin in childhood. A prevalence of 4-5/10.000 individuals is estimated. Tourette's syndrome patients frequently show comorbidity with other psychiatric disorders such as obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), anxiety, and affective disorders. Some forms of OCD seem to share a common genetic etiology with TS and to be a facultative part of the TS phenotypic spectrum. Based on MRI, positron emission tomography (PET), and single photon emission computed tomography (SPECT), data alterations in the cortico-striato-pallido-thalamo-cortical functional systems have been discussed. Within these systems, dopaminergic neurotransmission is thought to play an important role in the pathophysiology of TS. Autoimmunological mechanisms seem to be important in some subtypes of TS and OCD that are triggered or exacerbated by infections with hemolytic streptococci. In these cases, immune modulatory therapy proved to be efficient. To date, there is no established treatment regimen for TS. The medications used most frequently are antipsychotics.