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Abstract Background Recent studies have shown a lifetime prevalence of 5.7% for health anxiety/hypochondriasis resulting in increased healthcare service utilisation and disability as consequences. To the best of our knowledge, there has been no systematic review examining the global costs of hypochondriasis, encompassing both direct and indirect costs. Our objective was to synthesize the available evidence on the economic burden of health anxiety and hypochondriasis to identify research gaps and provide guidance and insights for policymakers and future research. Methods A systematic literature search was conducted using PubMed, Web of Science, PsycInfo, EconLit, IBSS and Google Scholar without any time limit, up until April 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in this search and the following article selection process. The included studies were systematically analysed and summarized using a predefined data extraction sheet. Results Of the 3044 articles identified; 10 publications met our inclusion criteria. The results displayed significant variance in the overall costs listed among the studies. The reported economic burden of hypochondriasis ranged from 857.19 to 21137.55 US$ per capita per year. Most of the investigated costs were direct costs, whereas the assessment of indirect costs was strongly underrepresented. Conclusion This systematic review suggests that existing studies underestimate the costs of hypochondriasis due to missing information on indirect costs. Furthermore, there is no uniform data collection of the costs and definition of the disease, so that the few existing data are not comparable and difficult to evaluate. There is a need for standardised data collection and definition of hypochondriasis in future studies to identify major cost drivers as potential target point for interventions.

Lipotoxicity has been considered the main cause of pancreatic beta-cell failure during type 2 diabetes development. Lipid droplets (LD) are believed to regulate the beta-cell sensitivity to free fatty acids (FFA), but the underlying molecular mechanisms are largely unclear. Accumulating evidence points, however, to an important role of intracellular sphingosine-1-phosphate (S1P) metabolism in lipotoxicity-mediated disturbances of beta-cell function. In the present study, we compared the effects of an increased irreversible S1P degradation (S1P-lyase, SPL overexpression) with those associated with an enhanced S1P recycling (overexpression of S1P phosphatase 1, SGPP1) on LD formation and lipotoxicity in rat INS1E beta-cells. Interestingly, although both approaches led to a reduced S1P concentration, they had opposite effects on the susceptibility to FFA. Overexpression of SGPP1 prevented FFA-mediated caspase-3 activation by a mechanism involving an enhanced lipid storage capacity and prevention of oxidative stress. In contrast, SPL overexpression limited LD biogenesis, content, and size, while accelerating lipophagy. This was associated with FFA-induced hydrogen peroxide formation, mitochondrial fragmentation, and dysfunction, as well as ER stress. These changes coincided with the upregulation of proapoptotic ceramides but were independent of lipid peroxidation rate. Also in human EndoC-βH1 beta-cells, suppression of SPL with simultaneous overexpression of SGPP1 led to a similar and even more pronounced LD phenotype as that in INS1E-SGPP1 cells. Thus, intracellular S1P turnover significantly regulates LD content and size and influences beta-cell sensitivity to FFA.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Liquid silicone rubber (LSR) is characterized by a wide range of advantageous properties and is therefore used in many branches and industries. However, the material is difficult to recycle due to the non-reversible cross-linking reaction. A promising approach to recycle the already cross-linked (post-industrial) waste is the mechanical recycling of LSR via grinding and addition of the powder as filler in virgin material. This research focused on the processing of such LSRpowder-compounds via injection molding and the influence of the powder content on mechanical properties. Compounds of virgin LSR and ambient ground powder were prepared and injection molded. Both the processability and the mechanical properties were analyzed. Compounds of up to 40 wt% powder content could be processed with standard injection molding machine equipment without any noticeable issues. The results show a similar compression set for the virgin as for the recycled compounds. Hardness decreases slightly but constantly. Tensile strength and elongation at break are at similar levels for all powder added compounds and drop only by 16.6% and 12.6% compared with the virgin LSR. The results are promising and should be the basis for further and more detailed investigations to industrialize the mechanical recycling of LSR. Highlights * Processing on standard injection molding machine with standard parameters. * Up to 40 wt% recycled silicone powder content. * Using recycled silicone particles has no effect on compression set. * Tensile strength and elongation at break decrease only by 16.6% and 12.6%. KEYWORDS injection molding, liquid silicone rubber, mechanical properties, mechanical recycling, recycling, silicone powder, 1 | INTRODUCTION Silicones, also known as polyorganosiloxanes, belong to the group of synthetic polymers and are characterized by repeating Si-O bonds, the so-called siloxane backbone. In addition, the silicon [...]

Abstract Anxiety disorders are the most prevalent mental health conditions. Besides psycho-pharmacotherapy, cognitive behavioral therapy with an exposure-based approach is considered the gold standard. However, not all patients benefit from this approach. Here, we aimed to translate laboratory findings on enhanced fear extinction with repetitive transcranial magnetic stimulation (TMS) to the clinic. In this double-blind, randomized, placebo-controlled clinical trial, 76 participants with acrophobia received an activating intermittent theta burst stimulation (iTBS) targeting the left posterior prefrontal cortex immediately before two virtual reality exposure therapy sessions. Phobic symptoms were assessed at baseline, post-intervention, and a 6-month follow-up. Results revealed a significant reduction in phobic symptoms from baseline to post-assessment and follow-up and confirmed the efficacy of virtual reality exposure therapy as a treatment for specific phobias. Interestingly, no additional effect was observed for active iTBS compared to sham iTBS. Our post-hoc analyses argue for an individualized TMS application. Further research is needed to determine optimal TMS parameters and validate these results in clinical trials, accounting for methodological and inter- and intra-individual variability, as well as alternative therapeutic processes.

ABSTRACT To prevent the spread of foodborne illnesses, the presence of pathogens in the food chain is monitored by government agencies and food producers. The culture-based methods currently employed are sensitive but time- and labor-intensive, leading to increasing interest in exploring culture-independent diagnostic tests (CIDTs) for pathogen detection. However, few studies quantify the relative sensitivity and reliability of these CIDTs compared to current approaches. To address this issue, we conducted a comparison of the limit of detection (LOD50) for Salmonella between a culture-based method and three CIDTs: qPCR (targeting invA and stn), metabarcode (16S) sequencing, and shotgun metagenomic sequencing. Samples of chicken feed and chicken caecal contents were spiked with S. serovar Enteritidis and subjected to culture- and DNA-based detection methods. To explore the impact of non-selective enrichment on LOD50, all samples underwent both immediate DNA extraction and overnight enrichment prior to gDNA extraction. In addition to this spike-in experiment, feed and caecal samples acquired from the field were tested with culturing, qPCR, and metabarcoding. In general, LOD50 was comparable between qPCR and shotgun sequencing methods. Overnight microbiological enrichment resulted in an improvement in LOD50 with up to a three-log decrease. However, Salmonella reads were detected in some unspiked feed samples, suggesting false-positive detection of Salmonella. In addition, the LOD50 in feeds was three logs lower than in caecal contents, underscoring the impact of background microbiota on Salmonella detection using all methods.IMPORTANCEThe appeal of culture-independent diagnostic tests (CIDTs) is increased speed with lowered cost, as well as the potential to detect multiple pathogen species in a single analysis and to monitor other areas of concern such as antimicrobial resistance genes or virulence factors. This study provides quantitative data on the sensitivity of CIDTs relative to current approaches, which is essential for determining the feasibility of implementing these methods in pathogen surveillance programs.