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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.

Abstract Background and Objectives Hypertension is one of the leading cardiovascular risk factors with high numbers of undiagnosed and untreated patients in Sub Saharan Africa (SSA). The health systems and affected people are often overwhelmed by the social and economic burden that comes with the disease. However, the research on the economic burden and consequences of hypertension treatment remains scare in SSA. The objective of our review was to compare different hypertension treatment costs across the continent and identify major cost drivers. Material and Methods Systematic literature searches were conducted in multiple databases (e.g., PubMed, Web of Science, Google Scholar) for peer reviewed articles written in English language with a publication date from inception to Jan. 2022. We included studies assessing direct and indirect costs of hypertension therapy in SSA from a provider or user perspective. The search and a quality assessment were independently executed by two researchers. All results were converted to 2021 US Dollar. Results Of 3999 results identified in the initial search, 33 were selected for data extraction. Costs differed between countries, costing perspectives and cost categories. Only 25% of the SSA countries were mentioned in the studies, with Nigeria dominating the research with a share of 27% of the studies. We identified 15 results each from a user or provider perspective. Medication costs were accountable for the most part of the expenditures with a range from 1.70$ to 97.06$ from a patient perspective and 0.09$ to 193.55$ from a provider perspective per patient per month. Major cost drivers were multidrug treatment, inpatient or hospital care and having a comorbidity like diabetes. Conclusion Hypertension poses a significant economic burden for patients and governments in SSA. Interpreting and comparing the results from different countries and studies is difficult as there are different financing methods and cost items are defined in different ways. However, our results identify medication costs as one of the biggest cost contributors. When fighting the economic burden in SSA, reducing medication costs in form of subsidies or special interventions needs to be considered. Trial registration Registration: PROSPERO, ID CRD42020220957.

The processing of optical liquid silicone rubber (LSR) formulations is associated with significant quality issues and high rejection rates. Often, the quality issues can be attributed to deviations in LSR dosing. To address these issues, specific mixing ratios of components A and B that deviate from the standard 1:1 ratio were intentionally created. These mixtures were characterized via differential scanning calorimetry, rheometer, and Fourier-transform infrared spectroscopy. The mixtures were then processed via injection molding and mechanical properties such as shrinkage, density, hardness, and tensile properties were determined and analyzed. The results show that deviating mixing ratios for optical LSR have a significant influence on processing in terms of shifts in cross-linking temperature and exothermic energy released, viscosity, and cavity pressure, as well as on the final component properties in terms of varying shrinkage, density, hardness, tensile strength, and elongation at break. This study shows that even small deviations have a major influence and should therefore be avoided. The requirements for the accuracy of the dosing system with regard to the mixing ratio must therefore be very high. In practice, such deviations in the mixing ratios are most likely to be detected in geometry via shrinkage, hardness, or tensile properties. Highlights * More component A leads to faster but less dense cross-linking * Component B can be characterized by Fourier-transform infrared spectroscopy via Si-H bending band at 905 [cm.sup.-1]. * More component B leads to higher shrinkage, density, hardness, and strength. * Deviations in the mixing ratio must be avoided as they lead to drastic changes. * A general shift of the mixing ratio in favor of component B is less dramatic. KEYWORDS DSC, FT-IR, injection molding, liquid silicone rubber, mechanical properties, optical LSR, 1 | INTRODUCTION The processing of liquid silicone rubber (LSR), especially optical LSR formulations for light-transmitting applications, is associated with significant quality issues and high rejection rates. Often, the dimensional [...]

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.

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 [...]

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.