Characterization of two common 5' polymorphisms in PEX1 and correlation to survival in PEX1 peroxisome biogenesis disorder patients

<p>Abstract</p> <p>Background</p> <p>Mutations in PEX1 are the most common primary cause of Zellweger syndrome. In addition to exonic mutations, deletions and splice site mutations two 5' polymorphisms at c.-137 and c.-53 with a potential influence on PEX1 protein levels have been described in the 5' untranslated region (UTR) of the <it>PEX1 </it>gene.</p> <p>Methods</p> <p>We used RACE and in silico promoter prediction analysis to study the 5' UTR of <it>PEX1</it>. We determined the distribution of <it>PEX1 </it>5' polymorphisms in a cohort of 30 Zellweger syndrome patients by standard DNA sequencing. 5' polymorphisms were analysed in relation to the two most common mutations in <it>PEX1 </it>and were incorporated into a novel genotype-phenotype analysis by correlation of three classes of <it>PEX1 </it>mutations with patient survival.</p> <p>Results</p> <p>We provide evidence that the polymorphism 137 bp upstream of the ATG codon is not part of the UTR, rendering it a promoter polymorphism. We show that the first, but not the second most common <it>PEX1 </it>mutation arose independently of a specific upstream polymorphic constellation. By genotype-phenotype analysis we identified patients with identical exonic mutation and identical 5' polymorphisms, but strongly differing survival.</p> <p>Conclusions</p> <p>Our study suggests that two different types of <it>PEX1 </it>5' polymorphisms have to be distinguished: a 5' UTR polymorphism at position c.-53 and a promoter polymorphism 137 bp upstream of the PEX1 start codon. Our results indicate that the exonic <it>PEX1 </it>mutation correlates with patient survival, but the two 5' polymorphisms analysed in this study do not have to be considered for diagnostic and/or prognostic purposes.</p

Abdominal obesity‐related disturbance of insulin sensitivity is associated with cd8+ emra cells in the elderly

Aging and overweight increase the risk of developing type 2 diabetes mellitus. In this cross‐sectional study, we aimed to investigate the potential mediating role of T‐EMRA cells and inflammatory markers in the development of a decreased insulin sensitivity. A total of 134 healthy older volunteers were recruited (age 59.2 (SD 5.6) years). T cell subpopulations were analyzed by flow cytometry. Furthermore, body composition, HOMA‐IR, plasma tryptophan (Trp) metabolites, as well as cytokines and adipokines were determined. Using subgroup and covariance analyses, the influence of BMI on the parameters was evaluated. Moreover, correlation, multiple regression, and mediation analyses were performed. In the subgroup of participants with obesity, an increased proportion of CD8+EMRA cells and elevated concentrations of plasma kynurenine (KYN) were found compared to the lower‐weight subgroups. Linear regression analysis revealed that an elevated HOMA‐IR could be predicted by a higher proportion of CD8+EMRA cells and KYN levels. A mediation analysis showed a robust indirect effect of the Waist‐to‐hip ratio on HOMA‐IR mediated by CD8+EMRA cells. Thus, the deleterious effects of abdominal obesity on glucose metabolism might be mediated by CD8+EMRA cells in the elderly. Longitudinal studies should validate this assumption and analyze the suitability of CD8+EMRA cells as early predictors of incipient prediabetes. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Mobile SARS‑CoV‑2 screening facilities for rapid deployment and university-based diagnostic laboratory

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a public crisis. Many medical and public institutions and businesses went into isolation in response to the pandemic. Because SARS-CoV-2 can spread irrespective of a patient's course of disease, these institutions’ continued operation or reopening based on the assessment and control of virus spread can be supported by targeted population screening. For this purpose, virus testing in the form of polymerase chain reaction (PCR) analysis and antibody detection in blood can be central. Mobile SARS-CoV-2 screening facilities with a built-in biosafety level (BSL)-2 laboratory were set up to allow the testing offer to be brought close to the subject group's workplace. University staff members, their expertise, and already available equipment were used to implement and operate the screening facilities and a certified diagnostic laboratory. This operation also included specimen collection, transport, PCR and antibody analysis, and informing subjects as well as public health departments. Screening facilities were established at different locations such as educational institutions, nursing homes, and companies providing critical supply chains for health care. Less than 4 weeks after the first imposed lockdown in Germany, a first mobile testing station was established featuring a build-in laboratory with two similar stations commencing operation until June 2020. During the 15-month project period, approximately 33,000 PCR tests and close to 7000 antibody detection tests were collected and analyzed. The presented approach describes the required procedures that enabled the screening facilities and laboratories to collect and process several hundred specimens each day under difficult conditions. This report can assist others in establishing similar setups for pandemic scenarios

Psychographische Verortung von Menschen mit Diabetes: Auswirkungen auf die Produktgestaltung und Kommunikation

Für den Erfolg eines Produktes oder einer Dienstleistung ist die umfassende Kenntnis der Bedürfnisse, Wahrnehmungs- und Entscheidungsfilter von Zielgruppen entscheidend. Nur eine zielgerichtete, zur Zielgruppe passende Produktentwicklung und -vermarktung kann Auf Dauer erfolgreich sein. Da soziodemographische Zielgruppendefinitionen heute alleine nicht valide genug sind, um Zielgruppen umfassend zu verstehen, werden im Marketing zu-nehmend psychographische Verortungen von Zielgruppen verwendet. Auch bei chronisch Kranken reichen rein soziodemographische und medizinische Kriterien nicht aus, um Produkte und Dienstleistungen passend zu gestalten. Psychographische Erkenntnisse können die klassischen Kriterien sinnvoll ergänzen. Am Beispiel von Menschen mit Diabetes wird in einer internationalen empirischen Studie gezeigt, dass sich Menschen mit Diabetes mit Hilfe eines neuropsychologisch fundierten, visuellen Testverfahrens (dem u.a. an der NORD-AKADEMIE entwickelten Visual Questionnaire, ViQ) eindeutig psychographisch verorten lassen. Die Implikationen und Anwendungsmöglichkeiten dieser psychographischen Erkenntnisse für die Produktentwicklung, Kommunikation, Vertrieb und Marketing bei Krankenkassen, medizinischem Personal und der Pharmabranche werden aufgezeigt und kritisch diskutiert. --

Direct and indirect effects of tree diversity drive soil microbial diversity in temperate deciduous forest

We investigated the link between aboveground and belowground diversity in temperate deciduous forest ecosystems. To this end, we determined the effects of the tree species composition on the biomass and composition of the soil microbial community using phospholipid fatty acid (PLFA) profiles in the Hainich National Park, a deciduous mixed forest on loess over limestone in Central-Germany. We investigated the effects of the leaf litter composition on the microbial community, hypothesizing that distinctive leaf litter compositions increase signature PLFAs. In addition, we studied the impact of clay content, pH and nutrient status of the soil on the microbial community in different surface soil layers. Consequently, soil was sampled from depths of 0–5 cm, 5–10 cm and 10–20 cm. Plots with highest leaf litter diversity had the largest total amounts of fatty acids, but only PLFA 16:1ω5, which is a common marker for arbuscular mycorrhizal fungi, was significantly increased. In the uppermost soil layer, the pH explained most of the variance in microbial composition. In the deeper surface soil layers, nutrients such as carbon, nitrogen and phosphorus determined the microbial abundances and composition. Our results suggest that the soil microbial community is mainly indirectly influenced by aboveground diversity. Changes in soil pH or the soil nutrient status that are driven by specific plant traits like leave litter quality drive these indirect changes. Specific direct interactions are most reasonable for mycorrhizal fungi

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Abstract Screening for fecal occult blood by means of guaiac tests has an unsatisfactory sensitivity for the detection of colorectal neoplasms. The immunological determination of human hemoglobin in feces has a higher sensitivity and specificity, but hemoglobin is degraded during its transport through the gastrointestinal tract. We compared the hemoglobin test to a newly developed immuno-chemiluminometric (ILMA) assay for quantifying the hemoglobin-haptoglobin complex in feces which shows high stability against degradation. From each of 621 patients with gastrointestinal complaints before scheduled colonoscopy we collected two 1-ml samples from a single stool; there were no dietary restrictions. The sensitivity for detecting colorectal carcinomas proved 87% with hemoglobin. With the hemoglobinhaptoglobin complex it was 87% at a cutoff level of 1.5 µg/g feces, 83% at 2.0 µg/g feces, and 78% at 2.5 and 3.0 µg/g feces. The sensitivity for detecting large adenomatous polyps was 54% with hemoglobin, 76% with the hemoglobin-haptoglobin complex at a cutoff point of 1.5 µg/g feces, 73% with the hemoglobin-haptoglobin complex at 2.0 and 2.5 µg/g feces, and 65% with the hemoglobin-haptoglobin complex at 3.0 µg/g feces. The optimal cutoff point for the hemoglobin-haptoglobin complex was estimated to be 2.0 µg/g stool. The specificity for hemoglobin (99%) was significantly higher than that for the hemoglobin-haptoglobin complex at 2.0 µg/g feces (96%). Immunological determination of the hemoglobin-haptoglobin complex in feces has a comparable sensitivity as the fecal hemoglobin assay for colorectal carcinomas and a significantly higher sensitivity for adenomatous polyps but a significantly lower specificity. Its use for colorectal cancer prevention is currently being evaluated in a screening study