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The interphotoreceptor matrix is a unique extracellular matrix occupying the space between the photoreceptors and the retinal pigment epithelium. Due to its putative function in the maintenance and integrity of the photoreceptor cells, it is conceivable that it is involved in retinal degeneration processes. More recently, a novel gene encoding a 150-kDa interphotoreceptor matrix proteoglycan, designated IMPG1, was cloned and shown to be expressed in both rod and cone photoreceptor cells. To assess this gene in human retinal dystrophies, we have now determined the genomic organization and chro- mosome location of IMPG1. It is composed of 17 exons ranging from 21 to 533 bp, including an alternatively spliced exon 2. Using somatic cell hybrid mapping and FISH analysis, we have assigned the IMPG1 locus to 6q13→q15. As this interval overlaps with the chromosomal loci of several human retinopathies, including autosomal dominant Stargardt-like macular dystrophy (STGD3), progressive bifocal chorioretinal atrophy (PBCRA), and North Carolina macular dystrophy (MCDR1), IMPG1 represents an attractive candidate for these 6q-linked disorders. [ABSTRACT FROM AUTHOR]

Background: Quality measurement in the German statutory program for quality in health care follows a two-step process. For selected areas of health care, quality is measured via performance indicators (first step). Providers failing to achieve benchmarks in these indicators subsequently enter into a peer review process (second step) and are asked by the respective regional authority to provide a written statement regarding their indicator results. The statements are then evaluated by peers, with the goal to assess the provider's quality of care. In the past, similar peer review-based approaches to the measurement of health care quality in other countries have shown a tendency to lack reliability. So far, the reliability of this component of the German statutory program for quality in health care has not been investigated., Method: Using logistic regression models, the influence of the respective regional authority on the peer review component of health care quality measurement in Germany was investigated using three exemplary indicators and data from 2016., Results: Both the probability that providers are asked to provide a statement as well as the results produced by the peer review process significantly depend on the regional authority in charge. This dependence cannot be fully explained by differences in the indicator results or by differences in case volume., Conclusions: The present results are in accordance with earlier findings, which show low reliability for peer review-based approaches to quality measurement. Thus, different results produced by the peer review component of the quality measurement process may in part be due to differences in the way the review process is conducted. This heterogeneity among the regional authorities limits the reliability of this process. In order to increase reliability, the peer review process should be standardized to a higher degree, with clear review criteria, and the peers should undergo comprehensive training for the review process. Alternatively, the future peer review component could be adapted to focus rather on identification of improvement strategies than on reliable provider comparisons., (Copyright © 2024. Published by Elsevier GmbH.)

Background: To advance rehabilitation we need a comprehensive understanding of functioning and disability of people after stroke., Objective: To present an overview of the methodology of the Life After Stroke In Northern Sweden Study, compare participants and non-participants regarding gender and age, and describe baseline sociodemographics, stroke characteristics and the participants' self-rated degree of recovery., Methods: Data were collected through a study specific questionnaire, from the participants' medical records and with internationally established self-assessment tools focusing on sleep disturbances, depressive symptoms, fatigue, physical activity, and remaining physical and cognitive impairments, activity limitations, participation restrictions and life satisfaction., Results: Of 301 potential participants, 160 comprise the final sample (response rate 53%; 86 men and 74 women, mean age 73 years±11, mean time since stroke onset 35 months±11; 18- 61). Most participants had an ischemic stroke (87%), were retired (84%), cohabitant (63%) and walked independently (71%). The mean self-rated degree of recovery was 75 (SD±24; 0- 100)., Conclusions: These baseline data together with forthcoming studies will describe stroke-related impairments, activity limitations, participation restrictions and life satisfaction more than one year after stroke, and deepen our understanding of factors of importance for a healthy and successful life after stroke.

For evaluating the quality of care provided by hospitals, special interest lies in the identification of performance outliers. The classification of healthcare providers as outliers or non-outliers is a decision under uncertainty, because the true quality is unknown and can only be inferred from an observed result of a quality indicator. We propose to embed the classification of healthcare providers into a Bayesian decision theoretical framework that enables the derivation of optimal decision rules with respect to the expected decision consequences. We propose paradigmatic utility functions for two typical purposes of hospital profiling: the external reporting of healthcare quality and the initiation of change in care delivery. We make use of funnel plots to illustrate and compare the resulting optimal decision rules and argue that sensitivity and specificity of the resulting decision rules should be analyzed. We then apply the proposed methodology to the area of hip replacement surgeries by analyzing data from 1,277 hospitals in Germany which performed over 180,000 such procedures in 2017. Our setting illustrates that the classification of outliers can be highly dependent upon the underlying utilities. We conclude that analyzing the classification of hospitals as a decision theoretic problem helps to derive transparent and justifiable decision rules. The methodology for classifying quality indicator results is implemented in an R package (iqtigbdt) and is available on GitHub., (© 2022 The Authors. Biometrics published by Wiley Periodicals LLC on behalf of International Biometric Society.)

Intestinal drug transporters are crucial determinants for absorption and oral bioavailability of drugs. In healthy tissue donors, a recent study revealed profound discrepancies between mRNA expression and protein abundance as well as differences in the protein content between small and large intestine for clinically relevant multidrug transporters as the ATP binding cassette transporter subfamily B member 1 (ABCB1) and subfamily C member 3 (ABCC3) and the solute carrier family 15 member 1 (SLC15A1, PEPT1). As the mechanisms underlying these observations remained unclear, the aim of the present study was to elucidate the intestinal regiospecific microRNA profile under physiological conditions and identify specific microRNAs contributing to the post-transcriptional regulation of major drug transporters. For this purpose, tissue samples were collected from six intestinal sites obtained from six healthy tissue donors. The expression of 754 microRNAs was determined using qRT-PCR based low density arrays, and microRNA expression levels were correlated with transporter protein abundance quantified by targeted proteomics. A total of 241 microRNA-transporter pairs were identified, showing significant negative correlations to protein abundance (p < 0.05). Out of these, for nine pairs, the binding of the microRNA to the respective transporter 3'-UTR was predicted in silico. Besides the already known interactions of miR-27a-3p-ABCB1 and miR-193a-3p-PEPT1, reporter gene assays confirmed binding of miR-192-5p to the ABCC3 3'-UTR (reduction of reporter gene activity by 31%; p = 0.0012), miR-409-3p to the ABCB1 3'-UTR (reduction by 38%; p = 0.0006), and miR-193b-3p as well as miR-27a-3p to PEPT1 3'-UTR (reduction by 49% (p = 0.0012) and 20% (p = 0.0043), respectively). These results suggest that mucosal microRNA expression contributes to the explanation of discrepancies between mRNA expression and protein abundance as well as site-dependent differences in protein content along the human intestine under physiological conditions, as exemplified for ABCB1, ABCC3, and PEPT1.

A triple mutant of an esterase from Pseudomonas fluorescens (PFE) that was created by directed evolution exhibited high enantioselectivity (E=89) in a kinetic resolution and yielded the building block (S)-but-3-yn-2-ol. Surprisingly, a mutation close to the active site caused the formation of inclusion bodies, but remote mutations were found to be responsible for the high selectivity. Back mutations gave a variant (double mutant PFE Ile76Val/Val175Ala) that showed excellent selectivity (E=96) and activity (20 min for 50% conversion, which corresponds to 1.25 U per mg of protein).

In order to extend the limited knowledge about crenarchaeal DNA polymerases, we cloned a gene encoding a family B DNA polymerase from the hyperthermophilic crenarchaeon Pyrobaculum islandicum. The enzyme shared highest sequence identities with a group of phylogenetically related DNA polymerases, designated B3 DNA polymerases, from members of the kingdom Crenarchaeota, Pyrodictium occultum and Aeropyrum pernix, and several members of the kingdom Euryarchaeota. Six highly conserved regions as well as a DNA-binding motif, indicative of family B DNA polymerases, were identified within the sequence. Furthermore, three highly conserved 3'-5' exonuclease motifs were also found. The gene was expressed in Escherichia coli, and the DNA polymerase was purified to homogeneity by heat treatment and affinity chromatography. Activity staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed an active polypeptide of approximately 90 kDa. For the recombinant DNA polymerase from P. islandicum, activated calf thymus DNA was used as a substrate rather than primed single-stranded DNA. The enzyme was strongly inhibited by monovalent cations and N-ethylmaleimide; it is moderately sensitive to aphidicolin and dideoxyribonucleoside triphosphates. The half-life of the enzyme at 100 and 90 degrees C was 35 min and >5 h, respectively. Interestingly, the pH of the assay buffer had a significant influence on the 3'-5' exonuclease activity of the recombinant enzyme. Under suitable assay conditions for PCR, the enzyme was able to amplify lambda DNA fragments of up to 1,500 bp.

During the years 1979-82, the Commission on Aging scrutinised public measures relating to the elderly and recommended adherence to the principles of continuity, self determination and use of own resources in future aging policy. A central point in the Commission's perception of aging was that a number of functional impairments previously considered exclusively a reflection of the biological aging processes were now seen as equally induced by loss of roles and social functions. The renewal of structures and development work carried out throughout the country are based on these principles, integrating social and psychological considerations. Work is also based on the Report on the Public Sector (1988) which recommends enhancement of social networks and self-help capabilities of the old as well as new forms of cooperation between the public sector and citizens. Self determination and self control have become new key words in current aging policy. The new policy is not only induced by financial pressure on the public sector, but equally to the realisation that many social tasks are best solved in cooperation with individuals. The renewal of aging policy is also adapted to the new generations of elderly people, who want freer lifestyles and more options than many of the old have today. They will very likely be more mobile and make more demands for their life. They have been accustomed to creating networks and cross-contacts, as their jobs and interests have required it, and their health and financial circumstances will frequently be better than those of the elderly generation today.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the study was to investigate the effect of a new 20% fat emulsion, containing 50% MCT and 50% LCT in comparison to a 20% fat emulsion containing only LCT, in the postoperative period. The possible influence on nitrogen loss, protein synthesis and fat metabolism was estimated. 20 patients after elective colon surgery were included in the trial. Parenteral nutrition was carried out for 5 days with two isonitrogenic and isocaloric nutritional regimens including either MCT/LCT or only LCT fat emulsions. Fat emulsions were administered over a period of 12 h with a total fat supply rate of 0.12 g/kg B.W./h. Blood samples for determination of protein synthesis, triglyceride and ketone bodies were taken under fat infusion as well as before and after infusion. 24-h urine samples were taken to measure nitrogen balance. Our results showed no difference in protein levels between the MCT- and LCT group. The 5-day nitrogen balance showed a significant increase in the MCT group (p less than 0.05, Mann-Whitney U-test). At the end of the infusion period triglyceride levels in the MCT group (mean value 244 +/- 15 mg%) differed significantly compared to the LCT group (m = 190 +/- 24 mg%). 2 h later triglycerides in both groups fell to basal levels. beta-Hydroxybutyrate (beta-HB) and aceto acetate (Ac-ac) concentrations showed significant differences between both groups. After 12 h infusion the MCT group had a mean level of 210 mumol/l beta-HB and 180 mumol/l Ac-ac vs. 90 mumol/l beta-HB and 120 mumol/l Ac-ac in the LCT group.(ABSTRACT TRUNCATED AT 250 WORDS)