Chemerin-156 is the Active Isoform in Human Hepatic Stellate Cells

The chemokine chemerin exists as C-terminally processed isoforms whose biological functions are mostly unknown. A highly active human chemerin variant (huChem-157) was protective in experimental hepatocellular carcinoma (HCC) models. Hepatic stellate cells (HSCs) are central mediators of hepatic fibrogenesis and carcinogenesis and express the chemerin receptors chemokine-like receptor 1 (CMKLR1) and G protein-coupled receptor 1 (GPR1). Here we aimed to analyse the effect of chemerin isoforms on the viability, proliferation and secretome of the human HSC cell line LX-2. Therefore, huChem-157, 156 and 155 were over-expressed in LX-2 cells, which have low endogenous chemerin levels. HuChem-157 produced in LX-2 cells activated CMKLR1 and GPR1, and huChem-156 modestly induced GPR1 signaling. HuChem-155 is an inactive chemerin variant. Chemerin isoforms had no effect on cell viability and proliferation. Cellular expression of the fibrotic proteins galectin-3 and alpha-smooth muscle actin was not regulated by any chemerin isoform. HuChem-156 increased IL-6, IL-8 and galectin-3 in cell media. HuChem-157 was ineffective, and accordingly, did not enhance levels of these proteins in media of primary human hepatic stellate cells when added exogenously. These analyses provide evidence that huChem-156 is the biologic active chemerin variant in hepatic stellate cells and acts as a pro-inflammatory factor

Disease heterogeneity of adult diabetes based on routine clinical parameters at diagnosis: Results from the German/Austrian DPV registry.

AIMS To cluster adults with diabetes using parameters from real-world clinical care at manifestation. MATERIALS AND METHODS We applied hierarchical clustering using Ward's method to 56,869 adults documented in the Prospective Diabetes Follow-up Registry (DPV). Clustering variables included age, sex, BMI, HbA1c, diabetic ketoacidosis (DKA), components of the metabolic syndrome (hypertension/dyslipidemia/hyperuricemia), and beta-cell antibody status. Time until use of oral antidiabetic drugs (OAD), use of insulin, chronic kidney disease (CKD), cardiovascular disease (CVD), retinopathy, or neuropathy were assessed using Kaplan Meier analysis and Cox regression models. RESULTS We identified eight clusters: Four clusters comprised early diabetes onset (median age between 40 and 50 years), but differed with regard to BMI, HbA1c, DKA and antibody positivity. Two clusters included adults with diabetes onset in their early 60s who met target HbA1c, but differed in BMI and sex distribution. Two clusters were characterized by late diabetes onset (median age 69 and 77 years) and relatively low BMI, but differences in HbA1c. Earlier insulin use was observed in adults with high HbA1c, and earlier OAD use was observed in those with high BMI. Time until CKD or CVD was shorter in those with late onset, whereas retinopathy occurred earlier in adults with late onset and high HbA1c, and in adults with early onset, but high HbA1c and high percentage of antibody positivity. CONCLUSIONS Adult diabetes is heterogeneous beyond classical type 1/type 2 diabetes, based on easily available parameters in clinical practice using an automated clustering algorithm which allows both continuous and binary variables. This article is protected by copyright. All rights reserved

Many Body Theory of Charge Transfer in Hyperthermal Atomic Scattering

We use the Newns-Anderson Hamiltonian to describe many-body electronic processes that occur when hyperthermal alkali atoms scatter off metallic surfaces. Following Brako and Newns, we expand the electronic many-body wavefunction in the number of particle-hole pairs (we keep terms up to and including a single particle-hole pair). We extend their earlier work by including level crossings, excited neutrals and negative ions. The full set of equations of motion are integrated numerically, without further approximations, to obtain the many-body amplitudes as a function of time. The velocity and work-function dependence of final state quantities such as the distribution of ion charges and excited atomic occupancies are compared with experiment. In particular, experiments that scatter alkali ions off clean Cu(001) surfaces in the energy range 5 to 1600 eV constrain the theory quantitatively. The neutralization probability of Na$^+$ ions shows a minimum at intermediate velocity in agreement with the theory. This behavior contrasts with that of K$^+$, which shows ... (7 figures, not included. Figure requests: [email protected])Comment: 43 pages, plain TeX, BUP-JBM-

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (< 5 years, 5–10 years, 10–20 years, and > 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (< 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs > 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (< 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs > 20 years: 0.62), and only surgeons with > 20 years of experience did not have substantial reliability on assessment 2 (< 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs > 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

Die modifizierte SLAM (scapholunate axis method) Technik zur sekundären SL-Band-Rekonstruktion – Erste Ergebnisse

Background The common techniques for scapholunate (SL) ligament reconstruction achieve pain relief and maintenance of reposition at the expense of mobility and grip strength. In contrast, the scapholunate axis method (SLAM) technique seems to stabilise the scaphoid and lunate bones without a loss of function. We modified the technique with an additional anchor fixation of the tendon graft to the capitate bone in order to prevent palmar dislocation of the scaphoid bone. Purpose This study aimed to examine whether or not it is possible to stabilise the scaphoid and lunate bones and to reduce pain without a loss of function and grip strength using the modified SLAM technique. Patients and Methods The SLAM technique was performed on 5 male patients aged between 36 and 60 years with an SL ligament lesion (3-10 months old). Preoperatively and after 12 months, the postoperative range of motion, grip strength, pain, SL angle, DASH Score and Mayo Wrist Score were assessed and compared to each other. Results An improvement of the DASH Score (60.4 to 34.4 on average) and the Mayo Wrist Score (41 to 74 on average) was observed at the 12-month follow-up. Grip strength was enhanced from an average of 24.6 kg to 38 kg. Pain was improved from an average of 1.4 to 0.2 (at rest) and from 5.4 to 1.4 (under load). The SL angle changed only marginally from an average of 64.8 degrees preoperatively to 63.2 degrees postoperatively. The average range of motion was improved (extension/flexion: 58-0-60 vs. 50-0-49; radial/ulnar duction: 19-0-45 vs. 15-0-25 und supination/pronation: 87-0-90 vs. 81-0-81): However, function did not improve in every patient and all planes. Conclusion The modified SLAM technique improved the DASH Score, the Mayo Wrist Score, grip strength and pain. However, the SL angle and range of motion did not improve in every patient and plane. Consequently, it cannot be confirmed that the modified SLAM technique ensures a reliable stabilisation of the scaphoid and lunate bones and reduction of pain without a loss of function

Reconstruction of chronic scapholunate dissociation with the modified scapholunate axis method (SLAM)

Introduction Injury to the scapholunate (SL) ligament represents a common trauma of the wrist but is frequently misdiagnosed because of non-specific pain. Established methods for SL reconstruction mainly focus on reducing pain and maintaining the reposition result at the expense of mobility and strength. This study aimed at restoring stability and reducing pain while simultaneously maintaining mobility and strength using the scapholunate axis method (SLAM). Material and methods 22 patients (19 male and 3 female) aged between 26 and 64 years with an SL ligament lesion underwent SLAM reconstruction. Mean duration between injury and operation was 7.9 +/- 5 (1-24) months. Hand functions using DASH, Mayo Wrist Score, range of motion, pain (at rest and weight-bearing) and grip strength were assessed prior and 12 months postoperative. Additionally SL angle was collected pre- and postoperative. Results Each of the 22 patients improved significantly postoperative in DASH and Mayo Wrist Score with regard to pain at rest and under weight-bearing. Additionally, grip strength could be improved up to 31% compared to preoperatively. In contrast, range of motion and SL angle and grip strength did not change essentially. Conclusions The secondary SL ligament reconstruction technique SLAM shows promising results. Pain was significantly relieved and grip strength was significantly increased. Additionally, DASH and Mayo Wrist Score could be significantly improved. However, SL angle and range of motion could not be improved in every patient and plane

Multidisciplinary lifestyle intervention is associated with improvements in liver damage and in surrogate scores of NAFLD and liver fibrosis in morbidly obese patients

Purpose Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Particularly morbidly obese patients are at risk of developing progressive liver disease. Nutritional and lifestyle intervention is recommended as the standard of care in NAFLD. However, there is a striking lack of evidence to support the efficacy of lifestyle intervention to treat NAFLD in morbidly obese patients. Here, we aimed to assess the impact of lifestyle intervention on NAFLD in the morbidly obese in a real-world setting. Methods 136 obese patients were included in an industry-independent, multiprofessional lifestyle intervention program with a lead-in phase of 12 weeks of formula diet and a total of 48 weeks intensive counselling. Body weight and markers of the metabolic syndrome were analyzed. Presence of NAFLD was screened for by use of non-invasive markers of fatty liver, non-alcoholic steatohepatitis and liver fibrosis. Results Weight loss goals (i.e. > 5% or > 10% of initial body weight, respectively, depending on baseline BMI) were achieved in 89.7% of subjects in the intention-to-treat analysis and 93.9% in the per-protocol analysis. This was associated with a pronounced improvement in serum ALT values. The percentage of subjects who fulfilled non-invasive criteria for fatty liver dropped from 95.2 to 54.8%. Risk of NASH improved and the number of patients at risk of liver fibrosis declined by 54.1%. Conclusion Lifestyle intervention was associated with a marked improvement of serum ALT and an improvement of surrogate scores indicative of NAFLD and, importantly, advanced fibrosis, in a real-world cohort of morbidly obese patients

The Impact of Different Types of Diet on the Prevention of Diseases among Polish Inhabitants, Including COVID-19 Disease

Proper nutrition may help in preventing deaths or at least alleviating the symptoms of many chronic diseases. While the COVID-19 disease was still taking its toll, the world had to adjust to new life conditions, which could change nutritional habits. In this observational, cross-sectional study, we aimed to identify the potential correlations between sociodemographic factors and diet and the presence of common chronic diseases among Polish inhabitants. Furthermore, we tried to determine whether the COVID-19 pandemic led to changes in nutritional habits. Therefore, based on the online study (the National Test for Poles’ Health (NTPH), we collected data from 376,102 and 200,000 respondents in two different time frames (before the COVID-19 pandemic: 2019–2020 and during the COVID-19 pandemic: 2021–2022, respectively). Despite the rapid global rise of the COVID-19 pandemic, among our study group, hypertension was still the most commonly occurring disease in both time frames (32.33% in 2019–2020 and 34.95% in 2021–2022, p p p p p = 0.001; and OR = 0.73, CI 95% (0.55–0.96), p = 0.026). In line with this, consuming meat meals increases the risk of hypertension (OR = 1.09, CI 95% (1.02–1.17), p = 0.009). Interestingly, a reduced-sodium diet has an association with decreased morbidity of COVID-19 disease (OR = 0.72, CI 95% (0.63–0.82), p < 0.001). This result brings new light to more research to be done to allow efficient prevention of this disease. In conclusion, our study shows the beneficial role of a balanced diet in reducing the incidence rate of common chronic diseases. Our findings may be educational for those who would like to change their nutritional habits and/or for public health professionals to suggest the implementation of proper diets to their patients

Chemokine (CC-motif) receptor-like 2 mRNA is expressed in hepatic stellate cells and is positively associated with characteristics of non-alcoholic steatohepatitis in mice and men

Chemokine (CC-motif) receptor-like 2 (CCRL2) is a decoy receptor and regulates the local responses of the chemokine chemerin. Recently our group has shown that the functional chemerin receptor, chemokine-like receptor 1 (CMKLR1), correlates with fibrosis and non-alcoholic steatohepatitis (NASH) score in males only. In our current study, we wanted to know whether CCRL2 shows similar correlations as CMKLR1. Therefore, we analyzed the hepatic expression of CCRL2 in murine NASH and in liver tissues obtained from 85 patients with non-alcoholic fatty liver disease (NAFLD) and 33 controls. CCRL2 mRNA was not significantly changed in murine and human NASH liver. CCRL2 mRNA levels were positively correlated with inflammation, fibrosis and NASH scores in the patients. Concordantly, CCRL2 was related to the mRNA levels of F4/80, transforming growth factor beta and alpha smooth muscle actin in murine NASH. In the human cohort, CCRL2 mRNA correlated with fibrosis score and CMKLR1 mRNA in both gender. CCRL2 mRNA was induced in the liver of type 2 diabetes and hypercholesterolemic patients, but still positively correlated with fibrosis score when these patients were excluded from calculations. Human hepatic stellate cells (HSC), hepatic sinusoidal endothelial cells and Kupffer cells (KC) express CCRL2 mRNA. TNF induces CCRL2 expression in HSC and lipopolysaccharide in KC suggesting that correlations identified in NAFLD patients are partly related to the activation of these cells