Unchanged gastric emptying and visceral perception in early Parkinson's disease after a high caloric test meal

Delayed gastric emptying (GE) is a frequent non-motor feature in Parkinson´s disease (PD). This prospective study (clinicaltrials.gov Identifier NCT01518751) investigated GE and visceral perception in early motor phase PD patients in comparison to age-matched and younger controls. In addition, the effect of Levodopa on GE was assessed in healthy aged controls. 16 PD patients (Hoehn & Yahr 2), 11 sex-/age-matched Ctrl1 and 10 young, male Ctrl2 subjects were subjected to a high caloric (428 kcal) (13)C-Sodium Octanoate breath test strictly OFF dopaminergic medication. Visceral appetite sensation was monitored using visual analogue scales (VAS). GE was similarly studied in 7 controls ON/OFF oral Levodopa. GE was not altered in PD patients compared to age-/sex-matched and younger controls (p = 0.76). Subjective appetite perception was not altered in the PD group in comparison to Ctrl1, but was significantly higher in Ctrl2 subjects (p = 0.02). 100 mg oral Levodopa/25 mg Benserazide significantly slowed GE by 18% among healthy controls (p = 0.04). In early motor stage PD OFF dopaminergic medication, there was no GE slowing after a high caloric test meal. Levodopa, however, caused a robust GE slowing in healthy aged individuals. Our data indicate that clinically relevant GE slowing in early PD is related to the iatrogenic effect of dopamine treatment. Subjective appetite perception is not affected in this disease stage. This data add to the understanding of gastrointestinal symptoms in early motor stage PD and highlight the influence of dopaminergic medication

First operation and drift field performance of a large area double phase LAr Electron Multiplier Time Projection Chamber with an immersed Greinacher high-voltage multiplier

We have operated a liquid-argon large-electron-multiplier time-projection chamber (LAr LEM-TPC) with a large active area of 76 $\times$ 40 cm$^2$ and a drift length of 60 cm. This setup represents the largest chamber ever achieved with this novel detector concept. The chamber is equipped with an immersed built-in cryogenic Greinacher multi-stage high-voltage (HV) multiplier, which, when subjected to an external AC HV of $\sim$1 kV$_{\mathrm{pp}}$, statically charges up to a voltage a factor of $\sim$30 higher inside the LAr vessel, creating a uniform drift field of $\sim$0.5 kV/cm over the full drift length. This large LAr LEM-TPC was brought into successful operation in the double-phase (liquid-vapor) operation mode and tested during a period of $\sim$1 month, recording impressive three-dimensional images of very high-quality from cosmic particles traversing or interacting in the sensitive volume. The double phase readout and HV systems achieved stable operation in cryogenic conditions demonstrating their good characteristics, which particularly suit applications for next-generation giant-scale LAr-TPCs.Comment: 26 pages, 19 figure

ArDM: first results from underground commissioning

The Argon Dark Matter experiment is a ton-scale double phase argon Time Projection Chamber designed for direct Dark Matter searches. It combines the detection of scintillation light together with the ionisation charge in order to discriminate the background (electron recoils) from the WIMP signals (nuclear recoils). After a successful operation on surface at CERN, the detector was recently installed in the underground Laboratorio Subterr\'aneo de Canfranc, and the commissioning phase is ongoing. We describe the status of the installation and present first results from data collected underground with the detector filled with gas argon at room temperature.Comment: 6 pages, 3 figures, Light Detection In Noble Elements (LIDINE 2013

Status of the ArDM Experiment: First results from gaseous argon operation in deep underground environment

The Argon Dark Matter (ArDM-1t) experiment is a ton-scale liquid argon (LAr) double-phase time projection chamber designed for direct Dark Matter searches. Such a device allows to explore the low energy frontier in LAr. After successful operation on surface at CERN, the detector has been deployed underground and is presently commissioned at the Canfranc Underground Laboratory (LSC). In this paper, we describe the status of the installation and present first results on data collected in gas phase.Comment: 21 pages, 20 figure

Dismal prognosis of patients with operative indication without surgical intervention in active left-sided infective endocarditis

INTRODUCTION Around 25% of patients with left-sided infective endocarditis and operative indication do not undergo surgery. Baseline characteristics and outcomes are underreported. This study describes characteristics and outcomes of surgical candidates with surgical intervention or medical treatment only. METHODS Retrospective analysis of ongoing collected data from a single-center from an observational cohort of patients with infective endocarditis (ENVALVE). Kaplan-Meier estimates for survival was calculated. Factors associated with survival were assessed using a bivariable Cox model. To adjust for confounding by indication, uni- and multivariable logistic regression for the propensity to receive surgery were adjusted. RESULTS From January 2018 and December 2021, 154 patients were analyzed: 116 underwent surgery and 38 received medical treatment only. Surgical candidates without surgery were older (70 vs. 62 years, p = 0.001). They had higher preoperative risk profile (EuroSCORE II 14% (7.2-28.6) vs. 5.8% (2.5-20.3), p = 0.002) and more comorbidities. One patient was lost-to-follow-up. Survival analysis revealed a significant higher one-year survival rate among patients following surgery (83.7% vs. 15.3% in the non-surgical group; log-rank test <0.0001). In the final multivariable adjusted model, surgery was less likely among patients with liver cirrhosis [OR = 0.03 (95% CI 0.00-0.30)] and with hemodialysis [OR = 0.014 (95% CI 0.00-0.47)]. CONCLUSION Patients with left-sided infective endocarditis who do not undergo surgery despite an operative indication are older, have more comorbidities and therefore higher preoperative risk profile and a low 1-year survival. The role of the Endocarditis Team may be particularly important for the decision-making process in this specific group

The pH of the skin surface and its impact on the barrier function

The `acid mantle' of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. However, the origin of the acidic pH, measurable on the skin surface, remains conjectural. Passive and active influencing factors have been proposed, e. g. eccrine and sebaceous secretions as well as proton pumps. In recent years, numerous investigations have been published focusing on the changes in the pH of the deeper layers of the stratum corneum, as well as on the influence of physiological and pathological factors. The pH of the skin follows a sharp gradient across the stratum corneum, which is suspected to be important in controlling enzymatic activities and skin renewal. The skin pH is affected by a great number of endogenous factors, e. g. skin moisture, sweat, sebum, anatomic site, genetic predisposition and age. In addition, exogenous factors like detergents, application of cosmetic products, occlusive dressings as well as topical antibiotics may influence the skin pH. Changes in the pH are reported to play a role in the pathogenesis of skin diseases like irritant contact dermatitis, atopic dermatitis, ichthyosis, acne vulgaris and Candida albicans infections. Therefore, the use of skin cleansing agents, especially synthetic detergents with a pH of about 5.5, may be of relevance in the prevention and treatment of those skin diseases. Copyright (c) 2006 S. Karger AG, Base

Endemicity of Zoonotic Diseases in Pigs and Humans in Lowland and Upland Lao PDR: Identification of Socio-cultural Risk Factors

In Lao People's Democratic Republic pigs are kept in close contact with families. Human risk of infection with pig zoonoses arises from direct contact and consumption of unsafe pig products. This cross-sectional study was conducted in Luang Prabang (north) and Savannakhet (central-south) Provinces. A total of 59 villages, 895 humans and 647 pigs were sampled and serologically tested for zoonotic pathogens including: hepatitis E virus (HEV), Japanese encephalitis virus (JEV) and Trichinella spiralis; In addition, human sera were tested for Taenia spp. and cysticercosis. Seroprevalence of zoonotic pathogens in humans was high for HEV (Luang Prabang: 48.6%, Savannakhet: 77.7%) and T. spiralis (Luang Prabang: 59.0%, Savannakhet: 40.5%), and lower for JEV (around 5%), Taenia spp. (around 3%) and cysticercosis (Luang Prabang: 6.1, Savannakhet 1.5%). Multiple correspondence analysis and hierarchical clustering of principal components was performed on descriptive data of human hygiene practices, contact with pigs and consumption of pork products. Three clusters were identified: Cluster 1 had low pig contact and good hygiene practices, but had higher risk of T. spiralis. Most people in cluster 2 were involved in pig slaughter (83.7%), handled raw meat or offal (99.4%) and consumed raw pigs' blood (76.4%). Compared to cluster 1, cluster 2 had increased odds of testing seropositive for HEV and JEV. Cluster 3 had the lowest sanitation access and had the highest risk of HEV, cysticercosis and Taenia spp. Farmers which kept their pigs tethered (as opposed to penned) and disposed of manure in water sources had 0.85 (95% CI: 0.18 to 0.91) and 2.39 (95% CI: 1.07 to 5.34) times the odds of having pigs test seropositive for HEV, respectively. The results have been used to identify entry-points for intervention and management strategies to reduce disease exposure in humans and pigs, informing control activities in a cysticercosis hyper-endemic village

Pro-fibrotic phenotype of bone marrow stromal cells in Modic type 1 changes

Modic type 1 changes (MC1) are painful vertebral bone marrow lesions frequently found in patients suffering from chronic low-back pain. Marrow fibrosis is a hallmark of MC1. Bone marrow stromal cells (BMSCs) are key players in other fibrotic bone marrow pathologies, yet their role in MC1 is unknown. The present study aimed to characterise MC1 BMSCs and hypothesised a pro-fibrotic role of BMSCs in MC1. BMSCs were isolated from patients undergoing lumbar spinal fusion from MC1 and adjacent control vertebrae. Frequency of colony-forming unit fibroblast (CFU-F), expression of stem cell surface markers, differentiation capacity, transcriptome, matrix adhesion, cell contractility as well as expression of pro-collagen type I alpha 1, α-smooth muscle actin, integrins and focal adhesion kinase (FAK) were compared. More CFU-F and increased expression of C-X-C-motif-chemokine 12 were found in MC1 BMSCs, possibly indicating overrepresentation of a perisinusoidal BMSC population. RNA sequencing analysis showed enrichment in extracellular matrix proteins and fibrosis-related signalling genes. Increases in pro-collagen type I alpha 1 expression, cell adhesion, cell contractility and phosphorylation of FAK provided further evidence for their pro-fibrotic phenotype. Moreover, a leptin receptor high expressing (LEPRhigh) BMSC population was identified that differentiated under transforming growth factor beta 1 stimulation into myofibroblasts in MC1 but not in control BMSCs. In conclusion, pro-fibrotic changes in MC1 BMSCs and a LEPRhigh MC1 BMSC subpopulation susceptible to myofibroblast differentiation were found. Fibrosis is a hallmark of MC1 and a potential therapeutic target. A causal link between the pro-fibrotic phenotype and clinical characteristics needs to be demonstrated

Taking up the cudgels against gay rights? Trends and trajectories in African Christian theologies on homosexuality

Against the background of the HIV epidemic and the intense public controversy on homosexuality in African societies, this article investigates the discourses of academic African Christian theologians on homosexuality. Distinguishing some major strands in African theology, that is, inculturation, liberation, women’s and reconstruction theology, the article examines how the central concepts of culture, liberation, justice, and human rights function in these discourses. On the basis of a qualitative analysis of a large number of publications, the article shows that stances of African theologians are varying from silence and rejection to acceptance. Although many African theologians have taken up the cudgels against gay rights, some “dissident voices” break the taboo and develop more inclusive concepts of African identity and African Christianity

First results on light readout from the 1-ton ArDM liquid argon detector for dark matter searches

ArDM-1t is the prototype for a next generation WIMP detector measuring both the scintillation light and the ionization charge from nuclear recoils in a 1-ton liquid argon target. The goal is to reach a minimum recoil energy of 30\,keVr to detect recoiling nuclei. In this paper we describe the experimental concept and present results on the light detection system, tested for the first time in ArDM on the surface at CERN. With a preliminary and incomplete set of PMTs, the light yield at zero electric field is found to be between 0.3-0.5 phe/keVee depending on the position within the detector volume, confirming our expectations based on smaller detector setups.Comment: 14 pages, 10 figures, v2 accepted for publication in JINS