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Background: Acute on chronic pancreatitis (ACP) is a relatively common condition, but there are significant gaps in our knowledge on the definition, incidence, diagnosis, treatment and prognosis. Methods: A systematic review that followed PICO (Population; Intervention; Comparator; Outcome) recommendation for quantitative questions and PICo (Population, Phenomenon of Interest, Context) for qualitative research was done to answer 10 of the most relevant questions about ACP. Quality of evidence was judged by the GRADE criteria (Grades of Recommendation, Assessment, Development and Evaluation). The manuscript was sent for review to 12 international experts from various disciplines and continents using a Delphi process. Results: The quality of evidence, for most statements, was low to very low, which means that the recommendations in general are only conditional. Despite that, it was possible to reach strong levels of agreement by the expert panel for all 10 questions. A new consensus definition of ACP was reached. Although common, the real incidence of ACP is not known, with alcohol as a major risk factor. Although pain dominates, other non-specific symptoms and signs can be present. Serum levels of pancreatic enzymes may be less than 3 times the upper limit of normal and cross-sectional imaging is considered more accurate for the diagnosis in many cases. It appears that it is less severe and with a lower mortality risk than acute pancreatitis.Conclusions: Although the evidence base is poor, this position statement provides a foundation from which to advance management of ACP.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background: The apprenticeship model of surgical training is the gold standard worldwide. However, increasing evidence shows that its traditional method of teaching surgical procedures covers cognitive skills inadequately. Therefore, the traditional teaching method for surgical procedures may be liable for producing surgeons who are not fully proficient in cognitive decision-making. This study designed a digital teaching method for surgical procedure cognitive skills and compared it to the traditional teaching method. Methods: This was a quantitative experimental study conducted in two phases. Participants were novice medical officers and general surgery residents at the Universities of Botswana and Pretoria. Ethical approval was obtained. The digital teaching method was designed using the ADDIE model and compared to the traditional teaching method. ADDIE is an iterative instructional design model composed of five stages: Analysis, Design, Development, Implementation and Evaluation. A crossover-repeated-measures study design was used to determine the difference in knowledge gain and retention between the two teaching methods. A satisfaction level survey was also conducted. Results: The digital teaching method for surgical procedure cognitive skills was designed and hosted on Moodle. Twenty-nine participants completed the study. The paired sample t-test showed that the mean differenced score for the digital teaching method (M = 3.59, SD = 1.48) was significantly greater than that of the traditional teaching method (M = 1.93, SD = 1.28), t (28) = -10.950, p < 0.001. Likewise, the mean differenced retention score for the digital teaching method (M = 2.96, SD = 1.480) was significantly higher than that of the traditional teaching method (M = 1.48, SD = 1.087). Seventy-two percent preferred the digital teaching method over the traditional one. Conclusion: Students taught surgical procedure cognitive skills using the digital teaching method had better knowledge gain and retention than those taught using the traditional teaching method. Participants rated the digital teaching method highly compared to the traditional method. We recommend the adoption of the digital teaching method for teaching surgical procedure cognitive skills to produce surgeons competent in decision-making. The assumption is that this would lead to improved surgical outcomes.

Returns are an inconvenient problem in the mail-order business, not only for the merchant but also for the customer. With an estimated return rate of 50% in the fashion sector, the seller has to deal with the expense of restocking and possibly reprocessing, the buyer, who must reship the return, and the environment. We do not consider returns to be generally bad, but rather an explicit, integral part of the online business model. Therefore, we investigate potentially suitable measures to avert or avoid returns in the pre-purchase, purchase, and post-purchase phases. We look at current and technological developments in return management and the most critical drivers for fashion assortment returns. The measures we investigate deliver a holistic view of the issue and target all three purchase phases. The resulting measures were assessed via an online questionnaire with 8393 participants (customers of a German fashion online retailer) to impact customer satisfaction using Kano’s method. There are clear measures that promise high customer satisfaction (such as 360° view) and a clear hierarchy regarding monetary and non-monetary measures. By applying a new method, the segmented Kano perspective, we found different customer segments, which are different in their expectations towards returns. That allowed us to conclude dynamics regarding return management. This assessment is followed by discussing the results, conclusions, and indications for further research fields.

BackgroundPatients with Fabry disease (FD) on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in chronic kidney disease epidemiology collaboration-based estimated glomerular filtration rate (eGFR) and a worsened plasma lyso-Gb3 decrease. Hence, the most effective dose is still a matter of debate.MethodsIn this prospective observational study, we assessed end-organ damage and clinical symptoms in 78 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, which were assigned to continue this treatment (agalsidase-beta, regular-dose group, n=17); received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n=22); or were re-switched to agalsidase-beta after receiving agalsidase-alfa for 12 months (re-switch group, n=39) with a follow-up of 88±25 months.ResultsNo differences for clinical events were observed for all groups. Patients within the re-switch group started with the worst eGFR values at baseline (p=0.0217). Overall, eGFR values remained stable in the regular-dose group (p=0.1052) and decreased significantly in the re-switch and switch groups (pConclusionsOur data suggest that a re-switch to high dosage of agalsidase results in a better biochemical response, but not in a significant renal amelioration especially in classical males.

Purpose: This study analyzed the physiological response during Yo-Yo Intermittent Recovery Level 1 (YYIR1) test and re-test by in-field ergospirometry and time-series analyses of respiratory parame...

Fabry disease (FD) is a lysosomal storage disease, treatable by enzyme replacement therapy (ERT) that substitutes deficient α-galactosidase A (AGAL). The formation of neutralising anti-drug antibodies (ADA) inhibiting AGAL activity during infusion is associated with disease progression in affected male patients. In this study we analysed if ADAs also inhibit endothelial enzyme uptake as well as intracellular enzyme activity. Therefore, fluorescence-labelled AGAL in combination with ADA-positive sera from FD patients (n = 8) was used to analyse enzyme uptake in endothelial and FD-specific cells. Furthermore, immune adsorption and a comprehensive ADA epitope mapping were performed. Pre-incubation of AGAL with ADAs significantly inhibited intracellular enzyme activity, which was rescued by immune adsorption (both P < .01). ADAs from some patients also inhibited enzyme uptake. ADA epitope mapping identified an epitope at position 121 to 140 aa potentially responsible for uptake inhibition for these patients. Further analyses revealed the presence of stable AGAL/ADA-immune complexes at pH 4.5 and decreased intracellular enzyme activity in endothelial cells (P < .001). Finally, the pre-incubation of AGAL with ADAs resulted in a reduced depletion of intracellular globotriaosylceramide in patient-derived AGAL-deficient cells, demonstrating a direct negative impact of ADAs on intracellular clearance. Neutralising ADAs may not only inhibit infused AGAL activity, but according to their epitopes can also inhibit endothelial AGAL uptake. Indeed, internalised AGAL/ADA-complexes may not dissociate, underlining the importance of novel therapeutic approaches for ADA reduction and prevention to increase therapy efficiency in affected patients.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to variants in the coding sequence of desmosomal genes. The potential contribution of non-coding desmoglein-2 (DSG2) variants for development of ARVC is undescribed. We sequenced 1450 base pairs upstream of ATG in the DSG2 gene in 65 unrelated patients diagnosed with ARVC (10 borderline cases). Identified variants was evaluated by cosegregation and allele population frequency analysis, in silico tools, immunohistological investigations of myocardial biopsies, gene reporter assays, electrophoretic mobility shift assays (EMSA), and chromatin immunoprecipitation. The genetic analysis identified one novel, rare heterozygous DSG2 upstream variant (-317G A) in a genetically unexplained ARVC patient. The variant segregated with signs of disease, was absent in publicly available databases, and affected a predicted binding site for activating protein-1 (AP-1). Immunohistochemical analysis of a myocardial biopsy from the -317G A patient showed a marked reduction in DSG2 protein levels compared to healthy controls. Luciferase reporter gene assays showed promoter activity of the identified DSG2 upstream region and a general reduction in transcriptional activity in the presence of the minor DSG2_A allele (p .01). Moreover, the DSG2_A allele reduced DSG2 activation by TGF-beta1 and a protein kinase C pathway activator (PMA; all p .001 vs. DSG2_G). EMSAs showed altered transcription factor binding in presence of the DSG2_A allele. Chromatin immunoprecipitation assays in wild type epithelial cells identified AP-1 components c-FOS and c-JUN at the -317 locus. In conclusion, the non-coding DSG2 promoter variant -317G A reduces DSG2 transcription in vitro and reduced myocardial DSG2 protein levels were observed in vivo. Our data support a contribution of non-coding DSG2 variants to the pathogenesis of ARVC.

Circulatory microRNAs (c-miRNAs) are regulated in response to physical activity and may exert anti-atherosclerotic effects. Since the vascular endothelium is an abundant source of c-miRNAs, we aimed to identify novel vasculoprotective exercise-induced c-miRNAs by the combined analysis of published endothelial miRNA array data followed by in vivo and in vitro validation. We identified 8 different array-based publications reporting 185 endothelial shear stress-regulated miRNAs of which 13 were identified in ≥3 independent reports. Nine miRNAs had already been associated with physical activity. Of the remaining novel miRNAs, miR-98-3p and miR-125-5p were selected for further analysis due to reported vasculoprotective effects. Analysis in two different 4-week high-intensity interval training (HIIT) groups (group 1 [n=27]: 4x30 s, group 2 [n=25]: 8x15 s; all-out running) suggested significantly elevated miR-98 and miR-125a-5p levels in response to acute exercise at baseline and at follow-up. Endothelial in vitro shear stress experiments revealed increased miR-125a-5p and miR-98-3p levels in medium of human umbilical vein endothelial cells at 30 dyn/cm2 after 20 and 60 min, respectively. Our results suggest that miR-98-3p and miR-125a-5p can be rapidly secreted by endothelial cells, which might be the source of increased c-miR-98-3p and -125a-5p levels in response to HIIT. Both miRNAs attenuate endothelial inflammation and may mediate vasculoprotective effects of physical exercise including HIIT.

Hochintensives Intervalltraining (HIIT) kann die korperliche Leistungsfahigkeit sowohl bei gesunden Menschen als auch bei Patienten mit lebensstilinduzierten Erkrankungen effektiv verbessern. Ziel der Studie war zu prufen, ob (I) die individuelle Leistungsfahigkeit und (II) eine HIIT-Intervention Auswirkungen auf optische Koharenztomographie Angiographie(OCTA)-Messungen am Augenhintergrund von jungen gesunden Erwachsenen haben. Es absolvierten 65 gesunde Probanden einen standardisierten stufenformigen Lauftest, um die individuelle Fitness zu erheben. Bestimmt wurde diese als Geschwindigkeit an der individuellen anaeroben Laktatschwelle und maximalen Laufgeschwindigkeit. Anschliesend folgte ein 4‑wochiges HIIT mit 2 Trainingseinheiten pro Woche. OCTA-Aufnahmen zur Messung der foveal avaskularen Zone (FAZ) sowie der Flussdichten in verschiedenen Segmentierungen an Makula und Sehnerv wurden in korperlicher Ruhe vor und nach HIIT durchgefuhrt. Es zeigte sich eine inverse Korrelation zwischen individueller Fitness und FAZ-Grose. Weitere Korrelationen zwischen individueller Fitness und anderen gemessenen OCTA-Parametern ergaben sich nicht. Als Antwort auf das HIIT verringerten sich die mittlere FAZ-Grose im tiefen retinalen Plexus und die makulare Flussdichte im superfiziellen retinalen Plexus um 14,00 ± 13,02 % bzw. um 1,26 ± 3,20 %. Die Flussdichte der peripapillaren „nerve head layer“ zeigte einen Anstieg von 1,94 ± 2,39 %. Alle anderen Parameter zeigten keine signifikanten Unterschiede zwischen den Messungen vor und nach HIIT. Es zeigten sich Unterschiede in OCTA-Messungen der FAZ in Abhangigkeit von der individuellen Leistungsfahigkeit. Durch HIIT lassen sich signifikante Veranderungen in einigen OCTA-Parametern induzieren. Daher scheint die OCTA eine vielversprechende Modalitat im Bereich der Sportmedizin zu sein.

BackgroundPatients with Fabry disease (FD) and amenable mutations can be treated with the chaperone migalastat to restore endogenous α-galactosidase A (AGAL) activity. However, certain amenable mutations do not respond biochemically in vivo as expected. Here, we aimed to establish a patient-specific and mutation-specific cell model to evaluate the amenability to chaperone therapy in FD.MethodsSince current tests to determine amenability are limited to heterologous mutation expression in HEK293T cells with endogenous AGAL activity, we generated CRISPR/Cas9-mediated AGAL-deficient HEK293T cells as a basis for mutant overexpression. Furthermore, primary urinary cells from patients were isolated and immortalised as a patient-specific cell model system to evaluate the amenability to chaperone therapy.ResultsUnder treatment (>13 months), carriers of p.N215S (n=6) showed a significant reduction of plasma lyso-Gb3 (pA cells.ConclusionWe conclude that repeated AGAL activity measurements in patients’ white blood cells are mandatory to assess the in vivo amenability to migalastat. Plasma lyso-Gb3 might be an appropriate tool to measure the biochemical response to migalastat. Patients with low AGAL activities and increasing lyso-Gb3 levels despite in vitro amenability might not benefit sufficiently from chaperone treatment.

Background Approximately 25% of patients with colorectal cancer (CRC) will be diagnosed with CRC liver metastases (CRCLM) during the course of their disease. No data regarding CRCLM presentation, management and survival outcomes has been published from either the private or public health care sectors in South Africa. This study aimed to address this deficit, reporting on a private sector cohort. Methods A retrospective review of a private health care funder's database from 1 January 2008 to 31 December 2015 was performed. ICD-10 diagnosis codes were used to identify CRC and CRCLM. Procedure codes assigned to hospital admissions were used to identify the type of surgical treatment. Chemotherapy was identified by the WHO Anatomical Therapeutic Chemical classification system of medicines. Treatment patterns were assessed and five-year overall survival (OS) was calculated. Survival was estimated using the Kaplan-Meier method, and Cox proportional-hazards regression was used for between group survival comparisons. Results Six hundred and one (601) of 3 412 patients presenting with CRC (17.6%) were diagnosed with CRCLM at presentation or during the follow-up period. Sixty patients with CRCLM (10.0%) underwent resection of the primary CRC and liver resection for metastases, 281 (46.8%) underwent CRC resection only, 180 (30%) received chemotherapy only, and 47 (7.8%) received no treatment. Five-year OS for these groups were 57.3%, 15.6%, 9.8% and 0% respectively. Conclusion Five-year OS of the various CRCLM treatment pathways in a South African private sector population compares to results published in international series. However, a smaller proportion of patients with CRCLM underwent liver resection, compared to international studies.

Background Colorectal anastomotic leaks remain one of the most significant complications following colorectal surgery. Various interventions to reduce anastomotic leaks have been investigated, however few have resulted in a significant improvement. To date antiseptic coated monofilament sutures for sutured bowel anastomoses have not been assessed, hence this study was undertaken to investigate whether or not triclosan impregnated polydioxanone suture material (PDS) results in fewer anastomotic leaks. Methods A rabbit colo-colonic anastomotic model was developed to compare the tensile strength and local inflammatory response between triclosan coated PDS and uncoated PDS. Results Of the 42 anastomoses there were 4 (9.5%) leaks. Of the remaining 38 anastomoses neither the leak pressures, degree of bowel wall inflammation or fibrosis were statistically different (P = .11; .813 and .658 respectively) when comparing the two suture materials. Conclusions In an animal model, triclosan coated PDS is as safe as uncoated PDS in performing colo-colonic anastomosis.

Optical coherence tomography angiography (OCT-A) represents the most recent modality in retinal imaging for non-invasive and depth-selective visualization of blood flow in retinal vessels. With regard to quantitative OCTA measurements for early detection of subclinical alterations, it is of great interest, which intra- and extra-ocular factors affect the results of OCTA measurements. Here, we performed OCTA imaging of the central retina in 65 eyes of 65 young healthy female and male participants and evaluated individual physical fitness levels by standard lactate diagnostic using an incremental maximal performance running test. The main finding was that OCTA measurements of the foveal avascular zone (FAZ) area were associated with physical fitness. Using multivariate regression analysis, we found that running speed at the individual lactate threshold, a marker strongly associated with aerobic performance capacity, significantly contributed to differences in FAZ area (β = 0.111, p = 0.032). The data indicates that smaller FAZ areas are likely observed in individuals with higher aerobic exercise capacity. Our findings are also of interest with respect to the potential use of retinal OCTA imaging to detect exercise-induced microvascular adaptations in future studies.

The current document offers a set of principles and issues to help local facilities (with the guidance of the local COVID-19 committees) plan for resumption of elective surgical care.

E-scooters have conquered urban areas as a means for individual mobility and compete with other modes of transportation. While some studies endorse e-scooters as eco-friendly solution for crowded cities, others report contradictory findings and highlight safety issues. To reveal factors affecting e-scooter usage from a consumer’s perspective, a study using an adapted Unified Theory of Acceptance and Use of Technology (UTAUT2) is conducted. Based on random sampling among German public transportation services, 749 responses were collected and analyzed. E-scooters are studied in the context of mobility alternatives, revealing that they are mostly viewed as fun objects, and perceived safety indeed impedes their usage. Additionally, environmental concerns and individual convenience (i.e., performance expectancy) evince to represent the main drivers for using e-scooter. Besides, differences in the motivation for (potential) usage were found between owners and non-owners. Regarding the ecological assessment of e-scooters, they may, in fact, substitute walking over short distances.

Aufgrund erkannter Limitationen und Probleme der Choice-Based Conjointanalyse (CBC) sowie mit dem Anspruch, diesen zu begegnen, wurde als Variante der CBC die so genannte Adaptive Choice-Based Conjointanalyse (ACBC) entwickelt und 2007 zusammen mit einem neuen Modul von Sawtooth Software auch in die kommerzielle Anwendung eingefuhrt. Ahnlich wie bei der Adaptiven Conjointanalyse (ACA) wird bei der ACBC ein kompositioneller Erhebungsteil mit einem dekompositionellen Erhebungs- und Auswertungsteil kombiniert. In diesem Kapitel werden die einzelnen Ablaufschritte einer ACBC vorgestellt und deren Vor- und Nachteile gegenuber einer CBC diskutiert. Es folgen typische Anwendungsfelder sowie eine Anwendung der ACBC am Beispiel der Gestaltung und Preisfindung einer neuartigen Sportjacke aus nachhaltigen Materialien.

Objective: Physical activity may protect from ocular complications of diabetic retinopathy (DR). We investigated exercise training effects on the retinal microvasculature using optical coherence tomography angiography (OCTA) in type 1 diabetes (T1D). Methods: Twenty T1D patients without clinical signs of DR performed four weeks of high-intensity interval training (HIIT). Cycle ergometry was used for determination of physical fitness. OCTA of the macula and optic nerve head was applied to analyze effects on the foveal avascular zone area, vessel density, vessel diameter index and fractal dimension of the superficial plexus, deep plexus and radial peripapillary capillaries. Results: Large effects for improvement of physical fitness in terms of power output at the individual lactate threshold (+10.7 ± 11.3%, p < .001, ES = 0.95) and maximal power output (+8.2 ± 6.4%, p < .001, ES = 1.4) were detected. Participants presented a reduced increase in heart rate (HR) and lactate (LA) at given exercise intensities at follow-up (p ≤ .0176). Baseline OCTA revealed that HbA 1c levels were associated with vessel density in the radial peripapillary capillary and the parafoveal superficial region (p ≤ .014). None of the analyzed microvascular parameters changed in response to the intervention. Conclusion: Despite favorable effects of HIIT on physical fitness of T1D patients, disease-specific training protocols may be needed to overcome potentially impaired retinal microvascular adaptations.

This study investigated the effects of a four-week HIIT intervention on the cardiometabolic risk profile, liver fat content, insulin requirement, hypoglycaemia, physical fitness, and health-related quality of life in patients with T1DM. A supervised exercise intervention with baseline to follow-up comparison between overweight (BMI = 28.6 ± 2.1 kg/m

Studies suggest that the rate gallstone disease in Africa is low. Previous studies suggested an increase in gallstone rates and cholecystectomies related to urbanization and the adoption of Western lifestyle habits. This study examined cholecystectomy rates for gallstone disease in South Africa (SA). An audit of cholecystectomies in SA was done by reviewing gallbladder specimens processed by the SA National Health Laboratory Service (NHLS) from 2004 and 2014. Urbanization rates were obtained from Statistics South Africa and BMI data from previously published studies. Fisher’s exact test, t test’s and Pearson’s R were used for comparisons; cholecystectomy rates were calculated per 100,000 population. 33,467 cholecystectomy specimens were analysed. There was a 92% absolute increase in cholecystectomies during the study period (Pearson r 0.94; p p ≤ 0.0001). The Northern Cape was the only province to show a decline in the cholecystectomy rate in this period and was also the only province to record a decline in urbanization. Population based studies in SA demonstrate increases in BMI and an association with increased urbanization. This nationwide African study demonstrates a sustained increase in cholecystectomies for gallstone disease. Increases in BMI and urbanization may be responsible for this trend.

The United Kingdom (UK) has reported a single detection of the eggs of the invasive mosquito vector Aedes albopictus in each of the three years from 2016 to 2018, all in southeast England. Here, we report the detection of mosquito eggs on three occasions at two sites in London and southeast England in September 2019. Mosquito traps were deployed at 56 sites, in England, Scotland, Wales, and Northern Ireland, as part of a coordinated surveillance programme with local authorities, Edge Hill University, and government departments. Response to each detection was coordinated by Public Health England&rsquo, s (PHE) local health protection teams, with technical support from PHE&rsquo, s Medical Entomology group, and control conducted by the respective local authority. Control, including source reduction and larviciding, was conducted within a 300 metre radius of the positive site. The response followed a National Contingency Plan for Invasive Mosquitoes: Detection of Incursions. Although the response to these incidents was rapid and well co-ordinated, recommendations are made to further develop mosquito surveillance and control capability for the UK.

Introduction The influence of trauma- and surgical stress-induced decrease of CD4 count on anastomotic leaks after penetrating abdominal trauma has to date not been investigated. A prospective study was performed to explore the effect of CD4 count 24 h after surgery on the anastomotic leak rate and to identify risk factors for anastomotic leaks. Methods This was a prospective study including 98 patients with small or large bowel resection and subsequent anastomosis due to penetrating abdominal trauma. Univariate analysis identified risk factors for the development of anastomotic leak and also investigated the predictive value of the CD4 count for this complication. Results Of the 98 patients 23 patients (23%) were HIV-infected. The overall leak rate was 13%. Univariate analysis including all potential risk factors with p-values 6units and delayed anastomosis after damage control surgery. Survival rates were analysed with the χ2 test and did not show a significantly higher mortality rate in patients with low CD4 count. The negative impact of trauma and subsequent surgery on the cell mediated immunity was demonstrated by the fact that 55 (73%) of the HIV-negative patients had a CD4 count less than 500 cells/μl 24 h postoperatively. HIV-infection had no significant influence on the leak rate, however all HIV infected patients that developed an anastomotic leak died. Conclusion A low post-operative CD4 count is a predictor for anastomotic leaks irrespective of HIV-serostatus. Low postoperative serum albumin, high injury severity, gunshot wound as mechanism of injury, blood transfusion requirement >6 units and delayed anastomosis were further risk factors for anastomotic complications. Postoperative CD4 count and serum albumin should be considered in the decision making process of performing an anastomosis or diverting stoma for patients after “clip and drop” of the bowel as part of damage control surgery.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types, and it is associated with a 5-year survival rate of

Severe acute pancreatitis (SAP) is characterised by two distinct clinical phases. Organ dysfunction and death is initially as a result of a systemic inflammatory response syndrome (SIRS). Systemic sepsis from infected pancreatic necrosis characterises the second phase, the so called 'second hit' of acute pancreatitis (AP). An immune imbalance during the second hit is postulated to contribute to the formation of the septic complications that occur in these patients. The pro-inflammatory T-helper (Th) 17 pathway has been shown to be an initiator of early SIRS in AP, however to date its role has not been established in the second hit in AP.Thirty-six patients with mild (n = 16), moderate (n = 10) and severe (n = 10) acute pancreatitis were enrolled. Peripheral blood samples were drawn on days 7, 9, 11 and 13 of illness for analysis of routine clinical markers as well as cytokine analysis. Flow cytometry and a IL-17A ELISA was performed to determine cytokine concentrations.There were no significant differences between days 7, 9, 11 and 13 for either the mild/moderate or SAP groups for IL-17A (CBA assay or ELISA), IFN-γ, TNF-α, IL-2 or IL-4. For each of the study days, the mean IL-6 and IL-10 concentrations were significantly higher in the SAP group compared to the mild/moderate group. WCC, CRP and PCT were all significantly higher in severe acute pancreatitis over the study days.An immune imbalance exists in patients with SAP, however secreted IL-17A is not responsible for the second hit in AP.

Demand for contactless payments has increased worldwide, but adoption varies by country. We propose a more parsimonious Diffusion of Innovations model (i.e., complexity is dropped and compatible advantage replaces relative advantage and compatibility) to investigate mobile wallet adoption, but with context-relevant extensions of security, privacy and ubiquity. The model is empirically tested for Canada, Germany and the United States. The findings support the proposed model. Furthermore, we find ubiquity, privacy concerns and security risks vary by country, and ubiquity plays a mediating role. This model can be utilized in future mobile app studies and provides country-specific guidance to practitioners.

Acute pancreatitis (AP) is an inflammation of the pancreas caused by various stimuli including excessive alcohol consumption, gallstone disease and certain viral infections. Managing specifically the severe form of AP is limited due to lack of an understanding of the complex immune events that occur during AP involving immune cells and inflammatory molecules such as cytokines. The relative abundance of various immune cells resulting from the immune dysregulation drives disease progression. In this review, we examine the literature on the adaptive immune cells in AP, the prognostic value of these cells in stratifying patients into appropriate care and treatment strategies based on cell frequency in different AP severities are discussed.

Background Fabry patients on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in estimated glomerular filtration rate (eGFR) and an increase of the Mainz Severity Score Index. Methods In this prospective observational study, we assessed end-organ damage and clinical symptoms in 112 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, who were (i) non-randomly assigned to continue this treatment regime (regular-dose group, n = 37); (ii) received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n = 38); or (iii) were re-switched to agalsidase-beta after receiving agalsidase-alfa for at least 12 months (re-switch group, n = 37) with a median follow-up of 53 (38-57) months. Results eGFR of patients in the regular-dose group remained stable. Patients in the switch group showed an annual eGFR loss of - 4.6 ± 9.1 mL/min/1.73 m2 (P

High dietary salt intake may lead to vascular stiffness, which predicts cardiovascular diseases such as heart failure, and myocardial and cerebral infarctions as well as renal impairment. The vascular endothelium is a primary target for deleterious salt effects leading to dysfunction and endothelial stiffness. We hypothesize that the Ca2+- and bicarbonate-activated soluble adenylyl cyclase (sAC) contributes to Na+/K+-ATPase expression regulation in vascular endothelial cells and is an important regulator of endothelial stiffness. In vitro stimulation of vascular endothelial cells with high sodium (150 mM Na+)-induced Na+/K+-ATPase-α and Na+/K+-ATPase-β protein expression determined by western blot. Promoter analyses revealed increased cAMP response element (CRE)-mediated Na+/K+-ATPase-α transcriptional activity under high sodium concentrations. Inhibition of sAC by the specific inhibitor KH7 or siRNA reduced the sodium effects. Flame photometry revealed increased intracellular sodium concentrations in response to high sodium stimulations, which were paralleled by elevated ATP levels. Using atomic force microscopy, a nano-technique that measures cellular stiffness and deformability, we detected significant endothelial stiffening under increased sodium concentrations, which was prevented by inhibition of sAC using KH7 and Na+/K+-ATPase using ouabain. Furthermore, analysis of primary aortic endothelial cells in an in vitro aging model revealed an impaired Na+/K+-ATPase-α sodium response and elevated intracellular sodium levels with cellular aging. We conclude that sAC mediates sodium-induced Na+/K+-ATPase expression in vascular endothelium and is an important regulator of endothelial stiffness. The reactivity of Na+/K+-ATPase-α expression regulation in response to high sodium seems to be impaired in aging endothelial cells and might be a component of endothelial dysfunction.