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Purpose: The purpose of this study was to assess the effect of training with a personal, portable laparoscopic endo-trainer (PLET) on residents' laparoscopic skills., Methods: The study took place at a tertiary-care academic university hospital in Switzerland. All participants were randomized to either a home- or hospital-based PLET training group, and surgical skill performance was assessed using five laparoscopic exercises. 24 surgical residents, 13 females and 11 males, were enrolled at any training stage. Nine residents completed the assessments. Endpoints consisted of subjective and objective assessment ratings as well as exercise time and qualitative data up to 12 weeks. The primary outcome was the difference in exercise time and secondary outcomes included performance scores as well as qualitative data., Results: The hospital-based training group performed exercises number 1, 3 and 4 faster at 12 weeks than at baseline (p = .003, < 0.001 and 0.024). Surgical skill performance was not statistically significantly different in any of the endpoints between the hospital- and home-based training groups at 12 weeks. Both the subjective and objective assessment ratings significantly improved in the hospital-based training group between baseline and 12 weeks (p = .006 and 0.003, respectively). There was no statistically significant improvement in exercise time as well as subjective and objective assessment ratings over time in the home-based training group. The qualitative data suggested that participants who were randomized to the hospital-based training group wished to have the PLET at home and vice versa. Several participants across groups lacked motivation because of their workload or time constraints, though most believed the COVID-19 pandemic had no influence on their motivation or the time they had for training., Conclusion: The PLET enhances laparoscopic surgical skills over time in a hospital-based training setting. In order to understand and optimize motivational factors, further research is needed., Trial Registration: This trial was retrospectively registered on clinicaltrials.gov (NCT06301230)., (© 2024. The Author(s).)

Ionic liquids (ILs) have gained considerable attention due to their versatile and designable properties. ILs show great potential as antibacterial agents, but understanding the mechanism of attack on bacterial cells is essential to ensure the optimal design of IL-based biocides. The final aim is to achieve maximum efficacy while minimising toxicity and preventing resistance development in target organisms. In this study, we examined a dose-response analysis of ILs' antimicrobial activity against two pathogenic bacteria with different Gram types in terms of molecular responses on a cellular level using Fourier-transform infrared (FTIR) spectroscopy. In total, 18 ILs with different antimicrobial active motifs were evaluated on the Gram-negative enteropathogenic Escherichia coli (EPEC) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). The results showed that most ILs impact bacterial proteins with increasing concentration but have a minimal effect on cellular membranes. Dose-response spectral analysis revealed a distinct ante-mortem response against certain ILs for MRSA but not for EPEC. We found that at sub-lethal concentrations, MRSA actively changed their membrane composition to counteract the damaging effect induced by the ILs. This suggests a new adaptive mechanism of Gram-positive bacteria against ILs and demonstrates the need for a better understanding before using such substances as novel antimicrobials.

Background: The most frequent complication of total thyroidectomy remains hypocalcemia due to low postoperative levels of serum intact parathyroid hormone (iPTH). The purpose of this study was to investigate the role of decreased iPTH at the end of surgery in predicting hypocalcemia. In addition, we examined the percentage decrease of iPTH as potential indicator of hypocalcemia., Methods: We retrospectively collected the data of patients who underwent total thyroidectomy for benign and malignant diseases at our institution between 2010 and 2022. The iPTH level was measured before and at the end of surgery, and serum calcium levels on the first postoperative day. Demographic, clinical, and biochemical characteristics of patients with low iPTH were compared with patients with normal iPTH levels using ANOVA for continuous variables and χ2-tests for categorical variables. Multivariable logistic regression analysis evaluated the association of iPTH at the end of surgery and the relative reduction of iPTH with postoperative hypocalcemia., Results: The mean age of the 607 patients in this study was 55.6 years, and the female-to-male ratio was 5:1. Goiter was the most common indication for surgery (N = 382, 62.9%), followed by Graves' disease (N = 135, 22.2%). The mean preoperative iPTH was 49.0 pg/ml, while the mean postoperative iPTH was 29.3 pg/ml. A total of 197 patients (32.5%) had an iPTH level below normal, 77 patients (39%), had iPTH levels of 10-15.0 pg/ml and 120 patients (61%) of < 10.0 pg/ml at the end of surgery. Among all patients, 124 (20.4%) developed hypocalcemia on the first postoperative day. The mean percentage of decrease of iPTH was highest among patients with iPTH < 10 pg/ml (76.9%, p < 0.01); this group of patients had also the highest rate of postoperative hypocalcemia on day one (45.0% vs. 26.0% vs 12.2%, p < 0.01)., Conclusions: Measurement of iPTH at the end of total thyroidectomy predicts patients who are at risk for postoperative hypocalcemia. The combination of low serum iPTH with a decrease in iPTH level of ≥ 50% may improve prediction of hypocalcemia compared to iPTH levels alone allowing for early calcium substitution in these patients at high risk of developing postoperative hypocalcemia., (© 2023. The Author(s).)

Lameness is an important health and welfare issue that causes considerable economic losses in dairy herds. The objective of this study was to investigate whether the hind feet position score (HFPS) can be used as an auxiliary trait for genetic evaluation of lameness. The HFPS is evaluated by visual scoring of the position of both the hind-digits to the mid-line of the cow's body. The higher the heel height of the lateral claw, the higher is the HFPS, and the higher is the risk for development of lameness. In total, 3,478 records from 1,064 Fleckvieh cows from 35 farms were obtained between September 1, 2021, and March 5, 2022. Data collection was carried out by the regional milk recording organizations. Hind feet position was scored visually by trained personnel during routine milk performance testing in the milking parlor using a 3-class scoring system: score 1 = 0° to <17° indicating a balanced heel height of both the medial and the lateral claw; score 2 = angle of 17° to 24°; score 3 = angle of >24°. After all cows had been milked, locomotion scoring was performed for each animal using a 5-class scoring system with locomotion scores ranging between 1 (normal) and 5 (severely lame). Using HFPS, sensitivity and specificity were 69.5% and 66.8%, respectively, for detecting lameness defined by locomotion score ≥2. For genetic analyses, a bivariate linear animal model was fitted with fixed effects of herd, parity, lactation stage, and classifier, and random effects of animal and permanent environment. Heritabilities for HFPS and locomotion score were 0.07 and 0.10, respectively, and the genetic correlation between the 2 traits studied was 0.80. These results suggest that the HFPS could be used for genetic evaluations to reduce lameness incidence in dairy cattle., (© 2023.)

This study aimed to develop a tool to detect mildly lame cows by combining already existing data from sensors, AMSs, and routinely recorded animal and farm data. For this purpose, ten dairy farms were visited every 30-42 days from January 2020 to May 2021. Locomotion scores (LCS, from one for nonlame to five for severely lame) and body condition scores (BCS) were assessed at each visit, resulting in a total of 594 recorded animals. A questionnaire about farm management and husbandry was completed for the inclusion of potential risk factors. A lameness incidence risk (LCS ≥ 2) was calculated and varied widely between farms with a range from 27.07 to 65.52%. Moreover, the impact of lameness on the derived sensor parameters was inspected and showed no significant impact of lameness on total rumination time. Behavioral patterns for eating, low activity, and medium activity differed significantly in lame cows compared to nonlame cows. Finally, random forest models for lameness detection were fit by including different combinations of influencing variables. The results of these models were compared according to accuracy, sensitivity, and specificity. The best performing model achieved an accuracy of 0.75 with a sensitivity of 0.72 and specificity of 0.78. These approaches with routinely available data and sensor data can deliver promising results for early lameness detection in dairy cattle. While experimental automated lameness detection systems have achieved improved predictive results, the benefit of this presented approach is that it uses results from existing, routinely recorded, and therefore widely available data.

Overexpression of MYC is a genuine cancer driver in lymphomas and related to poor prognosis. However, therapeutic targeting of the transcription factor MYC remains challenging. Here, we show that inhibition of the histone deacetylase 6 (HDAC6) using the HDAC6 inhibitor Marbostat-100 (M-100) reduces oncogenic MYC levels and prevents lymphomagenesis in a mouse model of MYC-induced aggressive B-cell lymphoma. M-100 specifically alters protein-protein interactions by switching the acetylation state of HDAC6 substrates, such as tubulin. Tubulin facilitates nuclear import of MYC, and MYC-dependent B-cell lymphoma cells rely on continuous import of MYC due to its high turn-over. Acetylation of tubulin impairs this mechanism and enables proteasomal degradation of MYC. M-100 targets almost exclusively B-cell lymphoma cells with high levels of MYC whereas non-tumor cells are not affected. M-100 induces massive apoptosis in human and murine MYC-overexpressing B-cell lymphoma cells. We identified the heat-shock protein DNAJA3 as an interactor of tubulin in an acetylation-dependent manner and overexpression of DNAJA3 resulted in a pronounced degradation of MYC. We propose a mechanism by which DNAJA3 associates with hyperacetylated tubulin in the cytoplasm to control MYC turnover. Taken together, our data demonstrate a beneficial role of HDAC6 inhibition in MYC-dependent B-cell lymphoma., (© 2022. The Author(s).)

This paper outlines a practical coordination approach of long- and short-term optimization. Pseudo prices are used as coupling variables. To take uncertainty aspects into account, fuzzy set theory is incorporated to evaluate the pseudo prices. In the paper, various aspects of the proposed approach are discussed, and its application to a real utility system is illustrated. KEYWORDS Generation planning, Long- and Short-Term Coordination, Pseudo Fuel Prices, Fuzzy Set Theory

While benchmarking is already used for the assessment of performance gaps in cattle herd management and welfare concerns, its application to quantifying claw health performance is relatively new. The goal here was to establish a benchmarking system for claw health in Austrian dairy cattle. We used electronically registered claw health data of cows from 512 dairy herds documented by professional hoof trimmers, culling data from the same herds, and locomotion scores taken at regular milk performance testings in 99 dairy herds during 2020. Mean, median and the 10th, 25th, 75th, and 90th percentiles of the incidences of risk of lameness, 13 common claw lesions, and the annual culling risk directly related to claw and limb disorders were used as key performance indicators. Only validated data sets were used and participating trimmers and locomotion scorers had to pass interobserver reliability tests with weighted Cohen's kappa values ≥ 0.61 indicating substantial interobserver agreement. This claw health benchmarking system is intended to be used henceforth in the transnational cattle data network (RDV) by all participating farmers and is also available for veterinarians and consultants, with the agreement of respective farmers.

Listeria monocytogenes is an environmentally adapted saprophyte that can change into a human and animal bacterial pathogen with zoonotic potential through several regulatory systems. In this review, the focus is on the occurrence of Listeria sensu stricto and sensu lato in different ecological niches, the detection methods, and their analytical limitations. It also highlights the occurrence of L. monocytogenes genotypes in the environment (soil, water, and wildlife), reflects on the molecular determinants of L. monocytogenes for the saprophytic lifestyle and the potential for antibiotic resistance. In particular, the strain-specific properties with which some genotypes circulate in wastewater, surface water, soil, wildlife, and agricultural environments are of particular interest for the continuously updating risk analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lourenco, Linke, Wagner and Stessl.)

Background: Rapid weight loss after bariatric surgery is a risk factor for gallstone formation. There are different strategies regarding its management in bariatric patients, including prophylactic cholecystectomy (CCE) in all patients, concomitant CCE only in symptomatic patients, or concomitant CCE in all patients with known gallstones. We present the safety and long-term results of the last concept., Method: Retrospective single-center analysis of a prospective database on perioperative and long-term results of patients with laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) over a 15-year period. The minimal follow-up was 24 months. Concomitant CCE was intended for all patients with gallstones detected by preoperative sonography., Setting: Academic teaching hospital in Switzerland., Results: After exclusion of patients with a history of CCE (11.5%), a total of 1174 patients (69.6% LRYGB, 30.4% LSG) were included in the final analysis. Preoperative gallbladder pathology was detected in 21.2% of patients, of whom 98.4%, or 20.9% of the total patients, received a concomitant CCE. The additional procedure prolonged the average operation time by 38 minutes (not significant) and did not increase the complication rate compared with bariatric procedure without CCE (3.7% versus 5.7%, P = .26). No complication was directly linked to the CCE. Postoperative symptomatic gallbladder disease was observed in 9.3% of patients (LRYGB 7.0% versus LSG 2.3%, P = .15), with 19.8% of those patients initially presenting with a complication., Conclusion: The concept of concomitant CCE in primary bariatric patients with gallstones was feasible and safe. Nevertheless, 9.3% of primary gallstone-free patients developed postoperative symptomatic gallbladder disease and required subsequent CCE despite routine ursodeoxycholic acid prophylaxis., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Disorders of the eye leading to visual impairment are a major issue that affects millions of people. On the other side ocular toxicities were described for e.g. molecularly targeted therapies in oncology and may hamper their development. Current ocular model systems feature a number of limitations affecting human-relevance and availability. To find new options for pharmacological treatment and assess mechanisms of toxicity, hence, novel complex model systems that are human-relevant and readily available are urgently required. Here, we report the development of a human immunocompetent Choroid-on-Chip (CoC), a human cell-based in vitro model of the choroid layer of the eye integrating melanocytes and microvascular endothelial cells, covered by a layer of retinal pigmented epithelial cells. Immunocompetence is achieved by perfusion of peripheral immune cells. We demonstrate controlled immune cell recruitment into the stromal compartments through a vascular monolayer and in vivo-like cytokine release profiles. To investigate applicability for both efficacy testing of immunosuppressive compounds as well as safety profiling of immunoactivating antibodies, we exposed the CoCs to cyclosporine and tested CD3 bispecific antibodies., (© 2022. The Author(s).)

Terpenes constitute one of the largest groups of secondary metabolites that are used, for example, as food-additives, fragrances or pharmaceuticals. Due to the formation of an intracytoplasmic membrane system and an efficient intrinsic tetraterpene pathway, the phototrophic α-proteobacterium Rhodobacter capsulatus offers favorable properties for the production of hydrophobic terpenes. However, research efforts have largely focused on sesquiterpene production. Recently, we have developed modular tools allowing to engineer the biosynthesis of terpene precursors. These tools were now applied to boost the biosynthesis of the diterpene casbene, the triterpene squalene and the tetraterpene β-carotene in R. capsulatus SB1003. Selected enzymes of the intrinsic isoprenoid pathway and the heterologous mevalonate (MVA) pathway were co-expressed together with the respective terpene synthases in various combinations. Remarkably, co-expression of genes ispA, idi and dxs enhanced the synthesis of casbene and β-carotene. In contrast, co-expression of precursor biosynthetic genes with the squalene synthase from Arabidopsis thaliana reduced squalene titers. Therefore, we further employed four alternative pro- and eukaryotic squalene synthases. Here, the synthase from Methylococcus capsulatus enabled highest product levels of 90 mg/L squalene upon co-expression with ispA. In summary, we demonstrate the applicability of R. capsulatus for the heterologous production of diverse terpene classes and provide relevant insights for further development of such platforms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Insufficient weight loss or secondary weight regain with or without recurrence of comorbidity can occur years after laparoscopic Roux en Y gastric bypass (LRYGB). In selected patients, increasing restriction or adding malabsorption may be a surgical option after conservative measures failed., Objectives: Evaluation of short and long term results of revisional surgery for insufficient weight loss or weight regain after LRYGB., Setting: Tertiary hospital., Methods: Retrospective analysis of prospectively collected data from a cohort of 1150 LRYGB patients. Included were patients, who underwent revisional bariatric surgery after LRYGB for insufficient weight loss with a follow-up of minimal 1 year., Results: Fifty-four patients were included in the analysis. After an interdisciplinary evaluation, patients with insufficient weight loss, signs of dumping syndrome, and lacking restriction were offered a nonadjustable band around the pouch (banded group, n = 34) and patients with sufficient restriction, excellent compliance, and adherence were offered a revision to laparoscopic biliopancreatic diversion (BPD group, n = 20). The revisional procedure was performed 3.3 ± 2.3 years after LRYGB in the banded-group and after 6.4 ± 4.3 years in the BPD group (P = .001). Mean body mass index at the time of the primary bariatric procedure was 41.7 ± 6.2 kg/m 2 in the banded group and 45.2 ± 8.2 kg/m 2 in the BPD group (P = .08); minimal body mass index between both operations was 29.1 ± 4.7 kg/m 2 in the banded group and 36.5 ± 9.4 kg/m 2 in the BPD group, and, at the time of revisional surgery, 31.4 ± 5.5 kg/m 2 in the banded group and 40.8 ± 6.7 kg/m 2 in the BPD group (P = .0001). The mean body mass index difference 1 year after revisional surgery was 1.3 ± 3.0 kg/m 2 in the banded group and 6.7 ± 4.5 kg/m 2 in the BPD group (P = .01). In the banded group, 11 patients (32.4%) needed removal of the band, 4 patients (11.8%) needed an adjustment, and 4 patients (11.8%) were later converted to BPD. In the BPD group, 2 (10.0%) patients needed revision for severe protein malabsorption., Conclusions: Insufficient weight loss or secondary weight regain after LRYGB is a rare indication for revisional surgery. Banded bypass has modest results for additional weight loss but can help patients suffering from dumping. In very carefully selected cases, BPD can achieve additional weight loss with acceptable complication rate but higher risk for reoperation. Future "adjuvant medical treatments," such as glucagon-like peptide 1 analogues and other pharmacologic treatment options could be an alternative for achieving additional weight loss and better metabolic response., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)