LAP2 Proteins Chaperone GLI1 Movement between the Lamina and Chromatin to Regulate Transcription.

Understanding transcription factor navigation through the nucleus remains critical for developing targeted therapeutics. The GLI1 transcription factor must maintain maximal Hedgehog pathway output in basal cell carcinomas (BCCs), and we have previously shown that resistant BCCs increase GLI1 deacetylation through atypical protein kinase Cι/λ (aPKC) and HDAC1. Here we identify a lamina-associated polypeptide 2 (LAP2) isoform-dependent nuclear chaperoning system that regulates GLI1 movement between the nuclear lamina and nucleoplasm to achieve maximal activation. LAP2ß forms a two-site interaction with the GLI1 zinc-finger domain and acetylation site, stabilizing an acetylation-dependent reserve on the inner nuclear membrane (INM). By contrast, the nucleoplasmic LAP2α competes with LAP2ß for GLI1 while scaffolding HDAC1 to deacetylate the secondary binding site. aPKC functions to promote GLI1 association with LAP2α, promoting egress off the INM. GLI1 intranuclear trafficking by LAP2 isoforms represents a powerful signal amplifier in BCCs with implications for zinc finger-based signal transduction and therapeutics.

Architecture of Microcin B17 Synthetase: An Octameric Protein Complex Converting a Ribosomally Synthesized Peptide into a DNA Gyrase Poison.

The introduction of azole heterocycles into a peptide backbone is the principal step in the biosynthesis of numerous compounds with therapeutic potential. One of them is microcin B17, a bacterial topoisomerase inhibitor whose activity depends on the conversion of selected serine and cysteine residues of the precursor peptide to oxazoles and thiazoles by the McbBCD synthetase complex. Crystal structures of McbBCD reveal an octameric B4C2D2 complex with two bound substrate peptides. Each McbB dimer clamps the N-terminal recognition sequence, while the C-terminal heterocycle of the modified peptide is trapped in the active site of McbC. The McbD and McbC active sites are distant from each other, which necessitates alternate shuttling of the peptide substrate between them, while remaining tethered to the McbB dimer. An atomic-level view of the azole synthetase is a starting point for deeper understanding and control of biosynthesis of a large group of ribosomally synthesized natural products.

Reconstitution of a biofilm adhesin system from a sulfate-reducing bacterium in Pseudomonas fluorescens.

Biofilms of sulfate-reducing bacterium (SRB) like Desulfovibrio vulgaris Hildenborough (DvH) can facilitate metal corrosion in various industrial and environmental settings leading to substantial economic losses. Although the mechanisms of biofilm formation by DvH are not yet well understood, recent studies indicate the large adhesin, DvhA, is a key determinant of biofilm formation. The dvhA gene neighborhood resembles the biofilm-regulating Lap system of Pseudomonas fluorescens but is curiously missing the c-di-GMP-binding regulator LapD. Instead, DvH encodes an evolutionarily unrelated c-di-GMP-binding protein (DVU1020) that we hypothesized is functionally analogous to LapD. To study this unusual Lap system and overcome experimental limitations with the slow-growing anaerobe DvH, we reconstituted its predicted SRB Lap system in a P. fluorescens strain lacking its native Lap regulatory components (ΔlapGΔlapD). Our data support the model that DvhA is a cell surface-associated LapA-like adhesin with a N-terminal "retention module" and that DvhA is released from the cell surface upon cleavage by the LapG-like protease DvhG. Further, we demonstrate DVU1020 (named here DvhD) represents a distinct class of c-di-GMP-binding, biofilm-regulating proteins that regulates DvhG activity in response to intracellular levels of this second messenger. This study provides insight into the key players responsible for biofilm formation by DvH, thereby expanding our understanding of Lap-like systems.

Lamin A/C phosphorylation at serine 22 is a conserved heat shock response to regulate nuclear adaptation during stress.

The heat shock (HS) response is crucial for cell survival in harmful environments. Nuclear lamin A/C, encoded by the LMNA gene, contributes towards altered gene expression during HS, but the underlying mechanisms are poorly understood. Here, we show that upon HS, lamin A/C was reversibly phosphorylated at serine 22 in concert with HSF1 activation in human cells, mouse cells and Drosophila melanogaster in vivo. Consequently, the phosphorylation facilitated nucleoplasmic localization of lamin A/C and nuclear sphericity in response to HS. Interestingly, lamin A/C knock-out cells showed deformed nuclei after HS and were rescued by ectopic expression of wild-type lamin A, but not by a phosphomimetic (S22D) lamin A mutant. Furthermore, HS triggered concurrent downregulation of lamina-associated protein 2α (Lap2α, encoded by TMPO) in wild-type lamin A/C-expressing cells, but a similar response was perturbed in lamin A/C knock-out cells and in LMNA mutant patient fibroblasts, which showed impaired cell cycle arrest under HS and compromised survival at recovery. Taken together, our results suggest that the altered phosphorylation stoichiometry of lamin A/C provides an evolutionarily conserved mechanism to regulate lamina structure and serve nuclear adaptation and cell survival during HS.

F127-SE-tLAP thermosensitive hydrogel alleviates bleomycin-induced skin fibrosis via TGF-ß/Smad pathway.

BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-ß1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-ß1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-ß1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE. METHODS: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-ß1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics. RESULTS: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis. CONCLUSION: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.

Analysis of the GFP-labelled ß-dystroglycan interactome in HEK-293 transfected cells reveals novel intracellular networks.

Dystroglycan (DG) is a cell adhesion complex that is widely expressed in tissues. It is composed by two subunits, α-DG, a highly glycosylated protein that interacts with several extracellular matrix proteins, and transmembrane ß-DG whose, cytodomain binds to the actin cytoskeleton. Glycosylation of α-DG is crucial for functioning as a receptor for its multiple extracellular binding partners. Perturbation of α-DG glycosylation is the central event in the pathogenesis of severe pathologies such as muscular dystrophy and cancer. ß-DG acts as a scaffold for several cytoskeletal and nuclear proteins and very little is known about the fine regulation of some of these intracellular interactions and how they are perturbed in diseases. To start filling this gap by identifying uncharacterized intracellular networks preferentially associated with ß-DG, HEK-293 cells were transiently transfected with a plasmid carrying the ß-DG subunit with GFP fused at its C-terminus. With this strategy, we aimed at forcing ß-DG to occupy multiple intracellular locations instead of sitting tightly at its canonical plasma membrane milieu, where it is commonly found in association with α-DG. Immunoprecipitation by anti-GFP antibodies followed by shotgun proteomic analysis led to the identification of an interactome formed by 313 exclusive protein matches for ß-DG binding. A series of already known ß-DG interactors have been found, including ezrin and emerin, whilst significant new matches, which include potential novel ß-DG interactors and their related networks, were identified in diverse subcellular compartments, such as cytoskeleton, endoplasmic reticulum/Golgi, mitochondria, nuclear membrane and the nucleus itself. Of particular interest amongst the novel identified matches, Lamina-Associated Polypeptide-1B (LAP1B), an inner nuclear membrane protein, whose mutations are known to cause nuclear envelopathies characterized by muscular dystrophy, was found to interact with ß-DG in HEK-293 cells. This evidence was confirmed by immunoprecipitation, Western blotting and immunofluorescence experiments. We also found by immunofluorescence experiments that LAP1B looses its nuclear envelope localization in C2C12 DG-knock-out cells, suggesting that LAP1B requires ß-DG for a proper nuclear localization. These results expand the role of ß-DG as a nuclear scaffolding protein and provide novel evidence of a possible link between dystroglycanopathies and nuclear envelopathies displaying with muscular dystrophy.

Enterolyin S, a Polythiazole-containing Hemolytic Peptide from Enterococcus caccae.

The ß-hemolytic factor streptolysin S (SLS) is an important linear azol(in)e-containing peptide (LAP) that contributes significantly to the virulence of Streptococcus pyogenes. Despite its discovery 85 years ago, SLS has evaded structural characterizing owing to its notoriously problematic physicochemical properties. Here, we report the discovery and characterization of a structurally analogous hemolytic peptide from Enterococcus caccae, termed enterolysin S (ELS). Through heterologous expression, site-directed mutagenesis, chemoselective modification, and high-resolution mass spectrometry, we found that ELS contains an intriguing contiguous octathiazole moiety. The discovery of ELS expands our knowledge of hemolytic LAPs by adding a new member to this virulence-promoting family of modified peptides.

Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex.

Diverse neocortical GABAergic neurons specialize in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in 2 distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBCs) had columnar "horsetail" axons descending through layers II-V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and nonpyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%), and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline) but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialized, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex.

Association of lipid accumulation product with all-cause and cardiovascular disease mortality: Result from NHANES database.

BACKGROUND AND AIM: At present, there are few studies on the relationship between lipid accumulation product (LAP) and mortality. This study aims to explore the relationship between adult LAP and all-cause and cardiovascular disease (CVD) mortality. METHODS AND RESULTS: The study people from the National Health and Nutrition Examination Survey (NHANES). Results of the mortality study were based on death data up to December 31, 2019. Cox proportional risk model was used to estimate the risk ratio (HR) and 95 % CI of all-cause and CVD mortality. A total of 50162 people were included in the study (the weighted average age and male proportion were 48.14 years and 48.64 % respectively). During the follow-up of 203460871 person-years, 6850 deaths were recorded, including 1757 CVD deaths. After multivariable adjustment, the increase of LAP was significantly correlated with all-cause and CVD mortality. Compared with the participants of Quartile 1 of LAP, the multivariable adjusted HRs and 95 % CI of the participants of Quartile 4 of LAP were 1.54 (1.32, 1.80) all-cause mortality (P for trend<0.001), and 1.55 (1.16, 2.09) CVD mortality (P for trend = 0.04). For every increase of natural log-transformed LAP, the all-cause mortality increased by 22 %, and the CVD mortality increased by 14 % (both P < 0.05). CONCLUSIONS: Our cohort study based on NHANES showed that higher LAP was significantly associated with higher all-cause and CVD mortality. Maintaining a low LAP status may reduce the risk of death.

The Health Monitoring of Bonded Composite Joints Using Both Thickness and Radial Impedance Resonance Responses.

With the advent of bonded composites in today's aircraft, there is a need to verify the structural integrity of the bonded joints that comprise their structure. To produce adequate joint integrity, strict process control is required during bonding operations. The latest non-destructive joint inspection techniques cannot quantify the strength of the bond and only indicate the presence of disbonds or delaminations. Expensive and timely proof-load testing of the joints is required to demonstrate structural performance. This work focuses on experimentally evaluating joint-health monitoring with piezoelectric sensors exposed to repeated loadings until failure. Single-lap-shear composite joints are structurally tested while using sensor electromechanical impedance response as a health indicator. Based on these experiments, validation of this novel method is achieved through detailed evaluation of the sensor impedance response characteristics during loading, which enable initial and prognostic joint health assessments. The experimental results indicate that the embedded piezoelectric sensors are able to measure the sensor impedance radial and thickness resonance response changes prior to joint failure, without sacrificing the joints' structural performance.

The aminopeptidase LAP3 suppression accelerates myogenic differentiation via the AKT-TFE3 pathway in C2C12 myoblasts.

Skeletal muscle maintenance depends largely on muscle stem cells (satellite cells) that supply myoblasts required for muscle regeneration and growth. The ubiquitin-proteasome system is the major intracellular protein degradation pathway. We previously reported that proteasome dysfunction in skeletal muscle significantly impairs muscle growth and development. Furthermore, the inhibition of aminopeptidase, a proteolytic enzyme that removes amino acids from the termini of peptides derived from proteasomal proteolysis, impairs the proliferation and differentiation ability of C2C12 myoblasts. However, no evidence has been reported on the role of aminopeptidases with different substrate specificities on myogenesis. In this study, therefore, we investigated whether the knockdown of aminopeptidases in differentiating C2C12 myoblasts affects myogenesis. The knockdown of the X-prolyl aminopeptidase 1, aspartyl aminopeptidase, leucyl-cystinyl aminopeptidase, methionyl aminopeptidase 1, methionyl aminopeptidase 2, puromycine-sensitive aminopeptidase, and arginyl aminopeptidase like 1 gene in C2C12 myoblasts resulted in defective myogenic differentiation. Surprisingly, the knockdown of leucine aminopeptidase 3 (LAP3) in C2C12 myoblasts promoted myogenic differentiation. We also found that suppression of LAP3 expression in C2C12 myoblasts resulted in the inhibition of proteasomal proteolysis, decreased intracellular branched-chain amino acid levels, and enhanced mTORC2-mediated AKT phosphorylation (S473). Furthermore, phosphorylated AKT induced the translocation of TFE3 from the nucleus to the cytoplasm, promoting myogenic differentiation through increased expression of myogenin. Overall, our study highlights the association of aminopeptidases with myogenic differentiation.

Hepatocyte-specific loss of LAP2α protects against diet-induced hepatic steatosis, steatohepatitis, and fibrosis in male mice.

There is increasing evidence for the importance of the nuclear envelope in lipid metabolism, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). Human mutations in LMNA, encoding A-type nuclear lamins, cause early-onset insulin resistance and NASH, while hepatocyte-specific deletion of Lmna predisposes to NASH with fibrosis in male mice. Given that variants in the gene encoding LAP2α, a nuclear protein that regulates lamin A/C, were previously identified in patients with NAFLD, we sought to determine the role of LAP2α in NAFLD using a mouse genetic model. Hepatocyte-specific Lap2α-knockout (Lap2α(ΔHep)) mice and littermate controls were fed normal chow or high-fat diet (HFD) for 8 wk or 6 mo. Unexpectedly, male Lap2α(ΔHep) mice showed no increase in hepatic steatosis or NASH compared with controls. Rather, Lap2α(ΔHep) mice demonstrated reduced hepatic steatosis, with decreased NASH and fibrosis after long-term HFD. Accordingly, pro-steatotic genes including Cidea, Mogat1, and Cd36 were downregulated in Lap2α(ΔHep) mice, along with concomitant decreases in expression of pro-inflammatory and pro-fibrotic genes. These data indicate that hepatocyte-specific Lap2α deletion protects against hepatic steatosis and NASH in mice and raise the possibility that LAP2α could become a potential therapeutic target in human NASH.NEW & NOTEWORTHY The nuclear envelope and lamina regulate lipid metabolism and susceptibility to nonalcoholic steatohepatitis (NASH), but the role of the nuclear lamin-binding protein LAP2α in NASH has not been explored. Our data demonstrate that hepatocyte-specific loss of LAP2α protects against diet-induced hepatic steatosis, NASH, and fibrosis in male mice, with downregulation of pro-steatotic, pro-inflammatory, and pro-fibrotic lamin-regulated genes. These findings suggest that targeting LAP2α could have future potential as a novel therapeutic avenue in NASH.

Long-term oncological outcomes for minimally invasive surgery versus open surgery for colon cancer-a population-based nationwide study with a non-inferiority design.

AIM: The study aimed to compare 5-year overall survival in a national cohort of patients undergoing curative abdominal resection for colon cancer by minimally invasive surgery (MIS) or by the open (OPEN) technique. METHODS: All patients diagnosed between 2010 and 2016 in Sweden with pathological Union International Contre le Cancer Stages I-III colon cancer localized in the caecum, ascending colon, hepatic flexure or sigmoid colon and those who underwent curative right sided hemicolectomy, sigmoid resection or high anterior resection by MIS or OPEN were included. Patients were identified in the Swedish Colorectal Cancer Registry from which all data were retrieved. The analyses were performed as intention-to-treat and the relationship between surgical technique (MIS or OPEN) and overall mortality within 5 years was analysed. For the primary research question a non-inferiority hypothesis was assumed with a statistical power of 90%, a one-side type I error of 2.5% and a non-inferiority margin of 2%. For the secondary analyses, multilevel survival regression models with the patients matched by propensity scores were employed, adjusted for patient- and tumour-related variables. RESULTS: A total of 11 605 pathological Union International Contre le Cancer Stages I-III patients were included with 3297 MIS (28.4%) and 8308 OPEN (71.6%) and were followed until 31 December 2020. The primary analysis demonstrated superiority for MIS compared to OPEN. The multilevel survival regression analyses confirmed that 5-year overall survival was higher in MIS with a hazard ratio of 0.874 (95% confidence interval 0.791-0.965), and if excluding pT4 the outcome was similar, with a hazard ratio of 0.847 (95% confidence interval 0.756-0.948). CONCLUSION: This observational study demonstrated that MIS was favourable to OPEN with regard to 5-year overall survival. These results support the use of laparoscopic colon cancer surgery in routine practice.

Synchronously construction of hierarchical porous channels and cationic surface charge on lanthanum-hydrogel for rapid phosphorus removal.

Phosphorus (P) removal from wastewater is critical for ecosystem operation and resource recovery. To facilitate the recycling of the used absorbents through balancing their adsorption and desorption performance on P, in this work, a novel porous magnetic La(OH)3-loaded MAPTAC/chitosan (CTS)/polyethyleneimine (PEI) ternary composite hydrogel (p-MTCH-La(OH)3) with enhanced bifunctional adsorption sites was synthesized by simultaneous dissolution of pre-embedded CaCO3 and CTS powder, followed by grafting PEI and loading La. Hierarchical porous channels promoted good dispersion of La(OH)3, bringing an excellent P adsorption capacity of 107.23 ± 4.96 mg P/g at neutral condition. PEI grafted with CTS increased the surface charge and enhanced the electrostatic attraction, which facilitated the desorption of P. The porous structure and abundant active sites also facilitated rapid adsorption with an adsorption rate constant of 0.1 g mg-1 h-1. p-MTCH-La(OH)3 maintained effective P adsorption despite co-existence with competing substances and after 5 cycles. Further mechanistic analysis indicated that La-P inner sphere complexation and LaPO4 crystalline transformation were the main pathways for P removal. However, electrostatic interactions contributed 17.5%-46.7% of the adsorption amount during the first 30 min of rapid adsorption, enabling 92.8% of the adsorbed P at this stage to be desorbed by alkaline solution. Based on the variations of adsorption and desorption capacity with adsorption time, a rapid unsaturated adsorption of 1-2 h was proposed to facilitate the recycling of the adsorbent. This study proposed a method to promote P adsorption and desorption by enhancing bifunctional adsorption sites, and proved that p-MTCH-La(OH)3 is a promising phosphate adsorbent.

Evaluation of the educational quality of publicly available online videos on laparoscopic jejunostomy by utilizing the LAP-VEGaS guidelines.

BACKGROUND: Despite its common nature, there is no data on the educational quality of publicly available laparoscopic jejunostomy training videos. The LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool, released in 2020, has been developed to ensure that teaching videos are of appropriate quality. This study applies the LAP-VEGaS tool to currently available laparoscopic jejunostomy videos. METHODS: A retrospective review of YouTube® videos was conducted for "laparoscopic jejunostomy." Included videos were rated by three independent investigators using LAP-VEGaS video assessment tool (0-18). Wilcoxon rank-sum test was used to evaluate differences in LAP-VEGaS scores between video categories and date of publication relative to 2020. Spearman's correlation test was performed to measure association between scores and length, number of views and likes. RESULTS: 27 unique videos met selection criteria. Academic and physician video walkthroughs did not demonstrate a significant difference in median scores (9.33 IQR 6.33, 14.33 vs. 7.67 IQR 4, 12.67, p = 0.3951). Videos published after 2020 demonstrated higher median scores than those published before 2020 (13 IQR 7.5, 14.67 vs. 5 IQR 3, 9.67, p = 0.0081). A majority of videos failed to provide patient position (52%), intraoperative findings (56%), operative time (63%), graphic aids (74%), and audio/written commentary (52%). A positive association was demonstrated between scores and number of likes (rs = 0.59, p = 0.0011) and video length (rs = 0.39, p = 0.0421), but not number of views (rs = 0.17, p = 0.3991). CONCLUSION: The majority of available YouTube® videos on laparoscopic jejunostomy fail to meet the basic educational needs of surgical trainees, and there is no difference between those produced by academic centers or independent physicians. However, there has been improvement in video quality following the release of the scoring tool. Standardization of laparoscopic jejunostomy training videos with the LAP-VEGaS score can ensure that videos are of appropriate educational value with logical structure.

Lipid accumulation product (LAP) index for the diagnosis of nonalcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis.

BACKGROUND: Lipid accumulation product (LAP) is an index calculated by waist circumference (WC) and triglyceride (TG), which reflects lipid toxicity. This study aims to investigate the association between the LAP index and nonalcoholic fatty liver disease (NAFLD) in a systematic review and meta-analysis. METHODS AND RESULTS: PubMed, Scopus, and Web of Science online databases were searched for eligible studies that investigated the association of the LAP index and NAFLD. Sixteen observational studies with 96,101 participants, including four cohort studies, one case‒control study and 11 cross-sectional studies with baseline data, were entered into this analysis. Fourteen studies reported a significant association between the LAP index and NAFLD, and two reported that this relation was not significant; two different meta-analyses (1- mean difference (MD) and 2- bivariate diagnostic test accuracy [DTA]) were conducted using Stata version 14. The LAP index was compared in subjects with and without NAFLD, and the difference was significant with 34.90 units (CI 95: 30.59-39.31, P < 0.001) of the LAP index. The DTA meta-analysis was conducted and showed that the LAP index pooled sensitivity and specificity for screening of NAFLD were 94% (CI95: 72%-99%, I2 = 99%, P < 0.001) and 85% (CI95: 62%-96%, I2 = 99%, P < 0.001), respectively. CONCLUSION: The LAP Index is an inexpensive, sensitive, and specific method to evaluate NAFLD and may be valuable for NAFLD screening.

Nasobiliary guided laparoscopic cholecystectomy following endoscopic retrograde cholangiopancreatography, randomized controlled trial.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC) is the most common management of gallstones combined with common bile duct (CBD) stones. This study aims to evaluate the impact of routine insertion of nasobiliary catheter during ERCP in cases of difficult LC. PATIENTS & METHODS: From total 110 patients who underwent ERCP followed by LC in the period from April 2019 to April 2020, nasobiliary (NB) catheter was inserted during ERCP in 55 patients after CBD clearance (NB group). In the other 55 patients, only CBD clearance was done (Control group). In the NB group, dynamic trans-nasobiliary intraoperative cholangiography (TN-IOC) was done during dissection of Calot's triangle. At the end of the procedure, trans-nasobiliay methylene blue (MB) test was done to detect any missed biliary injury. The primary outcome to be analyzed was the incidence and severity of bile duct injury (BDI), secondary outcomes were the operative time, conversion to open surgery, and hospital stay. RESULTS: Of the 110 patients, 57 patients (51.8%) were males and 53 (48.2%) were females. Median age was 55 years. One case of biliary leak was reported in the NB group (1.8%), while 2 cases (3.6%) were reported in the Control group. The average operative time in the NB group was 115 min versus 128 min in the Control group (P value < 0.001). No cases were converted to open cholecystectomy in the NB group (0%) with 5 cases (9.1%) converted to open in the Control group. The average postoperative hospital stay was 2 ± 0.1 days in the NB group versus 3.6 ± 5.3 days in the Control group (P value = 0.037). CONCLUSION: Routine insertion of nasobiliary tube during ERCP, in patients with combined gallbladder and CBD stones, is a simple, safe and dynamic method for IOC. This maneuver does not statistically decrease the incidence of BDI but can diagnose, minimize and treat BDI with shorter operative time and hospital stay.

Numerical Design of a Thread-Optimized Gripping System for Lap Joint Testing in a Split Hopkinson Apparatus.

Currently, few experimental methods exist that enable the mechanical characterization of adhesives under high strain rates. One such method is the Split Hopkinson Bar (SHB) test. The mechanical characterization of adhesives is performed using different specimen configurations, such as Single Lap Joint (SLJ) specimens. A gripping system, attached to the bars through threading, was conceived to enable the testing of SLJs. An optimization study for selecting the best thread was performed, analyzing the thread type, the nominal diameter, and the thread pitch. Afterwards, the gripping system geometry was numerically evaluated. The optimal threaded connection for the specimen consists of a trapezoidal thread with a 14 mm diameter and a 2 mm thread pitch. To validate the gripping system, the load-displacement (P-δ) curve of an SLJ, which was simulated as if it were tested on the SHB apparatus, was compared with an analogous curve from a validated drop-weight test numerical model.

Baseline-Free Damage Imaging of Composite Lap Joint via Parallel Array of Piezoelectric Sensors.

This paper presents a baseline-free damage imaging technique using a parallel array of piezoelectric sensors and a control board that facilitates custom combinations of sensor selection. This technique incorporates an imaging algorithm that uses parallel beams for generation and reception of ultrasonic guided waves in a pitch-catch configuration. A baseline-free reconstruction algorithm for probabilistic inspection of defects (RAPID) algorithm is adopted. The proposed RAPID method replaces the conventional approach of using signal difference coefficients with the maximum signal envelope as a damage index, ensuring independence from baseline data. Additionally, conversely to the conventional RAPID algorithm which uses all possible sensor combinations, an innovative selection of combinations is proposed to mitigate attenuation effects. The proposed method is designed for the inspection of lap joints. Experimental measurements were carried out on a composite lap joint, which featured two dissimilar-sized disbonds positioned at the lap joint's borderline. A 2D correlation coefficient was used to quantitatively determine the similarity between the obtained images and a reference image with correct defect shapes and locations. The results demonstrate the effectiveness of the proposed damage imaging method in detecting both defects. Additionally, parametric studies were conducted to illustrate how various parameters influence the accuracy of the obtained imaging results.

Differences in life attitudes between general population and hospitalized psychosomatic patients: a comparative cross-sectional study.

To compare the extent to which value-based life attitudes measured by means of the Life Attitude Profile (LAP-R) could differ between the general population and people suffering from mental disorders hospitalized in a psychosomatic ward. Cross-sectional comparative study between a sample of general population (n = 409) and a sample of unselected patients (n = 147) at admission in a psychosomatic ward. Comparisons were carried out by means of Cronbach's alpha, correlation matrix, t-tests, robust multivariate linear regression models (MLRM), and using propensity scores. The internal consistency of LAP-R is good (alpha = 0.90). Divergent validity with BFI dimensions is widely given. In MLRM general population scored higher for the indexes 'personal meaning' and 'existential transcendence', whereas psychosomatic patients for the dimensions 'responsibleness', 'death acceptance', 'goal seeking' and especially 'existential vacuum'. Sex, partnership and schooling display few associations. Neuroticism is negatively and agreeableness positively associated with life attitudes considered as protective. Norm values and differences were stratified by age ranges. This study demonstrates that basic human attitudes like personal transcendence, personal meaning, having a biographically supported mission in life, and belief in a reason for existence are so fundamental for individuals that they are to some degree given independently of having a mental disorder or not. Neuroticism is a risk trait and agreeableness a protective trait facing life attitudes. The findings of this study indicate that people suffering from mental disorders treated in a specialized psychosomatic unit in a general hospital have important value-based resources and simultaneously higher levels of existential vacuum that have to be considered in treatment planning but should also be embedded in a therapeutic alliance. The existential vacuum deserves special consideration in the treatment of patients, especially facing risk of suicide.