SCN1A intronic variants impact on Nav1.1 protein expression and sodium channel function, and associated with epilepsy phenotypic severity.

High-throughput sequencing has identified numerous intronic variants in the SCN1A gene in epilepsy patients. Abnormal mRNA splicing caused by these variants can lead to significant phenotypic differences, but the mechanisms of epileptogenicity and phenotypic differences remain unknown. Two variants, c.4853-1 G>C and c.4853-25 T>A, were identified in intron 25 of SCN1A, which were associated with severe Dravet syndrome (DS) and mild focal epilepsy with febrile seizures plus (FEFS+), respectively. The impact of these variants on protein expression, electrophysiological properties of sodium channels and their correlation with epilepsy severity was investigated through plasmid construction and transfection based on the aberrant spliced mRNA. We found that the expression of truncated mutant proteins was significantly reduced on the cell membrane, and retained in the cytoplasmic endoplasmic reticulum. The mutants caused a decrease in current density, voltage sensitivity, and an increased vulnerability of channel, leading to a partial impairment of sodium channel function. Notably, the expression of DS-related mutant protein on the cell membrane was higher compared to that of FEFS+-related mutant, whereas the sodium channel function impairment caused by DS-related mutant was comparatively milder than that caused by FEFS+-related mutant. Our study suggests that differences in protein expression levels and altered electrophysiological properties of sodium channels play important roles in the manifestation of diverse epileptic phenotypes. The presence of intronic splice site variants may result in severe phenotypes due to the dominant-negative effects, whereas non-canonical splice site variants leading to haploinsufficiency could potentially cause milder phenotypes.

The effect of genetic polymorphisms in STIM1 and ORAI1 on erythropoietin resistance in Egyptian patients with end-stage renal disease.

Chronic renal failure (CRF) is an incurable disease with unique challenges. Anemia is a frequent complication affecting dialysis patients. Erythropoietin (EPO) is used to treat anemia, but a poor response may result. We investigated genetic polymorphisms of store-operated calcium channel (SOC) signaling, an important erythropoietin-activated pathway that may induce EPO resistance in patients with renal failure. A total of 108 end stage renal disease (ESRD) patients were selected for this study. Patients were divided into two groups according to their erythropoietin resistance index (ERI): 39 patients with an ERI>10 and 69 patients with an ERI<10. We selected four tagging single nucleotide polymorphisms (tSNPs) in STIM1 and five in ORAI1 in our study. A polymerase chain reaction was performed, and genotyping against EPO resistance was correlated. Patients with the AG genotype of rs1561876 in STIM1, the TC genotype of rs6486795 in ORAI1, and the TG or GG genotypes of rs12320939 in ORAI1 were associated with an increased risk of erythropoietin resistance. Overall, we reported a moderately significant relationship between genetic polymorphisms of STIM1 and EPO resistance. We also reported a highly significant relationship between genetic polymorphisms of ORAI1 and EPO resistance. The (A-A-G) haplotype of STIM1 and the (G-T-G-T-A, G-C-G-C-G, or G-T-T-C-G) haplotypes of ORAI1 were significantly associated with EPO resistance.

Thermosensing ability of TRPC5: current knowledge and unsettled questions.

Our understanding of how the mammalian somatosensory system detects noxious cold is still limited. While the role of TRPM8 in signaling mild non-noxious coolness is reasonably understood, the molecular identity of channels transducing painful cold stimuli remains unresolved. TRPC5 was originally described to contribute to moderate cold responses of dorsal root ganglia neurons in vitro, but mice lacking TRPC5 exhibited no change in behavioral responses to cold temperature. The question of why a channel endowed with the ability to be activated by cooling contributes to the cold response only under certain conditions is currently being intensively studied. It seems increasingly likely that the physiological detection of cold temperatures involves multiple different channels and mechanisms that modulate the threshold and intensity of perception. In this review, we aim to outline how TRPC5 may contribute to these mechanisms and what molecular features are important for its role as a cold sensor.

Downregulation of PIEZO2 in the Detrusor of Men With Bladder Outlet Obstruction and Its Association With Urinary Retention and Decreased Bladder Compliance.

PURPOSE: Recent research has highlighted the mechanotransducer PIEZO2 as a crucial factor in lower urinary tract function, demonstrating associations with bladder compliance (BC), bladder wall thickening, and elevated bladder pressure. We explored the hypothesis that PIEZO2 expression may be associated with lower urinary tract dysfunction in men with bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH). METHODS: The study included a consecutive series of patients undergoing open prostatectomy for BPH at our hospital between September 2014 and January 2016. All participants underwent comprehensive preoperative evaluations, including urodynamic assessments. During prostatectomy, a full-thickness fragment of the bladder wall was obtained for subsequent PIEZO2 gene expression analysis. Cadaveric organ donors served as the control group. RESULTS: PIEZO2 expression was downregulated in the detrusor muscle of men with BPH compared to the control group. Among patients with BPH, those experiencing urinary retention and requiring an indwelling catheter exhibited significantly lower PIEZO2 messenger RNA (mRNA) expression than patients capable of spontaneous voiding. PIEZO2 mRNA expression was similar in men with and without detrusor overactivity. Additionally, a positive correlation was found between PIEZO2 mRNA expression levels and BC. CONCLUSION: Our findings indicate that PIEZO2 is downregulated in the detrusor muscle of men with BPH, particularly in those experiencing urinary retention and those with reduced BC. These results suggest a potential role for PIEZO2 in BOOinduced bladder dysfunction. Further research is required to clarify the role of PIEZO mechanotransducers in the bladder and to explore their therapeutic implications.

The role of TRPV1 in chronic prostatitis: a review.

Chronic prostatitis is a prevalent male urinary system disorder characterized by pelvic discomfort or pain, bladder dysfunction, sexual dysfunction, and infertility. Pain and lower urinary tract symptoms (LUTS) are the most common symptoms, significantly impacting patients' quality of life and driving them to seek medical attention. Transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective calcium ion-dependent cation channel in the TRPV channel family that is widely distributed in neural tissue and plays a role in signal transmission. In this review, we provide a comprehensive overview of the current understanding of the role of TRPV1 in chronic prostatitis. The discussion focuses on the connection between TRPV1 and prostatitis pain and LUTS, and highlights the potential for targeting this channel in the development of novel treatment strategies.

Enhanced diagnostics for generalized anxiety disorder: leveraging differential channel and functional connectivity features based on frontal EEG signals.

Generalized Anxiety Disorder (GAD) is a chronic anxiety condition characterized by persistent excessive worry, anxiety, and fear. Current diagnostic practices primarily rely on clinicians' subjective assessments and experience, highlighting a need for more objective and reliable methods. This study collected 10-minute resting-state electroencephalogram (EEG) from 45 GAD patients and 36 healthy controls (HC), focusing on six frontal EEG channels for preprocessing, data segmentation, and frequency band division. Innovatively, this study introduced the "Differential Channel" method, which enhances classification performance by enhancing the information related to anxiety from the data, thereby highlighting signal differences. Utilizing the preprocessed EEG signals, undirected functional connectivity features (Phase Lag Index, Pearson Correlation Coefficient, and Mutual Information) and directed functional connectivity features (Partial Directed Coherence) were extracted. Multiple machine learning models were applied to distinguish between GAD patients and HC. The results show that the Deep Forest classifier achieves excellent performance with a 12-second time window of DiffFeature. In particular, the classification of GAD and HC was successfully obtained by combining OriFeature and DiffFeature on Mutual Information with a maximum accuracy of 98.08%. Furthermore, it was observed that undirected functional connectivity features significantly outperformed directed functional connectivity when fewer frontal channels were used. Overall, the methodologies developed in this study offer accurate and practical identification strategies for the early screening and clinical diagnosis of GAD, offering the necessary theoretical and technical support for further enhancing the portability of EEG devices.

Dimensionality reduction of neuronal degeneracy reveals two interfering physiological mechanisms.

Neuronal systems maintain stable functions despite large variability in their physiological components. Ion channel expression, in particular, is highly variable in neurons exhibiting similar electrophysiological phenotypes, which raises questions regarding how specific ion channel subsets reliably shape intrinsic properties of neurons. Here, we use detailed conductance-based modeling to explore how stable neuronal function is achieved despite variability in channel composition among neurons. Using dimensionality reduction, we uncover two principal dimensions in the channel conductance space that capture most of the variance of the observed variability. These two dimensions correspond to two sources of variability that originate from distinct physiologically relevant mechanisms underlying the regulation of neuronal activity, providing quantitative insights into how channel composition is linked to the electrophysiological activity of neurons. These insights allow us to understand and design a model-independent, reliable neuromodulation rule for variable neuronal populations.

Safety of Diltiazem for Acute Management of Atrial Fibrillation (AF) in Patients with Heart Failure and Reduced Ejection Fraction in the Emergency Department.

BACKGROUND: Diltiazem is an effective rate control agent for atrial fibrillation with rapid ventricular rate (AF RVR). However, its negative inotropic effects may increase the risk for worsening heart failure in patients with a reduced ejection fraction (EF). OBJECTIVES: This observational study aims to describe the incidence of worsening heart failure in patients who receive intravenous diltiazem for acute atrial fibrillation management. METHODS: Adult patients that received diltiazem in the emergency department (ED) for AF RVR (heart rate ≥ 100 beats/min) from 2021 to 2022 and had a prior documented EF were included. The primary outcome is worsening heart failure within 24 h of diltiazem administration. Secondary outcomes include return ED visits and death within 7 days. EF percentage was compared across outcomes using Wilcoxon rank-sum tests. Outcomes were compared by reduced EF (< 50%) and preserved EF (≥ 50%). Continuous data were summarized with medians and interquartile ranges, and categorical features were summarized with frequency counts and percentages. Wilcoxon rank-sum tests were used for numeric outcomes and chi-squared tests or Fisher's exact tests for categorical outcomes, with a p-value < 0.05 considered statistically significant. RESULTS: There were 674 patients with AF RVR that received diltiazem, and 386 patients met the inclusion criteria for analysis. Baseline demographics included a median age of 72 (64-81) years, with 14.5% of patients having a prior diagnosis of congestive heart failure. EF < 50% was identified in 13.7% of patients (n = 53), of which approximately 30% of these patients safely discharged home after receiving i.v. diltiazem. The primary outcome of worsening heart failure occurred in 7/41 (17%) and 10/207 (4.8%) patients with reduced and preserved ejection fractions, respectively, who were admitted to the hospital (p = 0.005). CONCLUSION: The development of worsening heart failure is multifactorial and may include the use of diltiazem in critically ill patients requiring hospital admission.

MobileNet-V2: An Enhanced Skin Disease Classification by Attention and Multi-Scale Features.

The increasing prevalence of skin diseases necessitates accurate and efficient diagnostic tools. This research introduces a novel skin disease classification model leveraging advanced deep learning techniques. The proposed architecture combines the MobileNet-V2 backbone, Squeeze-and-Excitation (SE) blocks, Atrous Spatial Pyramid Pooling (ASPP), and a Channel Attention Mechanism. The model was trained on four diverse datasets such as PH2 dataset, Skin Cancer MNIST: HAM10000 dataset, DermNet. dataset, and Skin Cancer ISIC dataset. Data preprocessing techniques, including image resizing, and normalization, played a crucial role in optimizing model performance. In this paper, the MobileNet-V2 backbone is implemented to extract hierarchical features from the preprocessed dermoscopic images. The multi-scale contextual information is fused by the ASPP model for generating a feature map. The attention mechanisms contributed significantly, enhancing the extraction ability of inter-channel relationships and multi-scale contextual information for enhancing the discriminative power of the features. Finally, the output feature map is converted into probability distribution through the softmax function. The proposed model outperformed several baseline models, including traditional machine learning approaches, emphasizing its superiority in skin disease classification with 98.6% overall accuracy. Its competitive performance with state-of-the-art methods positions it as a valuable tool for assisting dermatologists in early classification. The study also identified limitations and suggested avenues for future research, emphasizing the model's potential for practical implementation in the field of dermatology.

Chemical mapping of the surface interactome of PIEZO1 identifies CADM1 as a modulator of channel inactivation.

The propeller-shaped blades of the PIEZO1 and PIEZO2 ion channels partition into the plasma membrane and respond to indentation or stretching of the lipid bilayer, thus converting mechanical forces into signals that can be interpreted by cells, in the form of calcium flux and changes in membrane potential. While PIEZO channels participate in diverse physiological processes, from sensing the shear stress of blood flow in the vasculature to detecting touch through mechanoreceptors in the skin, the molecular details that enable these mechanosensors to tune their responses over a vast dynamic range of forces remain largely uncharacterized. To survey the molecular landscape surrounding PIEZO channels at the cell surface, we employed a mass spectrometry-based proteomic approach to capture and identify extracellularly exposed proteins in the vicinity of PIEZO1. This PIEZO1-proximal interactome was enriched in surface proteins localized to cell junctions and signaling hubs within the plasma membrane. Functional screening of these interaction candidates by calcium imaging and electrophysiology in an overexpression system identified the adhesion molecule CADM1/SynCAM that slows the inactivation kinetics of PIEZO1 with little effect on PIEZO2. Conversely, we found that CADM1 knockdown accelerates inactivation of endogenous PIEZO1 in Neuro-2a cells. Systematic deletion of CADM1 domains indicates that the transmembrane region is critical for the observed effects on PIEZO1, suggesting that modulation of inactivation is mediated by interactions in or near the lipid bilayer.

Inhibition of TRPV1 by an antagonist in clinical trials is dependent on cholesterol binding.

TRP Vanilloid 1 (TRPV1) channel, one of the major members of the TRP family was discovered to play a critical role in pain sensation, particularly inflammatory pain, and is associated with hyperalgesia, an enhanced sensitivity to pain. A new study by Fanet al."Structural basis of TRPV1 inhibition by SAF312 and cholesterol" sheds new light on the mechanistic structural basis of TRPV1 inhibition by SAF312 (Libvatrep), a TRPV1 antagonist, currently in phase II clinical trials. They discover that the binding site of SAF312 in TRPV1 is in close vicinity and partially overlaps with the binding site of cholesterol and that removal of cholesterol interferes with the ability of SAF312 to suppress TRPV1 current.

A portable micro-nanochannel bio-3D printed liver microtissue biosensor for DON detection.

We investigated a portable micro-nanochannel biosensor 3D-printed liver microtissues for rapid and sensitive deoxynivalenol (DON) detection. The screen-printed carbon electrode (SPCE) was modified with nanoporous anodic aluminum oxide (AAO), gold nanoparticles (AuNPs), and cytochrome C oxidase (COx) to enhance sensor performance. Gelatin methacrylate hydrogel, combined with hepatocellular carcinoma cells, formed the bioink for 3D printing. Liver microtissues were prepared through standardized and high-throughput techniques via bio-3D printing technology. These microtissues were immobilized onto modified electrodes to fabricate liver microtissue sensors. The peak current of this biosensor was positively correlated with DON concentration, as determined by cyclic voltammetry (CV), within a linear detection range of 2∼40 µg/mL. The standard curve equation is denoted by ICV(µA) = = 18.76956 + 0.03107CDON(µg/mL), with a correlation coefficient R2 was 0.99471(n＝3). A minimum detection limit of 1.229 µg/mL was calculated from the formula, indicating the successful construction of a portable micro-nanochannel bio-3D printed liver microtissue biosensor. It provides innovative ideas for developing rapid and convenient instrumentation to detect mycotoxin hazards after grain production. It also holds significant potential for application in the prediction and assessment of post-production quality changes in grain.

The L-type calcium channel CaV1.3: A potential target for cancer therapy.

Cancer remains a prominent cause to life expectancy, and targeted cancer therapy stands as a pivotal approach in contemporary therapy. Calcium (Ca2+) signalling plays a multifaceted role in cancer progression, such as proliferation, invasion and distant metastasis. Otherwise, it also exerts an important influence on the efficacy of clinical treatment, including cancer therapy resistance. In this review we discuss the role of the L-type calcium channel CaV1.3 (calcium voltage-gated channel subunit alpha1 D) in different types of cancers, highlighting its potential as a therapeutic target for certain cancer types. The development of selective blockers of the CaV1.3 channel has been of great interest and is expected to be a new option for the treatment of cancers such as prostate cancer and endometrial cancer. We present the pharmacological properties of CaV1.3 and the current status of selective blocker development, and analyse the challenges and possible directions for breakthroughs in the development of tailored medicines.

Geomorphic index-based landscape evolution study for the extraction and interpretation of knickpoint and channel steepness in the mandakini catchment, western himalaya.

Geomorphometric analysis using geomorphic indices is essential to comprehend the evolution of a river basin including denudation, surface runoff, subsurface infiltration, differential erosion, lithological variations, possible surface tilting, landslides, and the influence of geological formations and structure. Research in morphometric measurements continues to face many challenges and difficulties despite all the effort carried out. These include the inaccuracy of morphometric measurements and the time it takes to obtain the expected results in large basins. Under such condition, the purpose of the study is to conduct an analysis for the group of indices which includes SL index, transverse topographic symmetry factor, and hypsometry curve along with its integral value in the Mandakini Catchment. Examining the spatial distribution of knickzones has not been well documented, particularly in the Mandakini Catchment; hence, we further analyzed the spatial distribution of knickpoints, channel steepness index, and chi-index along with the longitudinal river profile. Through this analysis, we aim to determine how these indices collectively contribute to the comprehensive characterization of the landscape evolution within the study area and to find the landscape signatures of the uplift by comparing different river profiles. Various knickpoints were found mainly in the upper reaches at higher elevation, validated through aerial imagery and then through detailed field observation. During the field investigation, various geomorphic indicators such as fluvial terraces, entrenched river meandering, active landslides, extensive toe erosion, and waterfalls associated were observed. The study also found out that the places near the Kedarnath, Sonprayag, and Kalimath-Kotma, show high SL index and high steepness index that may correlate with the presence of active thrust and faults.

Real-world efficacy of fimasartan vs. other angiotensin receptor blockers in combination with calcium channel blockers: a nationwide cohort study.

BACKGROUND: The antihypertensive efficacy of fimasartan was assessed based on the transition rate from a combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) to three-drug combination therapy, as compared to other ARBs. METHODS: This nationwide cohort study used data obtained from the Korean National Health Insurance Service database. Patients who had received national health checkups within 2 years prior to January 1, 2017, and were concurrently prescribed ARBs and CCBs for > 30 days during the 6 months from January 1, 2017, to June 30, 2017 were included in the study. Patients were categorized into the 'fimasartan group' (those prescribed fimasartan) and the 'non-fimasartan group' (those prescribed ARBs other than fimasartan). The index date was set as the last day of a 30-day prescription period for ARBs and CCBs, with a subsequent 2.5-year follow-up to observe the potential addition of a third drug, such as beta-blockers or diuretics. RESULTS: The study included 34,422 patients with a mean age of 60.3 years and 58.3% being male. The fimasartan group constituted 2.7% (n = 928) of the total, and the non-fimasartan group, 97.3% (n = 33,494). During the follow-up period, 38 patients in the fimasartan group (14.3 per 1,000 person-years) and 3,557 patients in the non-fimasartan group (42.8 per 1,000 person-years) required additional antihypertensive medications. After multivariate adjustment for age, sex, diabetes mellitus, dyslipidemia, cancer, heart failure, systolic blood pressure, and diastolic blood pressure, the fimasartan group showed a significantly lower rate of adding a third medication (hazard ratio 2.68, 95% confidence interval 1.95-3.69) compared to that of the non-fimasartan group. CONCLUSIONS: Fimasartan is associated with a lower need for additional antihypertensive drugs compared to other ARBs. This implies its greater effectiveness in hypertension management, potentially enhancing cardiovascular outcomes, and minimizing polypharmacy.

N318L Blocks the Interaction of Fluralaner but Not Broflanilide or Fipronil with the Insect GABA Receptor In Vivo.

Fluralaner is a novel insecticide targeting the ionotropic GABA receptor (GABAR) subunit, RDL. A recent study revealed that N316L, a substitution of asparagine (N) with leucine (L), in the second transmembrane (M2)-spanning region reduced the antagonist action of fluralaner on the housefly Musca domestica RDL (MdRDL) in vitro. To verify the impact of N316L in vivo, the corresponding mutation (N318L) in the fruitfly Drosophila melanogaster RDL (DmRDL) was constructed using CRISPR/Cas9 genome editing. The homozygous DmRDLN318L mutant showed a 9.87-fold resistance to fluralaner compared with w1118 while still being highly sensitive to broflanilide and fipronil, which is consistent with those findings observed in the electrophysiology assays of the homomeric DmRDLWT or DmRDLN318L channel. Moreover, DmRDLN318L led to malformed ovaries, stunted eggs, and sterility in homozygous females. These results highlighted N318 as a molecular site for fluralaner in vivo and in vitro and might elucidate the resistance mechanisms of insects against fluralaner.

Chronic ethanol exposure in mice evokes pre- and postsynaptic deficits in GABAergic transmission in ventral tegmental area GABA neurons.

BACKGROUND AND PURPOSE: GABAergic neurons in mouse ventral tegmental area (VTA) exhibit elevated activity during withdrawal following chronic ethanol exposure. While increased glutamatergic input and decreased GABAA receptor sensitivity have been implicated, the impact of inhibitory signaling in VTA GABA neurons has not been fully addressed. EXPERIMENTAL APPROACH: We used electrophysiological and ultrastructural approaches to assess the impact of chronic intermittent ethanol vapour exposure in mice on GABAergic transmission in VTA GABA neurons during withdrawal. We used CRISPR/Cas9 ablation to mimic a somatodendritic adaptation involving the GABAB receptor (GABABR) in ethanol-naïve mice to investigate its impact on anxiety-related behaviour. KEY RESULTS: The frequency of spontaneous inhibitory postsynaptic currents was reduced in VTA GABA neurons following chronic ethanol treatment and this was reversed by GABABR inhibition, suggesting chronic ethanol strengthens the GABABR-dependent suppression of GABAergic input to VTA GABA neurons. Similarly, paired-pulse depression of GABAA receptor-dependent responses evoked by optogenetic stimulation of nucleus accumbens inputs from ethanol-treated mice was reversed by GABABR inhibition. Somatodendritic currents evoked in VTA GABA neurons by GABABR activation were reduced following ethanol exposure, attributable to the suppression of GIRK (Kir3) channel activity. Mimicking this adaptation enhanced anxiety-related behaviour in ethanol-naïve mice. CONCLUSIONS AND IMPLICATIONS: Chronic ethanol weakens the GABAergic regulation of VTA GABA neurons in mice via pre- and postsynaptic mechanisms, likely contributing to their elevated activity during withdrawal and expression of anxiety-related behaviour. As anxiety can promote relapse during abstinence, interventions targeting VTA GABA neuron excitability could represent new therapeutic strategies for treatment of alcohol use disorder.

Design, In silico Screening, Synthesis, Characterisation and DFT-based Electronic Properties of Dihydropyridine-based Molecule as L-type Calcium Channel Blocker.

BACKGROUND: People of all nationalities and social classes are now affected by the growing issue of hypertension. Over time, there has been a consistent rise in the fatality rate. A range of therapeutic compounds, on the other hand, are often used to handle hypertension. OBJECTIVES: The objectives of this study are first to design potential antihypertensive drugs based on the DHP scaffold, secondly, to analyse drug-likeness properties of the ligands and investigate their molecular mechanisms of binding to the model protein Cav1.2 and finally to synthesise the best ligand. MATERIALS AND METHODS: Due to the lack of 3D structures for human Cav1.2, the protein structure was modelled using a homology modelling approach. A protein-ligand complex's strength and binding interaction were investigated using molecular docking and molecular dynamics techniques. DFT-based electronic properties of the ligand were calculated using the M06-2X/ def2- TZVP level of theory. The SwissADME website was used to study the ADMET properties. RESULTS: In this study, a series of DHP compounds (19 compounds) were properly designed to act as calcium channel blockers. Among these compounds, compound 16 showed excellent binding scores (-11.6 kcal/mol). This compound was synthesised with good yield and characterised. To assess the structural features of the synthesised molecule quantum chemical calculations were performed. CONCLUSION: Based on molecular docking, molecular dynamics simulations, and drug-likeness properties of compound 16 can be used as a potential calcium channel blocker.

Long-term Outcome of the Dutch Common Channel Trial (DUCATI): Preservation of Superior Weight Loss Results Without Significant Malnutrition Side Effects.

PURPOSE: The optimal bowel limb lengths for laparoscopic Roux-en-Y gastric bypass (LRYGB) to maximize weight loss while minimizing nutritional deficiencies in severe obesity treatment remain a topic of debate. The multi-center Dutch Common Channel Trial (DUCATI) aims to compare the outcomes of a very long Roux Limb Roux-en-Y gastric bypass (VLRL-LRYGB) with a standard Roux-en-Y gastric bypass (S-LRYGB). METHODS: A total of 444 patients were randomly assigned in a 1:1, double-blind manner to undergo either VLRL-RYGB or S-LRYGB. Five-year follow-up data were assessed, concentrating on weight loss, obesity-related medical conditions, complications, re-operations, and malnutrition. RESULTS: Both groups had comparable total alimentary lengths (RL + CC). The VLRL-LRYGB group demonstrated significantly greater %TWL (32.2% vs. 28.6%, p = 0.002) and %EWL (81.2% vs. 70.3%, p = 0.002) at 5 years. Eight (3.6%) patients in the VLRL-LRYGB group versus 2 (0.9%) in the S-LRYGB group (p = 0.055) needed modification surgery for malabsorption. Suboptimal clinical response rate was significantly higher (22.0% vs. 8.3%) in S-LRYGB group. No significant differences for nutrient deficiencies in favor of the S-LRYGB group were found. CONCLUSION: A 100-cm common channel with a relatively long Roux limb provides superior, sustainable weight loss over 5 years, without significantly increased rate of malabsorption-related re-operations. These results suggest that a longer Roux limb can still ensure adequate micronutrient uptake in the total alimentary tract. These findings should be considered in discussions regarding the optimal Roux-en-Y limb length for severe obesity treatment.

Hydrodynamic frictional performance of fouled panels: a comparative study of different coating types.

This research study delves into the hydrodynamic frictional characteristics of fouled panels coated with different types of coatings, investigating how fouling coverage and surface roughness influence drag. The investigation incorporates data on the overall percentage coverage of fouling, as well as roughness measurements obtained through a 3D profilometer. Drag data collected from a flowcell simulation of real-world flow conditions complements these measurements. Notably, the determination of the level of fouling leverages the capabilities of CIE L*a*b as an image analysis method, focusing on the overall coverage rather than individual fouling species. The objective is to illustrate how fouled panels perform under varying flow and coating conditions compared to their clean counterparts. Furthermore, the paper proposes a roughness scaling approach that considers both the percentage coverage and measured areal roughness for each coating type, encompassing both fouled and unfouled areas. This approach provides valuable insights into the combined effects of fouling and surface roughness on hydrodynamic performance, enhancing our understanding of the intricate interplay between these factors.