Size Matters: Gastric Pouch Size as a Predictor of Weight Loss Following Laparoscopic Roux-Y Gastric Bypass

Introduction: The identification of relevant components of successful weight reduction surgery is the most important endeavor in the latest research aiming to increase excess weight loss. Over the past twenty years there has been ongoing discussion about the importance of gastric pouch size as one of the key factors influencing weight loss after restrictive weight reduction surgery. The goal of our analysis is to determine the relationship between pouch size and weight reduction following laparoscopic Roux-Y gastric bypass (LRYGB). Methods: Between August 2002 and March 2005, 321 LRYGB procedures were performed at the same institution. Patient demographics were entered into a longitudinal, prospective database. Upper gastrointestinal series were performed in all patients on postoperative day one. Assuming that pouch depth remained constant, pouch size was calculated as area (cm²) utilizing digital imaging technology and internal standardization for measurement. Linear regression analysis was performed to determine the association between pouch size and weight loss at 6 and 12 months postoperatively. Adjustment was made for age, gender, and preoperative BMI. Results: Mean age was 41 years (range, 17-64); 262 patients were female (81.6%); mean preoperative BM I was 51.1 kg/m² (range, 36.1-89.9 kg/m²). Mean 6 month %EWL was 50.5 (range, 13.4-85.5%) and mean 12 month %EWL was 62.5 (range, 14.6-98.1). Mean pouch size was 63.9 cm2 (range, 8.6-248.0 cm² ). A statistically significant inverse correlation between pouch size and %EWL was found at 6 months (β = -0.241, p\u3c0.01) and at 12 months (β = -0.302, p\u3c0.02). A significant correlation was found between pouch size, male gender and preoperative BMI but not between pouch size and age. Conclusion: Our analysis demonstrates that gastric pouch size is one important component for successful weight reduction following LRYGB. The creation of a small gastric pouch should be encouraged as an initial step towards ideal weight loss

A thermodynamically self-consistent theory for the Blume-Capel model

We use a self-consistent Ornstein-Zernike approximation to study the Blume-Capel ferromagnet on three-dimensional lattices. The correlation functions and the thermodynamics are obtained from the solution of two coupled partial differential equations. The theory provides a comprehensive and accurate description of the phase diagram in all regions, including the wing boundaries in non-zero magnetic field. In particular, the coordinates of the tricritical point are in very good agreement with the best estimates from simulation or series expansion. Numerical and analytical analysis strongly suggest that the theory predicts a universal Ising-like critical behavior along the $\lambda$-line and the wing critical lines, and a tricritical behavior governed by mean-field exponents.Comment: 11 figures. to appear in Physical Review

HCV Causes Chronic Endoplasmic Reticulum Stress Leading to Adaptation and Interference with the Unfolded Protein Response

BACKGROUND: The endoplasmic reticulum (ER) is the cellular site for protein folding. ER stress occurs when protein folding capacity is exceeded. This stress induces a cyto-protective signaling cascades termed the unfolded protein response (UPR) aimed at restoring homeostasis. While acute ER stress is lethal, chronic sub-lethal ER stress causes cells to adapt by attenuation of UPR activation. Hepatitis C virus (HCV), a major human pathogen, was shown to cause ER stress, however it is unclear whether HCV induces chronic ER stress, and if so whether adaptation mechanisms are initiated. We wanted to characterize the kinetics of HCV-induced ER stress during infection and assess adaptation mechanisms and their significance. METHODS AND FINDINGS: The HuH7.5.1 cellular system and HCV-transgenic (HCV-Tg) mice were used to characterize HCV-induced ER stress/UPR pathway activation and adaptation. HCV induced a wave of acute ER stress peaking 2-5 days post-infection, which rapidly subsided thereafter. UPR pathways were activated including IRE1 and EIF2α phosphorylation, ATF6 cleavage and XBP-1 splicing. Downstream target genes including GADD34, ERdj4, p58ipk, ATF3 and ATF4 were upregulated. CHOP, a UPR regulated protein was activated and translocated to the nucleus. Remarkably, UPR activity did not return to baseline but remained elevated for up to 14 days post infection suggesting that chronic ER stress is induced. At this time, cells adapted to ER stress and were less responsive to further drug-induced ER stress. Similar results were obtained in HCV-Tg mice. Suppression of HCV by Interferon-α 2a treatment, restored UPR responsiveness to ER stress tolerant cells. CONCLUSIONS: Our study shows, for the first time, that HCV induces adaptation to chronic ER stress which was reversed upon viral suppression. These finding represent a novel viral mechanism to manipulate cellular response pathways

A Concerted HIF-1α/MT1-MMP Signalling Axis Regulates the Expression of the 3BP2 Adaptor Protein in Hypoxic Mesenchymal Stromal Cells

Increased plasticity, migratory and immunosuppressive abilities characterize mesenchymal stromal cells (MSC) which enable them to be active participants in the development of hypoxic solid tumours. Our understanding of the oncogenic adaptation of MSC to hypoxia however lacks the identification and characterization of specific biomarkers. In this study, we assessed the hypoxic regulation of 3BP2/SH3BP2 (Abl SH3-binding protein 2), an immune response adaptor/scaffold protein which regulates leukocyte differentiation and motility. Gene silencing of 3BP2 abrogated MSC migration in response to hypoxic cues and generation of MSC stably expressing the transcription factor hypoxia inducible factor 1alpha (HIF-1α) resulted in increased endogenous 3BP2 expression as well as cell migration. Analysis of the 3BP2 promoter sequence revealed only one potential HIF-1α binding site within the human but none in the murine sequence. An alternate early signalling cascade that regulated 3BP2 expression was found to involve membrane type-1 matrix metalloproteinase (MT1-MMP) transcriptional regulation which gene silencing abrogated 3BP2 expression in response to hypoxia. Collectively, we provide evidence for a concerted HIF-1α/MT1-MMP signalling axis that explains the induction of adaptor protein 3BP2 and which may link protein binding partners together and stimulate oncogenic MSC migration. These mechanistic observations support the potential for malignant transformation of MSC within hypoxic tumour stroma and may contribute to evasion of the immune system by a tumour

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection

IMPORTANCE: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. OBJECTIVE: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. EXPOSURE: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: PASC and 44 participant-reported symptoms (with severity thresholds). RESULTS: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. CONCLUSIONS AND RELEVANCE: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC

Testing a prediction model for the H-mode density pedestal against JET-ILW pedestals

The neutral ionisation model proposed by Groebner et al (2002 Phys. Plasmas 9 2134) to determine the plasma density profile in the H-mode pedestal, is extended to include charge exchange processes in the pedestal stimulated by the ideas of Mahdavi et al (2003 Phys. Plasmas 10 3984). The model is then tested against JET H-mode pedestal data, both in a 'standalone' version using experimental temperature profiles and also by incorporating it in the Europed version of EPED. The model is able to predict the density pedestal over a wide range of conditions with good accuracy. It is also able to predict the experimentally observed isotope effect on the density pedestal that eludes simpler neutral ionization models

The role of ETG modes in JET-ILW pedestals with varying levels of power and fuelling

We present the results of GENE gyrokinetic calculations based on a series of JET-ITER-like-wall (ILW) type I ELMy H-mode discharges operating with similar experimental inputs but at different levels of power and gas fuelling. We show that turbulence due to electron-temperature-gradient (ETGs) modes produces a significant amount of heat flux in four JET-ILW discharges, and, when combined with neoclassical simulations, is able to reproduce the experimental heat flux for the two low gas pulses. The simulations plausibly reproduce the high-gas heat fluxes as well, although power balance analysis is complicated by short ELM cycles. By independently varying the normalised temperature gradients (omega(T)(e)) and normalised density gradients (omega(ne )) around their experimental values, we demonstrate that it is the ratio of these two quantities eta(e) = omega(Te)/omega(ne) that determines the location of the peak in the ETG growth rate and heat flux spectra. The heat flux increases rapidly as eta(e) increases above the experimental point, suggesting that ETGs limit the temperature gradient in these pulses. When quantities are normalised using the minor radius, only increases in omega(Te) produce appreciable increases in the ETG growth rates, as well as the largest increases in turbulent heat flux which follow scalings similar to that of critical balance theory. However, when the heat flux is normalised to the electron gyro-Bohm heat flux using the temperature gradient scale length L-Te, it follows a linear trend in correspondence with previous work by different authors

Spectroscopic camera analysis of the roles of molecularly assisted reaction chains during detachment in JET L-mode plasmas

The roles of the molecularly assisted ionization (MAI), recombination (MAR) and dissociation (MAD) reaction chains with respect to the purely atomic ionization and recombination processes were studied experimentally during detachment in low-confinement mode (L-mode) plasmas in JET with the help of experimentally inferred divertor plasma and neutral conditions, extracted previously from filtered camera observations of deuterium Balmer emission, and the reaction coefficients provided by the ADAS, AMJUEL and H2VIBR atomic and molecular databases. The direct contribution of MAI and MAR in the outer divertor particle balance was found to be inferior to the electron-atom ionization (EAI) and electron-ion recombination (EIR). Near the outer strike point, a strong atom source due to the D+2-driven MAD was, however, observed to correlate with the onset of detachment at outer strike point temperatures of Te,osp = 0.9-2.0 eV via increased plasma-neutral interactions before the increasing dominance of EIR at Te,osp < 0.9 eV, followed by increasing degree of detachment. The analysis was supported by predictions from EDGE2D-EIRENE simulations which were in qualitative agreement with the experimental observations

Shattered pellet injection experiments at JET in support of the ITER disruption mitigation system design

A series of experiments have been executed at JET to assess the efficacy of the newly installed shattered pellet injection (SPI) system in mitigating the effects of disruptions. Issues, important for the ITER disruption mitigation system, such as thermal load mitigation, avoidance of runaway electron (RE) formation, radiation asymmetries during thermal quench mitigation, electromagnetic load control and RE energy dissipation have been addressed over a large parameter range. The efficiency of the mitigation has been examined for the various SPI injection strategies. The paper summarises the results from these JET SPI experiments and discusses their implications for the ITER disruption mitigation scheme

New H-mode regimes with small ELMs and high thermal confinement in the Joint European Torus

New H-mode regimes with high confinement, low core impurity accumulation, and small edge-localized mode perturbations have been obtained in magnetically confined plasmas at the Joint European Torus tokamak. Such regimes are achieved by means of optimized particle fueling conditions at high input power, current, and magnetic field, which lead to a self-organized state with a strong increase in rotation and ion temperature and a decrease in the edge density. An interplay between core and edge plasma regions leads to reduced turbulence levels and outward impurity convection. These results pave the way to an attractive alternative to the standard plasmas considered for fusion energy generation in a tokamak with a metallic wall environment such as the ones expected in ITER.& nbsp;Published under an exclusive license by AIP Publishing