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Gallium oxide is a newly emerged ultrawide bandgap (4.9 eV) semiconductor that is suitable as a combined electronics and radiation detection platform. We have experimentally demonstrated fast neutron and gamma-ray scintillation from Czochralski-grown β-Ga2O3 in a recent series (October 2023) of experiments at the unmoderated pulsed neutron spallation source located at the Los Alamos Neutron Science Center. Using the neutron time-of-flight (TOF) technique and a fast-gated intensified CCD camera, we observed energy-dependent neutron scintillation for neutron energies ranging from 1 to 400 MeV, including the 14.1 MeV neutron energy relevant to D-T fusion. Neutron flux is quantified and calibrated by cascading the scintillator after the fission chamber, enabling a detailed analysis of temporal and energy-dependent characteristics of the scintillation events. A pronounced scintillation signal from the spallation gamma flash with a temporal full width of half maximum of ∼4 ns is indicative of the material's rapid response. Neutron energy dependent scintillation is observed using the TOF method at a 22.6-m distance from the neutron source. These results highlight the possibility of developing a Ga2O3 based fusion neutron diagnostic platform integrated with both scintillation and electronics functions on the integrated chip scale., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: As the COVID-19 pandemic persists, infections continue to surge globally. Presently, the most effective strategies to curb the disease and prevent outbreaks involve fostering immunity, promptly identifying positive cases, and ensuring their timely isolation. Notably, there are instances where the SARS-CoV-2 virus remains infectious even after patients have completed their quarantine., Objective: Understanding viral persistence post-quarantine is crucial as it could account for localized infection outbreaks. Therefore, studying and documenting such instances is vital for shaping future public health policies., Design: This study delves into a unique case of SARS-CoV-2 persistence in a 60-year-old female healthcare worker with a medical history of hypertension and hypothyroidism. The research spans 55 days, marking the duration between her initial and subsequent diagnosis during Chile's first COVID-19 wave, with the analysis conducted using RT-qPCR., Results: Genomic sequencing-based phylogenetic analysis revealed that the SARS-CoV-2 detected in both Nasopharyngeal swab samples (NPSs) was consistent with the 20B clade of the Nextstrain classification, even after a 55-day interval., Conclusion: This research underscores the need for heightened vigilance concerning cases of viral persistence. Such instances, albeit rare, might be pivotal in understanding sporadic infection outbreaks that occur post-quarantine., 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., (© 2024 Published by Elsevier Ltd.)

Background: LGBTQ+ individuals have experienced many barriers to receiving quality health care, but the worldwide implementation of person-centred care should make a positive change. However, as forthright disclosures are difficult to find using traditional methods, novel approaches should be utilized to uncover opinions and experiences on LGBTQ+ health care. Twitter could be a place where people post on this topic., Aim: This study aimed to explore tweets mentioning LGBTQ+ (centred) health care., Methods: The methods consisted of an explorative qualitative content analysis of tweets. The tweets were collected between 26 February and 30 March 2021, resulting in 2524 tweets of which 659 were relevant for content analysis., Results: The results showed an excess of political tweets involving LGBTQ+ health care. Many tweets included general statements on the need for LGBTQ+ health care. The few tweets on personal experiences in LGBTQ+ health care showed the overwhelming need for quality care that has been made difficult by political developments., Conclusion: Most tweets were made to inform others of the necessity of quality health care for LGBTQ+ individuals, but the utilization of person-centred care is hardly noticeable., Public Contribution: This study was conducted with the involvement of a public partner (second author) who contributed to the design, data analyses and writing of the paper. Moreover, this study involves the analysis of data provided by the public and published on social media., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

The variant of concern (VOC) SARS-CoV-2 Omicron (B.1.1529) has been described as a highly contagious variant but less virulent than the current variant being monitored (VBM) Delta (B.1.617.2), causing fewer cases of hospitalizations, symptomatology, and deaths associated with COVID-19 disease. Although the epidemiological comparison of both variants has been previously reported in other countries, no report indicates their behavior and severity of infection in Chile. In this work, we report for the first time the effect of the Omicron and Delta variants in a cohort of 588 patients from the Hospital de Urgencia Asistencia pública (HUAP), a high-complexity health center in Santiago, Chile. This report is framed at the beginning of Chile's third wave of the COVID-19 pandemic, with a marked increase in the Omicron variant and a decrease in the circulating Delta variant. Our results indicated a similar proportion of patients with a complete vaccination schedule for both variants. However, the Delta variant was associated with a higher prevalence of hospitalization and more significant symptomatology associated with respiratory distress. On the other hand, our data suggest that vaccination is less effective in preventing infection by the Omicron variant. This antecedent, with a low severity but high contagiousness, suggests that the Omicron variant could even collapse the primary health care service due to the high demand for health care., 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 Mella-Torres, Escobar, Barrera-Avalos, Vargas-Salas, Pirazzoli, Gonzalez, Valdes, Rojas, Luraschi, Vallejos-Vidal, Imarai, Sandino, Reyes-López, Vera and Acuña-Castillo.)

Soil Aquifer Treatment (SAT) can provide supplementary treatment of trace organic compounds (TrOCs) such as pharmaceutical and industrial compounds present in Secondary Treated Wastewater (STWW). Concern on presence of unregulated TrOCs in natural systems has raised recently as well as the interest in SAT systems for remediation. The present study quantifies, at the field scale over35 m of lateral groundwater flow, the effectiveness of the Agon-Coutainville SAT system (Manche, Normandy, France) for TrOCs removal by sorption and biodegradation through monitoring of seven TrOCs (oxazepam, carbamazepine, benzotriazole, tolyltriazole, caffein, paracetamol, ibuprofen) and major inorganic compounds as intrinsic tracers in STWW and groundwater during a 34-day STWW infiltration experiment during operational use of the SAT. Cationic exchanges and mixing between groundwater and STWW during the experiment were highlighted by major ions and geochemical simulations. Due to the low thickness of the unsaturated zone, a 1D analytical solution of the advection-dispersion equation (ADE) was applied on chloride data. Chloride was used as conservative intrinsic tracer to calibrate the horizontal flow and transport parameters such as the aquifer dispersion coefficient (D) and the average pore water velocity (ν) allowing estimation of the groundwater residence time. Transport and attenuation of the TrOCs were simulated assuming first-order degradation constant (μ) and linear retardation coefficient (R), calibrated to simulate the observed temporal changes in the breakthrough of TrOCs. Sorption was found to play a role in the transport of TrOCs, notably for oxazepam with a higher linear retardation coefficient value of 2.2, whereas no significant differences of retardation were observed for carbamazepine, tolyltriazole, benzotriazole (1.37, 1.35, 1.36 respectively). Estimated first order degradation rate constants, between 0.03d -1 for carbamazepine and 0.09d -1 for tolyltriazole, were generally high compared to the literature, possibly due to favourable redox conditions and important microbial activities within the system. This study provides evidence of the efficiency of the Agon-Coutainville SAT system for the removal of TrOCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Before the declaration of the COVID-19 pandemic in March 2020, primary care in most countries relied on face-to-face consultations, with relatively limited use of telemedicine. Lockdowns and social distancing measures during the early stages of the pandemic led to rapid, widely spread telemedicine adoption in healthcare settings. The rapid uptake that occurred following the onset of these pandemic-induced measures in countries such as the UK, Canada and New Zealand prompts questions around the drivers, extent and sustainability of this transformation in clinical practice at the global level, as the research in this area is still emerging. The purpose of this scoping review is to explore the global evidence surrounding the rapid adoption of telemedicine in primary care settings during the first 2 years of the COVID-19 pandemic through three lenses: patient experience, health inequalities and patient-clinician trust, with the purpose of identifying elements contributing to the sustainability of this innovation., Methods: A draft protocol was tested through an initial search on Ovid Medline, Web of Science and Google Scholar with additional searches on the Cochrane Database. This informed the final selection of terms which will be used to search Ovid, Web of Science, Google Scholar, PROSPERO, Cochrane Library and others, filtering for studies from the pandemic declaration onwards. Additional grey literature reports will be sourced through simplified searches on Google in widely spoken languages. Duplicates will be removed by screening titles. Abstracts and grey literature text extracts will be screened based on pre-set eligibility criteria by two researchers. Abstracts (and extracts in the case of grey literature) will be mapped against the domains of the Non-adoption, Abandonment, and challenges to Scale-up, Spread and Sustainability (NASSS) framework by two researchers. Data will be presented in table format., Discussion: This review will map the current literature to identify current gaps in evidence related to the adoption of telemedicine after the declaration of the pandemic in March 2020. The use of simplified searches in the several spoken languages in the world is aimed at capturing more immediate non-academic reflections and experiences on this major service change at a global level., Systematic Review Registration: The study has been registered on Open Science Framework and can be accessed through the following URL: https://osf.io/4z5ut/., (© 2022. The Author(s).)

The identification and tracking of SARS-CoV-2 infected patients in the general population are essential components of the global strategy to limit the COVID-19 viral spread, specifically for maintaining traceability and suppressing the resurgence of local outbreaks. Public health programs that include continuous RT-qPCR testing for COVID-19 in the general population, viral sequencing, and genomic surveillance for highly contagious forms of the virus have allowed for the identification of SARS-CoV-2 infections and reinfections. This work identified SARS-CoV-2 reinfection in a homeless person, which occurred 58 days after the first COVID-19 diagnosis. Genomic sequencing identified a different Nextstrain classification clade (20A and 20B) and PANGO lineage, with a divergence of 4 single nucleotide variants (SNVs) in S and ORF1ab genes, suggesting reinfection by different viral variants. This study is the first from the great metropolitan area of Santiago, Chile, one of the top ten countries in the world to live during the COVID-19 pandemic. We support the importance of performing intensive genomic surveillance programs in the whole population and high-risk groups, such as homeless people, nearly 20 thousand people in Chile, and have limited access to health care services and poor viral traceability., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Claudio Acuña-Castillo et al.)

Background: Neoadjuvant therapy and liver transplantation is an effective treatment for perihilar cholangiocarcinoma (pCCA). Living donor liver transplantation (LDLT) addresses the problem of organ shortage, but has higher risk of technical complication that can be aggravated by radiotherapy. We investigated the incidence of vascular and biliary complication in pCCA compared with non-pCCA patients and their impact on patient and graft survival., Study Design: All consecutive LDLTs (n = 247) performed between 2000 and 2017 were reviewed, including demographics, donor variables, operative details, and postoperative outcomes. Logistic regression models were used to investigate the relationship between variables and outcomes., Results: Seventy-four LDLTs (30.0%) were performed for pCCA and 173 for other indications. Forty-nine patients (66.2%) had primary sclerosing cholangitis-associated pCCA; the remainder had de novo pCCA. LDLT for pCCA was associated with nonstandard arterial (p = 0.001) or portal vein reconstruction (p < 0.001) and Roux-en-Y choledochojejunostomy (p < 0.001). The incidence of early hepatic artery thromboses was similar (5.4% vs 7.6%; p = 0.54). Late hepatic artery (18.9% vs 4.1%; p < 0.001) and portal vein (37.8% vs 8.7%; p < 0.001) complication was more common in the pCCA group. Anastomotic biliary complications occurred in 39.2% vs 54.1% (p = 0.032) of patients. Overall survival for pCCA at 1, 5, and 10 years was 84.9%, 66.5%, and 55.6%, respectively. Cancer recurred in 12.3%. Residual tumor on explant prognosticated inferior survival (hazard ratio 5.69; 95% CI, 1.97 to 16.35) and vascular and biliary complications did not., Conclusions: Late vascular complication is common after LDLT for pCCA, but do not adversely affect long-term survival. LDLT provides excellent survival, particularly for patients with no residual disease at the time of transplantation., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

A rapid analysis of pesticides using on-line Solid phase extraction LC MS/MS (Agilent Technology) was performed using only 2-mL water samples. SPE cartridge PLRP-s was used for the pre-concentration sample with methanol elution in back flush. Sensitive transitions and mass spectrometry conditions were optimized by direct infusion of individual standard solutions in a positive electrospray mode. Water samples were spiked with internal standards to compensate the matrix effect. The limit of quantification was calculated to be 20 ng L -1 using the standard deviation of blank analysis injected ten times and uncertainties were estimated at less than 20% on concentrations. This method was validated to study leaching water samples for which only small quantities of water were available.•Only 2 mL water sample was used.•Samples were filtered at 0.2 µm and spiked with individual standard.•Compounds were separated in an 18.5-min elution time using the dynamic MRM program., Competing Interests: Authors declare no conflict of interest., (© 2020 The Authors. Published by Elsevier B.V.)

Groundwater in the Chalk aquifer is an important water resource whose quality has degraded due to fertilizer and pesticide use. Atrazine, classified as a priority substance, has been one of the most applied pesticides and also one of the most frequently detected pesticides in groundwater. The present study investigated the transfer and degradation of atrazine in the unsaturated zone of the Chalk aquifer in Northern France. The study was conducted in an underground quarry (Saint-Martin-le-Noeud), which provides a direct access to the water table and intercepts the unsaturated zone at different depths. The lake and the ceiling percolation of 16 sites throughout the quarry were followed. For 16 sites, the percolating flow rate and lake level were measured and the lake water was sampled for nitrate, atrazine and deethylatrazine (DEA, main degradation product of atrazine) analysis over 2.5 years. High spatial variations in hydrodynamics (percolating flow rate and lake level) and in lake water quality (atrazine between 55±11 and 202±40 ng L -1 and DEA between 269±53 and 1727±345 ng L -1 ) indicate that the properties of the unsaturated zone influence the transfer and the degradation of atrazine. A counterclockwise hysteresis characterizes the relationship between the lake level and atrazine concentration. Temporal variation shows that the atrazine is transferred through the matrix and fractures with a delay caused by the sorption process that differs in atrazine and DEA. The layer of clay-with-flints is shown to favor the degradation of atrazine near the surface. Preferential pathways may be created below clay-with-flints, through which the transfer of atrazine is quicker., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The water quality of the Chalk aquifer is degrading due to fertilizers and pesticides use which are classified as toxic to public health. The study aims to provide a better understanding of the transfer processes in the unsaturated zone of the Chalk aquifer using different environmental tracers (nitrate, atrazine and tritium). The study was conducted in an underground quarry in northern France (St. Martin le Noeud). The quarry provides direct access to the lower part of the unsaturated zone of the Chalk at a depth of 18-30 m. Fifteen sites throughout the quarry display percolation directly from the unsaturated zone. Since percolation intensity is heterogeneous at one site, a comparison was made between the variation of geochemical properties of ten samples from one site and the spatial variation of samples from 15 sites throughout the quarry. Using the Siegel-Tukey and Wilcoxon tests, we found that the variation between the sites is higher than the variation within one site. Therefore, one percolation sample can be used to represent one site. The transfer time of nitrate and atrazine is estimated based on its use in the cultivated fields. Pore water with no contamination indicates water infiltrated before the use of contaminants at the surface, and pore water with a high concentration of contaminants indicates water infiltrated during the use of contaminants at the surface. The transfer time of water molecules is estimated using the time series of tritium. Transfer velocities were computed for each environmental tracer (nitrate, atrazine and tritium) by dividing the estimated transfer time by the depth of each site. Two transfer velocity ranges are determined: (1) <0.32 ± 0.02 m/year and (2) between 0.72 ± 0.14 and 2.15 ± 0.43 m/year, showing most water transfer through the matrix but also a mixture of water with different velocities., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Obesity is increasingly common before and after liver transplantation (LT), yet optimal management remains unclear. The aim of this study was to analyze the long-term outcomes for obese patients undergoing LT, including a noninvasive weight loss program and combined LT and sleeve gastrectomy (SG). Since 2006, all patients referred for LT with a body mass index (BMI) ≥35 kg/m 2 were enrolled. Patients who achieved weight loss (BMI <35) underwent LT alone, and those who did not underwent simultaneous LT + SG. Analysis of long-term outcomes for patients ≥3 years posttransplant was performed. Since 2006, there were 36 in the weight loss intervention (LT cohort) and 13 in the LT + SG cohort with >3 years of follow-up, whereas overall, a total of 29 patients underwent LT + SG. Patients in the LT cohort had less severe obesity at enrollment (40.0 ± 2.7 vs. LT + SG cohort 46.0 ± 4.5; P < 0.001). In the LT cohort, 83.3% (30 of 36) achieved >10% loss in total body weight (TBW) pre-LT. Three years posttransplant, 29.4% of patients in the LT cohort maintained >10% loss in TBW, whereas 100% of the LT + SG patients did (P < 0.001). Patients who underwent LT + SG maintained a significantly higher percentage of total body weight loss after 3 years of follow-up (LT cohort 3.9 ± 13.3% vs. LT + S G cohort 34.8 ± 17.3%; P < 0.001). Patients in the LT + SG also had a lower prevalence of hypertension, insulin resistance, and hepatic steatosis and required fewer antihypertensive medications and lipid agents at last follow-up., Conclusion: Whereas weight loss before transplantation was achieved by obese patients, weight regain was common in the LT cohort. Combined LT + SG resulted in more effective and more durable weight loss, as well as fewer metabolic complications at last follow-up. (Hepatology 2018)., (© 2018 by the American Association for the Study of Liver Diseases.)

Background: Chemical exposures pose a significant threat to life. A rapid assessment by first responders and emergency nurses is required to reduce death and disability. Currently, no informatics tools exist to process victims of chemical exposures efficiently. The surge of patients into a hospital emergency department during a mass casualty incident creates additional stress on an already overburdened system, potentially placing patients at risk and challenging staff to process patients for appropriate care and treatment efficacy. Traditional emergency department triage models are oversimplified during highly stressed mass casualty incident scenarios in which there is little margin for error. Emerging mobile technology could alleviate the burden placed on nurses by allowing the freedom to move about the emergency department and stay connected to a decision support system., Objective: This study aims to present and evaluate a new mobile tool for assisting emergency department personnel in patient management and triage during a chemical mass casualty incident., Methods: Over 500 volunteer nurses, students, and first responders were recruited for a study involving a simulated chemical mass casualty incident. During the exercise, a mobile application was used to collect patient data through a kiosk system. Nurses also received tablets where they could review patient information and choose recommendations from a decision support system. Data collected was analyzed on the efficiency of the app to obtain patient data and on nurse agreement with the decision support system., Results: Of the 296 participants, 96.3% (288/296) of the patients completed the kiosk system with an average time of 3 minutes, 22 seconds. Average time to complete the entire triage process was 5 minutes, 34 seconds. Analysis of the data also showed strong agreement among nurses regarding the app's decision support system. Overall, nurses agreed with the system 91.6% (262/286) of the time when it came to choose an exposure level and 84.3% (241/286) of the time when selecting an action., Conclusions: The app reliably demonstrated the ability to collect patient data through a self-service kiosk system thus reducing the burden on hospital resources. Also, the mobile technology allowed nurses the freedom to triage patients on the go while staying connected to a decision support system in which they felt would give reliable recommendations., (©Nicholas Boltin, Diego Valdes, Joan M. Culley, Homayoun Valafar. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 22.06.2018.)

Liver transplant (LT) for perihilar cholangiocarcinoma (CCA) offers an opportunity for survival among patients with early-stage but anatomically unresectable disease. The 5-year survival rate after LT is 65% to 70%, higher among patients with primary sclerosing cholangitis, who are often diagnosed earlier, and lower among patients with de novo CCA. The results of LT for hilar CCA, along with recent limited data suggesting favorable survival among patients with very early intrahepatic CCA (ICC), have reignited interest in the subject. This article discusses LT following neoadjuvant therapy for CCA and the early data on LT alone for ICC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Liver disease is a major cause of mortality worldwide. Liver transplantation (LT) is the most effective treatment for end stage liver disease. Available resources and social circumstances have led to different ways of implementing LT around the world. The experience with pediatric LT corroborates the hypothesis that a combination of surgical strategies can be beneficial. The goal of this manuscript is to describe the strategies used by LT centers in North America, Europe and Asia and how these strategies can be applied to reduce waitlist mortality and increase access to LT.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC ≥2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies (hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach.

Food and feeding-state dependent changes in chemoreceptor gene expression may allow Caenorhabditis elegans to modify their chemosensory behavior, but the mechanisms essential for these expression changes remain poorly characterized. We had previously shown that expression of a feeding state-dependent chemoreceptor gene, srh-234, in the ADL sensory neuron of C. elegans is regulated via the MEF-2 transcription factor. Here, we show that MEF-2 acts together with basic helix-loop-helix (bHLH) transcription factors to regulate srh-234 expression as a function of feeding state. We identify a cis-regulatory MEF2 binding site that is necessary and sufficient for the starvation-induced down regulation of srh-234 expression, while an E-box site known to bind bHLH factors is required to drive srh-234 expression in ADL. We show that HLH-2 (E/Daughterless), HLH-3 and HLH-4 (Achaete-scute homologs) act in ADL neurons to regulate srh-234 expression. We further demonstrate that the expression levels of srh-234 in ADL neurons are regulated remotely by MXL-3 (Max-like 3 homolog) and HLH-30 (TFEB ortholog) acting in the intestine, which is dependent on insulin signaling functioning specifically in ADL neurons. We also show that this intestine-to-neuron feeding-state regulation of srh-234 involves a subset of insulin-like peptides. These results combined suggest that chemoreceptor gene expression is regulated by both cell-autonomous and non-cell-autonomous transcriptional mechanisms mediated by MEF2 and bHLH factors, which may allow animals to fine-tune their chemosensory responses in response to changes in their feeding state.

Living donor liver transplantation reduces time and mortality on the waiting list. Bleeding is a serious complication; however, "overcorrection" of coagulopathy may lead to hepatic artery thrombosis. We report a case where desmopressin (DDAVP) was used in the management of persistent postreperfusion bleeding (44 red blood cell units transfused). After 1 dose of DDAVP, bleeding improved significantly and the recipient had an unremarkable recovery. DDAVP should be considered for persisting bleeding after correcting common coagulation abnormalities where complexity of the anastomosis may preclude the use of more aggressive procoagulant drugs in liver transplantation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Growth hormone-releasing hormone agonists (GHRH-As) stimulate cardiac repair following myocardial infarction (MI) in rats through the activation of the GHRH signaling pathway within the heart. We tested the hypothesis that the administration of GHRH-As prevents ventricular remodeling in a swine subacute MI model., Methods and Results: Twelve female Yorkshire swine (25 to 30 kg) underwent transient occlusion of the left anterior descending coronary artery (MI). Two weeks post MI, swine were randomized to receive injections of either 30 μg/kg GHRH-A (MR-409) (GHRH-A group; n=6) or vehicle (placebo group; n=6). Cardiac magnetic resonance imaging and pressure-volume loops were obtained at multiple time points. Infarct, border, and remote (noninfarcted) zones were assessed for GHRH receptor by immunohistochemistry. Four weeks of GHRH-A treatment resulted in reduced scar mass (GHRH-A: -21.9 ± 6.42%; P=0.02; placebo: 10.9 ± 5.88%; P=0.25; 2-way ANOVA; P=0.003), and scar size (percentage of left ventricular mass) (GHRH-A: -38.38 ± 4.63; P=0.0002; placebo: -14.56 ± 6.92; P=0.16; 2-way ANOVA; P=0.02). This was accompanied by improved diastolic strain. Unlike in rats, this reduced infarct size in swine was not accompanied by improved cardiac function as measured by serial hemodynamic pressure-volume analysis. GHRH receptors were abundant in cardiac tissue, with a greater density in the border zone of the GHRH-A group compared with the placebo group., Conclusions: Daily subcutaneous administration of GHRH-A is feasible and safe in a large animal model of subacute ischemic cardiomyopathy. Furthermore, GHRH-A therapy significantly reduced infarct size and improved diastolic strain, suggesting a local activation of the GHRH pathway leading to the reparative process., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Rationale: The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes., Objective: Here, we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire., Methods and Results: Female Yorkshire pigs (n=31) underwent experimental myocardial infarction (MI), and 3 days later, received transendocardial injections of allogeneic male bone marrow-derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit(+) CSCs increased 20-fold in MSC-treated animals versus controls (P<0.001), there was a 6-fold increase in GATA-4(+) CSCs in MSC versus control (P<0.001), and mitotic myocytes increased 4-fold (P=0.005). Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit(+) CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2-5 and troponin I., Conclusions: MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics.

This geographical study aimed to show natural or water-processing-related factors of faecal contamination incidents (FCIs) of drinking water in continental France. We defined a FCI as the occurrence of at least 20 colony-forming Escherichia coli or enterococci among all the 100 mL samples collected for regulatory purpose within one day from a given drinking water supply zone (SZ). We explored correlations between the standardized number of FCIs per département (N&#95;Pols) and various indicators related to weather, land cover, topography, geology and water management for three SZ size sub-classes. In 2003-2004, 2,739 FCIs occurred in SZs supplying fewer than 2,000 people, mainly with simply disinfected groundwater. N&#95;Pols correlates with four covariates: (1) precipitation; (2) the extension of the karst outcrops; (3) the extent of disinfection; and (4) catchment protection. One hundred millimetres of yearly excess in precipitation increases the pollution risk by 28-37%, depending on the sub-class. A 10% extension of the karst areas, a 10% increase of unprotected resources, or of SZs with no disinfection, could entail a higher risk of FCI by about 10%. The correlations are reproducible over the three sub-classes and corroborate expert appraisals. These results encourage the ongoing effort to generalize disinfection and catchment protection.

The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC) remain highly controversial. Here we tested the hypothesis that MSCs regenerate chronically infarcted myocardium through mechanisms comprising long-term engraftment and trilineage differentiation. Twelve weeks after myocardial infarction, female swine received catheter-based transendocardial injections of either placebo (n = 4) or male allogeneic MSCs (200 million; n = 6). Animals underwent serial cardiac magnetic resonance imaging, and in vivo cell fate was determined by co-localization of Y-chromosome (Y(pos)) cells with markers of cardiac, vascular muscle, and endothelial lineages. MSCs engrafted in infarct and border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4, Nkx2.5, and alpha-sarcomeric actin. In addition, Y(pos) MSCs exhibited vascular smooth muscle and endothelial cell differentiation, contributing to large and small vessel formation. Infarct size was reduced from 19.3 +/- 1.7% to 13.9 +/- 2.0% (P < 0.001), and ejection fraction (EF) increased from 35.0 +/- 1.7% to 41.3 +/- 2.7% (P < 0.05) in MSC but not placebo pigs over 12 weeks. This was accompanied by increases in regional contractility and myocardial blood flow (MBF), particularly in the infarct border zone. Importantly, MSC engraftment correlated with functional recovery in contractility (R = 0.85, P < 0.05) and MBF (R = 0.76, P < 0.01). Together these findings demonstrate long-term MSC survival, engraftment, and trilineage differentiation following transplantation into chronically scarred myocardium. MSCs are an adult stem cell with the capacity for cardiomyogenesis and vasculogenesis which contribute, at least in part, to their ability to repair chronically scarred myocardium.

Karst aquifers display a range of geologic and geomorphic characteristics in a wide range of climatic and land-use settings; identification of transport dynamics representative of karst aquifers in general could help advance our understanding of these complex systems. To this end, nutrient, turbidity, and major ion dynamics in response to storms were compared at multiple sites in two karst aquifers with contrasting characteristics and settings: the Chalk aquifer (Eure Department, Normandy, France) and the Barton Springs segment of the Edwards Aquifer (Texas, U.S.A.). The Chalk aquifer is typified by high matrix porosity, thick surficial deposits (up to 30 m thick), and agricultural land use; the Barton Springs segment is typified by low matrix porosity, outcropping limestone, and urban land use. Following one to three storms, from 5 to 16 samples from springs and wells were analyzed for major ions, and specific conductance and turbidity were monitored continuously. Comparison of the chemographs indicated some generalized responses, including an increase in turbidity and potassium concentrations and a decrease in major ion and nitrate concentrations with infiltrating storm runoff. Factor analysis of major ions and turbidity revealed strikingly similar behavior of the chemical variables for the two aquifers: The first two factors, explaining more than 75% of the variability, illustrate that dynamics of most major ions (including nitrate) are opposed to those of turbidity and of potassium. The results demonstrate that potassium and nitrate are effective tracers of infiltrating storm runoff and resident ground water, respectively, and the similar results for these two highly contrasting aquifers suggest that the dynamics identified might be applicable to karst systems in general.

Background and Aim: Fatty infiltration and fibrosis are major issues in chronic liver disease. Recent reports suggest a role for the endocannabinoid system in these processes., Aim: To characterize localization and expression of CB2 in normal liver and nonalcoholic fatty liver., Methods: We studied 64 liver biopsies: eight were considered normal; 56 had a diagnosis of nonalcoholic fatty liver disease (NAFLD); 32 with nonalcoholic steatosis and 24 nonalcoholic steatohepatitis (NASH). CB2 immunolocalization was studied in 38 samples in paraffin blocks using immunohistochemistry, and a computerized semiquantitative analysis was carried out. CB2 mRNA expression was assessed through RT-PCR in 26 frozen liver samples and the ratio CB2/beta-actin was used to evaluate differences between groups. Statistical analysis was performed with central tendency measures and the Mann-Whitney U-test. We considered as significant differences those with a P-value <0.05., Results: Neither parenchymal nor nonparenchymal cells in normal liver tissue react towards anti-CB2 antibodies. All the samples from patients with steatosis and nonalcoholic steatohepatitis showed hepatocellular immunoreactivity. Cholangiocytes were positive only in the NAFLD group. Normal liver tissue showed a normalized CB2/beta-actin ratio of 0.001+/-0.01, steatosis 6.52+/-17.3 (P=0.05 vs normal) and NASH 6.49+/-12.2 (P=0.06 vs normal and P=0.6 vs steatosis)., Conclusion: CB2 receptors are expressed by hepatocytes in nonalcoholic fatty liver disease but not in normal liver.

Aim: To explore the role of ghrelin in gallstone disease., Methods: We carried out a cross-sectional study in 150 subjects, 38 with gallstones (cases) and 112 controls. We also did a real-time PCR-RT study in twenty gallbladder samples each. Body mass index (BMI), serum insulin, ghrelin, and serum lipids were measured. Logistic regression analyses (univariate and multivariate) were conducted to estimate the probability of gallstone disease associated with serum ghrelin concentrations., Results: Cases were statistically different from controls in gender distribution (P = 0.01), age (53 vs 44 yr, P = 0.002), BMI (28 vs 25; P = 0.004), and glucose (5.26 vs 4.98 mmol/L; P = 0.05). The prevalence of ghrelin serum levels above the third tercile was lower in subjects without metabolic syndrome (P < 0.05). In a multivariate model, we found a protective effect, when ghrelin values were higher than the median value (OR = 0.27, 95%CI 0.09-0.82, P = 0.02). Twenty (20%) gallbladder specimens expressed ghrelin mRNA., Conclusion: Serum ghrelin concentrations are associated with a protective effect of GD.

Aim: Obesity and insulin resistance (IR) are closely related to hepatic steatosis (HS), and adiponectin is a hepatic insulin sensitizer that has important effects in liver function. This study aims at investigating the relationship between serum adiponectin concentration and the presence of HS., Methods: We carried out a cross-sectional study in a check-up unit of a University Hospital in Mexico City. We enrolled 196 subjects, comprising 98 subjects with HS (27 women, 71 men) and 98 controls (37 women and 61 men). Anthropometric, metabolic and biochemical variables were measured in the two groups. Serum adiponectin and leptin concentrations were determined, their association with grade of HS tested, and concentrations, according to quartiles, compared between cases and controls. chi(2) analysis for linear trends was used to test for a dose-response relationship and logistic regression analysis was conducted to test for a protective effect of adiponectin., Results: The HS subjects were older and more obese than controls, with a central obesity pattern. In the fourth quartile of adiponectin concentrations, HS was less common and severe. In a multivariate model of the fourth quartile of the adiponectin concentrations, we observed a protective effect (OR = 0.17, 95%CI: 0.04-0.67, P = 0.01). In subjects with more severe HS, we observed higher leptin concentrations, and caloric intakes, total fat and iron consumption were higher than in controls., Conclusion: The results of the present study suggest that a high serum concentration of adiponectin is associated with a protective effect against HS.

Background: Prostaglandin-E(2) and platelet-activating factor (PAF) are embryonic-derived signals that time embryo passage into the uterus in the mare and hamster respectively. PAF-like activity is detectable in the spent media of preimplantation human embryos and it has been suggested that PAF may be the embryonic signal that controls embryo transport to the uterus in our species. The actions of PAF are regulated at the level of its synthesis and degradation as well as the expression of a specific cell surface receptor (PAFr). The enzyme PAF acetylhydrolase (PAF-AH) degrades PAF. This study was undertaken to examine whether or not PAFr and PAF-AH are expressed in the human Fallopian tube and to identify the cell types in which they are expressed., Methods: The presence of PAFr mRNA in tissue extracts was investigated using reverse transcription-polymerase chain reaction. We amplified the predicted amplicon for PAFr mRNA from RNA samples extracted from Fallopian tubes. The expression of PAF-AH was detected by Western blot and the localization of PAFr and PAF-AH proteins was detected by immunohistochemistry., Results: Utilizing antibodies against PAFr and PAF-AH, co-localization of the two proteins in the epithelium and stromal cells were demonstrated., Conclusions: These observations show that the human Fallopian tube expresses PAFr and PAF-AH at a location compatible with the proposed paracrine role of early embryo-derived PAF.