Dynamic changes in the mouse hepatic lipidome following warm ischemia reperfusion injury.

Liver failure secondary to metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common cause for liver transplantation in many parts of the world. Moreover, the prevalence of MASLD not only increases the demand for liver transplantation, but also limits the supply of suitable donor organs because steatosis predisposes grafts to ischemia-reperfusion injury (IRI). There are currently no pharmacological interventions to limit hepatic IRI because the mechanisms by which steatosis leads to increased injury are unclear. To identify potential novel mediators of IRI, we used liquid chromatography and mass spectrometry to assess temporal changes in the hepatic lipidome in steatotic and non-steatotic livers after warm IRI in mice. Our untargeted analyses revealed distinct differences between the steatotic and non-steatotic response to IRI and highlighted dynamic changes in lipid composition with marked changes in glycerophospholipids. These findings enhance our knowledge of the lipidomic changes that occur following IRI and provide a foundation for future mechanistic studies. A better understanding of the mechanisms underlying such changes will lead to novel therapeutic strategies to combat IRI.

Unifying principles of cryopreservation protocols for new plant materials based on alternative cryoprotective agents (cpas) and a systematic approach.

This review addresses a frequently encountered problem of designing an effective cryopreservation procedure for new (not previously cryopreserved) or difficult plant materials. This problem hinders worldwide efforts of applying cryopreservation across a wide genetic base of wild and a number of cultivated plants. We review recent advances in modifications of routinely applied cryoprotective solutions (CPAs) and suggest a practical approach to protocol development which embraces the physiological complexity of plant tissues as well as a wide spectrum of behaviours under CPA treatment. We suggest that vegetative plant materials are classified into four categories based on their size, structure, and the response to osmotic and chemical stresses provoked by CPA mixtures of varied composition and concentration, including alternative osmoprotection and vitrification solutions. A number of up to 15 preset protocols designed specifically for each category is then applied to the material. The protocols resulting in the best regrowth are then combined into the optimized procedure. The main advantage of this system over a conventional "trial-and-error" search for working cryopreservation protocol is a minimal amount of starting materials required for the tests and a relatively accurate prediction of material behaviour under cryopreservation stress provided by the relatively few CPAs treatments. The unifying principles revealed by this approach could broaden a spectrum of wild species and materials which can be safely conserved by cryopreservation. Also anticipated is application of this approach to plant materials of biotechnological value as well as cultivars of agricultural and horticultural crops which do not respond well to standard protocols developed for their kind. doi.org/10.54680/fr23110110112.

Social capital, food insecurity, and health outcomes in the US during the COVID-19 pandemic.

AIMS: The purpose of this study was first, to investigate the harmful effects of food insufficiency on health outcomes - self-rated health (SRH) and self-assessed depressive symptoms - during the COVID-19 pandemic and, second, to test whether these effects fluctuated across the US in terms of state-level social capital. METHODS: Data were drawn from the Census Household Pulse Survey (fielded between April 2020 and February 2021) consisting of community-dwelling American adults (N = 1.5M+). Social capital measures were taken from the 'Social Capital Project' sponsored by the US Congress. We estimated three-level mixed effects models to analyze multiple waves of repeated cross-sectional surveys. RESULTS: Post-COVID-19 food insufficiency was significantly negatively associated with SRH and positively associated depression, adjusting for controls including food insufficiency prior to the onset of the pandemic. These relationships were also more pronounced in areas with higher aggregate social capital. CONCLUSIONS: The health burdens of the new coronavirus disease have fallen disproportionately on the economically marginalized, as measured by food insufficiency. Contrary to the conventional literature, living in a state with a greater stock of social capital worsened its health effects.

Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids.

Hepatic gluconeogenesis from amino acids contributes significantly to diabetic hyperglycemia, but the molecular mechanisms involved are incompletely understood. Alanine transaminases (ALT1 and ALT2) catalyze the interconversion of alanine and pyruvate, which is required for gluconeogenesis from alanine. We find that ALT2 is overexpressed in the liver of diet-induced obese and db/db mice and that the expression of the gene encoding ALT2 (GPT2) is downregulated following bariatric surgery in people with obesity. The increased hepatic expression of Gpt2 in db/db liver is mediated by activating transcription factor 4, an endoplasmic reticulum stress-activated transcription factor. Hepatocyte-specific knockout of Gpt2 attenuates incorporation of 13C-alanine into newly synthesized glucose by hepatocytes. In vivo Gpt2 knockdown or knockout in liver has no effect on glucose concentrations in lean mice, but Gpt2 suppression alleviates hyperglycemia in db/db mice. These data suggest that ALT2 plays a significant role in hepatic gluconeogenesis from amino acids in diabetes.

Characteristics, risk factors, and outcomes of neutropenia after liver or kidney transplantation in children.

BACKGROUND: While prior adult studies have shown that approximately 20%-38% of subjects undergoing solid-organ transplant develop neutropenia, similar analyses in pediatric subjects are scarce. METHODS: We conducted a retrospective chart review of liver transplant (LT) and kidney transplant (KT) recipients at our center during the period 2008-2018. All of the KT and none of the LT subjects during this time period had induction with either anti-thymocyte globulin (ATG) or basiliximab at time of transplant. Neutropenia was defined as absolute neutrophil count (ANC) value ≤1000/mm3 . RESULTS: One hundred subjects with LT and 82 subjects with KT were included. The incidence of neutropenia within the first year of transplant in KT was higher compared to LT (54.8% vs 39%, p = .01). The median number of hospitalizations (p = .001) and infectious complications (p = .04) was significantly higher only in the KT subjects who developed neutropenia (compared to those who did not). Multivariate analysis identified factors associated with severity of liver disease at transplant, namely h/o upper gastrointestinal bleeding (p = .02), weight deficit (p = .01), and pre-LT ANC (p = .01), along with high or moderate risk cytomegalovirus status (p = .05) as predictors of neutropenia in LT subjects. Female gender (p = .03) predicted neutropenia, while BK virus infection was protective for neutropenia (p = .04) in KT subjects. CONCLUSIONS: The incidence of and morbidity associated with neutropenia within 1 year post-transplant is higher in KT subjects compared to LT subjects. The likely reason for this is the use of induction therapy (ATG, basiliximab) at the time of transplant in KT subjects.

Short-term outcomes of a multicentre randomized clinical trial comparing laparoscopic pylorus-preserving gastrectomy with laparoscopic distal gastrectomy for gastric cancer (the KLASS-04 trial).

BACKGROUND: There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer. METHODS: The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days. RESULTS: Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups. CONCLUSION: Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov).

Charge Density Waves in YBa_{2}Cu_{3}O_{6.67} Probed by Resonant X-Ray Scattering under Uniaxial Compression.

We report a comprehensive Cu L_{3}-edge resonant x-ray scattering (RXS) study of two- and three-dimensional (2D and 3D) incommensurate charge correlations in single crystals of the underdoped high-temperature superconductor YBa_{2}Cu_{3}O_{6.67} under uniaxial compression up to 1% along the two inequivalent Cu─O─Cu bond directions (a and b) in the CuO_{2} planes. We confirm the strong in-plane anisotropy of the 2D charge correlations and observe their symmetric response to pressure: pressure along a enhances correlations along b, and vice versa. Our results imply that the underlying order parameter is uniaxial. In contrast, 3D long-range charge order is only observed along b in response to compression along a. Spectroscopic RXS measurements show that the 3D charge order resides exclusively in the CuO_{2} planes and may thus be generic to the cuprates. We discuss implications of these results for models of electronic nematicity and for the interplay between charge order and superconductivity.

Ammonium-free medium is critical for regeneration of shoot tips of the endangered species Pogostemon yatabeanus cryopreserved using droplet-vitrification.

BACKGROUND: Pogostemon yatabeanus, synonym Dysophylla yatabeana, (Labiatae) is an endangered wild species in Korea. It has has a limited natural habitat and requires urgent conservation measures. OBJECTIVE: To develop an efficient cryopreservation protocol using in vitro shoot tips to complement traditional conservation approaches in case seeds are unavailable, or insufficient in number for conservation programs. MATERIALS AND METHODS: Node-cutting induced shoot tips of in vitro plants were produced and cryopreserved using a droplet-vitrification method following improvements in preculture, osmoprotection, vitrification solution (VS) and regrowth treatments. The starting protocol included preculture with 10% sucrose for 31 h, followed by osmoprotection with C4-35% (17.5% glycerol + 17.5% sucrose) for 40 min, and cryoprotection with A3-80% (33.3% glycerol + 13.3% DMSO + 13.3% EG + 20.1% sucrose) for 60 min on ice, cooling and warming using aluminum foil strips, and regrowth in MS hormone-free medium. RESULTS: Shoot tips of Pogostemon yatabeanus were sensitive to the osmotic stress evidenced by low survival after step-wise preculture with 17.5% sucrose and cryopreservation without osmoprotection. Among VS tested, including PVS2, PVS3 and their alternatives, A3-80% on ice for 60 min resulted in the highest post-cryopreservation survival (80%) and regeneration (20%). Post-cryopreservation regeneration significantly improved (up to 73%) by incubation of cryopreserved shoot tips on ammonium-free medium followed by GA X3-containing medium and medium without growth regulators. CONCLUSION: Cryopreservation of in vitro shoot tips using droplet-vitrification was developed as a complementary conservation approach for D. yatabeana. Adjustment of medium composition during the recovery stage was important for regeneration of healthy plants from both cryoprotected-control and cryopreserved shoot tips.

Monoacylglycerol Acyltransferase 1 Knockdown Exacerbates Hepatic Ischemia/Reperfusion Injury in Mice With Hepatic Steatosis.

Nonalcoholic fatty liver disease (NAFLD) is becoming the most common indication for liver transplantation. The growing prevalence of NAFLD not only increases the demand for liver transplantation, but it also limits the supply of available organs because steatosis predisposes grafts to ischemia/reperfusion injury (IRI) and many steatotic grafts are discarded. We have shown that monoacylglycerol acyltransferase (MGAT) 1, an enzyme that converts monoacylglycerol to diacylglycerol, is highly induced in animal models and patients with NAFLD and is an important mediator in NAFLD-related insulin resistance. Herein, we sought to determine whether Mogat1 (the gene encoding MGAT1) knockdown in mice with hepatic steatosis would reduce liver injury and improve liver regeneration following experimental IRI. Antisense oligonucleotides (ASO) were used to knockdown the expression of Mogat1 in a mouse model of NAFLD. Mice then underwent surgery to induce IRI. We found that Mogat1 knockdown reduced hepatic triacylglycerol accumulation, but it unexpectedly exacerbated liver injury and mortality following experimental ischemia/reperfusion surgery in mice on a high-fat diet. The increased liver injury was associated with robust effects on the hepatic transcriptome following IRI including enhanced expression of proinflammatory cytokines and chemokines and suppression of enzymes involved in intermediary metabolism. These transcriptional changes were accompanied by increased signs of oxidative stress and an impaired regenerative response. We have shown that Mogat1 knockdown in a mouse model of NAFLD exacerbates IRI and inflammation and prolongs injury resolution, suggesting that Mogat1 may be necessary for liver regeneration following IRI and that targeting this metabolic enzyme will not be an effective treatment to reduce steatosis-associated graft dysfunction or failure.

Clinicopathologic Characteristics of Centrilobular Injury in Pediatric Liver Transplantation.

Centrilobular injury (CLI) is defined as the presence of perivenular mononuclear inflammation, hepatocyte dropout, and extravasated erythrocytes. In pediatric liver allografts, CLI has been associated with advanced fibrosis and chronic rejection (CR). We sought to better characterize the clinicopathologic features of CLI in the setting of T cell-mediated rejection (TCMR) and its association with complement component 4d (C4d) deposition. A total of 206 posttransplant pediatric patients (491 allograft liver biopsies) were available from 2000 to 2018, of which 63 patients (102 biopsies) showed evidence of TCMR and were included in the study. Of the patients, 35 (55.6%) had CLI on their initial episode of TCMR; those patients with CLI were significantly associated with the type of immunosuppression treatment (P = 0.03), severity of TCMR (P < 0.001), higher gamma-glutamyltransferase (P = 0.01), and advanced fibrosis (P = 0.03). There was a trend to shorter time interval from transplantation to presentation of CLI compared with those without CLI (P = 0.06). No difference was observed in graft or overall survival in the patients with CLI. In 20 patients with CLI, additional biopsies were available; in 45% of these patients, CLI was a persistent/recurrent finding. C4d deposition was noted in 12% of all biopsies (6 patients) with CLI. No significant correlation was noted in C4d deposition and CLI, CR, or graft/overall survival. In conclusion, CLI, although not significantly associated with worse graft survival, was significantly associated with severe TCMR and degree of fibrosis, which highlights the importance of active clinical management and follow-up for these patients.

Viral antigen nanoparticles for discriminated and quantitative detection of different subtypes of anti-virus immunoglobulins.

The aim of this study is to develop a novel method for the accurate diagnosis of the infection status of viral diseases, which requires discriminated and quantitative detection of different anti-virus immunoglubulin subtypes. Considering hepatitis A as a representative model disease, viral antigen nanoparticles (vAgNPs) were designed and synthesized by genetically presenting hepatitis A virus (HAV) antigens on the surface of human heavy chain ferritin (hFTH) nanoparticles to detect anti-HAV antibodies with discriminating immunoglobulin subtypes M and G (IgM and IgG, respectively). The vAgNPs also display multi-copies of hexa-histidine peptide (H6) on their surface to chemisorb gold ions (Au3+), which is vital for the autonomous generation of quantitatively meaningful detection signals. The quantitative level of anti-HAV IgM or IgG in 30 patient sera was successfully analyzed using the vAgNPs of HAV, which was performed through label-free one-step-immunoassay based on the self-enhancement of optical signals from gold nanoparticles clustered on the viral antigen nanoparticles. The diagnostic performance was compared with that of enzyme-linked immunosorbent assay (ELISA), which did not enable accurate quantitative assay due to the poor linearity between the antibody concentration and detection signal. Furthermore, these vAgNP-based immunoassays did not produce any false negative/positive signals, indicating 100% sensitivity and 100% specificity.

Cryopreservation of Endangered Wild Species, Aster altaicus var. uchiyamae Kitam, Using Droplet-Vitrification Procedure.

BACKGROUND: Aster altaicus var. uchiyamae Kitam is an endemic and endangered species in urgent need of a comprehensive conservation strategy. OBJECTIVE: To develop an efficient cryopreservation protocol using in vitro shoot tips to complement traditional conservation approaches in case seeds are not available or insufficient for conservation programs. METHODS: Shoot tips of in vitro plants were cryopreserved using a droplet-vitrification method following improvement of pre-culture, osmoprotection, vitrification solution (VS), unloading and post-culture treatments. The starting protocol included step-wise pre-culture with 10% and 17.5% sucrose for 55 h and 17 h, respectively, followed by osmoprotection with C4-35% (17.5% glycerol + 17.5% sucrose) for 30 min, and cryoprotection with B5-80% (40% glycerol + 40% sucrose) for 60 min. RESULTS: Shoot tips of A. altaicus were found to be moderately sensitive to the osmotic stress. Pre-culture and osmoprotection were not critical for the regeneration of cryopreserved explants when either of these treatments was applied. Osmoprotection with C4-35% on ice for 60 min followed by cryoprotection with A3-80%, a modified and diluted PVS2, on ice for 60 min resulted in the highest (65.3%) regeneration of cryopreserved shoot tips. Among alternative VSs tested, A3-80% and B5-80% were superior to PVS2 and PVS3 used under the same conditions. Step-wise recovery of shoot tips on ammonium-free medium followed by GA3-containing medium and medium without growth regulators were critical for the normal regeneration of both VS-treated and cryopreserved shoot tips. CONCLUSIONS: Cryopreservation of in vitro shoot tips using droplet-vitrification was developed as a complementary conservation approach for A. altaicus. Adjustment of the composition of regrowth media depending on recovery stage was important for the regeneration of healthy plants from cryopreserved shoot tips.

Uniaxial pressure control of competing orders in a high-temperature superconductor.

Cuprates exhibit antiferromagnetic, charge density wave (CDW), and high-temperature superconducting ground states that can be tuned by means of doping and external magnetic fields. However, disorder generated by these tuning methods complicates the interpretation of such experiments. Here, we report a high-resolution inelastic x-ray scattering study of the high-temperature superconductor YBa2Cu3O6.67 under uniaxial stress, and we show that a three-dimensional long-range-ordered CDW state can be induced through pressure along the a axis, in the absence of magnetic fields. A pronounced softening of an optical phonon mode is associated with the CDW transition. The amplitude of the CDW is suppressed below the superconducting transition temperature, indicating competition with superconductivity. The results provide insights into the normal-state properties of cuprates and illustrate the potential of uniaxial-pressure control of competing orders in quantum materials.

Metabolic importance of adipose tissue monoacylglycerol acyltransferase 1 in mice and humans.

Adipocyte triglyceride storage provides a reservoir of energy that allows the organism to survive times of nutrient scarcity, but excessive adiposity has emerged as a health problem in many areas of the world. Monoacylglycerol acyltransferase (MGAT) acylates monoacylglycerol to produce diacylglycerol; the penultimate step in triglyceride synthesis. However, little is known about MGAT activity in adipocytes, which are believed to rely primarily on another pathway for triglyceride synthesis. We show that expression of the gene that encodes MGAT1 is robustly induced during adipocyte differentiation and that its expression is suppressed in fat of genetically-obese mice and metabolically-abnormal obese human subjects. Interestingly, MGAT1 expression is also reduced in physiologic contexts where lipolysis is high. Moreover, knockdown or knockout of MGAT1 in adipocytes leads to higher rates of basal adipocyte lipolysis. Collectively, these data suggest that MGAT1 activity may play a role in regulating basal adipocyte FFA retention.

The impact of diet-induced hepatic steatosis in a murine model of hepatic ischemia/reperfusion injury.

The prevalence of obesity-associated nonalcoholic fatty liver disease has significantly increased over the past decade, and end-stage liver disease secondary to nonalcoholic steatohepatitis has become 1 of the most common indications for liver transplantation. This both increases the demand for organs and decreases the availability of donor livers deemed suitable for transplantation. Although in the past many steatotic livers were discarded due to concerns over enhanced susceptibility to ischemia/reperfusion injury (IRI) and organ failure, the discrepancy between supply and demand has resulted in increasing use of expanded criteria donor organs including steatotic livers. However, it remains controversial whether steatotic livers can be safely used for transplantation and how best to improve the performance of steatotic grafts. We aimed to evaluate the impact of diet-induced hepatic steatosis in a murine model of IRI. Using a diet of high trans-fat, fructose, and cholesterol (HTF-C) and a diet high in saturated fats, sucrose, and cholesterol (Western diet), we were able to establish models of mixed macrovesicular and microvesicular steatosis (HTF-C) and microvesicular steatosis (Western). We found that the presence of hepatic steatosis, whether it is predominantly macrovesicular or microvesicular, significantly worsens IRI as measured by plasma alanine aminotransferase levels and inflammatory cytokine concentration, and histological evaluation for necrosis. Additionally, we report on a novel finding in which hepatic IRI in the setting of steatosis results in the induction of the necroptosis factors, receptor interacting protein kinase (RIPK) 3, RIPK1, and mixed-lineage kinase domain-like. These data lay the groundwork for additional experimentation to test potential therapeutic approaches to limit IRI in steatotic livers by using a genetically tractable system. Liver Transplantation 24 908-921 2018 AASLD.

Particularized trust, generalized trust, and immigrant self-rated health: cross-national analysis of World Values Survey.

OBJECTIVES: This research examined the associations between two types of trust, generalized and particularized, and self-rated health among immigrants. STUDY DESIGN: Data were drawn from the World Values Survey (WVS6), the latest wave of cross-sectional surveys based on face-to-face interviews. METHODS: The immigrant subsample analyzed herein contains 3108 foreign-born individuals clustered from 51 countries. Given the hierarchically nested data, two-level logistic regressions models were estimated using HLM (Hierarchical Linear Modeling) 7.1. RESULTS: At the individual level, net of socio-economic and demographic factors (age, gender, marital status, education, income, neighborhood security, and subjective well-being), particularized trust was positively related to physical health (odds ratio [OR] = 1.11, P < .001). Generalized trust, however, was not a significant predictor. At the country level, based on alternative models, the aggregate measure of particularized trust was negatively associated with subjective health. The odds of being healthy were on average about 30% lower. CONCLUSION: The interdisciplinary literature on social determinants of health has largely focused on the salubrious impact of trust and other forms of social capital on physical well-being. Many previous studies based on general, not immigrant, populations also did not differentiate between generalized and particularized types of trust. Results from this study suggest that this conceptual distinction is critical in understanding how and to what extent the two are differentially related to immigrant well-being across multiple levels of analysis.

Strategies for controlling dog-mediated human rabies in Asia: using 'One Health' principles to assess control programmes for rabies.

Over 99% of human rabies cases in endemic areas are transmitted by dogs. Without the elimination of dog rabies, it is not easy to reduce human rabies infection. Controlling dog rabies, especially in ownerless or free-roaming dogs, is critical if we are to decrease the rate of human rabies infection. There are several components in a strategy to eliminate dog-mediated rabies in Asia. Each government must make sure that rabies is either a reportable disease or a notifiable disease and enforce the reporting requirements accordingly. They must also focus on organising and operating special rabies control committees that work with relevant agencies under the 'One Health' banner. They should also implement a national rabies control programme that includes mass dog vaccination, laboratory-based surveillance, stable budget allocation, a rapidreporting system, management of dog populations, international cooperation, prevention of animal introductions from other countries, and risk assessment to analyse the programme's weaknesses. As several developed countries have shown, an effective rabies control strategy leads to rabies-free status. In the Republic of Korea, human rabies has not occurred since 2004, and there have not been any confirmed cases of dog rabies or cases of rabies in wild animals, including raccoon dogs, since 2014. The successful implementation of the key strategies used to eliminate rabies in the Republic of Korea will enable other Asian countries to eliminate dog-mediated human rabies.

Plus de 99 % des cas humains de rage survenant dans les zones où cette maladie est endémique sont dus à des morsures de chiens. Il paraît difficile de réduire le nombre d'êtres humains infectés par le virus de la rage sans éliminer la rage canine. Le contrôle de la rage canine, en particulier dans les populations de chiens sans propriétaire ou errants est une condition essentielle si nous voulons faire baisser l'incidence de la rage humaine. La stratégie d'élimination de la rage transmise par les chiens en Asie comporte plusieurs composantes. Les gouvernements doivent s'assurer que la rage est une maladie à déclaration ou notification obligatoires et que les dispositions prévues en matière de déclaration sont bien appliquées. Ils doivent également axer leurs efforts sur la mise en place et le bon fonctionnement de commissions compétentes en matière de lutte contre la rage, qui opéreront en collaboration avec les agences pertinentes sous la bannière « Une seule santé ¼. En outre, chaque pays mettra en oeuvre un programme national de lutte contre la rage en intégrant toutes ses composantes : vaccination des chiens, surveillance sérologique, enveloppe budgétaire stable, système de notification accélérée, gestion des populations de chiens, coopération internationale, prévention de l'introduction d'animaux à partir d'autres pays et enfin évaluation des risques en vue d'analyser les faiblesses du programme. Ainsi que l'ont montré plusieurs pays développés, les stratégies efficaces de lutte contre la rage permettent d'atteindre le statut indemne de rage. En république de Corée, aucun cas de rage n'a été signalé chez l'homme depuis 2004 ; de même, aucun cas de rage n'a été confirmé chez le chien ni dans la faune sauvage, y compris chez le chien viverrin, depuis 2014. L'exemple des stratégies d'élimination de la rage appliquées avec succès en république de Corée permettra à d'autres pays asiatiques de venir à bout de la rage humaine transmise par le chien.

Los perros son los transmisores de más del 99% de los casos de rabia humana que se dan en las zonas de endemismo. De ahí la dificultad de reducir el número de personas infectadas si no se logra previamente eliminar la enfermedad en el perro, o dicho de otro modo: el control de la rabia canina, sobre todo en los perros vagabundos o sin dueño, es esencial para lograr menores índices de infección humana. Una estrategia encaminada a eliminar la rabia transmitida por perros en Asia ha de tener varios componentes. Todos los gobiernos deben hacer de la rabia una enfermedad de notificación obligatoria y hacer aplicar en consecuencia las reglas al respecto. También deben privilegiar la creación y el funcionamiento de comités especiales de lucha antirrábica que trabajen con los organismos competentes desde la lógica y los postulados de «Una sola salud¼. Además, deben instituir un programa nacional de lucha contra la rabia que, además de la vacunación masiva de perros, incluya planes de vigilancia en laboratorio, una partida presupuestaria estable, un sistema de notificación rápida, la gestión de las poblaciones caninas, la cooperación internacional, la prevención de la introducción de animales desde otros países y un proceso de determinación del riesgo para analizar los puntos débiles del programa. Como ha quedado patente en varios países desarrollados, una estrategia eficaz de lucha antirrábica acaba conduciendo a la condición de país libre de la enfermedad. En la República de Corea no se han producido casos de rabia humana desde 2004, y no ha habido ningún caso confirmado de rabia canina ni de rabia en animales silvestres, perros mapaches inclusive, desde 2014. La eficaz aplicación de las estrategias fundamentales empleadas en la República de Corea para eliminar la enfermedad hará posible que otros países asiáticos logren eliminar la rabia humana transmitida por perros.

Long-term Survival Outcomes of Primary Breast Cancer in Women With or Without Preoperative Magnetic Resonance Imaging: A Matched Cohort Study.

AIMS: To investigate whether preoperative magnetic resonance imaging (MRI) in patients with primary breast cancer is predictive of disease-free (DFS) and overall survival and to determine the prognostic factors indicating survival. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. From 2009 to 2010, 828 women with primary breast cancer and preoperative MRI were matched with 1613 women without such imaging. Patients were matched with regards to 25 patient and tumour-related covariates. A Cox proportional hazards model was used to investigate the time to recurrence and to estimate the hazard ratio for preoperative MRI. Log-rank tests and Cox proportional hazards survival analysis were carried out on total recurrence DFS and overall survival in the unmatched datasets. RESULTS: In total, 799 matched pairs were available for survival analysis. The MRI group showed a tendency towards better survival outcome; however, there were no significant differences in DFS and overall survival. Age at diagnosis (DFS hazard ratio = 0.98; overall survival hazard ratio = 1.04), larger tumour size (DFS hazard ratio = 1.01; overall survival hazard ratio = 1.02), triple negative breast cancer (DFS hazard ratio = 2.64; overall survival hazard ratio = 3.44) and the presence of lymphovascular invasion (DFS hazard ratio = 2.12; overall survival hazard ratio = 2.70) were independent significant variables for worse DFS and overall survival. CONCLUSION: Preoperative MRI did not result in an improvement in a patient's outcome. Age at diagnosis, tumour size, molecular subtype and lymphovascular invasion were significant independent factors affecting both DFS and overall survival.

Capture of heavy hydrogen isotopes in a metal-organic framework with active Cu(I) sites.

The production of pure deuterium and the removal of tritium from nuclear waste are the key challenges in separation of light isotopes. Presently, the technological methods are extremely energy- and cost-intensive. Here we report the capture of heavy hydrogen isotopes from hydrogen gas by selective adsorption at Cu(I) sites in a metal-organic framework. At the strongly binding Cu(I) sites (32 kJ mol-1) nuclear quantum effects result in higher adsorption enthalpies of heavier isotopes. The capture mechanism takes place most efficiently at temperatures above 80 K, when an isotope exchange allows the preferential adsorption of heavy isotopologues from the gas phase. Large difference in adsorption enthalpy of 2.5 kJ mol-1 between D2 and H2 results in D2-over-H2 selectivity of 11 at 100 K, to the best of our knowledge the largest value known to date. Combination of thermal desorption spectroscopy, Raman measurements, inelastic neutron scattering and first principles calculations for H2/D2 mixtures allows the prediction of selectivities for tritium-containing isotopologues.