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Frailty and sarcopenia are well-recognized factors related to worse outcomes in patients with cirrhosis, including liver transplant (LT) candidates. Implications of pre-LT functional and muscle deterioration also affect post-LT outcomes. Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have a lower survival rate, both before and after LT. There is a need to better identify those patients with ACLF who would benefit from LT. This review aims to present the available data about frailty and sarcopenia in patients with ACLF in the LT setting. An exhaustive review of the published literature was conducted. Data regarding frailty and sarcopenia in LT candidates with ACLF are scarce and heterogeneous. Studies evaluating frailty and sarcopenia in critically ill patients outside the liver literature are also presented in this review to enrich the knowledge of this field in expansion. Frailty and sarcopenia seem to contribute to worse outcomes in LT candidates with ACLF, both before and after LT. Sarcopenia evaluation may be the most prudent approach for those very sick patients. Skeletal muscle index assessed by computed tomography is recommended to evaluate sarcopenia. The role of muscle ultrasound and bioelectrical impedance analysis is to be determined. Frailty and sarcopenia are crucial factors to consider on a case-by-case basis in LT candidates with ACLF to improve patient outcomes., Competing Interests: Conflicts of interest IC-V: Travel grant and lecture fees from Chiesi. MS-T: consulting fees from Grifols., (Copyright © 2024 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

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.

Monitoring of bioinoculants once released into the field remains largely unexplored; thus, more information is required about their survival and interactions after root colonization. Therefore, specific primers were used to perform a long-term tracking to elucidate the effect of Hartmannibacter diazotrophicus on wheat and barley production at two experimental organic agriculture field stations. Three factors were evaluated: organic fertilizer application (with and without), row spacing (15 and 50 cm), and bacterial inoculation (H. diazotrophicus and control without bacteria). Hartmannibacter diazotrophicus was detected by quantitative polymerase chain reaction on the roots (up to 5 × 105 copies g-1 dry weight) until advanced developmental stages under field conditions during two seasons, and mostly in one farm. Correlation analysis showed a significant effect of H. diazotrophicus copy numbers on the yield parameters straw yield (increase of 453 kg ha-1 in wheat compared to the mean) and crude grain protein concentration (increase of 0.30% in wheat and 0.80% in barley compared to the mean). Our findings showed an apparently constant presence of H. diazotrophicus on both wheat and barley roots until 273 and 119 days after seeding, respectively, and its addition and concentration in the roots are associated with higher yields in one crop., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Background & Aims: Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution., Methods: Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8 mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients., Results: A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% ( p <0.001). Patients with worse liver function during follow-up showed a simultaneous aggravation in SPSS distribution. Non-cured patients (n = 191) experienced a significant worsening in liver function, more episodes of liver decompensation and lower transplant-free survival compared to cured patients (n = 191). However, no differences were observed regarding SPSS distribution at inclusion and at follow-up, with both groups showing a trend to worsening. Total shunt diameter increased more in non-cured (52%) than in cured patients (28%). However, total shunt area (TSA) significantly increased only in non-cured patients (74 to 122 mm 2 , p <0.001)., Conclusions: The presence of SPSS in cirrhosis increases over time and parallels liver function deterioration. Aetiological intervention in these patients reduces liver-related complications, but SPSS persist although progression is decreased., Impact and Implications: There is no information regarding the evolution of spontaneous portosystemic shunts (SPSS) during the course of cirrhosis, and especially after disease regression with aetiological interventions, such as HCV treatment with direct-acting antivirals or alcohol abstinence. These results are relevant for clinicians dealing with patients with cirrhosis and portal hypertension because they have important implications for the management of cirrhosis with SPSS after disease regression. From a practical point of view, physicians should be aware that in advanced cirrhosis with portal hypertension, after aetiological intervention, SPSS mostly persist despite liver function improvement, and complications related to SPSS may still develop., Competing Interests: JG has received consulting fees from Boehringer Ingelheim and speaking fees from Echosens. MS-T has received consulting fees from Grifols. AK has served as speaker for Novo Nordisk, Norgine, Siemens and Nordic Bioscience and participated in advisory boards for Norgine, Siemens, Resalis Therapeutics, Boehringer Ingelheim and Novo Nordisk, all outside the submitted work. Research support Norgine, Siemens, Nordic Bioscience, Astra, Echosense. Consulting Takeda, Resalis Therapeutics, Zealand Pharma, Novo Nordisk, Boehringer Ingelheim. Board member and co-founder Evido. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

On-surface synthesis has emerged as an attractive method for the atomically precise synthesis of new molecular nanostructures, being complementary to the widespread approach based on solution chemistry. It has been particularly successful in the synthesis of graphene nanoribbons and nanographenes. In both cases, the target compound is often generated through cyclodehydrogenation reactions, leading to planarization and the formation of hexagonal rings. To improve the flexibility and tunability of molecular units, however, the incorporation of other, nonbenzenoid, subunits is highly desirable. In this letter, we thoroughly analyze sequential cyclodehydrogenation reactions with a custom-designed molecular precursor. We demonstrate the step-by-step formation of hexagonal and pentagonal rings from the nonplanar precursor within fjord and cove regions, respectively. Computer models comprehensively support the experimental observations, revealing that both reactions imply an initial hydrogen abstraction and a final [1,2] hydrogen shift, but the formation of a pentagonal ring proceeds through a radical mechanism.

Development of the mammalian neocortex requires proper inside-out migration of developing cortical neurons from the germinal ventricular zone toward the cortical plate. The mechanics of this migration requires precise coordination of different cellular phenomena including cytoskeleton dynamics, membrane trafficking, and cell adhesion. The small GTPases play a central role in all these events. The small GTPase Rab21 regulates migration and neurite growth in developing neurons. Moreover, regulators and effectors of Rab21 have been implicated in brain pathologies with cortical malformations, suggesting a key function for the Rab21 signaling pathway in cortical development. Mechanistically, it has been posited that Rab21 influences cell migration by controlling the trafficking of endocytic vesicles containing adhesion molecules. However, direct evidence of the participation of Rab21 or its mechanism of action in the regulation of cortical migration is still incomplete. In this study, we demonstrate that Rab21 plays a critical role in the differentiation and migration of pyramidal neurons by regulating the levels of the amyloid precursor protein on the neuronal cell surface. Rab21 loss of function increased the levels of membrane-exposed APP, resulting in impaired cortical neuronal differentiation and migration. These findings further our understanding of the processes governing the development of the cerebral cortex and shed light onto the molecular mechanisms behind cortical development disorders derived from the malfunctioning of Rab21 signaling effectors., (© 2023 International Society for Neurochemistry.)

The term 'perinatal environment' refers to the period surrounding birth, which plays a crucial role in brain development. It has been suggested that dynamic communication between the neuro-immune system and gut microbiota is essential in maintaining adequate brain function. This interaction depends on the mother's status during pregnancy and/or the newborn environment. Here, we show experimental and clinical evidence that indicates that the perinatal period is a critical window in which stress-induced immune activation and altered microbiota compositions produce lasting behavioral consequences, although a clear causative relationship has not yet been established. In addition, we discuss potential early treatments for preventing the deleterious effect of perinatal stress exposure. In this sense, early environmental enrichment exposure (including exercise) and melatonin use in the perinatal period could be valuable in improving the negative consequences of early adversities. The evidence presented in this review encourages the realization of studies investigating the beneficial role of melatonin administration and environmental enrichment exposure in mitigating cognitive alteration in offspring under perinatal stress exposure. On the other hand, direct evidence of microbiota restoration as the main mechanism behind the beneficial effects of this treatment has not been fully demonstrated and should be explored in future studies.

Background: The Caribbean spiny lobster Panulirus argus is heavily fished throughout its Greater Caribbean and Gulf of Mexico distribution, suggesting a heightened susceptibility to a fisheries collapse. In 2017, a nemertean worm, Carcinonemertes conanobrieni was described from ovigerous females of P. argus in Florida, USA. A year later, the presence of the same egg predator was recorded along the southern Caribbean coast (Colombia). The effect of this egg predator on the reproductive performance, including fecundity, embryo mortality, and reproductive output, of its host is unknown. This study tested whether C. conanobrieni affects embryo mortality, fecundity, and reproductive output in brooding females of P. argus., Results: Artisan fishers caught 90 ovigerous lobsters near Pueblo Viejo, Magdalena, Colombia. Each ovigerous female was examined for the presence/absence of the egg predator. Lobster egg mortality (%), fecundity (nº eggs female -1 ), and reproductive output (%) were estimated. Prevalence of C. conanobrieni in the studied population was 87.78%. The mean intensity of C. conanobrieni (all life stages) in the population was 11.68 (± 1.98) egg predators per brood mass sample. Infected females brooding late-stage embryos exhibited lower fecundity, lower reproductive performance values, and higher embryo mortality compared to infected females brooding early-stage embryos. Embryo stage and worm infection level negatively impacted fecundity and reproductive output. Worm infection level and the number of adult nemertean worms also negatively affected embryo mortality., Conclusions: These results demonstrate an adverse effect of C. conanobrieni on the reproductive performance of P. argus. The interactive impact of this egg predator, natural stressors, and anthropogenic stressors on individual P. argus reproductive performance could facilitate losses at large-scale fisheries levels., (© 2023. The Author(s).)

Neurocognitive research on social concepts underscores their reliance on fronto-temporo-limbic regions mediating broad socio-cognitive skills. Yet, the field has neglected another structure increasingly implicated in social cognition: the cerebellum. The present exploratory study examines this link combining a novel naturalistic text paradigm, a relevant atrophy model and functional magnetic resonance imaging. Fifteen cerebellar ataxia (CA) patients with focal cerebellar atrophy and 29 matched controls listened to a social text (highlighting interpersonal events) as well as a non-social text (focused on a single person's actions), and answered comprehension questionnaires. We compared behavioural outcomes between groups and examined their association with cerebellar connectivity. CA patients showed deficits in social text comprehension and normal scores in the non-social text. Also, social text outcomes in controls selectively correlated with connectivity between the cerebellum and key regions subserving multi-modal semantics and social cognition, including the superior and medial temporal gyri, the temporal pole and the insula. Conversely, brain-behaviour associations involving the cerebellum were abolished in the patients. Thus, cerebellar structures and connections seem involved in processing social concepts evoked by naturalistic discourse. Such findings invite new theoretical and translational developments integrating social neuroscience with embodied semantics. This article is part of the theme issue 'Concepts in interaction: social engagement and inner experiences'.

Background: Visible abdominal distension has been attributed to: (A) distorted perception, (B) intestinal gas accumulation, or (C) abdominophrenic dyssynergia (diaphragmatic push and anterior wall relaxation)., Methods: A pool of consecutive patients with functional gut disorders and visible abdominal distension included in previous studies (n = 139) was analyzed. Patients (61 functional bloating, 74 constipation-predominant irritable bowel syndrome and 4 with alternating bowel habit) were evaluated twice, under basal conditions and during a self-reported episode of visible abdominal distension; static abdominal CT images were taken in 104 patients, and dynamic EMG recordings of the abdominal walls in 76, with diaphragmatic activity valid for analysis in 35., Key Results: (A) Objective evidence of abdominal distension was obtained by tape measure (increase in girth in 138 of 139 patients), by CT imaging (increased abdominal perimeter in 96 of 104 patients) and by abdominal EMG (reduced activity, i.e., relaxation, in 73 of 76 patients). (B) Intestinal gas volume was within ±300 ml from the basal value in 99 patients, and above in 5 patients, who nevertheless exhibited a diaphragmatic descent. (C) Diaphragmatic contraction was detected in 34 of 35 patients by EMG (increased activity) and in 82 of 103 patients by CT (diaphragmatic descent)., Conclusions and Inferences: In most patients complaining of episodes of visible abdominal distention: (A) the subjective claim is substantiated by objective evidence; (B) an increase in intestinal gas does not justify visible abdominal distention; (C) abdominophrenic dyssynergia is consistently evidenced by dynamic EMG recording, but static CT imaging has less sensitivity., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Our aim was to determine the reliability of plain abdominal radiographs for the evaluation of abdominal gas content in patients with functional digestive symptoms., Methods: Abdominal CT scan scout views, mimicking a conventional plain abdominal radiograph, were obtained from 30 patients both during episodes of abdominal distension and basal conditions. Physicians (n = 50) were instructed to rate the estimated volume of gas in the 60 images presented in random sequence using a scale graded from 0 to ≥600 ml., Key Results: The gas volumes estimated in the scout views differed from those measured by CT by a median of 90 (95% CI 70-102) ml, and the misestimation was not related to the absolute volume in the image. The accuracy of the observers, measured by their mean misestimation, was not related to their specialty or the training status (misestimation by 96 (95% CI 85-104) ml in staff vs 78 (70-106) ml in residents; p = 0.297). The accuracy was independent of the order of presentation of the images. Gas volume measured by CT in the images obtained during episodes of abdominal distension differed by a median of 39 (95% CI 29-66) ml from those during basal conditions, and this difference was misestimated by a median of 107 (95% CI 94-119) ml. The accuracy of these estimations was not related to the absolute gas volumes (R = -0.352; p < 0.001) or the magnitude of the differences., Conclusions & Inferences: Plain abdominal radiographs have limited value for the evaluation of abdominal gas volume in patients with functional gut disorders., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Cognitive impairment and dementia have a high prevalence among the elderly and cause significant socio-economic impact. Any progress in their prevention can benefit millions of people. Current data indicate that cardiovascular risk (CVR) factors increase the risk of developing cognitive impairment and dementia. Using models to calculate CVR specific for the Spanish population can be useful for estimating the risk of cognitive deterioration since research on this topic is limited and predicting this risk is mainly based on outcomes in the Anglo-Saxon population. The aim of this study is to assess the relationship between CVR in the Spanish population, as calculated using the FRESCO (Función de Riesgo Española de acontecimientos Coronarios y Otros) and REGICOR (Registre Gironí del Cor) CVR tables, and the change in cognitive performance at a 5-year follow-up., Methods: Design: Observational, analytic, prospective cohort study, with a 5-year follow-up. Ambit: Population. Population: Subjects 55 to 74 years of age, included in the NEDICES2 (2014-2017) cohort, who did not present dementia and had undergone the neuropsychological evaluation (N = 962). Variables: Exposure factors (CVR factors and estimated risk according to the CVR predictors by REGICOR and FRESCO), dependent variables (change in the score of the brief neuropsychological test in the study NEDICES2 five years after the first evaluation), and clinical and socio-demographic variables. Statistical analysis: Analysis of data quality. Descriptive analysis: socio-demographic and clinical variables of subjects. Bivariate analysis: relationship between basal CVR and change in neuropsychological tests. Multivariate analysis: relationship between basal CVR and change in neuropsychological tests adjusted by co-variables. Analysis and comparison of the reliable change in independent samples., Discussion: The Spanish population can benefit from determining if individuals with high CVR, which is commonly detected in usual clinical practice, will present decreased cognitive performance compared to subjects with lower CVR. This study can affect how to address CVR factors and the design of effective prevention strategies for cognitive deterioration., Trial Registration: Clinicaltrials.gov, NCT03925844., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Tapias-Merino et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The synthesis of novel organic prototypes combining different functionalities is key to achieve operational elements for applications in organic electronics. Here we set the stage towards individually addressable magneto-optical transducers by the on-surface synthesis of optically active manganese-phthalocyanine derivatives (MnPc) obtained directly on a metallic substrate. We created these 2D nanostructures under ultra-high vacuum conditions with atomic precision starting from a simple phthalonitrile precursor with reversible photo-induced reactivity in solution. These precursors maintain their integrity after powder sublimation and coordinate with the Mn ions into tetrameric complexes and then transform into MnPcs on Ag(111) after a cyclotetramerization reaction. Using scanning tunnelling microscopy and spectroscopy together with DFT calculations, we identify the isomeric configuration of two bi-stable structures and show that it is possible to switch them reversibly by mechanical manipulation. Moreover, the robust magnetic moment brought by the central Mn ion provides a feasible pathway towards magneto-optical transducer fabrication. This work should trigger further research confirming such magneto-optical effects in MnPcs both on surfaces and in liquid environments.

Introduction and Objectives: Spontaneous portosystemic shunts (SPSS) are a common cause of recurrent hepatic encephalopathy (HE). Shunt occlusion is an effective and safe procedure when performed in patients with cirrhosis and preserved liver function. We aimed to describe our experience with SPSS embolization after liver transplantation (LT)., Patients: We identified five patients who underwent SPSS embolization after LT. Clinical, biochemical and technical procedure data were collected., Results: At presentation, all patients had developed graft cirrhosis and HE after LT. Median Model for End-stage Liver Disease (MELD) at embolization was 9 (range 7-12), median Child-Pugh was 8 (range 7-9). Splenorenal and mesocaval shunt were the most frequent types of SPSS found. Three patients have been completely free of HE. Of the two patients who had HE recurrence after embolization, one patient had two episodes of HE which was controlled well with medications. The other patient required three embolizations because of recurrent HE. Median follow-up was 4.4 years (range 1.0-5.0) and MELD score at last follow up was 13 (range 10-18) and median Child-Pugh score B, 7 points (range 5-12)., Conclusions: SPSS can be considered as a cause of HE after LT. SPSS embolization is feasible and safe in LT recipients., Competing Interests: Conflicts of interest The authors have no conflicts of interest to disclose, (Copyright © 2022 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: To analyze the incidence of type 2 diabetes (T2D) in Central Spain and its association with the socioeconomic status (SES), educational level, and other risk factors (RF) in the elderly population of three communities., Methods: Data for 5278 elderly participants (≥65 years old) were obtained using a census population-based survey. There was a first and a second survey three years later. The association between SES, educational level, RF, and T2D incidence was analyzed., Results: The incidence rate for T2D was 9.8/1000 person-years without gender differences. Incident T2D was associated with low SES and lower educational levels. Baseline and follow-up BMI were also the main RFs for T2D. Communities' incidence rates were: (1) Margarita, working-class area: 11.3/1000 person-years; (2) Arévalo, agricultural region: 10.1/1000 person-years and; (3) Lista, professional high-income class area: 7.6/1000 person-years., Conclusion: We found an incidence rate of 9.8/1000 person-years of T2D in the elderly population. The risk of T2D was associated with a lower income and educational level. An increase in BMI may mediate this association. Our results emphasize the necessity of strategies for the prevention of diabetes that includes an approach to SES, educational levels, and other RF among older individuals in Spanish community settings., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The Sierra Nevada de Santa Marta (SNSM) is a mountain range in northern Colombia, recognized for its high biological richness. To date, the existence of 27 species of tardigrades is known for this particular region. Morphological and morphometric analysis of 51 specimens, found in 16 samples of bryophytes and lichens collected at the SNSM, and deposited in the tardigrade collection of the "Centro de Colecciones Científicas de la Universidad del Magdalena" between 2011 and 2016 was carried out. The species Mixibius gibbosus sp. nov. is described based on the following main traits: presence of gibbosities (up to date never reported for any species of the genus Mixibius), isodiametric tubercles and relevant morphometric differences with respect to the most similar congeneric species. Additionally, the species Diphascon pingue pingue sensu lato, Hypsibius cf. allisoni and Adropion onorei are, for the first time, recorded for Colombia and the latter is recorded for the first time out of Ecuador. All records are new for the SNSM.

Neurons are the largest known cells, with complex and highly polarized morphologies and consist of a cell body (soma), several dendrites, and a single axon. The establishment of polarity necessitates initial axonal outgrowth in concomitance with the addition of new membrane to the axon's plasmalemma. Axolemmal expansion occurs by exocytosis of plasmalemmal precursor vesicles primarily at the neuronal growth cone membrane. The multiprotein exocyst complex drives spatial location and specificity of vesicle fusion at plasma membrane. However, the specific participation of its different proteins on neuronal differentiation has not been fully established. In the present work we analyzed the role of Sec3, a prominent exocyst complex protein on neuronal differentiation. Using mice hippocampal primary cultures, we determined that Sec3 is expressed in neurons at early stages prior to neuronal polarization. Furthermore, we determined that silencing of Sec3 in mice hippocampal neurons in culture precluded polarization. Moreover, using in utero electroporation experiments, we determined that Sec3 knockdown affected cortical neurons migration and morphology during neocortex formation. Our results demonstrate that the exocyst complex protein Sec3 plays an important role in axon formation in neuronal differentiation and the migration of neuronal progenitors during cortex development., (© 2021 International Society for Neurochemistry.)

During gestation, stress exposure increases the risk of developing cognitive and physiological alterations in either the long or short term. Among them, metabolic alterations have been described. Adipose tissue is responsible for the secretion of several factors involved in controlling body weight and energy expenditure, the regulation of insulin sensitivity, and the development of inflammation, among others. Moreover, the liver regulates glucose homeostasis and lipid metabolism, playing an essential role in developing insulin resistance. In this work, we analyzed if prenatal stress leads to alterations in metabolism and the relationship between these alterations and gene expression in the adipose tissue and the liver. Prenatal stress-exposed animals developed disturbances in the glucose and insulin response curve, showing in both tests higher glycemia than the control group. However, they did not exhibit increased body weight. At the same time, in the adipose tissue, we observed an increase in mRNA expression of Leptin and Resistin and a decrease in Adiponectin . In the liver, we observed a lower mRNA expression of several genes involved in glucose metabolism and fatty acid oxidation, such as Sirt1, Pgc1α, Pparα, among others. In both tissues, we observed a lower expression of inflammatory genes. These results suggest that prenatal stress exposure produces insulin resistance at both physiological and molecular levels without pro-inflammatory signaling or obesity.

Prenatal insults during fetal development result in increased likelihood of developing chronic disease. Obesity, the biggest risk factor for the development of metabolic disease, is affected by several genetic and environmental factors. High-fat diet (HFD) consumption is usually linked with the development of obesity. The main goal of this study was to analyze the impact of the exposure to a HFD in prenatally stressed animals. For this purpose, we subjected pregnant BALB/c mice to restraint stress for 2 h a day between gestational day (GD) 14 and GD 21. Prenatally stressed and control offspring of both sexes were postnatally exposed to a HFD for 24 weeks. We found that prenatal stress (PS) per se produced disturbances in males such as increased total blood cholesterol and triglycerides, with a decrease in mRNA expression of sirtuin-1. When these animals were fed a HFD, we observed a rise in glucose and insulin levels and an increase in visceral adipose tissue gene expression of leptin, resistin, and interleukin-1 beta. Although females proved to be more resilient to PS consequences, when they were fed a HFD, they showed significant metabolic impairment. In addition to the changes observed in males, females also presented an increase in body weight and adiposity and a rise in cholesterol levels.

Neurodegenerative diseases (NDD) are disorders characterized by the progressive loss of neurons affecting motor, sensory, and/or cognitive functions. The incidence of these diseases is increasing and has a great impact due to their high morbidity and mortality. Unfortunately, current therapeutic strategies only temporarily improve the patients' quality of life but are insufficient for completely alleviating the symptoms. An interaction between the immune system and the central nervous system (CNS) is widely associated with neuronal damage in NDD. Usually, immune cell infiltration has been identified with inflammation and is considered harmful to the injured CNS. However, the immune system has a crucial role in the protection and regeneration of the injured CNS. Nowadays, there is a consensus that deregulation of immune homeostasis may represent one of the key initial steps in NDD. Dr. Michal Schwartz originally conceived the concept of "protective autoimmunity" (PA) as a well-controlled peripheral inflammatory reaction after injury, essential for neuroprotection and regeneration. Several studies suggested that immunizing with a weaker version of the neural self-antigen would generate PA without degenerative autoimmunity. The development of CNS-related peptides with immunomodulatory neuroprotective effect led to important research to evaluate their use in chronic and acute NDD. In this review, we refer to the role of PA and the potential applications of active immunization as a therapeutic option for NDD treatment. In particular, we focus on the experimental and clinical promissory findings for CNS-related peptides with beneficial immunomodulatory effects., (© 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

People who do not eat enough fruit and vegetables (F&V) have incremental health risks. Most Europeans do not comply with health recommendations relating to F&V consumption and this is especially true for those with lower-level education, which reinforces structural inequalities in health and wellbeing among Europeans. This study investigated the role of key behavioural triggers - capabilities, opportunities and motivation (in the COM-B model) - as pathways for educational differentials in F&V intake in Europe. A cross-sectional survey-based study was conducted in five European countries differing widely in their consumption habits, wealth, and climatic conditions. A structural equation model was designed to study how capabilities (diet perceived knowledge, health purchase criteria), opportunities (financial availability, social norms), and motivations (health value, habits strength) affect educational inequalities in the intake of F&V (5 portions a day) as mediators. Multi-group comparisons assessed country differences. People with higher levels of education were more likely to eat the recommended diet, i.e., at least 5 portions of F&V a day. Countries in the sample vary significantly in the percentage of people complying with the recommendation, but not significantly in terms of relative education differentials. The educational gap in the intake of F&V is mainly explained by education differentials in financial availability, diet knowledge, and habits in inserting F&V in main meals. Policies targeting dietary inequalities should address behavioural triggers affecting dietary intake, for example by subsidising F&V, developing targeted dietary awareness campaigns, or by intervening in mass catering contexts to facilitate the implementation of healthy habits., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cisplatin is one of the most widely used chemotherapeutic agents in oncology, although its nephrotoxicity limits application and dosage. We present the results of a clinical study on prophylaxis of cisplatin-induced nephrotoxicity in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC-cisplatin). Prophylaxis was with imipenem/cilastatin. Cilastatin is a selective inhibitor of renal dehydropeptidase I in the proximal renal tubule cells that can reduce the nephrotoxicity of cisplatin. Unfortunately, cilastatin is not currently marketed alone, and can only be administered in combination with imipenem. The study has a retrospective part that serves as a control ( n = 99 patients receiving standard surgical prophylaxis) and a prospective part with imipenem/cilastatin prophylaxis corresponding to the study group ( n = 85 patients). In both groups, we collected specific data on preoperative risk factors of renal damage, fluid management, hemodynamic control, and urine volume during surgery (including the hyperthermic chemotherapy perfusion), as well as data on hemodynamic and renal function during the first seven days after surgery. The main finding of the study is that cilastatin may exert a nephroprotective effect in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal cisplatin perfusion. Creatinine values remained lower than in the control group (ANOVA test, p = 0.037). This translates into easier management of these patients in the postoperative period, with significantly shorter intensive care unit (ICU) and hospital stay.

Ataxias are one of the most frequent complaints in Neurogenetics units worldwide. Currently, more than 50 subtypes of spinocerebellar ataxias and more than 60 recessive ataxias are recognized. We conducted an 11-year prospective, observational, analytical study in order to estimate the frequency of pediatric and adult genetic ataxias in Argentina, to describe the phenotypes of this cohort and evaluate the diagnostic yield of the algorithm used in our unit. We included 334 ataxic patients. Our diagnostic approach was successful in one-third of the cohort. A final molecular diagnosis was reached in 113 subjects. This rate is significantly higher in the subgroup of patients with a positive family history, where the diagnostic yield increased to 55%. The most prevalent dominant and recessive ataxias in Argentina were SCA-2 (36% of dominant ataxias) and FA (62% of recessive ataxias), respectively. Next generation sequencing-based assays were diagnostic in the 65% of the patients requiring these tests. These results provide relevant epidemiological information, bringing a comprehensive knowledge of the most prevalent subtypes of genetic ataxias and their phenotypes in our territory and laying the groundwork for rationally implementing genetic diagnostic programs for these disorders in our country.

Portal hypertension is the main consequence of liver cirrhosis, leading to severe complications such as variceal hemorrhage, ascites or hepatic encephalopathy. As an attempt to decompress the portal venous system, portal flow is derived into the systemic venous system through spontaneous portosystemic shunts (SPSSs), bypassing the liver. In this review, we aim to provide an overview of the published reports in relation to the prevalence and physiopathology behind the appearance of SPSS in liver cirrhosis, as well as the complications derived from its formation and its management. The role of SPSS embolization is specifically discussed, as SPSSs have been assessed as a therapeutic target, mainly for patients with recurrent/persistent hepatic encephalopathy and preserved liver function. Furthermore, different aspects of the role of SPSS in liver transplantation, as well as in candidates for transjugular intrahepatic portosystemic shunt are reviewed. In these settings, SPSS occlusion has been proposed to minimize possible deleterious effects, but results are so far inconclusive., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

The on-surface synthesis of edge-functionalized graphene nanoribbons (GNRs) is challenged by the stability of the functional groups throughout the thermal reaction steps of the synthetic pathway. Edge fluorination is a particularly critical case in which the interaction with the catalytic substrate and intermediate products can induce the complete cleavage of the otherwise strong C-F bonds before the formation of the GNR. Here, we demonstrate how a rational design of the precursor can stabilize the functional group, enabling the synthesis of edge-fluorinated GNRs. The survival of the functionalization is demonstrated by tracking the structural and chemical transformations occurring at each reaction step with complementary X-ray photoelectron spectroscopy and scanning tunneling microscopy measurements. In contrast to previous attempts, we find that the C-F bond survives the cyclodehydrogenation of the intermediate polymers, leaving a thermal window where GNRs withhold more than 80% of the fluorine atoms. We attribute this enhanced stability of the C-F bond to the particular structure of our precursor, which prevents the cleavage of the C-F bond by avoiding interaction with the residual hydrogen originated in the cyclodehydrogenation. This structural protection of the linking bond could be implemented in the synthesis of other sp 2 -functionalized GNRs.

Context: As a part of interstellar dust, polycyclic aromatic hydrocarbons (PAHs) are processed by the interaction with vacuum ultra-violet (VUV) photons that are emitted by hot young stars. This interaction leads to the emission of the well-known aromatic infrared bands but also of electrons, which can significantly contribute to the heating of the interstellar gas., Aims: Our aim is to investigate the impact of molecular size on the photoionization properties of cationic PAHs., Methods: Trapped PAH cations of sizes between 30 and 48 carbon atoms were submitted to VUV photons in the range of 9 to 20 eV from the DESIRS beamline at the synchrotron SOLEIL. All resulting photoproducts including dications and fragment cations were mass-analyzed and recorded as a function of photon energy., Results: Photoionization is found to be predominant over dissociation at all energies, which differs from an earlier study on smaller PAHs. The photoionization branching ratio reaches 0.98 at 20 eV for the largest studied PAH. The photoionization threshold is observed to be between 9.1 and 10.2 eV, in agreement with the evolution of the ionization potential with size. Ionization cross sections were indirectly obtained and photoionization yields extracted from their ratio with theoretical photoabsorption cross sections, which were calculated using time-dependent density functional theory. An analytical function was derived to calculate this yield for a given molecular size., Conclusions: Large PAH cations could be efficiently ionized in H i regions and provide a contribution to the heating of the gas by photoelectric effect. Also, at the border of or in H ii regions, PAHs could be exposed to photons of energy higher than 13.6 eV. Our work provides recipes to be used in astronomical models to quantify these points.

The new genus of the macrobiotoid family Richtersiidae Guidetti, Rebecchi, Bertolani, Jönsson, Kristensen Cesari, 2016 Crenubiotus gen. nov. is described, based on Crenubiotus crenulatus comb. nov. (Richters, 1904a) and on Colombian specimens formerly attributed to Macrobiotus cf. crenulatus and here described, after re-examination, as Crenubiotus revelator sp. nov. The new genus is characterised by an additional ventral thickening on the anterior portion of the ventral lamina, dorsal apophysis absent or very reduced, modified stylet furcae, claws equal in structure to those of Richtersius Pilato Binda, 1989, and very probably also Adorybiotus Maucci Ramazzotti, 1981 and Diaforobiotus Guidetti, Rebecchi, Bertolani, Jönsson, Kristensen Cesari, 2016; and, in the known species, cuticular pores, two macroplacoids, large well dentate lunules and a characteristic egg. The new species Crenubiotus revelator sp. nov. differs from Crenubiotus crenulatus comb. nov. in having smaller cuticular pores, a medio-ventral tooth in the buccal armature, more slender buccal tube, slightly more caudal stylet supports, slightly more slender claws, and in details of the egg. The description of the new genus, and new observations on Adorybiotus, Richtersius and Diaforobiotus, allowed the authors to complete the morphological scenario within the family Richtersiidae giving further support to such family.

Differentiation of neuronal cells is crucial for the development and function of the nervous system. This process involves high rates of membrane expansion, during which the synthesis of membrane lipids must be tightly regulated. In this work, using a variety of molecular and biochemical assays and approaches, including immunofluorescence microscopy and FRET analyses, we demonstrate that the proto-oncogene c-Fos (c-Fos) activates cytoplasmic lipid synthesis in the central nervous system and thereby supports neuronal differentiation. Specifically, in hippocampal primary cultures, blocking c-Fos expression or its activity impairs neuronal differentiation. When examining its subcellular localization, we found that c-Fos co-localizes with endoplasmic reticulum markers and strongly interacts with lipid-synthesizing enzymes, whose activities were markedly increased in vitro in the presence of recombinant c-Fos. Of note, the expression of c-Fos dominant-negative variants capable of blocking its lipid synthesis-activating activity impaired neuronal differentiation. Moreover, using an in utero electroporation model, we observed that neurons with blocked c-Fos expression or lacking its AP-1-independent activity fail to initiate cortical development. These results highlight the importance of c-Fos-mediated activation of lipid synthesis for proper nervous system development., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Rodríguez-Berdini et al.)

The opening up of green spaces could provide significant benefits to society. This study develops a framework to assess the economic benefits and costs of public interventions providing citizen access to urban green spaces. The Thinking Fadura project in Getxo (Spain) was used as a case study. A method for participatory benefit-cost analysis is developed, where a stakeholder-participatory evaluation is combined with a standard cost-benefit analysis. The participatory evaluation followed a bottom-up approach in a sequential evaluation including three main focal points: key stakeholders and experts, visitors and the general public. The assessment demonstrates that the Thinking Fadura project's benefits outweigh the costs. The results suggest that projects designed with the purpose of improving green space accessibility to the general public can be beneficial from a societal perspective. The highest economic benefits were an increase in the amenity and recreational value and an increase in people's physical activity. The participatory evaluation indicates that giving access to people of lower socio-economic status and vulnerable groups and improving recreational use were perceived as the most beneficial. An increase in noise, dirt, and risk of criminal activities as well as potential conflicts between green space users were perceived as the most negative impacts of opening a previously restricted area to the general public. The economic assessment of Thinking Fadura project could serve as a model in the decision-making process in locations where the use of greenspaces is restricted., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Gastrointestinal stromal tumor (GIST) initiation and evolution is commonly framed by KIT/PDGFRA oncogenic activation, and in later stages by the polyclonal expansion of resistant subpopulations harboring KIT secondary mutations after the onset of imatinib resistance. Thus, circulating tumor (ct)DNA determination is expected to be an informative non-invasive dynamic biomarker in GIST patients., Methods: We performed amplicon-based next-generation sequencing (NGS) across 60 clinically relevant genes in 37 plasma samples from 18 GIST patients collected prospectively. ctDNA alterations were compared with NGS of matched tumor tissue samples (obtained either simultaneously or at the time of diagnosis) and cross-validated with droplet digital PCR (ddPCR)., Results: We were able to identify cfDNA mutations in five out of 18 patients had detectable in at least one timepoint. Overall, NGS sensitivity for detection of cell-free (cf)DNA mutations in plasma was 28.6%, showing high concordance with ddPCR confirmation. We found that GIST had relatively low ctDNA shedding, and mutations were at low allele frequencies. ctDNA was detected only in GIST patients with advanced disease after imatinib failure, predicting tumor dynamics in serial monitoring. KIT secondary mutations were the only mechanism of resistance found across 10 imatinib-resistant GIST patients progressing to sunitinib or regorafenib., Conclusions: ctDNA evaluation with amplicon-based NGS detects KIT primary and secondary mutations in metastatic GIST patients, particularly after imatinib progression. GIST exhibits low ctDNA shedding, but ctDNA monitoring, when positive, reflects tumor dynamics.

Introduction and Objectives: Leukodystrophies and genetic leukoencephalopathies constitute a vast group of pathologies of the cerebral white matter. The large number of etiopathogenic genes and the frequent unspecificity on the clinical-radiological presentation generate remarkable difficulties in the diagnosis approach. Despite recent and significant developments, molecular diagnostic yield is still less than 50%. Our objective was to develop and explore the usefulness of a new diagnostic procedure using standardized molecular diagnostic tools, and next-generation sequencing techniques., Materials and Methods: A prospective, observational, analytical study was conducted in a cohort of 46 patients, evaluated between May 2008 and December 2016, with a suspected genetic leukoencephalopathy or leukodystrophy. A diagnostic procedure was set up using classical monogenic tools in patients with characteristic phenotypes, and next-generation techniques in nonspecific ones., Results: Global diagnostic procedure yield was 57.9%, identifying the etiological pathogenesis in 22 of the 38 studied subjects. Analysis by subgroups, Sanger method, and next-generation sequencing showed a yield of 64%, and 46.1% respectively. The most common pathologies were adrenoleukodystrophy, cerebral autosomal-dominant arteriopathy with subcortical infarcts (CADASIL), and vanishing white matter disease., Conclusions: Our results confirm the usefulness of the proposed diagnostic procedure expressed in a high diagnostic yield and suggest a more optimal cost-effectiveness in an etiological analysis phase., (© 2019 John Wiley & Sons Ltd/University College London.)

This article aims at exploring, understanding and comparing European citizens' insights and perceptions towards "My life between realities", a positive future scenario which depicts a narrative of reaching healthier, more equitable and sustainable societies by 2040 with the support of technology and technological solutions. It responds to the need for gathering and incorporating more citizen insights into future policy developments and strategic actions to tackle the global challenge of unsustainable development. Citizens of five European countries-the Czech Republic, Germany, North Macedonia, Spain and the United Kingdom-have been consulted through focus groups. The exercise has uncovered citizens' preferences and attitudes towards four main lifestyle areas; namely, green spaces, energy efficient housing, active mobility and (food) consumption. The technological attributes of the scenario led to citizens expressing diametrically opposed and critical perceptions and attitudes. Given the prospects of technology in driving sustainable development, based on these insights, policy recommendations for the better integration and acceptance of technological advances by the public are discussed herein.

PROVE is a Portuguese program that empowers small-scale farmers organized into local networks to directly commercialize baskets of locally produced fruits and vegetables to consumers. This study applied a post-test-only non-equivalent group design to evaluate the resulting influence on the social empowerment of farmers and on consumer diets. The method included conducting a survey of PROVE farmers ( n = 36) and a survey of PROVE consumers ( n = 294) that were compared against matched samples of Portuguese respondents of international surveys (European Social Survey , n = 36 and the INHERIT Five-Country Survey, n = 571, respectively). PROVE farmers reported higher scores for perceived influence on the work environment than the national sample. PROVE consumers were more likely to eat five or more portions of fruits and vegetables a day in comparison to the matched sample of Portuguese citizens (average odds ratio: 3.05, p < 0.05). Being a PROVE consumer also generated an impact on the likelihood of consuming no more than two portions of red meat a week (average odds ratio: 1.56, p < 0.05). The evaluation study suggests that the promotion of short supply chains of fruits and vegetables can make a positive contribution to a healthier, more sustainable, and fairer future in food consumption., Competing Interests: : The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

The world's challenges of climate change, damage to ecosystems, and social and health inequalities require changes in human behaviours at every level of organisation, among governments, business, communities, and individuals. An important question is how behaviour change can be enabled and supported at the scale and speed required. The research reported in this paper describes important lessons for good practice in changing contexts to modify behaviours for a triple win for health, equity and environmental sustainability. Authors synthesised learning from qualitative, quantitative and cost benefit evaluations of 15 case studies conducted in 12 countries in Europe. The case studies address ways of living (green spaces and energy efficient housing), moving (active transport) and consuming (healthy and sustainable diets) that support the triple win. Ten lessons for good practice were identified. These include bringing a triple win mindset to policy and practice in planning interventions, with potential to improve environmental sustainability, health and equity at the same time. The lessons for good practice are intended to support governmental and non-governmental actors, practitioners and researchers planning to work across sectors to achieve mutual benefits for health and environmental sustainability and in particular to benefit poorer and more socio-economically disadvantaged groups., Competing Interests: The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Urbanization, costs of green space maintenance, and diminishing connection between people and nature all exert pressures on urban green space. This is regrettable as green space has the potential to create wins for environmental sustainability, health, and health equity. This paper explores this potential triple win and investigates how to increase the use of urban green space through behavior change. A narrative literature review was conducted and was supplemented with literature suggested by experts. Results show that creating well-designed green spaces and stimulating people to use them can indeed deliver this triple win. Providing accessible, attractive, well-maintained green space with room for socialization, and where people feel safe, may increase the opportunity and motivation of people to use it more often. Informing and educating people and organizing activities may increase capability (and motivation) to use green space. Since the use of green space depends on life stage, lifestyle factors and individual values, it is important to involve potential users in its design. We recommend a specific focus on those groups who may benefit most from the use of green space. More evaluation is needed to inform effective green space interventions and to assess related economic, social, and environmental benefits.

A new genus of Itaquasconinae, Meplitumen gen. nov. , and a new species, Meplitumenaluna sp. nov. , are described. The new genus has characters present in other genera of Itaquasconinae but in a unique combination. The spiral thickening of the bucco-pharyngeal tube is also present anteriorly to the insertion point of the stylet supports, excluding only the short portion where the apophyses for the insertion of the stylet muscles (AISM) are present. This character is similar to Astatumen Pilato, 1997 but Meplitumen gen. nov. differs from this genus as stylet furcae are shaped differently and as stylet supports and placoids are present. The presence of a spiral thickening in a portion of the buccal tube anterior to the stylet supports distinguishes the new genus from Mesocrista Pilato, 1987, Platicrista Pilato, 1987 and Itaquascon de Barros, 1939. Meplitumen gen. nov. also differs from Mesocrista , in having the caudal processes of the AISM pointing laterally (instead of postero-laterally), and the apices of the caudal processes of the stylet furcae unswollen. From Itaquascon the new genus also differs by having more robust stylet supports, pharyngeal bulb with placoids, stylet furcae differently shaped. Meplitumen gen. nov. also differs from Platicrista in having caudal processes of the AISM more robust and not flexible, and more slender stylet supports. The new species, Meplitumenaluna sp. nov. , has a cuticle with a very faint roughness at the caudal extremity of the body, and eyes probably absent. The pharyngeal bulb is long, with two long, narrow, rod-shaped macroplacoids; a microplacoid and septulum are absent. The claws are well developed with main branches provided with accessory points, and at the base of the claws, a structure interpretable as a very thin lunule is present. Other cuticular thickenings on the legs are absent.

The water supply for human consumption in the Chaco-Pampean region in Argentina is restricted by the low quality of groundwater due to elevated concentrations of arsenic and other trace elements. Previous studies indicated a complex concurrence of factors and processes that are believed responsible to control the distribution of arsenic in groundwater. For a better understanding of the origin of trace elements in the Pampean aquifer, flow-through experiments with loess and calcrete samples representative of the sediments that constitute the aquifer were carried out in continuous flow reactors. The aqueous solutions were collected and the concentrations of SiO 2 (aq), Ca 2+ , SO 4 2- , Na + , Cl - , F - and trace elements (Ba, Sr, V, and As) were measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES), high performance liquid chromatography (HPLC) and capillary electrophoresis. The experiments showed differences in the release rate of elements to the solution according to the type of sediment. The highest concentrations of V, Ba, and As were measured in experiments conducted with loess, and these elements were released quickly to the solution in the first minute of the test. In the case of loess, V and As are suggested to be adsorbed on the solid particles surface. Conversely, the experiments conducted with calcrete showed a lower but continuous release of those elements. This last result may indicate that the trace elements were coprecipitated in the calcite. In addition, it was demonstrated that F did not come from the dissolution of minerals such as fluorapatite, but both desorption from solid surface and dissolution from calcite minerals account for the release of F. This study support that both dissolution and adsorption-desorption processes can control the mobility of trace elements, with an emphasis on the role of calcrete in the retention and the mobilization of trace elements in the Pampean aquifer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mexico is one of the five largest producers of papaya worldwide, but losses caused by pathogens, mainly fungus, at the pre- and post-harvest stages are often more than 50% of the crop. Papaya anthracnose, caused by three different species of the Colletotrichum genus in Mexico, occupies a preponderant place in this problem. Although two of these species, C. gloeosporiodes and C. truncatum, have been characterized morphologically and genotypically, this has not occurred with C. magnum, the third species involved, about which there is very little information. Because of this, it is vital to know its genetic characterization, much more so considering that the studies carried out on the other two species reveal a wide genetic diversity, differences in pathogenicity and in the response to fungicides of the different strains characterized. In this work, Colletotrichum spp. isolates were collected at different papaya orchards in the south-southeast of Mexico. C. magnum isolates identified by species-specific primers were characterized by morphological and molecular approaches. Differences in colony characteristics resulted in five morphological groups. AP-PCR, DAMD and ISSR markers were found to be very efficient for revealing the interspecific variability of this species. The high genetic variability found in the accessions of C. magnum was linked to the geographical area where they were collected. Isolates from Chiapas State were the most variable, showing point mutations in the ITS1-ITS2 region. These results will enable a better phytosanitary management of anthracnose in papaya in this region of Mexico.

This paper addresses the impact that changes in natural ecosystems can have on health and wellbeing focusing on the potential co-benefits that green spaces could provide when introduced as climate change adaptation measures. Ignoring such benefits could lead to sub-optimal planning and decision-making. A conceptual framework, building on the ecosystem-enriched Driver, Pressure, State, Exposure, Effect, Action model (eDPSEEA), is presented to aid in clarifying the relational structure between green spaces and human health, taking climate change as the key driver. The study has the double intention of (i) summarising the literature with a special emphasis on the ecosystem and health perspectives, as well as the main theories behind these impacts, and (ii) modelling these findings into a framework that allows for multidisciplinary approaches to the underlying relations between human health and green spaces. The paper shows that while the literature based on the ecosystem perspective presents a well-documented association between climate, health and green spaces, the literature using a health-based perspective presents mixed evidence in some cases. The role of contextual factors and the exposure mechanism are rarely addressed. The proposed framework could serve as a multidisciplinary knowledge platform for multi-perspecitve analysis and discussion among experts and stakeholders, as well as to support the operationalization of quantitative assessment and modelling exercises., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The use of stress ulcer prophylaxis (SUP) has risen in recent years, even in patients without a clear indication for therapy., Aim: To evaluate the efficacy of an electronic medical record (EMR)-based alarm to improve appropriate SUP use in hospitalized patients., Methods: We conducted an uncontrolled before-after study comparing SUP prescription in intensive care unit (ICU) patients and non-ICU patients, before and after the implementation of an EMR-based alarm that provided the correct indications for SUP., Results: 1627 patients in the pre-intervention and 1513 patients in the post-intervention cohorts were included. The EMR-based alarm improved appropriate (49.6% vs. 66.6%, p<0.001) and reduced inappropriate SUP use (50.4% vs. 33.3%, p<0.001) in ICU patients only. These differences were related to the optimization of SUP in low risk patients. There was no difference in overt gastrointestinal bleeding between the two cohorts. Unjustified costs related to SUP were reduced by a third after EMR-based alarm use., Conclusions: The use of an EMR-based alarm improved appropriate and reduced inappropriate use of SUP in ICU patients. This benefit was limited to optimization in low risk patients and associated with a decrease in SUP costs., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

The need for analysis and action across the interrelated domains of human behaviors and lifestyles, environmental sustainability, health and inequality is increasingly apparent. Currently, these areas are often not considered in conjunction when developing policies or interventions, introducing the potential for suboptimal or conflicting outcomes. The INHERIT model has been developed within the EU-funded project INHERIT as a tool to guide thinking and intersectoral action towards changing the behaviors and lifestyles that play such an important role in today&rsquo;s multidisciplinary challenges. The model integrates ecological public health and behavioral change models, emphasizing inequalities and those parts of the causal process that are influenced by human behaviors and lifestyles. The model was developed through web-based and live discussions with experts and policy stakeholders. To test the model&rsquo;s usability, the model was applied to aspects of food consumption. This paper shows that the INHERIT model can serve as a tool to identify opportunities for change in important &minus;food-related behaviors and lifestyles and to examine how they impact on health, health inequalities, and the environment in Europe and beyond. The INHERIT model helps clarify these interrelated domains, creating new opportunities to improve environmental health and health inequality, while taking our planetary boundaries into consideration.

Here we present a new method that integrates atomic force microscopy (AFM) with analytical tools such as high-performance liquid chromatography (HPLC) with diode-array ultraviolet-visible (UV) absorbance, and mass spectrometry (MS) along with synthetic chemistry. This allows the detection, identification, and quantification of novel polycyclic aromatic hydrocarbons (PAH) in complex molecular mixtures. This multidisciplinary methodology is employed to characterize the supercritical pyrolysis products of n-decane, a model fuel. The pyrolysis experiments result in a complex mixture of both unsubstituted as well as highly methylated PAH. We demonstrate the AFM-driven discovery of a novel compound, benz[ l]indeno[1,2,3- cd]pyrene, with the chemical structure assignment serving as input for the chemical synthesis of such molecule. The synthesis is verified by AFM, and the synthesized compound is used as a reference standard in analytical measurements, establishing the first-ever unequivocal identification and quantification of this PAH as a fuel product. Moreover, the high-resolution AFM analysis detected several five- to eight-ring PAH, which represents novel fuel pyrolysis and/or combustion products. This work provides a route to develop new analytical standards by symbiotically using AFM, chemical synthesis, and modern analytical tools.

The metal-catalyzed [2+2+2] cocycloaddition of arynes with pyramidalized alkenes is presented. The generation of a highly reactive pyramidalized alkene in the presence of a large excess of in situ-produced arynes led to the corresponding cocyclotrimerization (1 : 2)-adducts in good yields, establishing the first example of a palladium-based reaction of a pyramidalized alkene.

Here, will review current evidence regarding the signaling pathways and mechanisms underlying membrane addition at sites of active growth during axon formation. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 170-180, 2018., (© 2017 Wiley Periodicals, Inc.)