Integrated transcriptomic landscape of the effect of anti-steatotic treatments in high-fat diet mouse models of non-alcoholic fatty liver disease.

High-fat diet (HFD) mouse models are widely used in research to develop medications to treat non-alcoholic fatty liver disease (NAFLD), as they mimic the steatosis, inflammation, and hepatic fibrosis typically found in this complex human disease. The aims of this study were to identify a complete transcriptomic signature of these mouse models and to characterize the transcriptional impact exerted by different experimental anti-steatotic treatments. For this reason, we conducted a systematic review and meta-analysis of liver transcriptomic studies performed in HFD-fed C57BL/6J mice, comparing them with control mice and HFD-fed mice receiving potential anti-steatotic treatments. Analyzing 21 studies broaching 24 different treatments, we obtained a robust HFD transcriptomic signature that included 2,670 differentially expressed genes and 2,567 modified gene ontology biological processes. Treated HFD mice generally showed a reversion of this HFD signature, although the extent varied depending on the treatment. The biological processes most frequently reversed were those related to lipid metabolism, response to stress, and immune system, whereas processes related to nitrogen compound metabolism were generally not reversed. When comparing this HFD signature with a signature of human NAFLD progression, we identified 62 genes that were common to both; 10 belonged to the group that were reversed by treatments. Altered expression of most of these 10 genes was confirmed in vitro in hepatocytes and hepatic stellate cells exposed to a lipotoxic or a profibrogenic stimulus, respectively. In conclusion, this study provides a vast amount of information about transcriptomic changes induced during the progression and regression of NAFLD and identifies some relevant targets. Our results may help in the assessment of treatment efficacy, the discovery of unmet therapeutic targets, and the search for novel biomarkers. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The current landscape of antifibrotic therapy across different organs: A systematic approach.

Fibrosis is a common pathological process that can affect virtually all the organs, but there are hardly any effective therapeutic options. This has led to an intense search for antifibrotic therapies over the last decades, with a great number of clinical assays currently underway. We have systematically reviewed all current and recently finished clinical trials involved in the development of new antifibrotic drugs, and the preclinical studies analyzing the relevance of each of these pharmacological strategies in fibrotic processes affecting tissues beyond those being clinically studied. We analyze and discuss this information with the aim of determining the most promising options and the feasibility of extending their therapeutic value as antifibrotic agents to other fibrotic conditions.

Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry.

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Determinant factors for first-line treatment choice and effectiveness in pediatric eosinophilic esophagitis: an analysis of the EUREOS EoE CONNECT registry.

This study compared short-term effectiveness of proton pump inhibitors (PPI), swallowed topical corticosteroids (STC), and dietary therapies in reversing clinical and histological features in pediatric patients with eosinophilic esophagitits (EoE). Determinants for treatment choice and PPI therapy effectiveness were also assessed.  A cross-sectional study analysis of patients under 18 years old recruited onto the multicenter EoE CONNECT registry was performed. Clinico-histological response was defined as symptomatic improvement plus a peak eosinophil count below 15 per high-power field after treatment. Effectiveness of first-line options used in monotherapy was compared. Overall, 393 patients (64% adolescents) receiving PPI, STC, or dietary monotherapy to induce EoE remission were identified. PPI was the preferred option (71.5%), despite STC providing the highest clinico-histological response rates (66%) compared to PPI (44%) and diet (42%). Logistic regression identified fibrotic features and recruitment at Italian sites independently associated to first-line STC treatment; age under 12 associated to dietary therapy over other options. Analysis of 262 patients in whom PPI effectiveness was evaluated after median (IQR) 96 (70-145) days showed that this effectiveness was significantly associated with management at pediatric facilities and use of high PPI doses. Among PPI responders, decrease in rings and structures in endoscopy from baseline was documented, with EREFS fibrotic subscore for rings also decreasing among responders (0.27 ± 0.63 vs. 0.05 ± 0.22, p < 0.001). Conclusion: Initial therapy choice for EoE depends on endoscopic phenotype, patient's age, and patients' origin. High PPI doses and treatment in pediatric facilities significantly determined effectiveness, and reversed fibrotic endoscopic features among responders. What is Known: • Proton pump inhibitors are widely used to induce and maintain remission in EoE in real practice, despite other first-line alternative therapies possibly providing higher effectiveness. What is New: • Proton pump inhibitors represent up to two-thirds of first-line monotherapies used to induce EoE remission in pediatric and adolescent patients with EoE. The choice of STC as first-line treatment for EoE was significantly associated with fibrotic features at baseline endoscopy and recruitment in Italian centers; age less than 12 years was associated with dietary therapy. • PPI effectiveness was found to be determined by use of high doses, attendance at pediatric facilities, presenting inflammatory instead of fibrotic or mixed phenotypes, and younger age. Among responders, PPI therapy reversed both inflammatory and fibrotic features of EoE after short-term treatment.

Exploring adolescents' experiences of continuing to wear face masks during COVID-19: A qualitative descriptive study in Barcelona (Spain).

BACKGROUND: The COVID-19 pandemic prompted the use of face masks as a social distancing measure. Although evidence supports their effectiveness in preventing infection, it remains unclear why some adolescents choose to continue wearing them postpandemic, even when it is no longer mandatory. This study aims to explore adolescents' experiences of wearing face masks during the COVID-19 pandemic when their use was no longer mandatory. METHOD: In this exploratory qualitative study, data were collected from 16 adolescents through face-to-face semistructured interviews. The participants were asked about the reasons and feelings associated with continuing to wear masks, as well as the contexts in which they felt safe without a mask. The collected data were analysed using Braun and Clarke's thematic analysis. RESULTS: Three main themes were identified: (1) Navigating complex decision-making: balancing safety and self-image, (2) peer influence dynamics and (3) managing the future: weather dynamics and pandemic evolution. DISCUSSION: The potential implications of withdrawing COVID-19 preventive measures, such as mask-wearing, beyond the pandemic remain understudied. It is crucial to further investigate the perceptions related to wearing masks and its cessation, especially amongst vulnerable individuals. PATIENT OR PUBLIC CONTRIBUTION: Due to methodological constraints associated with participants' age, they were not engaged in the design, data analysis, data interpretation or manuscript preparation phases of the study.

Exertional Stress-induced Pathogenic Luminal Content Translocation - Friend or Foe?

The incidence of perturbed gastrointestinal integrity, as well as resulting systemic immune responses and gastrointestinal symptoms, otherwise known as exercised-induced gastrointestinal syndrome (EIGS), is common among individuals who partake in prolonged exercise. EIGS may cause the translocation of pathogenic material, including whole bacteria and bacterial endotoxins, from the lumen into circulation, which may progress into clinical consequences such as sepsis, and potentially subsequent fatality. However, further investigation is warranted to assess the possibility of food allergen and/or digestive enzyme luminal to circulatory translocation in response to exercise, and the clinical consequences. Findings from this narrative literature review demonstrate evidence that whole bacteria and bacterial endotoxins translocation from the gastrointestinal lumen to systemic circulation occurs in response to exercise stress, with a greater propensity of translocation occurring with accompanying heat exposure. It has also been demonstrated that food allergens can translocate from the lumen to systemic circulation in response to exercise stress and initiate anaphylaxis. To date, no research investigating the effect of exercise on the translocation of digestive enzymes from the lumen into systemic circulation exists. It is evident that EIGS and consequential pathogenic translocation presents life-threatening clinical implications, warranting the development and implementation of effective management strategies in at-risk populations.

Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain. AIM: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg). METHODS: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection. RESULTS: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection. CONCLUSIONS: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety.

Antidepressant and Neuroprotective Effects of 3-Hydroxy Paroxetine, an Analog of Paroxetine in Rats.

BACKGROUND: Paroxetine (PX) is a widely used antidepressant with side effects such as weakness, dizziness, and trouble sleeping. In search of novel compounds with better efficacy and fewer side effects, we synthesized 3HPX, a hydroxylated analog of PX, and compared the 2 in silico for their pharmacokinetic and binding properties and in vivo for their antidepressant and potential neuroprotective effects. METHODS: In silico studies compared pharmacological properties as well as interactions of PX and 3HPX with the serotonin transporter. In vivo studies utilized an animal model of comorbid depression-Parkinson disease. Adult male Wistar rats were injected (sterotaxically) with lipopolysaccharide in the striatum (unilaterally), followed by 14 days of once-daily injections (i.p.) of 10 mg/kg PX or 3HPX. Animals were tested for motor asymmetry and locomotor activity as well as indices of anhedonia and helplessness using sucrose preference and forced swim tests, respectively. Brains of these animals were collected after the last test, and tyrosine hydroxylase-positive neurons in substantia nigra pars compacta and Iba-1-positive stained microglia in ipsilateral striatum were measured. RESULTS: In silico findings indicated that 3HPX could bind stronger to serotonin transporter and also have a better clearance and hence less toxicity compared with PX. In vivo results revealed a more effective reversal of immobility in the swim test, substantial increase in tyrosine hydroxylase-positive cells in the substantia nigra pars compacta, and more ramified Iba-1+ cells by 3HPX compared with PX. CONCLUSION: The findings suggest superior effectiveness of 3HPX as an antidepressant and neuroprotectant compared with PX and hence potential utility in Parkinson disease depression co-morbidity.

Implementation of a vascular access specialist team in a tertiary hospital: a cost-benefit analysis.

BACKGROUND: The use of peripherally inserted central catheters and midline catheters is growing due to their potential benefits. These devices can increase patient safety and satisfaction while reducing the use of resources. As a result, many hospitals are establishing vascular access specialist teams staffed by nurses who are trained in the insertion and maintenance of these catheters. The objective of the study is to evaluate previously to the implementation whether the benefits of introducing ultrasound-guided peripheral venous catheters, midline catheters and peripherally inserted central catheters compared to current practice by a vascular access specialist team outweigh their costs. METHODS: Cost-benefit analysis from the perspective of the healthcare provider based on administrative data. The study estimates the reduction in resources used when changing the current practice for the use of ultrasound-guided midline and PICC catheters, as well as the additional resources required for their use. RESULTS: The use of an ultrasound-guided device on peripherally inserted central carheter, results in a measurable resource reduction of approximately €31. When 3 peripheral venous catheters are replaced by an ultrasound-guided peripherally inserted central catheter, the saving is €63. Similarly, the use of an ultrasound-guided device on a midline catheter, results in a reduction of €16, while each ultrasound-guided midline catheter replacing 3 peripheral venous catheters results in a reduction of €96. CONCLUSION: The benefits of using ultrasound-guided midline and PICC catheters compared to current practice by introducing a vascular access specialist team trained in the implantation of ultrasound-guided catheters, outweigh its cost mainly because of the decrease in hospital stay due to the lowered risk of phebitis. These results motivate the implementation of the service, adding to previous experience suggesting that it is also preferable from the point of view of patient safety and satisfaction.

The impact of survivorship care plans on adolescent and young adult head and neck cancer survivors and their primary care providers.

PURPOSE: A cross sectional study of adolescent and young adult (AYA) head and neck (H&N) cancer survivors was performed to assess late effects. Survivorship care plans (SCPs) were generated and evaluated by participants and their primary care providers (PCPs). METHODS: AYA H&N survivors who had been discharged over 5 years prior from our institution were assessed in recall consultation by a radiation oncologist. Late effects were assessed and individualized SCPS were created for each participant. Participants completed a survey evaluating the SCP. PCPs were surveyed before the consultation and after evaluating the SCP. RESULTS: 31/36 participants (86%) completed the SCP evaluation. The SCP was considered to be a positive experience for 93% of participants. Most of the AYA participants indicated that the information provided in the SCP helped them understand the need for follow-up to assess late effects (90%). The pre-consultation PCP survey response rate was 13/27 (48%) and only 34% were comfortable in providing survivorship care for AYA H&N cancer patients. The PCP response rate to the survey that accompanied the SCP was 15/27 (55%) and the majority (93%) reported that the SCP would be helpful to care for other AYA and non-AYA cancer survivors in their practice. CONCLUSIONS: Our research suggested that AYA head and neck cancer survivors valued the SCPs as did their PCPs. IMPLICATIONS FOR CANCER SURVIVORS: The introduction of SCPs is likely to help improve survivorship and transitioning of care from the oncology clinic to PCP in this population.

Influence of COVID-19 on treatment adherence and psychological well-being in a sample of hypertensive patients: a cross-sectional study.

OBJECTIVE: The COVID-19 pandemic has caused a global health crisis. This situation has affected the general population, especially the most vulnerable populations such as individuals with cardiovascular diseases. The main objective of this study was to analyse adherence to treatment and psychological well-being in hypertensive patients before and after the COVID-19 lockdown in Spain. METHODS: A cross-sectional study was performed in a Basic Health Area of Toledo, Spain. Adherence and psychological well-being (resilience, self-esteem, and health-related quality of life [HRQoL]) were measured in hypertensive patients, a group of patients before the COVID-19 lockdown and, in another group after the COVID-19 lockdown using a heteroadministered and anonymous questionnaire. A factorial multivariate analysis of variance (MANOVA) was applied for the outcome variables using pre- and post-COVID-19 lockdown assessment, gender, and age (< 65 years-old vs. ≥ 65 years-old) as independent variables. Univariate F follow-up tests were conducted within the multivariate significant overall differences. RESULTS: The sample of the present study included 331 hypertensive patients. The mean age was 67.68 years (SD = 10.94). Women comprise 53.5% of the sample and men account for the remaining 46.5%. A total of 144 questionnaires were collected before the COVID-19 pandemic and 187 questionnaires were collected after the onset of the pandemic and once the lockdown was over. MANOVA showed significant main effects for pandemic lockdown (F = 13.383, p < 0.001,) age group (F = 3.74, p = 0.003) and gender (F = 8.85, p < 0.001). Therapeutic adherence decreased after the lockdown (F = 15.393, p < 0.001). However, scores on resilience (F = 17.771, p < 0.001), self-esteem (F = 4.789, p = 0.029), and physical component of HRQoL (F = 13.448, p < 0.001) increased after the lockdown. Regarding age, the univariate test showed a significant effect for the physical component of HRQoL, with scores decreasing in those aged ≥ 65 years (F = 9.375, p = 0.002). Regarding gender, women scored lower on resilience (F = 20.280 p < 0.001), self-esteem (F = 18.716, p < 0.001), the physical component of HRQoL (F = 5.722, p = 0.017), and the mental component of HRQoL (F = 28.912, p < 0.001). CONCLUSIONS: The COVID-19 pandemic had a negative effect on treatment adherence of hypertensive patients in Spain. However, variables related to psychological well-being have increased in these patients, which may serve as a protective factor against pandemic stress.

Mitochondrial Impairment: A Link for Inflammatory Responses Activation in the Cardiorenal Syndrome Type 4.

Cardiorenal syndrome type 4 (CRS type 4) occurs when chronic kidney disease (CKD) leads to cardiovascular damage, resulting in high morbidity and mortality rates. Mitochondria, vital organelles responsible for essential cellular functions, can become dysfunctional in CKD. This dysfunction can trigger inflammatory responses in distant organs by releasing Damage-associated molecular patterns (DAMPs). These DAMPs are recognized by immune receptors within cells, including Toll-like receptors (TLR) like TLR2, TLR4, and TLR9, the nucleotide-binding domain, leucine-rich-containing family pyrin domain-containing-3 (NLRP3) inflammasome, and the cyclic guanosine monophosphate (cGMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (cGAS-STING) pathway. Activation of these immune receptors leads to the increased expression of cytokines and chemokines. Excessive chemokine stimulation results in the recruitment of inflammatory cells into tissues, causing chronic damage. Experimental studies have demonstrated that chemokines are upregulated in the heart during CKD, contributing to CRS type 4. Conversely, chemokine inhibitors have been shown to reduce chronic inflammation and prevent cardiorenal impairment. However, the molecular connection between mitochondrial DAMPs and inflammatory pathways responsible for chemokine overactivation in CRS type 4 has not been explored. In this review, we delve into mechanistic insights and discuss how various mitochondrial DAMPs released by the kidney during CKD can activate TLRs, NLRP3, and cGAS-STING immune pathways in the heart. This activation leads to the upregulation of chemokines, ultimately culminating in the establishment of CRS type 4. Furthermore, we propose using chemokine inhibitors as potential strategies for preventing CRS type 4.

Varicella zoster virus encephalitis: a potentially serious complication during treatment with vedolizumab.

Vedolizumab is a monoclonal antibody that has demonstrated efficacy and a good safety profile in patients with inflammatory bowel disease. Varicella zoster virus encephalitis is a potentially serious complication not previously described with its use, highlighting the importance of vaccination, as well as early diagnosis and treatment of infections in this type of patients.

Recurrent abdominal pain as the only clinical manifestation of hereditary angioedema type II.

Recurrent abdominal pain is a common reason for consultation in Gastroenterology. The differential diagnosis includes hereditary angioedema (HAE), a rare disorder characterized by recurrent episodes of angioedema, without urticaria or pruritus, which most often affects the skin, but also mucosal tissues of the gastrointestinal tract, triggered by diverse factors such as infections, trauma, surgery, drugs, or stress. It is a disease with a difficult diagnosis due to its heterogeneous and transitory clinical features, so having a clinical suspicion in the appropriate context would allow the administration of a specific treatment and avoid unnecessary examinations. We present the case of a 19-year-old male followed-up for recurrent abdominal pain that, after numerous microbiological, endoscopic, and radiological examinations, complement tests were requested, obtaining low levels of C4 with increased levels of C1 inhibitor and reduced functional activity, being diagnosed with HAE type II.

Ulcerative colitis induced by obinutuzumab in a patient treated for a folicular lymphoma.

An increasing use of immunomodulatory drugs has led to a corresponding increase in treatment-related pathologies such as inflammatory bowel disease. Here, we present a case of ulcerative colitis due to Obinutuzumab, an antiCD20 monoclonal approved for the treatment of Non-Hodgkin lymphomas.

Edaphic properties as pieces of evidence of tailings deposit on soils.

Mine tailings are one of the primary contaminant sources of heavy metals and metalloids in the soil. Besides increasing the concentration of potentially toxic elements (PTEs), tailings may modify the edaphic conditions and decrease the buffer capacity of impacted soils. The influence of tailings may reach distances far from the impoundments depending on the transport path and the specific transport mean: air, rain (runoff and infiltration), or acid mine drainage. In this study, soil samples from various horizons were collected in trial pits along a transect, at different distances from sulfide tailings. Soil analysis included texture, organic matter, alkalinity, porous space, carbonates, pH, electrical conductivity, real density, apparent density, total sulfur, main mineralogy, and total concentrations of As, Cd, Pb, Fe, and Zn. Graphical and statistical interpretation of the results showed that real density and porous space are the leading indicators of the tailings dispersion and accumulation and that pH is not a significant parameter (all values were above the neutrality) due to the limestone abundance in the area. However, Zn and Cd concentrations had an inverse relation with pH. Differences in the concentrations of PTEs between the superficial and deep layers that increased toward the tailings were also observed. Gypsum was only present in the closest samples to the tailings and may also be an indicator of tailings' influence on soils. This study allowed us to identify general edaphic parameters as a first and quick means to determine the tailings contamination of soils.

The Impact of COVID-19 on Adolescents' Mental Health in Catalonia (Spain): A Qualitative Study.

This study aimed to understand the experiences of adolescents regarding the perceived impact of COVID-19 on their mental health in Catalonia (Spain). A qualitative exploratory methodology was used with a purposive sample of 30 high-school students regarding their experiences of the self-perceived impact of COVID-19 on their mental health. Data were thematically analyzed using Braun and Clarke method. Three main themes emerged from the data: (a) the challenge of living confined, (b) the footprint of COVID-19 on adolescents' mental health, and (c) school dynamics during the lockdown. The COVID-19 pandemic negatively impacted adolescents' mental health, and adolescents perceived a lack of emotional support from educational centers. Therefore, incorporating emotional support in educational centers and offering emotional self-management tools to young students should be a priority. School nurses can play an essential role in recognizing and managing emotional needs and being the natural link between educational and primary care centers.

Early inflammatory changes and CC chemokine ligand-8 upregulation in the heart contribute to uremic cardiomyopathy.

Uremic cardiomyopathy is a common complication in chronic kidney disease (CKD) patients, accounting for a high mortality rate. Several mechanisms have been proposed to link CKD and cardiac alterations; however, the early cardiac modifications that occur in CKD that may trigger cardiac remodeling and dysfunction remain largely unexplored. Here, in a mouse model of CKD induced by 5/6 nephrectomy, we first analyzed the early transcriptional and inflammatory changes that occur in the heart. Five days after 5/6 nephrectomy, RNA-sequencing showed the upregulation of 54 genes in the cardiac tissue of CKD mice and the enrichment of biological processes related to immune system processes. Increased cardiac infiltration of T-CD4+ lymphocytes, myeloid cells, and macrophages during early CKD was observed. Next, since CC chemokine ligand-8 (CCL8) was one of the most upregulated genes in the heart of mice with early CKD, we investigated the effect of acute and transient CCL8 inhibition on uremic cardiomyopathy severity. An increase in CCL8 protein levels was confirmed in the heart of early CKD mice. CCL8 inhibition attenuated the early infiltration of T-CD4+ lymphocytes and macrophages to the cardiac tissue, leading to a protection against chronic cardiac fibrotic remodeling, inflammation and cardiac dysfunction induced by CKD. Altogether, our data show the occurrence of transcriptional and inflammatory changes in the heart during the early phases of CKD and identify CCL8 as a key contributor to the early cardiac inflammatory state that triggers further cardiac remodeling and dysfunction in uremic cardiomyopathy.

Functional diversity regulates the effects of habitat degradation on biocrust phylogenetic and taxonomic diversities.

Biocrusts are major contributors to dryland diversity, functioning, and services. However, little is known about how habitat degradation will impact multiple facets of biocrust diversity and measurable functional traits. We evaluated changes in taxonomic, functional, and phylogenetic diversity of biocrust-forming lichens along a habitat degradation gradient related to the presence of linear infrastructure (i.e., a road) and a profound agricultural driven transformation. To do so, we selected 50 remnants of a Mediterranean shrubland. We considered several surrogates of habitat quality and causal disturbance on the various diversity facets of biocrusts by using structural equation modeling, hypothesizing that habitat degradation primarily affects functional diversity, which in turn regulates changes in taxonomic and phylogenetic diversities, and also that taxonomic and phylogenetic diversities are coupled. Fragment connectivity, distance to linear infrastructure (i.e., a road) and, particularly, soil fertility (i.e., soil P concentration), had mostly negative effects on biocrust functional diversity, which in turn affected both taxonomic and phylogenetic diversities. However, we found no direct effects of habitat degradation variables on the taxonomic and phylogenetic diversities. We also found that increases in phylogenetic diversity had a positive effect on taxonomic diversity along the habitat degradation gradient. Our results indicate that functional diversity of biocrusts is strongly affected by habitat degradation, which may profoundly alter their contribution to ecosystem functioning and services. Furthermore, functional diversity regulates the response of biocrust taxonomic and phylogenetic diversity to habitat degradation. These findings indicate that habitat degradation alters and simplifies the diversity of functional traits of biocrust-forming lichens, leading to biodiversity loss, with important consequences for the conservation of global drylands biodiversity.

Association between enrollment in an enhanced recovery program for colorectal cancer surgery and long-term recurrence and survival.

INTRODUCTION: Enhanced Recovery After Surgery (ERAS) programs have been shown to minimize the surgical inflammatory response in colorectal cancer. Our objective was to determine the association between an ERAS program for colorectal cancer surgery and oncologic recurrence and survival. METHODS: A before-after intervention study was designed, including patients who underwent colorectal cancer surgery between November 2010 and March 2016. Cox hazard regression analysis was performed per cumulative year of follow-up to evaluate the association between ERAS program exposure and overall survival. Subgroup analysis was performed by cancer stage (low [I/II] vs. advanced [III/IV]). RESULTS: In total, 646 patients were included, of which 339 were pre-ERAS and 307 were ERAS. Our overall median compliance rate with ERAS interventions was 90% (interquartile range: 85%-95%). Overall survival rates were higher in the ERAS group within the first 2 years after surgery (89.2% vs.  83.2%; p = 0.04). Multivariable analysis revealed that the ERAS enrollment was associated with a significantly lower risk in 5-year oncologic recurrence (adjusted hazard ratio [aHR]: 0.55; 95% confidence interval [CI]: 0.33-0.94; p = 0.03) and higher 3-year survival (aHR: 0.55; 95% CI: 0.33-0.93; p = 0.03) among patients with advanced cancer stage compared to pre-ERAS counterparts. CONCLUSIONS: Patients with advanced colorectal cancer were less likely to suffer oncologic recurrence when managed during the ERAS period.