Serpine1 mRNA confers mesenchymal characteristics to the cell and promotes CD8+ T cells exclusion from colon adenocarcinomas.

Serine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression and plays a crucial role in metastasis. Here, we solve this apparent paradox and report that Serpine1 mRNA per se, independent of its protein-coding function, confers mesenchymal properties to the cell, promoting migration, invasiveness, and resistance to anoikis and increasing glycolytic activity by sequestering miRNAs. Expression of Serpine1 mRNA upregulates the expression of the TRA2B splicing factor without affecting its mRNA levels. Through transcriptional profiling, we found that Serpine1 mRNA expression downregulates through TRA2B the expression of genes involved in the immune response. Analysis of human colon tumor samples showed an inverse correlation between SERPINE1 mRNA expression and CD8+ T cell infiltration, unveiling the potential value of SERPINE1 mRNA as a promising therapeutic target for colon tumors.

Involvement of CB1 and CB2 receptors in neuroprotective effects of cannabinoids in experimental TDP-43 related frontotemporal dementia using male mice.

BACKGROUND: The elevation of endocannabinoid levels through inhibiting their degradation afforded neuroprotection in CaMKIIα-TDP-43 mice, a conditional transgenic model of frontotemporal dementia. However, which cannabinoid receptors are mediating these benefits is still pending to be elucidated. METHODS: We have investigated the involvement of the CB1 and the CB2 receptor using chronic treatments with selective ligands in CaMKIIα-TDP-43 mice, analysis of their cognitive deterioration with the Novel Object Recognition test, and immunostaining for neuronal and glial markers in two areas of interest in frontotemporal dementia. RESULTS: Our results confirmed the therapeutic value of activating either the CB1 or the CB2 receptor, with improvements in the animal performance in the Novel Object Recognition test, preservation of pyramidal neurons, in particular in the medial prefrontal cortex, and attenuation of glial reactivity, in particular in the hippocampus. In addition, the activation of both CB1 and CB2 receptors reduced the elevated levels of TDP-43 in the medial prefrontal cortex of CaMKIIα-TDP-43 mice, an effect exerted by mechanisms that are currently under investigation. CONCLUSIONS: These data reinforce the notion that the activation of CB1 and CB2 receptors may represent a promising therapy against TDP-43-induced neuropathology in frontotemporal dementia. Future studies will have to confirm these benefits, in particular with one of the selective CB2 agonists used here, which has been thoroughly characterized for clinical development.

Learning analytics for enhanced professional capital development: a systematic review.

Background/Motivation: This article presents a systematic review aimed at examining the utilization of learning analytics (LA) to enhance teachers' professional capital. Aim: The study focuses on three primary research questions: (1) exploring the characteristics and approaches of LA in professional capital, (2) investigating suggestions from LA for assessing and improving professional capital, and (3) examining variables studied in enhancing the most intricate dimension of professional capital using LA. Methodology: To address the research objectives, a systematic review was conducted focusing on the key concepts "learning analytics" and "professional capital." Following the procedures outlined encompassed in four stages: identification, screening, inclusion, and adequacy. The PRISMA 2009 protocol guided the systematic review process. Principal findings: The findings of the study underscore the efficacy of LA as a catalyst for improving professional capital, particularly through collaborative learning and the utilization of tools like forums and online learning platforms. Social capital emerges as a pivotal component in integrating diverse types of professional capital, fostering opportunities for knowledge creation and social networking. Conclusion/Significance: In conclusion, the study highlights the paramount significance of addressing teachers' professional capital development through collaborative approaches and leveraging technology, particularly in primary education. The article concludes by emphasizing the imperative for more research and knowledge dissemination in this field, aiming to ensure equity in learning and address the challenges posed by the COVID-19 pandemic.

Effects of Minimalist vs. Traditional Running Shoes on Abdominal Lumbopelvic Muscle Activity in Women Running at Different Speeds: A Randomized Cross-Over Clinical Trial.

This study aimed to investigate if the characteristics of different running shoes could influence intra-abdominal pressure during running. A single-centre, randomized, prospective cross-over clinical trial was performed measuring activity patterns of internal oblique (IO), lumbar erector (LE), and gluteus maximus (GM) muscles in healthy women when running with minimalist shoes (MS). Participants were randomly allocated into two-sequence (MS/TS or TS/MS) treadmill running at six, nine, and eleven km/h. The surface electromyographic activity of IO, LE, and GM muscles were recorded while running. A repeated measures ANOVA explored the interaction effects of three-muscle x three speeds x two shoes. Significance was set at p ≤ 0.05. Fifty-one healthy nulliparous women (mean age: 26.55 ± 5.11 years; body mass index: 21.29 ± 2.07 Kg/m2) were included. Our findings revealed lower activations of the LE compared to the internal oblique IO and GM, irrespective of running speed and footwear used. Electromyographic activation significantly increased with higher running speeds (p < 0.001) for all muscles, regardless of the type of footwear. Although electromyographic records with MS consistently showed higher values than those with TS, the differences were not statistically significant for all muscles at all speeds. Our results indicate that electromyographic activation patterns vary according to the muscle group, exhibiting higher values with increased running speed. No significant differences were observed between MS and TS.

From Alzheimer's disease to vascular dementia: Different roads leading to cognitive decline.

LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

Safety, Efficacy, and Cost-effectiveness of Outpatient Surgery for Uncomplicated Acute Appendicitis: The PENDI-CSI Randomized Clinical Trial.

OBJECTIVE: To evaluate the safety, efficacy, and cost-effectiveness of outpatient appendectomy in patients with uncomplicated acute appendicitis. BACKGROUND: Given that acute appendicitis is the most common cause of acute abdomen, the introduction of outpatient appendectomy protocols could significantly improve the effectiveness and sustainability of health care systems. METHODS: A total of 300 patients were enrolled from October 2018 to June 2021 in the PENDI-CSI randomized clinical trial: 149 were assigned to the outpatient surgery (OPS) group and 151 to the inpatient surgery (IPS) group, followed by 1 month postoperatively. All patients were aged older than 14 years and had uncomplicated acute appendicitis. Exclusion criteria were pregnancy, neoplasms, inflammatory bowel disease, and high anesthetic risk (ASA IV). The OPS group was discharged from the postanesthesia care unit while the IPS group was admitted. RESULTS: In total, 128 patients in the OPS group (85.9%) were discharged without admission. Predictors whether patients in the OPS group had to be admitted were aged over 31 years [relative risk (RR): 2.42 (1.04-5.65)], hypertension [RR: 6.21 (3.22-11.97)], anesthetic risk II-III [RR: 2.63 (1.17-5.94)], previous abdominal surgery [RR: 3.34 (1.55-7.20)], postoperative pain with visual analog scale >6 [RR: 4.28 (2.67-6.86)], and postoperative fear [RR: 2.2 (1.04-4.67)]. There were no differences in terms of complications, readmissions, and reinterventions, and the perceived quality was similar in both groups. The outpatient modality produced savings of €1 034.97 per patient ( P < 0.001). CONCLUSIONS: Outpatient appendectomy is safe and effective for uncomplicated acute appendicitis. Patient-perceived quality is similar to that of IPS, although it successfully reduces hospital costs compared with inpatient appendectomy.

Validation of the Spanish version of the five-item General Self-Efficacy (GSE) scale in a sample of nursing students: Evidence of validity, reliability, longitudinal invariance and changes in general self-efficacy and resilience in a two-wave cross-lagged panel model.

AIM: The aim of this study is to validate the Spanish version of the five-item General Self-Efficacy scale in a sample of nursing students, by: 1) offering evidence of validity and reliability; 2) studying the longitudinal measurement invariance of the scale; 3) providing evidence on the changes in the levels of self-efficacy that occur after one year of nursing education; and 4) offering longitudinal evidence on the relationship between nursing students' self-efficacy and resilience levels. BACKGROUND: Nurses' general self-efficacy has been related to both personal and organizational outcomes. In Spain, some competencies the students must acquire during the Degree in Nursing implicitly refer to self-efficacy. For the measurement of general self-efficacy, the General Self-Efficacy Scale is one of the most widely used in Europe. DESIGN: A longitudinal design was used. Research took place at the University of Valencia and the University of the Balearic Islands (Spain). Participants were 324 nursing students, in the first year of the Nursing Degree. METHODS: The five-item General Self-Efficacy scale and the Brief Resilience Coping Scale were used. Analyses included descriptive statistics, reliability estimates, confirmatory factor analysis, a longitudinal measurement invariance routine and several competing cross-lagged models. RESULTS: Evidence of reliability shown by the scale was adequate and a one-factor solution for the structure was found. Additionally, the five-item GSE showed evidence of invariance over time. A causal effect of self-efficacy on nursing students' levels of resilience was found. CONCLUSIONS: The Spanish version of the five-item General Self-Efficacy scale is a brief instrument that can contribute to the assessment of some of the basic competencies of the Degree in Nursing, which improve during their education and how these changes are related to other skills important for the nursing profession, such as resilience.

Fast relocking and afterslip-seismicity evolution following the 2015 Mw 8.3 Illapel earthquake in Chile.

Large subduction earthquakes induce complex postseismic deformation, primarily driven by afterslip and viscoelastic relaxation, in addition to interplate relocking processes. However, these signals are intricately intertwined, posing challenges in determining the timing and nature of relocking. Here, we use six years of continuous GNSS measurements (2015-2021) to study the spatiotemporal evolution of afterslip, seismicity and locking after the 2015 Illapel earthquake ([Formula: see text] 8.3). Afterslip is inverted from postseismic displacements corrected for nonlinear viscoelastic relaxation modeled using a power-law rheology, and the distribution of locking is obtained from the linear trend of GNSS stations. Our results show that afterslip is mainly concentrated in two zones surrounding the region of largest coseismic slip. The accumulated afterslip (corresponding to [Formula: see text] 7.8) exceeds 1.5 m, with aftershocks mainly occurring at the boundaries of the afterslip patches. Our results reveal that the region experiencing the largest coseismic slip undergoes rapid relocking, exhibiting the behavior of a persistent velocity weakening asperity, with no observed aftershocks or afterslip within this region during the observed period. The rapid relocking of this asperity may explain the almost regular recurrence time of earthquakes in this region, as similar events occurred in 1880 and 1943.

Kidney transplant to vesicostomy: A safe strategy for children with end stage renal disease and lower urinary tract anomalies.

INTRODUCTION: Resolution of underlying urinary tract anomalies prior to kidney transplantation in patients with end stage renal disease (ESRD) secondary to uropathy, has been historically supported under the argument that this would help prevent infectious complications and graft loss. We propose to perform earlier kidney transplantation with a transient vesicostomy, deferring resolution of the uropathy to the post-transplantation period. The aim of this study was to evaluate the outcomes of kidney transplantation in children with a vesicostomy. MATERIAL AND METHODS: A retrospective, multicenter study was performed including all patients under 18 years of age who underwent kidney transplantation with a vesicostomy, between January 2005 and December 2020 and had at least one year of follow up. Data related with the indication and timing of vesicostomy, time until transplantation, post-transplantation complications, urinary tract infections (UTI) and graft survival rate were collected. RESULTS: Of the 758 transplantations performed in the study period, 16 patients met the inclusion criteria. Mean age at transplantation was 58 months (range 20-151), and mean weight was 13.5 Kg (range 8.4-20). Mean time from vesicostomy to kidney transplantation was 30 months (range 0-70). There were 2 (12.5%) ureteral complications that required reoperation. Eighteen episodes of UTI were identified in 8 patients (50%), accounting for 0.4 UTIs per patient-year of follow-up. UTIs did not lead to graft loss in any of the cases. Urinary tract reconstruction was performed in 5 patients (31.3%) at an interval of 1-91 months post-transplantation. After a mean follow-up of 44.8 months (range 13-200) from transplantation, patients with vesicostomy had a mean creatinine clearance of 86.6 ml/min/1.73 m2, with a mean serum creatinine level of 0.6 mg/dl. Graft survival rate was 100%. DISCUSSION: Early kidney transplantation into a vesicostomy permits a resolution of the ESRD, avoiding deleterious effects related to dialysis. With a low rate of UTIs, we found no graft loss due to infectious complications. This strategy permits careful planning and better timing for the urinary tract reconstruction without delaying kidney transplantation. CONCLUSION: Kidney transplantation in pediatric patients with vesicostomy seems to be a safe and effective strategy. UTI rate was similar to that reported in the literature of patients with corrected urinary anomalies undergoing kidney transplantation without urinary diversion.

Personalized additive manufacturing of devices for the management of enteroatmospheric fistulas.

Additive manufacturing techniques allow the customized design of medical devices according to the patient's requirements. Enteroatmospheric fistula is a pathology that benefits from this personalization due to its extensive clinical variability since the size and morphology of the wound differ extensively among patients. Standard prosthetics do not achieve proper isolation of the wound, leading to a higher risk of infections. Currently, no effective personalized technique to isolate it has been described. In this work, we present the workflow for the design and manufacture of customized devices adapted to the fistula characteristics as it evolves and changes during the treatment with Negative Pressure Wound Therapy (NPWT). For each case, a device was designed with dimensions and morphology depending on each patient's requirements using white light scanning, CAD design, and additive manufacturing. The design and manufacture of the devices were performed in 230.50 min (184.00-304.75). After the placement of the device, the wound was successfully isolated from the intestinal content for 48-72 h. The therapy was applied for 27.71 ± 13.74 days, and the device was redesigned to adapt to the wound when geometrical evolutionary changes occur during the therapy. It was observed a decrease in weekly cures from 23.63 ± 10.54 to 2.69 ± 0.65 (p = 0.001). The fistulose size was reduced longitudinal and transversally by 3.25 ± 2.56 cm and 6.06 ± 3.14 cm, respectively. The wound depth also decreased by 1.94 ± 1.08 cm. In conclusion, customization through additive manufacturing is feasible and offers promising results in the generation of personalized devices for the treatment of enteroatmospheric fistula.

Effect of immunology biomarkers associated with hip fracture and fracture risk in older adults.

Osteoporosis is a skeletal disease that can increase the risk of fractures, leading to adverse health and socioeconomic consequences. However, current clinical methods have limitations in accurately estimating fracture risk, particularly in older adults. Thus, new technologies are necessary to improve the accuracy of fracture risk estimation. In this observational study, we aimed to explore the association between serum cytokines and hip fracture status in older adults, and their associations with fracture risk using the FRAX reference tool. We investigated the use of a proximity extension assay (PEA) with Olink. We compared the characteristics of the population, functional status and detailed body composition (determined using densitometry) between groups. We enrolled 40 participants, including 20 with hip fracture and 20 without fracture, and studied 46 cytokines in their serum. After conducting a score plot and two unpaired t-tests using the Benjamini-Hochberg method, we found that Interleukin 6 (IL-6), Lymphotoxin-alpha (LT-α), Fms-related tyrosine kinase 3 ligand (FLT3LG), Colony stimulating factor 1 (CSF1), and Chemokine (C-C motif) ligand 7 (CCL7) were significantly different between fracture and non-fracture patients (p < 0.05). IL-6 had a moderate correlation with FRAX (R2 = 0.409, p < 0.001), while CSF1 and CCL7 had weak correlations with FRAX. LT-α and FLT3LG exhibited a negative correlation with the risk of fracture. Our results suggest that targeted proteomic tools have the capability to identify differentially regulated proteins and may serve as potential markers for estimating fracture risk. However, longitudinal studies will be necessary to validate these results and determine the temporal patterns of changes in cytokine profiles.

Development of a liver graft assessment expert machine-learning system: when the artificial intelligence helps liver transplant surgeons.

Background: The complex process of liver graft assessment is one point for improvement in liver transplantation. The main objective of this study is to develop a tool that supports the surgeon who is responsible for liver donation in the decision-making process whether to accept a graft or not using the initial variables available to it. Material and method: Liver graft samples candidate for liver transplantation after donor brain death were studied. All of them were evaluated "in situ" for transplantation, and those discarded after the "in situ" evaluation were considered as no transplantable liver grafts, while those grafts transplanted after "in situ" evaluation were considered as transplantable liver grafts. First, a single-center, retrospective and cohort study identifying the risk factors associated with the no transplantable group was performed. Then, a prediction model decision support system based on machine learning, and using a tree ensemble boosting classifier that is capable of helping to decide whether to accept or decline a donor liver graft, was developed. Results: A total of 350 liver grafts that were evaluated for liver transplantation were studied. Steatosis was the most frequent reason for classifying grafts as no transplantable, and the main risk factors identified in the univariant study were age, dyslipidemia, personal medical history, personal surgical history, bilirubinemia, and the result of previous liver ultrasound (p < 0.05). When studying the developed model, we observe that the best performance reordering in terms of accuracy corresponds to 76.29% with an area under the curve of 0.79. Furthermore, the model provides a classification together with a confidence index of reliability, for most cases in our data, with the probability of success in the prediction being above 0.85. Conclusion: The tool presented in this study obtains a high accuracy in predicting whether a liver graft will be transplanted or deemed non-transplantable based on the initial variables assigned to it. The inherent capacity for improvement in the system causes the rate of correct predictions to increase as new data are entered. Therefore, we believe it is a tool that can help optimize the graft pool for liver transplantation.

Urological outcome with the use of salvage continent vesicostomy in pediatric reconstructive surgery. A single tertiary center experience.

PURPOSE: To report our experience and results in terms of complications, reoperation rate and urinary continence with the Salvage Continent Vesicostomy (SCV) technique in pediatric patients with history or need of enterocystoplasty and absent appendix. METHODS: Retrospective review of all patients with a history of a continent catheterizable channel surgery performed in our institution between June 2016 and January 2022. Only patients with a SCV surgery with a minimum 6-month post operative follow up were included in this cohort and divided in group 1 (history of previous bladder augmentation) and group 2 (simultaneous bladder augmentation and SCV). Primary outcome of the study was to assess both continence and postoperative complication rates. Early complications were assessed using the Clavien-Dindo classification (I-V). Late complications were focused on the need of further subfascial revision. RESULTS: 84 patients with a history of a continent stoma creation surgery were identified. In 20 of them (12 males) a SCV was performed. The mean age at surgery was 10.38 (range 4.87-15.6) years and the median postoperative follow-up time was 32 (range 6-64) months. Eleven patients were included in Group 1, while 9 patients in Group 2. Early complications occurred in 4 patients (20%), two of them required a re-intervention (Clavien-Dindo IIIb). Stoma subfascial revision was further required in 2 patient (10%). Continence rate at last follow up was 95%. CONCLUSIONS: In our early experience, the salvage continent vesicostomy has proven to be a simple continent stoma technique with acceptable both continence and complication rates that can be used in selected patients with a history or need of bladder augmentation and absent appendix.

The Cannabigerol Derivative VCE-003.2 Exerts Therapeutic Effects in 6-Hydroxydopamine-Lesioned Mice: Comparison with The Classic Dopaminergic Replacement Therapy.

(1) Background: A cannabigerol aminoquinone derivative, so-called VCE-003.2, has been found to behave as a neuroprotective agent (administered both i.p. and orally) in different experimental models of Parkinson's disease (PD) in mice. These effects were exerted through mechanisms that involved the activation of a regulatory site within the peroxisome proliferator-activated receptor-γ (PPAR-γ). (2) Methods: We are now interested in comparing such neuroprotective potential of VCE-003.2, orally administered, with the effect of the classic dopaminergic replacement therapy with L-DOPA/benserazide in similar conditions, using 6-hydroxydopamine-lesioned mice. (3) Results: The oral administration of VCE-003.2 during 14 days at the dose of 20 mg/kg improved, as expected, the neurological status (measured in motor tests) in these mice. This correlated with a preservation of TH-labelled neurons in the substantia nigra. By contrast, the treatment with L-DOPA/benserazide (during 7 days at 2 mg/kg) was significantly less active in these experimental conditions, in concordance with their profile as a mere symptom-alleviating agent. (4) Conclusions: Our results confirmed again the therapeutic profile of VCE-003.2 in experimental PD and revealed a different and more relevant effect, as a disease modifier, compared to the classic symptom-alleviating L-DOPA treatment. This reinforces the interest in VCE-003.2 for a future clinical development in this disease.

Diseño de un nuevo indicador de mortalidad en el síndrome coronario agudo al ingreso en la Unidad de Cuidados Intensivos / Design of a new mortality indicator in acute coronary syndrome on admission to the Intensive Care Unit

Objetivo: Diseñar un indicador de mortalidad del síndrome coronario agudo (SCA) en el servicio de medicina intensiva (SMI). Diseño: Estudio descriptivo observacional multicéntrico. Participantes: Pacientes con SCA ingresados en SMI incluidos en el registro ARIAM- SEMICYUC entre enero del 2013 y abril del 2019. Intervenciones: Ninguna. Variables de interés principales: Las variables analizadas fueron demográficas, tiempo de acceso al sistema sanitario y estado clínico. Se analizó la terapia de revascularización, los fármacos y la mortalidad. Se realizó un análisis de regresión logística de COX y posteriormente se diseñó una red neuronal. Se elaboró una curva ROC para calcula la potencia del nuevo score. Finalmente, la utilidad clínica o relevancia del indicador ARIAM se evaluará mediante un gráfico de Fagan. Resultados: Se incluyó a 17.258 pacientes, con una mortalidad al alta del SMI del 3,5% (605). Las variables analizadas con significación estadística (p<0,001) fueron introducidas en el modelo predictivo supervisado, una red neuronal artificial. El nuevo indicador ARIAM mostro una media de 0,0257 (IC del 95%, 0,0245-0,0267) en los pacientes dados de alta de UCI y de 0,27085 (IC del 95%, 0,2533-0,2886) en los que fallecieron, p <0,001. El área ROC del modelo conseguido fue de 0,918 (IC del 95%, 0,907-0,930). En el test de Fagan se demostró que el indicador ARIAM muestra que la probabilidad de fallecimiento es del 19% (IC del 95%, 18-20%) cuando es positivo y del 0,9% (IC del 95%, 0,8-1,01%) cuando es negativo. Conclusiones: Es posible crear un nuevo indicador de mortalidad del SCA en el SMI que sea más exacto, reproducible y actualizable periódicamente. (AU)

Objective: To design a mortality indicator for acute coronary syndrome (ACS) in the intensive care unit (ICU). Design: Multicenter observational descriptive study. Participants: ACS patients admitted to SMI included in the ARIAM-SEMICYUC registry between January 2013 and April 2019. Interventions: None. Main variables of interest: Variables analyzed were demographic, time of access to the health system, and clinical condition. Revascularization therapy, drugs, and mortality were analyzed. A COX regression analysis was performed and subsequently a neural network was designed. An ROC curve was developed to calculate the power of the new score. Finally, the clinical utility or relevance of the ARIAM's indicator will be evaluated using a Fagan test. Results: 17,258 patients were included, with a 3.5% (605) mortality at discharge from the ICU. The variables analyzed with statistical significance (p<0.001) were entered into the supervised predictive model, an artificial neural network. The new ARIAM's indicator showed a mean of 0.0257 (95% CI: 0.0245–0.0267) in patients discharged from the ICU and 0.27085 (95% CI: 0.2533–0.2886) in those who died, p<0.001. The ROC area of the model achieved was 0.918 (95% CI: 0.907–0.930). The Fagan test showed that the ARIAM's Indicator shows that the probability of death is 19% (95% CI: 18%–20%) when it is positive and 0.9% (95% CI: 0.8%–1.01%) when it is negative. Conclusions: It is possible to create a new mortality indicator for ACS in the ICU that is more accurate, reproducible, and periodically updated. (AU)

BtuB TonB-dependent transporters and BtuG surface lipoproteins form stable complexes for vitamin B12 uptake in gut Bacteroides.

Vitamin B12 (cobalamin) is required for most human gut microbes, many of which are dependent on scavenging to obtain this vitamin. Since bacterial densities in the gut are extremely high, competition for this keystone micronutrient is severe. Contrasting with Enterobacteria, members of the dominant genus Bacteroides often encode several BtuB vitamin B12 outer membrane transporters together with a conserved array of surface-exposed B12-binding lipoproteins. Here we show that the BtuB transporters from Bacteroides thetaiotaomicron form stable, pedal bin-like complexes with surface-exposed BtuG lipoprotein lids, which bind B12 with high affinities. Closing of the BtuG lid following B12 capture causes destabilisation of the bound B12 by a conserved BtuB extracellular loop, causing translocation of the vitamin to BtuB and subsequent transport. We propose that TonB-dependent, lipoprotein-assisted small molecule uptake is a general feature of Bacteroides spp. that is important for the success of this genus in colonising the human gut.

Predictability of the community-function landscape in wine yeast ecosystems.

Predictively linking taxonomic composition and quantitative ecosystem functions is a major aspiration in microbial ecology, which must be resolved if we wish to engineer microbial consortia. Here, we have addressed this open question for an ecological function of major biotechnological relevance: alcoholic fermentation in wine yeast communities. By exhaustively phenotyping an extensive collection of naturally occurring wine yeast strains, we find that most ecologically and industrially relevant traits exhibit phylogenetic signal, allowing functional traits in wine yeast communities to be predicted from taxonomy. Furthermore, we demonstrate that the quantitative contributions of individual wine yeast strains to the function of complex communities followed simple quantitative rules. These regularities can be integrated to quantitatively predict the function of newly assembled consortia. Besides addressing theoretical questions in functional ecology, our results and methodologies can provide a blueprint for rationally managing microbial processes of biotechnological relevance.

Bronchogenic Cyst: Lessons Learned in 20 Years of Experience at a Tertiary Pediatric Center.

BACKGROUND: Bronchogenic cysts are benign congenital malformations of the primitive ventral foregut. The aim of this study is to analyze and report 20 years of experience in the diagnosis and treatment of bronchogenic cysts at a tertiary pediatric center. METHODS: A retrospective review was conducted of all patients diagnosed with a bronchogenic cyst between 2000-2020. Presence of symptoms, cyst location, surgical technique, postoperative complications, need for pleural drainage, and recurrence were reviewed. RESULTS: Forty-five children were included in the study. In 37 patients a partial resection of the cyst was done, followed by cauterization or chemical obliterateration with iodopovidone of the mucosa of the remaining cyst wall that was adherent to the airway. A lobectomy was done in patients who had intrapulmonary cysts (n = 8). Cyst location was subcarinal in 23 (51.1%), paratracheal in 14 (31.1%), and intrapulmonary in eight patients (17.8%). The majority of subcarinal and paratracheal cysts (90%) were approached by thoracoscopy. Complications occurred in seven patients (15%): subcutaneous emphysema after pleural drain removal in one, extubation failure in two, reoperation due to bleeding in one, surgical site infection in one, bronchopleural fistula in one, and pneumothorax in one. Reoperation due to cyst recurrence was necessary in two patients (4.4%). Mean follow-up was 56 months (range, 0-115). CONCLUSION: A minimally invasive approach is a safe option for the management of paratracheal and subcarinal bronchogenic cysts with no history of infection in specialized pediatric surgery center. Thoracoscopic partial resection is a feasible option in most patients with subcarinal and paratracheal bronchogenic cysts with a low complication and reoperation rate. LEVEL OF EVIDENCE: IV.

Repetitive ambulatory levosimendan as a bridge to heart transplantation.

INTRODUCTION AND OBJECTIVES: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. METHODS: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. RESULTS: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients' clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). CONCLUSIONS: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations.

Disease-modifying effects of cannabidiol, ß-caryophyllene and their combination in Syn1-Cre/Scn1aWT/A1783V mice, a preclinical model of Dravet syndrome.

Cannabidiol (CBD) has been recently approved as an antiseizure agent in Dravet Syndrome (DS), a pediatric epileptic encephalopathy, but CBD could also be active against associated comorbidities. Such associated comorbidities were also attenuated by the sesquiterpene ß-caryophyllene (BCP). Here, we have compared the efficacy of both compounds and further initiated the analysis of a possible additive effect between both compounds in relation with these comorbidities using two experimental approaches. The first experiment was aimed at comparing the benefits of CBD and BCP, including their combination in conditional knock-in Scn1a-A1783V mice, an experimental model of DS, treated since the postnatal day 10th to 24th. As expected, DS mice showed impairment in limb clasping, delay in the appearance of hindlimb grasp reflex and additional behavioural disturbances (e.g., hyperactivity, cognitive deterioration, social interaction deficits). This behavioural impairment was associated with marked astroglial and microglial reactivities in the prefrontal cortex and the hippocampal dentate gyrus. BCP and CBD administered alone were both able to partially attenuate the behavioural disturbances and the glial reactivities, with apparently greater efficacy against glial reactivities obtained with BCP, whereas superior effects in a few specific parameters were obtained when both compounds were combined. In the second experiment, we investigated this additive effect in cultured BV2 cells treated with BCP and/or CBD and stimulated with LPS. As expected, addition of LPS induced a marked increase in several inflammation-related markers (e.g., TLR4, COX-2, iNOS, catalase, TNF-α, IL-1ß), as well as elevated Iba-1 immunostaining. Treatment with BCP or CBD attenuated these elevations, but, again and in general, superior results were obtained when both cannabinoids were combined. In conclusion, our results support the interest to continue investigating the combination of BCP and CBD to improve the therapeutic management of DS in relation with their disease-modifying properties.