Translating B cell immunology to the treatment of antibody-mediated allograft rejection.

Antibody-mediated rejection (AMR), including chronic AMR (cAMR), causes ~50% of kidney allograft losses each year. Despite attempts to develop well-tolerated and effective therapeutics for the management of AMR, to date, none has obtained FDA approval, thereby highlighting an urgent unmet medical need. Discoveries over the past decade from basic, translational and clinical studies of transplant recipients have provided a foundation for developing novel therapeutic approaches to preventing and treating AMR and cAMR. These interventions are aimed at reducing donor-specific antibody levels, decreasing graft injury and fibrosis, and preserving kidney function. Innovative approaches emerging from basic science findings include targeting interactions between alloreactive T cells and B cells, and depleting alloreactive memory B cells, as well as donor-specific antibody-producing plasmablasts and plasma cells. Therapies aimed at reducing the cytotoxic antibody effector functions mediated by natural killer cells and the complement system, and their associated pro-inflammatory cytokines, are also undergoing evaluation. The complexity of the pathogenesis of AMR and cAMR suggest that multiple approaches will probably be required to treat these disease processes effectively. Definitive answers await results from large, double-blind, multicentre, randomized controlled clinical trials.

Using Immersive Virtual Reality Distraction to Reduce Fear and Anxiety before Surgery.

Presurgical anxiety is very common and is often treated with sedatives. Minimizing or avoiding sedation reduces the risk of sedation-related adverse events. Reducing sedation can increase early cognitive recovery and reduce time to discharge after surgery. The current case study is the first to explore the use of interactive eye-tracked VR as a nonpharmacologic anxiolytic customized for physically immobilized presurgery patients. Method: A 44-year-old female patient presenting for gallbladder surgery participated. Using a within-subject repeated measures design (treatment order randomized), the participant received no VR during one portion of her preoperative wait and interactive eye-tracked virtual reality during an equivalent portion of time in the presurgery room. After each condition (no VR vs. VR), the participant provided subjective 0-10 ratings and state-trait short form Y anxiety measures of the amount of anxiety and fear she experienced during that condition. Results: As predicted, compared to treatment as usual (no VR), the patient reported having 67% lower presurgical anxiety during VR. She also experienced "strong fear" (8 out of 10) during no VR vs. "no fear" (0 out of 10) during VR. She reported a strong sense of presence during VR and zero nausea. She liked VR, she had fun during VR, and she recommended VR to future patients during pre-op. Interactive VR distraction with eye tracking was an effective nonpharmacologic technique for reducing anticipatory fear and anxiety prior to surgery. The results add to existing evidence that supports the use of VR in perioperative settings. VR technology has recently become affordable and more user friendly, increasing the potential for widespread dissemination into medical practice. Although case studies are scientifically inconclusive by nature, they help identify new directions for future larger, carefully controlled studies. VR sedation is a promising non-drug fear and anxiety management technique meriting further investigation.

Decreased Fatty Acid Oxidation Gene Expression in Pre-Eclampsia According to the Onset and Presence of Intrauterine Growth Restriction.

Mitochondrial fatty acid oxidation (FAO) is lower in placentas with pre-eclampsia. The aim of our study was to compare the placental mRNA expression of FAO enzymes in healthy pregnancies vs. different subgroups of pre-eclampsia according to the severity, time of onset, and the presence of intrauterine growth restriction (IUGR). By using real-time qPCR, we measured the mRNA levels of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), medium-chain acyl-CoA dehydrogenase (MCAD), and carnitine palmitoyltransferases 1A and 2 (CPT1A, CPT2) on the maternal side (anchoring villi in the basal decidua) and on the fetal side (chorionic plate) of the placenta (n = 56). When compared to the controls, LCHAD, MCAD, and CPT2 mRNA had decreased in all pre-eclampsia subgroups globally and on the fetal side. On the maternal side, LCHAD mRNA was also lower in all pre-eclampsia subgroups; however, MCAD and CPT2 mRNA were only reduced in severe and early-onset disease, as well as CPT2 in IUGR (p < 0.05). There were no differences in CPT1A mRNA expression. We conclude that the FAO enzymes mRNA in the placenta was lower in pre-eclampsia, with higher reductions observed in severe, early-onset, and IUGR cases and more striking reductions on the fetal side.

Real-world persistence to first-line DMTs in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: disease-modifying treatments (DMT) for Multiple Sclerosis (MS) have expanded in recent years making the shared-decision process challenging. Moreover, no head-to-head studies are available within the first-line options. Our aim is to compare therapeutic persistence within first-line DMT: teriflunomide (TER), dimethyl fumarate (DMF), and injectable drugs (INJ) in a real-world setting. METHODS: Retrospective observational study analyzing diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) who started DMT between January 2015 and April 2022 (TER=117, DMF=117, INJ=123). Clinical, radiological, and demographic variables were collected. The primary outcome was the median time to discontinuation of any DMT. Dropout was defined as discontinuation for 6 months for any reason. RESULTS: Of the total of 357 patients, 155 withdraw with a median time-to-discontinuation of 1.427 years (IQR 2.410). The discontinuation rate was higher in the injectable group, 49.6%; compared to teriflunomide 40.2%, and dimethyl fumarate 39.8% (p = 0.201). The most frequent reason of discontinuation differs within groups (lack of efficacy in TER, 63.8%, and adverse effects in DMF and INJ (40.4% and 40.9% respectively). No difference in persistence was observed between DMT (p = 0.30). After 2018 there has been a tendency to treat in a quick and early manner (lower EDSS; relapse rate and number of naïve patients), statistically significant for TER (p = 0.005, p = 0.010, and p = 0.045). CONCLUSIONS: Our study demonstrated no differences in persistence between the actual first-line DMT in a real-world setting, although a trend to favor oral-DMT was seen. Reasons for discontinuation differs within groups.

Evolutionarily conserved regulators of tau identify targets for new therapies.

Tauopathies are neurodegenerative diseases that involve the pathological accumulation of tau proteins; in this family are Alzheimer disease, corticobasal degeneration, and chronic traumatic encephalopathy, among others. Hypothesizing that reducing this accumulation could mitigate pathogenesis, we performed a cross-species genetic screen targeting 6,600 potentially druggable genes in human cells and Drosophila. We found and validated 83 hits in cells and further validated 11 hits in the mouse brain. Three of these hits (USP7, RNF130, and RNF149) converge on the C terminus of Hsc70-interacting protein (CHIP) to regulate tau levels, highlighting the role of CHIP in maintaining tau proteostasis in the brain. Knockdown of each of these three genes in adult tauopathy mice reduced tau levels and rescued the disease phenotypes. This study thus identifies several points of intervention to reduce tau levels and demonstrates that reduction of tau levels via regulation of this pathway is a viable therapeutic strategy for Alzheimer disease and other tauopathies.

Revisión de revisiones sobre la eficacia de los tratamientos psicológicos para adolescentes con trastorno de la personalidad límite / Review of reviews on the efficacy of psychological treatments for adolescents with borderline personality disorder

La literatura científica señala que es importante llevar a cabo una intervención psicológica temprana en el trastorno de la personalidad límite (TPL)debido a que en la adolescencia es cuando se observa un mayor auge de los síntomas graves. Sin embargo, existe poca literatura científica sobrequé tratamientos psicológicos son más eficaces para esta población. El objetivo de este trabajo es realizar una revisión de revisiones sobre losdatos de eficacia de los tratamientos psicológicos para adolescentes con rasgos o diagnóstico de TPL o desregulación emocional. Se seleccionaron revisiones que evaluaran la eficacia de tratamientos psicológicos en adolescentes (entre 12 y 19 años) con esta problemática. Se realizó unabúsqueda de literatura científica en diversas bases de datos (Web of Science, PsycInfo, Pubmed, Dialnet) y se incluyeron un total de 5 revisiones.Resultados: La Terapia Dialéctica Comportamental para adolescentes (DBT-A) y la Terapia Basada en la Mentalización para adolescentes (MBT-A)han demostrado su eficacia para reducir la ideación suicida, los síntomas de TPL, los niveles de ansiedad y depresión, así como mejorar la adaptación social y la calidad de vida después de la intervención. Sin embargo, algunas revisiones sugieren que la MBT-A podría no ser tan efectiva debidoa las altas tasas de abandonos. Las intervenciones psicológicas con más evidencia consiguen reducir los síntomas más graves y mejorar la calidadde vida de los adolescentes con este problema. Es fundamental intervenir lo antes posible, lo que ayudará a prevenir el desarrollo y cronicidad deun trastorno grave y difícil de tratar. (AU)

The scientific literature indicatesthat it is important to carry out early psychological intervention in borderline personality disorder (BPD) due to the fact that adolescence is when agreater upsurge of the most severe symptoms is observed. However, there is little scientific literature on which psychological treatments are mosteffective for this population. The aim of this paper is to conduct a review of reviews on the efficacy data of psychological treatments for adolescentswith traits or diagnosis of BPD or emotional dysregulation. We selected reviews that evaluated the efficacy of psychological treatments in adolescents (between 12 and 19 years old) with this problem. A search of scientific literature was carried out in various databases (Web of Science,PsycInfo, Pubmed, Dialnet) and a total of 5 reviews were included. Dialectical Behavior Therapy for Adolescents (DBT-A) and Mentalization-BasedTherapy for Adolescents (MBT-A) have demonstrated efficacy in reducing suicidal ideation, BPD symptoms, anxiety and depression levels, as wellas improving social adjustment and quality of life after the intervention. However, some reviews suggest that MBT-A may not be as effective due tohigh dropout rates. Psychological interventions with more evidence achieve to reduce the most severe symptoms and improve the quality of life ofadolescents with this problem. It is essential to intervene as early as possible, which will help prevent the development and chronicity of a severeand difficult-to-treat disorder. (AU)

El asistente sexual como figura de apoyo para las personas que se encuentran en situación de discapacidad: percepción sobre su reconocimiento jurídico y soporte económico / The Sexual Assistant as a Support Person for the People that Are in a Situation of Disability: Perceptionabout its Legal Recognition and Financial Support

La asistencia sexual, entendida desde un enfoque de derechos humanos, se constituye como la herramienta para que aquellas personas que se encuentran en situación de discapacidad puedan acceder a su propio cuerpo y desarrollar así su sexualidad. Dicha figura está envuelta en una gran polémica, por lo que en este artículo se aborda una de sus cuestiones más controvertidas: su reconocimiento jurídico y soporte económico. En las siguientes páginas se incluye un estudio de tipo cualitativo a través de documentos escritos y entrevistas a aquellas personas vinculadas directamente con la temática (asistentes sexuales y personas que reciben este apoyo), junto con los testimonios de dos expertos en esta materia. En tanto que se trata de una figura emergente y poco conocida hasta el momento, se expone la diversidad de paradigmas que giran en torno a la misma y la necesidad de visibilizar el ejercicio libre del derecho a vivir una sexualidad libre y plena. (AU)

Sexual assistance understood from a human rights perspective is consti-tuted as the tool for those people who are in a situation of disability to access their own body and thus develop their sexuality. This figure is involved in a great controversy, so this article addresses one of its most controversial issues: its legal recognition and finan-cial support. The following pages include a qualitative study through written documents and interviews with those people directly linked to the subject (sexual assistant and peo-ple who receiving this support) with the testimonies of two experts in this topic. As it is an emerging figure and little known so far, through this article are shown the diversity of paradigms that revolve around it and the need to make visible the free exercise of the right to live a free and full sexuality. (AU)

Metformin for treatment of cytopenias in children and young adults with Fanconi anemia.

Fanconi anemia (FA), a genetic DNA repair disorder characterized by marrow failure and cancer susceptibility. In FA mice, metformin improves blood counts and delays tumor development. We conducted a single institution study of metformin in nondiabetic patients with FA to determine feasibility and tolerability of metformin treatment and to assess for improvement in blood counts. Fourteen of 15 patients with at least 1 cytopenia (hemoglobin < 10 g/dL; platelet count < 100 000 cells/µL; or an absolute neutrophil count < 1000 cells/µL) were eligible to receive metformin for 6 months. Median patient age was 9.4 years (range 6.0-26.5 ). Thirteen of 14 subjects (93%) tolerated maximal dosing for age; 1 subject had dose reduction for grade 2 gastrointestinal symptoms. No subjects developed hypoglycemia or metabolic acidosis. No subjects had dose interruptions caused by toxicity, and no grade 3 or higher adverse events attributed to metformin were observed. Hematologic response based on modified Myelodysplastic Syndrome International Working Group criteria was observed in 4 of 13 evaluable patients (30.8%; 90% confidence interval, 11.3-57.3). Median time to response was 84.5 days (range 71-128 days). Responses were noted in neutrophils (n = 3), platelets (n = 1), and red blood cells (n = 1). No subjects met criteria for disease progression or relapse during treatment. Correlative studies explored potential mechanisms of metformin activity in FA. Plasma proteomics showed reduction in inflammatory pathways with metformin. Metformin is safe and tolerable in nondiabetic patients with FA and may provide therapeutic benefit. This trial was registered at as #NCT03398824.

Development of a scale for the evaluation of the quality of the shared decision process in multiple sclerosis patients.

In the last years, therapeutic decisions in multiple sclerosis (MS) have become challenging due to expanded options with different treatment profiles attending to efficacy, safety, and route and frequency of administration. Moreover, patients with multiple sclerosis (PwMS) increasingly wish to be involved in their therapeutic decision process. Therefore, a new, patient-centric shared decision model (SDM), is gaining relevance. However, validated scales oriented to assess the quality of the process itself are lacking. The AGA-25 scale is a fit-for-purpose 25-item scale based on two validated scales in MS (Treatment Satisfaction Questionnaire for Medication (TSQM) and Decisional Conflict Scale (DCS)). The aim of this work is to develop and validate the AGAS-25 in Spanish. Two hundred and three PwMS (aged 17 to 67; 155 [76.4%] females) undergoing stable disease modifying treatment in the last 6 months were consecutively recruited. The Principal Component Analysis suggested a four-factor structure for the 25-item version of the questionnaire: 1) satisfaction with the SDM process 2) adverse events with the DMT, 3) convenience of the chosen-DMT and 4) information reliability. The internal consistency of the measurement was adequate (Cronbach's alpha = 0.88). Our results support the use of the AGAS-25 scale to assist SDM in Spanish-speaking PwMS.

Assessment of Acceptability and Initial Effectiveness of a Unified Protocol Prevention Program to Train Emotional Regulation Skills in Female Nursing Professionals during the COVID-19 Pandemic.

Healthcare professionals, especially women, have shown increases in anxious-depressive symptoms as a consequence of the COVID-19 pandemic. The aim of this pilot study was to evaluate the acceptability and preliminary effectiveness of a Unified Protocol (UP) prevention program to provide emotional regulation skills to cope with stressful situations. The sample consisted of 27 nursing professionals (100% women; mean age: 45.67; SD = 7.71) working in a Spanish public hospital during COVID-19, who were randomized to an immediate treatment group (ITG, n = 13) or to a delayed treatment group (DTG, n = 14, which served as the waiting list control group and received the program 5 weeks after the ITG had received it). The program consisted of five-weekly, two-hour, UP-based group sessions. Variables related to emotional symptomatology, emotional regulation, personality, burnout, and perceived quality of life were evaluated at the following time points: pre- and post-intervention and at 1-, 3-, and 6-month follow-ups. Statistically significant between-group differences showed lower emotional exhaustion and personal accomplishment in favor of the ITG after the intervention. Regarding the effect over time for all participants who received the UP (n = 27), statistically significant reductions were observed in neuroticism, personal accomplishment, and subjective distress caused by traumatic events (-0.23 ≤ d ≤ -0.73). A statistically significant interaction "Time*Condition" was found in anxiety, with increases in the DTG. Participants showed high satisfaction with the UP. These findings show good acceptability and preliminary effectiveness of the UP to reduce the emotional impact of the pandemic in female nursing workers.

The Relationship between Angiogenic Factors and Energy Metabolism in Preeclampsia.

Antiangiogenic factors are currently used for the prediction of preeclampsia. The present study aimed to evaluate the relationship between antiangiogenic factors and lipid and carbohydrate metabolism in maternal plasma and placenta. We analyzed 56 pregnant women, 30 healthy and 26 with preeclampsia (including early and late onset). We compared antiangiogenic factors soluble Fms-like Tyrosine Kinase-1 (sfLt-1), placental growth factor (PlGF), and soluble endoglin (sEng)), lipid and carbohydrate metabolism in maternal plasma, and lipid metabolism in the placenta from assays of fatty acid oxidation, fatty acid esterification, and triglyceride levels in all groups. Antiangiogenic factors sFlt-1, sFlt-1/PlGF ratio, and sEng showed a positive correlation with triglyceride, free fatty acid, and C-peptide maternal serum levels. However, there was no relationship between angiogenic factors and placental lipid metabolism parameters. Free fatty acids were predictive of elevated sFlt-1 and sEng, while C-peptide was predictive of an elevated sFlt1/PlGF ratio. The findings in this study generate a model to predict elevated antiangiogenic factor values and the relationship between them with different products of lipid and carbohydrate metabolism in maternal serum and placenta in preeclampsia.

Ecological momentary intervention to enhance emotion regulation in healthcare workers via smartphone: a randomized controlled trial protocol.

BACKGROUND: CUIDA-TE is an APP that offers transdiagnostic cognitive behavioral therapy focused on enhancing emotion regulation. As a novelty, it incorporates ecological momentary interventions (EMI), which can provide psychological support in real time, when suffering arises. The main goal of the study is to evaluate the efficacy of CUIDA-TE to improve emotion regulation in healthcare workers, a population that has been particularly emotionally impacted by the COVID-19 pandemic. METHODS: In this three-arm, randomized controlled trial (RCT) the study sample will be composed of a minimum of 174 healthcare workers. They will be randomly assigned to a 2-month EMI group (CUIDA-TE APP, n ≥ 58), a 2-month ecological momentary assessment (EMA) only group (MONITOR EMOCIONAL APP, n ≥ 58), or a wait-list control group (no daily monitoring nor intervention, n ≥ 58). CUIDA-TE will provide EMI if EMA reveals emotional problems, poor sleep quality/quantity, burnout, stress, or low perceived self-efficacy when regulating emotions. Depression will be the primary outcome. Secondary outcomes will include emotion regulation, quality of life, and resilience. Treatment acceptance and usability will also be measured. Primary and secondary outcomes will be obtained at pre- and post-intervention measurements, and at the 3-month follow-up for all groups. DISCUSSION: To our knowledge, this is the first RCT that evaluates the efficacy of an APP-based EMI to improve emotion regulation skills in healthcare workers. This type of intervention might ultimately help disseminate treatments and reach a larger number of individuals than traditional face-to-face individual therapies. TRIAL REGISTRATION: ClinicalTrial.gov : NCT04958941 Registered 7 Jun 2021. STUDY STATUS: Participant recruitment has not started.

Preventing Emotional Dysregulation: Acceptability and Preliminary Effectiveness of a DBT Skills Training Program for Adolescents in the Spanish School System.

Emotional dysregulation is a key factor in the development and maintenance of multiple disabling mental disorders through a person's lifespan. Therefore, there is an urgent need to prevent emotional dysregulation as early as possible. The main aim of this study was to evaluate the acceptability and preliminary effectiveness of an adapted Dialectical Behavior Therapy Skills Training program for Emotional Problem Solving in Adolescents (DBT STEPS-A) during secondary school. The sample included 93 adolescents (mean age = 12.78; SD = 0.54; and 53% female) studying in their 2nd year of secondary school in a public center in Catalonia (Spain). Measures of acceptability, difficulties of emotional regulation, mental health problems, and life satisfaction were completed before and after participation in the DBT STEPS-A program during one academic year. The majority of students rated the program as useful (64%) and enjoyed the classes (62%) and 48% of them reported practicing the newly learned skills. Statistically significant improvements were revealed in some emotional regulation-related variables, namely the number of peer problems (p = 0.003; d = 0.52) and prosocial behaviors (p < 0.001; d = -0.82). Although non-significant, the scores in the remaining outcomes indicated a general positive trend in emotional dysregulation, mental health, and life satisfaction. The adapted DBT STEPS-A was very well-accepted and helped overcome some emotional regulation difficulties in Spanish adolescents.

Unified Protocol in a Group Format for Improving Specific Symptoms of Emotional Disorders in the Spanish Public Health System.

BACKGROUND: The Unified Protocol (UP) for the transdiagnostic treatment of emotional disorders (EDs) has demonstrated its efficacy in improving dimensions shared by EDs, but there is insufficient evidence regarding the specific symptoms of each ED. The main objective of the study was to evaluate the efficacy of the UP applied in a group format compared with individual Treatment as Usual (TAU), in improving specific ED symptoms. METHODS: The study sample (n=243) was a subset of participants of a randomized controlled trial conducted in the Spanish public health system. Specific symptoms assessed from pre-treatment to the six-month follow-up were: depressive, agoraphobic, generalized anxiety, panic, and obsessive-compulsive symptoms. Personality dimensions and quality of life were also measured. RESULTS: There were statistically significant changes after the UP in all the study variables (0.44 = d = 1.35). Changes in depressive symptoms, obsessive-compulsive disorder, and perceived quality of life were superior in the UP. CONCLUSIONS: The results support the efficacy of group UP for improving both transdiagnostic dimensions and specific ED symptoms, as well as quality of life, through the public health-care system.

Unifi ed Protocol in a Group Format for Improving Specifi c Symptoms of Emotional Disorders in the Spanish Public Health System / Protocolo Unifi cado en Formato Grupal Para la Mejora de losSíntomas de los Trastornos Emocionales en el Sistema de Salud Público

Background: The Unifi ed Protocol (UP) for the transdiagnostic treatment of emotional disorders (EDs) has demonstrated its effi cacy in improvingdimensions shared by EDs, but there is insuffi cient evidence regarding thespecifi c symptoms of each ED. The main objective of the study was toevaluate the effi cacy of the UP applied in a group format compared withindividual Treatment as Usual (TAU), in improving specifi c ED symptoms.Methods: The study sample (n=243) was a subset of participants of arandomized controlled trial conducted in the Spanish public health system.Specifi c symptoms assessed from pre-treatment to the six-month follow-upwere: depressive, agoraphobic, generalized anxiety, panic, and obsessivecompulsive symptoms. Personality dimensions and quality of life werealso measured. Results: There were statistically signifi cant changes afterthe UP in all the study variables (0.44 = d = 1.35). Changes in depressivesymptoms, obsessive-compulsive disorder, and perceived quality of lifewere superior in the UP. Conclusions: The results support the effi cacyof group UP for improving both transdiagnostic dimensions and specifi cED symptoms, as well as quality of life, through the public health-caresystem.

Antecedentes: el Protocolo Unifi cado (PU) para el tratamiento transdiagnóstico de los trastornos emocionales (TEs) ha demostradoefi cacia en la mejora de las dimensiones compartidas por los TEs, perono hay sufi ciente evidencia respecto a los síntomas específi cos de cadauno de los TEs. El objetivo principal de este estudio fue evaluar la efi caciadel PU aplicado en formato grupal, en comparación con un Tratamiento Habitual (TH) individual, para mejorar los síntomas específi cos de losTEs. Método: la muestra del estudio (n=243) fueron un subgrupo departicipantes de un ensayo controlado aleatorizado en el sistema desalud público español. Los síntomas evaluados antes y hasta los 6 mesesde seguimiento fueron: depresión, agorafobia, ansiedad generalizada,pánico y obsesivo-compulsivo. También se midieron dimensiones de lapersonalidad y la calidad de vida. Resultados: se produjeron cambiosestadísticamente signifi cativos tras el PU en todas las variables (0.44 =d = 1.35). Los cambios en síntomas de depresión, trastorno obsesivocompulsivo y calidad de vida fueron superiores en el PU. Conclusiones: los resultados apoyan la efi cacia del PU en grupo para mejorar tanto lasdimensiones transdiagnósticas, como los síntomas específi cos de los TEs,así como la calidad de vida en nuestro sistema público de salud.

Pleiotrophin Deficiency Induces Browning of Periovarian Adipose Tissue and Protects against High-Fat Diet-Induced Hepatic Steatosis.

(1) Background: Pleiotrophin preserves insulin sensitivity, regulates adipose tissue lipid turnover and plasticity, energy metabolism and thermogenesis. The aim of this study was to determine the role of pleiotrophin in hepatic lipid metabolism and in the metabolic crosstalk between the liver and brown and white adipose tissue (AT) in a high-fat diet-induced (HFD) obesity mice model. (2) Methods: We analyzed circulating variables, lipid metabolism (hepatic lipid content and mRNA expression), brown AT thermogenesis (UCP-1 expression) and periovarian AT browning (brown adipocyte markers mRNA and immunodetection) in Ptn-/- mice either fed with standard-chow diet or with HFD and in their corresponding Ptn+/+ counterparts. (3) Results: HFD-Ptn-/- mice are protected against the development of HFD-induced insulin resistance, had lower liver lipid content and lower expression of the key enzymes involved in triacylglycerides and fatty acid synthesis in liver. HFD-Ptn-/- mice showed higher UCP-1 expression in brown AT. Moreover, Ptn deletion increased the expression of specific markers of brown/beige adipocytes and was associated with the immunodetection of UCP-1 enriched multilocular adipocytes in periovarian AT. (4) Conclusions: Ptn deletion protects against the development of HFD-induced insulin resistance and liver steatosis, by increasing UCP-1 expression in brown AT and promoting periovarian AT browning.

Pd-C Catalytic Thin Films Prepared by Magnetron Sputtering for the Decomposition of Formic Acid.

Formic acid is an advantageous liquid organic hydrogen carrier. It is relatively nontoxic and can be synthesized by the reaction of CO2 with sustainable hydrogen or by biomass decomposition. As an alternative to more widely studied powdery catalysts, supported Pd-C catalytic thin films with controlled nanostructure and compositions were newly prepared in this work by magnetron sputtering on structured supports and tested for the formic acid decomposition reaction. A two-magnetron configuration (carbon and tailored Pd-C targets) was used to achieve a reduction in Pd consumption and high catalyst surface roughness and dispersion by increasing the carbon content. Activity and durability tests were carried out for the gas phase formic acid decomposition reaction on SiC foam monoliths coated with the Pd-C films and the effects of column width, surface roughness and thermal pre-reduction time were investigated. Activity of 5.04 molH2·gPd-1·h-1 and 92% selectivity to the dehydrogenation reaction were achieved at 300 °C for the catalyst with a lower column width and higher carbon content and surface roughness. It was also found that deactivation occurs when Pd is sintered due to the elimination of carbon and/or the segregation and agglomeration of Pd upon cycling. Magnetron sputtering deposition appears as a promising and scalable route for the one-step preparation of Pd-C catalytic films by overcoming the different deposition characteristics of Pd and C with an appropriate experimental design.

Role of Receptor Protein Tyrosine Phosphatase ß/ζ in Neuron-Microglia Communication in a Cellular Model of Parkinson's Disease.

Pleiotrophin (PTN) is a neurotrophic factor that regulates glial responses in animal models of different types of central nervous system (CNS) injuries. PTN is upregulated in the brain in different pathologies characterized by exacerbated neuroinflammation, including Parkinson's disease. PTN is an endogenous inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) ß/ζ, which is abundantly expressed in the CNS. Using a specific inhibitor of RPTPß/ζ (MY10), we aimed to assess whether the PTN/RPTPß/ζ axis is involved in neuronal and glial injury induced by the toxin MPP+. Treatment with the RPTPß/ζ inhibitor MY10 alone decreased the viability of both SH-SY5Y neuroblastoma cells and BV2 microglial cultures, suggesting that normal RPTPß/ζ function is involved in neuronal and microglial viability. We observed that PTN partially decreased the cytotoxicity induced by MPP+ in SH-SY5Y cells underpinning the neuroprotective function of PTN. However, MY10 did not seem to modulate the SH-SY5Y cell loss induced by MPP+. Interestingly, we observed that media from SH-SY5Y cells treated with MPP+ and MY10 decreases microglial viability but may elicit a neuroprotective response of microglia by upregulating Ptn expression. The data suggest a neurotrophic role of microglia in response to neuronal injury through upregulation of Ptn levels.