Demographic and clinical characteristics of a Spanish population of people living with type 1 diabetes who practice nonprofessional sports: The DIABESPORT survey.

AIM: To determine the characteristics of people with type 1 diabetes mellitus (T1D) who practice sports, the support they receive, and the way in which they manage their disease during sports. METHODS: An observational cross-sectional study designed as a web-based survey released through social media was carried out, directed to physically active people with T1D. RESULTS: A total of 342 subjects completed the survey (16 children; 67.5% males). The duration of living with T1D was 18.6 ± 11.4 years. The mean glycosylated hemoglobin concentration (HbA1c) was 6.7 ± 0.8%, and the mean time in range (TIR) was 72.9 ± 15.8%. Only 27.2% started sports activity following the diagnosis of T1D. The most frequently used basal insulin was insulin degludec (38.6%). The usual treatment modification before doing sports consisted of bolus reduction (42.5%) or only the adjustment of nutritional supplements (19.7%). In cases of long-acting insulin users, the basal dose usually remained unchanged during sports. One-quarter of the participants were insulin pump users, and of these, 12.5% always disconnected the pump during physical activities. Severe hypoglycemia on the day of physical activity was experienced by 5% of the participants in the last 6 months. One-third reported a lack of support from their physician, and 61% had learned to manage glycemic control during sports by themselves. CONCLUSIONS: This study highlights the adjustments made by people living with T1D during sports practice, and the lack of support received from healthcare professionals.

Predictive Factors of Renal Function Decline in Patients with Type 2 Diabetes Treated with Canagliflozin in the Real-Wecan Study.

The Real-WECAN study evaluated the real-life effectiveness and safety of canagliflozin 100 mg daily (initiated in SGLT-2 inhibitors naïve patients) and canagliflozin 300 mg daily (switching from canagliflozin 100 mg or other SGLT-2 inhibitors) in individuals with type 2 diabetes. The objectives of this sub-analysis were to estimate the eGFR slope over the follow-up period and to identify predictive factors of eGFR decline in a multiple linear regression analysis. A total of 583 patients (279 on canagliflozin 100 mg and 304 on canagliflozin 300 mg) were included, with median follow-up at 13 months. The patients had a mean age of 60.4 years, HbA1c of 7.76%, BMI of 34.7 kg/m2, eGFR below 60 mL/min/1.73 m2 8.6%, and urine albumin-to-creatinine ratio (UACR) above 30 mg/g 22.8%. eGFR decreased by −1.9 mL/min/1.73 m2 (p < 0.0001) by the end of the study. The mean eGFR slope during the maintenance phase was −0.16 mL/min/1.73 m2 per year. There were no significant differences between both doses of canagliflozin in the eGFR reduction or in the eGFR slope. The best predictive multivariate model of eGFR decline after canagliflozin therapy included age, hypertension, combined hyperlipidemia, heart failure, eGFR and severely increased albuminuria. All these variables except hypertension were independently associated with the outcome. In conclusion, in this real-world study, individuals with older age, combined hyperlipidemia, heart failure, higher eGFR and UACR > 300 mg/g showed a greater decline in their eGFR after canagliflozin treatment.

Real-World Clinical Outcomes Associated with Canagliflozin in Patients with Type 2 Diabetes Mellitus in Spain: The Real-Wecan Study.

The aims of this multicentric retrospective study were to assess in a real-world setting the effectiveness and safety of canagliflozin 100 mg/d (CANA100) as an add-on to the background antihyperglycemic therapy, and to evaluate the intensification of prior sodium-glucose co-transporter type 2 inhibitor (SGLT-2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. One cohort of SGLT2i-naïve patients with T2DM who were initiated on CANA100 and a second cohort of patients with prior background SGLT-2i therapy who switched to CANA300 were included in the study. The primary outcome of the study was the mean change in HbA1c over the follow-up time. In total, 583 patients were included-279 in the cohort of CANA100 (HbA1c 8.05%, weight 94.9 kg) and 304 in the cohort of CANA300 (HbA1c 7.51%, weight 92.0 kg). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. CANA100 was associated to significant reductions in HbA1c (-0.90%) and weight (-4.1 kg) at the end of the follow-up. In those patients with baseline HbA1c > 8% (mean 9.25%), CANA100 lowered HbA1c levels by 1.51%. In the second cohort, patients switching to CANA300 experienced a significant decrease in HbA1c (-0.35%) and weight (-2.1 kg). In those patients with baseline HbA1c > 8% (mean 8.94%), CANA300 lowered HbA1c levels by 1.12%. There were significant improvements in blood pressure in both cohorts. No unexpected adverse events were reported. In summary, CANA100 (as an add-on therapy) and CANA300 (switching from prior SGLT-2i therapy) significantly improved several cardiometabolic parameters in patients with T2DM.

[The technological tools of the diagnosis and treatment of attention deficit disorder and hyperactivity]. / Herramientas tecnológicas del diagnóstico y tratamiento del trastorno por déficit de atención e hiperactividad.

Attention deficit disorder and hyperactivity (ADHD) is the main reason for consultation in most Pediatric Neurology units in Spain. The new technologies also associate benefits for both patients and professionals and the health system itself, which makes its rational implementation essential. Genetics, neuroimaging or virtual reality, for example, are clear exponents of the results that can be achieved by optimizing traditional processes. The different technologies that we collect in this article are fully operational and have thousands of experience in patients. The incorporation of them to the usual clinical practice is in our hands.

El trastorno por déficit de atención e hiperactividad (TDAH) es el principal motivo de consulta en la mayoría de las unidades de Neurología Pediátrica en España. Las nuevas tecnologías asocian además beneficios tanto para los pacientes como para los profesionales y el propio sistema sanitario. Se hace imprescindible su implementación racional. La genética, la neuroimagen o la realidad virtual por ejemplo, son claros exponentes de los resultados que se pueden conseguir al optimizar los procesos tradicionales. Las diferentes tecnologías que recogemos en este artículo están completamente operativas y cuentan con miles de pacientes de experiencia. La incorporación de las mismas a la práctica clínica habitual está en nuestras manos.

Herramientas tecnológicas del diagnóstico y tratamiento del trastorno por déficit de atención e hiperactividad / The technological tools of the diagnosis and treatment of attention deficit disorder and hyperactivity

El trastorno por déficit de atención e hiperactividad (TDAH) es el principal motivo de consulta en la mayoría de las unidades de Neurología Pediátrica en España. Las nuevas tecnologías asocian además beneficios tanto para los pacientes como para los profesionales y el propio sistema sanitario. Se hace imprescindible su implementación racional. La genética, la neuroimagen o la realidad virtual por ejemplo, son claros exponentes de los resultados que se pueden conseguir al optimizar los procesos tradicionales. Las diferentes tecnologías que recogemos en este artículo están completamente operativas y cuentan con miles de pacientes de experiencia. La incorporación de las mismas a la práctica clínica habitual está en nuestras manos.

Attention deficit disorder and hyperactivity (ADHD) is the main reason for consultation in most Pediatric Neurology units in Spain. The new technologies also associate benefits for both patients and professionals and the health system itself, which makes its rational implementation essential. Genetics, neuroimaging or virtual reality, for example, are clear exponents of the results that can be achieved by optimizing traditional processes. The different technologies that we collect in this article are fully operational and have thousands of experience in patients. The incorporation of them to the usual clinical practice is in our hands.

Eficacia de la lisdexanfetamina en la mejora sintomática conductual y cognitiva del trastorno por déficit de atención/ hiperactividad: tratamiento monitorizado mediante el test AULA Nesplora de realidad virtual / Efficacy of lisdexamphetamine to improve the behavioural and cognitive symptoms of attention deficit hyperactivity disorder: treatment monitored by means of the AULA Nesplora virtual reality test

Introducción. La lisdexanfetamina (LDX) es el fármaco para el trastorno por déficit de atención/hiperactividad (TDAH) con mayor volumen de investigación de los últimos años. No obstante, no hay estudios que certifiquen su utilidad para la mejoría del funcionamiento cognitivo en el TDAH. Objetivo. Evaluar la eficacia de la LDX en la mejora sintomática conductual y cognitiva en un grupo de pacientes con TDAH. Dicha eficacia fue medida mediante la administración del test AULA Nesplora de realidad virtual antes de la prescripción del tratamiento farmacológico y después del tratamiento con LDX. Pacientes y métodos. La muestra estaba compuesta por 85 pacientes de 6-16 años, con diagnóstico clínico de TDAH y que asistían a tratamiento en una consulta de neuropediatría. Todos los pacientes iniciaron el tratamiento farmacológico con la correspondiente dosis de LDX tras la entrevista clínica y la primera administración del test AULA. Tras un tratamiento medio de 7,5 meses, se les administró AULA nuevamente y se valoró el progreso del tratamiento farmacológico sobre la sintomatología cognitiva y motora. Resultados. Se apreciaron mejorías muy significativas en la atención selectiva y sostenida, la calidad del foco atencional y la hiperactividad, mejorías moderadas en la impulsividad, y una incidencia casi nula en la velocidad de procesamiento. Conclusiones. La LDX constituye un tratamiento adecuado para la mejora sustancial de la atención e hiperactividad, y dicha mejora puede monitorizarse de forma precisa mediante el test de realidad virtual AULA (AU)

Introduction. Lisdexanfetamine (LDX) is the drug for attention deficit hyperactivity disorder (ADHD) undergoing the largest research volume in the latest years. However, no studies certify its usefulness for the improvement of cognitive functioning in ADHD. Aim. To evaluate the efficacy of LDX in the behavioral and cognitive improvement of a group of patients with ADHD. Such efficacy was measured by means of the administration of AULA Nesplora virtual reality test before the prescription of pharmacological treatment and right after the treatment with LDX. Patients and methods. The sample comprised 85 patients between 6 and 16 years, with clinical diagnosis of ADHD, who attended treatment in a neuropediatrics consultation. All patients started pharmacological treatment with the proper dose of LDX after the clinical interview and the first administration of AULA test. After an average treatment of 7.5 months, AULA was administered again and the treatment progress based on cognitive and motor symptomatology was assessed. Results. Results showed highly significant improvements in selective and sustained attention, quality of attention focus and hyperactivity; moderate improvements in impulsivity; and an incidence close to zero in processing speed. Conclusions. LDX constitutes an adequate treatment for the substantial improvement of attention and hyperactivity; such improvement can be monitored accurately by means of AULA virtual reality test (AU)

Psicosis infantil secundaria a metilfenidato / Infantile psychosis secondary to methylphenidate

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Identification and characterization of associated with lipid droplet protein 1: A novel membrane-associated protein that resides on hepatic lipid droplets.

Alcoholic and nonalcoholic liver steatosis and steatohepatitis are characterized by the massive accumulation of lipid droplets (LDs) in the cytosol of hepatocytes. Although LDs are ubiquitous and dynamic organelles found in the cells of a wide range of organisms, little is known about the mechanisms and sites of LD biogenesis. To examine the participation of these organelles in the pathophysiological disorders of steatotic livers, we used a combination of mass spectrometry (matrix-assisted laser desorption ionization-time of flight and LC-MS electrospray) and Western blot analysis to study the composition of LDs purified from rat liver after a partial hepatectomy. Fifty proteins were identified. Adipose differentiation-related protein was the most abundant, but other proteins such as calreticulin, TIP47, Sar1, Rab GTPases, Rho and actin were also found. In addition, we identified protein associated with lipid droplets I ALDI (tentatively named Associated with LD protein 1), a novel protein widely expressed in liver and kidney corresponding to the product of 0610006F02Rik (GI:27229118). Our results show that, upon lipid loading of the cells, ALDI translocates from the endoplasmic reticulum into nascent LDs and indicate that ALDI may be targeted to the initial lipid deposits that eventually form these droplets. Moreover, we used ALDI expression studies to view other processes related to these droplets, such as LD biogenesis, and to analyze LD dynamics. In conclusion, here we report the composition of hepatic LDs and describe a novel bona fide LD-associated protein that may provide new insights into the mechanisms and sites of LD biogenesis.

Caveolin-1 is essential for liver regeneration.

Liver regeneration is an orchestrated cellular response that coordinates cell activation, lipid metabolism, and cell division. We found that caveolin-1 gene-disrupted mice (cav1-/- mice) exhibited impaired liver regeneration and low survival after a partial hepatectomy. Hepatocytes showed dramatically reduced lipid droplet accumulation and did not advance through the cell division cycle. Treatment of cav1-/- mice with glucose (which is a predominant energy substrate when compared to lipids) drastically increased survival and reestablished progression of the cell cycle. Thus, caveolin-1 plays a crucial role in the mechanisms that coordinate lipid metabolism with the proliferative response occurring in the liver after cellular injury.

Infecciones del tracto urinario causadas por bacterias del género Aeromonas / Urinary tract infection caused by bacteria of the genus Aeromonas

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Cholesterol and fatty acids regulate dynamic caveolin trafficking through the Golgi complex and between the cell surface and lipid bodies.

Caveolins are a crucial component of plasma membrane (PM) caveolae but have also been localized to intracellular compartments, including the Golgi complex and lipid bodies. Mutant caveolins associated with human disease show aberrant trafficking to the PM and Golgi accumulation. We now show that the Golgi pool of mainly newly synthesized protein is detergent-soluble and predominantly in a monomeric state, in contrast to the surface pool. Caveolin at the PM is not recognized by specific caveolin antibodies unless PM cholesterol is depleted. Exit from the Golgi complex of wild-type caveolin-1 or -3, but not vesicular stomatitis virus-G protein, is modulated by changing cellular cholesterol levels. In contrast, a muscular dystrophy-associated mutant of caveolin-3, Cav3P104L, showed increased accumulation in the Golgi complex upon cholesterol treatment. In addition, we demonstrate that in response to fatty acid treatment caveolin can follow a previously undescribed pathway from the PM to lipid bodies and can move from lipid bodies to the PM in response to removal of fatty acids. The results suggest that cholesterol is a rate-limiting component for caveolin trafficking. Changes in caveolin flux through the exocytic pathway can therefore be an indicator of cellular cholesterol and fatty acid levels.

Intracellular trafficking during liver regeneration. Alterations in late endocytic and transcytotic pathways.

BACKGROUND/AIMS: Liver growth, induced by partial hepatectomy of the organ is a precisely regulated process during which a radical reorganisation of metabolism occurs as the hepatocytes become committed to enter the cell cycle. Recent studies have shown the importance of the endocytic compartment in the control of lipid and protein intracellular trafficking but also in the control of the signal transduction events, which eventually will trigger the initiation of DNA synthesis and the subsequent cell division. METHODS: We isolated endosomes at different times after partial hepatectomy in male rats and compared with endosomes isolated from sham-operated animals. Also, bile was collected and analysed by 2D-gel electrophoresis. RESULTS: The amount of late endosomes isolated from regenerating livers decreased, concomitant with decreased cathepsin D specific enzyme activity. Furthermore, secretion of horseradish peroxidase, pIgA and transferrin increased in the pre-replicative phase of liver regeneration. CONCLUSIONS: At the early stages of liver regeneration, the hepatocellular transport pathway towards degradation (late endosomes and lysosomal pathway) decreases, but the transcytosis and the bile secretion of several major proteins increases.

Dynamic and regulated association of caveolin with lipid bodies: modulation of lipid body motility and function by a dominant negative mutant.

Caveolins are a crucial component of caveolae but have also been localized to the Golgi complex, and, under some experimental conditions, to lipid bodies (LBs). The physiological relevance and dynamics of LB association remain unclear. We now show that endogenous caveolin-1 and caveolin-2 redistribute to LBs in lipid loaded A431 and FRT cells. Association with LBs is regulated and reversible; removal of fatty acids causes caveolin to rapidly leave the lipid body. We also show by subcellular fractionation, light and electron microscopy that during the first hours of liver regeneration, caveolins show a dramatic redistribution from the cell surface to the newly formed LBs. At later stages of the regeneration process (when LBs are still abundant), the levels of caveolins in LBs decrease dramatically. As a model system to study association of caveolins with LBs we have used brefeldin A (BFA). BFA causes rapid redistribution of endogenous caveolins to LBs and this association was reversed upon BFA washout. Finally, we have used a dominant negative LB-associated caveolin mutant (cavDGV) to study LB formation and to examine its effect on LB function. We now show that the cavDGV mutant inhibits microtubule-dependent LB motility and blocks the reversal of lipid accumulation in LBs.

Aspirin-induced apoptosis in jurkat cells is not mediated by peroxisome proliferator-activated receptor delta.

Nonsteroidal antiinflammatory drugs may induce apoptosis via inhibition of peroxisome proliferator-activated receptor delta (PPARdelta) activity. Here we analyze the role of PPARdelta in aspirin-induced apoptosis of Jurkat cells, which, together with other lymphoid cell lines, express PPARdelta mRNA. Aspirin increased PPARdelta mRNA levels in Jurkat cells, but decreased the activity of both PPARdelta and PPARalpha/gamma, assayed using the luciferase reporter constructs DRE and ACO, respectively. The DNA binding of PPARdelta was not affected by 10 mM aspirin, which induces apoptosis in Jurkat cells. Moreover, neither addition of a specific ligand of PPARdelta nor transient transfection of PPARdelta expression vectors protected Jurkat cells from aspirin-induced apoptosis. These results indicate that PPARdelta is not involved in aspirin-induced apoptosis. Therefore, the mechanism by which aspirin mediates cell death in Jurkat cells remains unknown.