Effects of a High-Fat Diet on Insulin-Related miRNAs in Plasma and Brain Tissue in APPSwe/PS1dE9 and Wild-Type C57BL/6J Mice.

Insulin resistance (IR)-related miRNAs have been associated with the development and progression of Alzheimer's disease (AD). The dietary modulation of these miRNAs could become a potential strategy to manage AD. The aim of this study was to evaluate the effect of a high-fat diet (HFD), which aggravates AD-related pathogenic processes, on serum, cortex and hippocampus IR-related miRNA expression. C57BL/6J WT and APPSwe/PS1dE9 mice were fed either an HFD or a conventional diet till 6 months of age. The mice fed with the HFD showed a significant increase in body weight and worsening glucose and insulin metabolism. miR-19a-3p was found to be up-regulated in the cortex, hippocampus and serum of APP/PS1 mice and in the serum and hippocampus of WT mice fed with the HFD. miR-34a-5p and miR-146a-5p were up-regulated in the serum of both groups of mice after consuming the HFD. Serum miR-29c-3p was overexpressed after consuming the HFD, along with hippocampal miR-338-3p and miR-125b-5p, only in WT mice. The HFD modulated the expression of peripheral and brain miRNAs related to glucose and insulin metabolism, suggesting the potential role of these miRNAs not only as therapeutic targets of AD but also as peripheral biomarkers for monitoring AD.

Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing.

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the presence of autoantibodies against factor VIII (FVIII). As with other autoimmune diseases, its etiology is complex and its genetic basis is unknown. The aim of this study was to identify the immunogenetic background that predisposes individuals to AHA. HLA and KIR gene clusters, as well as KLRK1, were sequenced using next-generation sequencing in 49 AHA patients. Associations between candidate genes involved in innate and adaptive immune responses and AHA were addressed by comparing the alleles, genotypes, haplotypes, and gene frequencies in the AHA cohort with those in the donors' samples or Spanish population cohort. Two genes of the HLA cluster, as well as rs1049174 in KLRK1, which tags the natural killer (NK) cytotoxic activity haplotype, were found to be linked to AHA. Specifically, A*03:01 (p = 0.024; odds ratio (OR) = 0.26[0.06-0.85]) and DRB1*13:03 (p = 6.8 × 103, OR = 7.56[1.64-51.40]), as well as rs1049174 (p = 0.012), were significantly associated with AHA. In addition, two AHA patients were found to carry one copy each of the low-frequency allele DQB1*03:09 (nallele = 2, 2.04%), which was completely absent in the donors. To the best of our knowledge, this is the first time that the involvement of these specific alleles in the predisposition to AHA has been proposed. Further molecular and functional studies will be needed to unravel their specific contributions. We believe our findings expand the current knowledge on the genetic factors involved in susceptibility to AHA, which will contribute to improving the diagnosis and prognosis of AHA patients.

"Pharyngolab": a new surgical simulator for pharyngoplasties.

Pharyngoplasty represents one of the most widely performed surgical procedures for the treatment of obstructive sleep apnea (OSA) in the presence of palate-oropharyngeal collapse. The learning curve for pharyngoplasties is steep and success is conditional on the correct use of the sutures and the careful application of the surgical steps in a narrow surgical field. The use of synthetic models may be conveniently and safely employed for hands-on surgical practice in pharyngoplasties, especially when fresh frozen cadaveric specimens are not available. We present the "Pharyngolab", a new simulator for pharyngoplasties.

Osteotomía de Evans sin injerto óseo en el pie plano estadio IIB del adulto / Evans osteotomy without bone graft in stage IIB adult flatfoot deformity

Objetivo: Evaluar los resultados radiográficos y funcionales al año de la cirugía, en una serie consecutiva de pacientes con diagnóstico de pie plano valgo estadio IIB, sometidos a una osteotomía de Evans sin injerto óseo. Materiales y Métodos: Se evaluó, en forma retrospectiva, a dos grupos de pacientes: grupo 1 (placa con espaciador, n = 12) y grupo 2 (celdas de PEEK, n = 14). La edad promedio era de 47 años (DE 18) en el grupo 1 y de 54 años (DE 12) en el grupo 2. Resultados:Se evaluó a 26 pacientes (28 pies operados); 20 (77%) eran mujeres. Las mediciones radiográficas: ángulo de inclinación del calcáneo, ángulo astrágalo-calcáneo (perfil), ángulo astrágalo-calcáneo (frente), cobertura astragalonavicular, altura de la columna medial, longitud de la columna externa, arrojaron diferencias estadísticamente significativas entre las determinaciones preoperatorias y al año de la cirugía. El puntaje promedio de la escala de la AOFAS al año fue de 96 (DE 4,70) en el grupo 1 y de 95 (DE 4,98) en el grupo 2. El puntaje en la escala analógica visual para dolor fue de 1,2 (DE 0,42) en el grupo 1 y 1,16 (DE 0,46) en el grupo 2.Conclusiones:De acuerdo con los resultados obtenidos, concluimos en que la osteotomía de Evans sin el uso de injerto óseo logra preservar las correcciones obtenidas en el mediano plazo utilizando placas con espaciador o celdas de PEEK. Nivel de Evidencia: III

Objective: To evaluate the radiological and functional outcomes one year after surgery in a consecutive series of patients diagnosed with stage IIB adult-acquired flatfoot deformity who underwent Evans osteotomy without the use of bone graft. Materials and Methods: Two groups of patients were retrospectively evaluated: group 1 (spacer plate, n=12) and group 2 (PEEK cage, n=14). The mean age was 47 years (SD 18) in group 1 and 54 years (SD 12) in group 2. Results:26 patients (28 feet) were evaluated; 14 (84%) of the patients were women. Radiographic measurements calcaneal pitch angle, (lateral) talocalcaneal angle, (AP) talocal-caneal angle, talonavicular coverage angle, medial column height, lateral column length yielded statistically significant differences between preoperative measurements and those taken one year after surgery. The mean score on the AOFAS scale one year after surgery was 96 (SD 4.70) in group 1 and 95 (SD 4.98) in group 2. Regarding the visual analog scale, it was 1.2 (SD 0.42) in group 1 and 1.16 (SD 0.46) in group 2. Conclusions: According to the results obtained, we conclude that Evans osteotomy without the use of bone graft manages to preserve the corrections obtained in the medium term, using either spacer plates or PEEK cages. Level of Evidence: III

Rol de la alineación de la prótesis y las calcificaciones heterotópicas en la artroplastia total de tobillo / Role of prosthetic alignment and heterotopic calcifications in total ankle arthroplasty

Introducción: El objetivo principal fue evaluar la relación entre la formación de calcificaciones heterotópicas y los parámetros de alineación de la prótesis. Materiales y Métodos: La población estaba formada por 31 pacientes. Se evaluaron variables radiográficas de alineación, como ángulos alfa y beta, centro de rotación astragalino y el porcentaje de cobertura posterior de la tibia en el posoperatorio inmediato y a los 2 años. Las variables de evaluación clínica fueron: la escala analógica visual y la escala de la AOFAS, y el cuestionario SF-36 para evaluar la calidad de vida al final del seguimiento. Resultados: La etiología más frecuente de la artrosis fue la postraumática (67,7%). En el posoperatorio inmediato, el ángulo alfa promedio fue de 88,7° (rango 82-92,6; DE ± 2,61); el ángulo beta, de 84,46° (rango 78,62-91,40; DE ± 3,59). La alineación del componente tibial en el plano frontal fue neutra en 25 pacientes (80,6%), en valgo en 6 (19,4%) y en varo (0%). A los 2 años de seguimiento, el 96% tenía calcificaciones heterotópicas. Mejoraron los puntajes en la escala de la AOFAS (preoperatorio/posoperatorio: 31,90/80,94) y en la escala analógica visual (preoperatorio/posoperatorio: 8,7/1,97) (p <0,05). Conclusiones: No se halló una relación entre calcificaciones heterotópicas y peores resultados funcionales ni de dolor, excepto en los parámetros de calidad de vida (SF-36), como el rol físico, la limitación emocional y la percepción de la salud general, que empeoraron a medida que aumentó el grado de calcificaciones alrededor de la prótesis. Nivel de Evidencia: IV

Introduction: The main objective of this work is to evaluate the relationship between the formation of heterotopic calcifications and the alignment parameters of the prosthesis. Materials and Methods: The population under study comprised 31 patients. The radiographic alignment variables evaluated were alpha and beta angles, the talar center of rotation, and the percentage of posterior coverage of the tibia in the immediate postoperative period and after 2 years. The clinical evaluation variables were: VAS, AOFAS, and the SF-36 questionnaire to evaluate quality of life at the end of follow-up. Results: The most frequent etiology of osteoarthritis was post-traumatic (67.7%). In the immediate postoperative period, the mean alpha angle was 88.7° (range 82-92.6°; SD± 2.61); the mean beta angle was 84.46° (range 78°, 62-91.40°; SD ±3.59). The alignment of the tibial component in the anteroposterior plane was neutral in 25 patients (80.6%), valgus in 6 (19.4%), and varus in none. At 2 years of follow-up, 96% presented het-erotopic calcifications. An improvement was verified both in the AOFAS (pre/post 31.90/80.94) and in the VAS scales (pre/post: 8.7/1.97) (p<0.05). Conclusions: No relationship was found between heterotopic calcification and worse functional outcomes or pain, except for quality-of-life parameters (SF-36) such as physical condition, emotional limitation, and general health perception, which worsened as the degree of calcifications around the prosthesis increased. Level of Evidence: IV

Identification of Leishmania infantum Epidemiology, Drug Resistance and Pathogenicity Biomarkers with Nanopore Sequencing.

The emergence of drug-resistant strains of the parasite Leishmania infantum infecting dogs and humans represents an increasing threat. L. infantum genomes are complex and unstable with extensive structural variations, ranging from aneuploidies to multiple copy number variations (CNVs). These CNVs have recently been validated as biomarkers of Leishmania concerning virulence, tissue tropism, and drug resistance. As a proof-of-concept to develop a novel diagnosis platform (LeishGenApp), four L. infantum samples from humans and dogs were nanopore sequenced. Samples were epidemiologically typed within the Mediterranean L. infantum group, identifying members of the JCP5 and non-JCP5 subgroups, using the conserved region (CR) of the maxicircle kinetoplast. Aneuploidies were frequent and heterogenous between samples, yet only chromosome 31 tetrasomy was common between all the samples. A high frequency of aneuploidies was observed for samples with long passage history (MHOM/TN/80/IPT-1), whereas fewer were detected for samples maintained in vivo (MCRI/ES/2006/CATB033). Twenty-two genes were studied to generate a genetic pharmacoresistance profile against miltefosine, allopurinol, trivalent antimonials, amphotericin, and paromomycin. MHOM/TN/80/IPT-1 and MCRI/ES/2006/CATB033 displayed a genetic profile with potential resistance against miltefosine and allopurinol. Meanwhile, MHOM/ES/2016/CATB101 and LCAN/ES/2020/CATB102 were identified as potentially resistant against paromomycin. All four samples displayed a genetic profile for resistance against trivalent antimonials. Overall, this proof-of-concept revealed the potential of nanopore sequencing and LeishGenApp for the determination of epidemiological, drug resistance, and pathogenicity biomarkers in L. infantum.

Protein tyrosine phosphatase 1B (PTP1B) as a potential therapeutic target for neurological disorders.

Protein tyrosine phosphatase 1B (PTP1B) is a typical member of the PTP family, considered a direct negative regulator of several receptor and receptor-associated tyrosine kinases. This widely localized enzyme has been involved in the pathophysiology of several diseases. More recently, PTP1B has attracted attention in the field of neuroscience, since its activation in brain cells can lead to schizophrenia-like behaviour deficits, anxiety-like effects, neurodegeneration, neuroinflammation and depression. Conversely, PTP1B inhibition has been shown to prevent microglial activation, thus exerting a potent anti-inflammatory effect and has also shown potential to increase the cognitive process through the stimulation of hippocampal insulin, leptin and BDNF/TrkB receptors. Notwithstanding, most research on the clinical efficacy of targeting PTP1B has been developed in the field of obesity and type 2 diabetes mellitus (TD2M). However, despite the link existing between these metabolic alterations and neurodegeneration, no clinical trials assessing the neurological advantages of PTP1B inhibition have been performed yet. Preclinical studies, though, have provided strong evidence that targeting PTP1B could allow to reach different pathophysiological mechanisms at once. herefore, specific interventions or trials should be designed to modulate PTP1B activity in brain, since it is a promising strategy to decelerate or prevent neurodegeneration in aged individuals, among other neurological diseases. The present paper fails to include all neurological conditions in which PTP1B could have a role; instead, it focuses on those which have been related to metabolic alterations and neurodegenerative processes. Moreover, only preclinical data is discussed, since clinical studies on the potential of PTP1B inhibition for treating neurological diseases are still required.

Impact of New Drugs for Therapeutic Intervention in Alzheimer's Disease.

The increases in population ageing and growth are leading to a boosting in the number of people living with dementia, Alzheimer's disease (AD) being the most common cause. In spite of decades of intensive research, no cure for AD has been found yet. However, some treatments that may change disease progression and help control symptoms have been proposed. Beyond the classical hypotheses of AD etiopathogenesis, i.e., amyloid beta peptide (Aß) accumulation and tau hyperphosphorylation, a trend in attributing a key role to other molecular mechanisms is prompting the study of different therapeutic targets. Hence, drugs designed to modulate inflammation, insulin resistance, synapses, neurogenesis, cardiovascular factors and dysbiosis are shaping a new horizon in AD treatment. Within this frame, an increase in the number of candidate drugs for disease modification treatments is expected, as well as a focus on potential combinatory multidrug strategies.The present review summarizes the latest advances in drugs targeting Aß and tau as major contributors to AD pathophysiology. In addition, it introduces the most important drugs in clinical studies targeting alternative mechanisms thought to be involved in AD's neurodegenerative process.

Clinical Efficacy and Safety of Fanhdi®, a Plasma-Derived VWF/Factor VIII Concentrate, in von Willebrand Disease in Spain: A Retrospective Study.

OBJECTIVE: To evaluate the efficacy and safety of a plasma-derived factor VIII concentrate containing von Willebrand Factor (pdVWF/FVIII) in standard clinical practice in von Willebrand Disease (VWD) patients. METHODS: A retrospective, multicentric, observational study of VWD patients treated with Fanhdi®, a pdVWF/FVIII concentrate, from January 2011 to December 2017 was conducted at 14 centers in Spain. Efficacy and safety were evaluated for acute bleeding episodes, for prevention of bleeding in surgeries, and for secondary long-term prophylaxis. RESULTS: Seventy-two eligible patients, type 1, 2, 3 VWD (25%/38.9%/36.1%) were treated for spontaneous and traumatic bleeding (140 episodes, n = 41 patients), to prevent surgical bleeding (69 episodes, n = 43 patients); and for secondary long-term prophylaxis (18 programs, n = 13 patients). Replacement therapy with pdVWF/FVIII showed an excellent to good clinical efficacy in 96.7% of the bleeding episodes, 100% during surgical procedures and 100% during prophylaxis. No adverse events (AEs), nor serious AEs related to the product were observed. CONCLUSIONS: Fanhdi® was effective, safe and well tolerated in the management of bleeding episodes, the prevention of bleeding during surgeries, and for secondary long-term prophylaxis in VWD patients.

GSPE pre-treatment protects against long-term cafeteria diet-induced mitochondrial and inflammatory affectations in the hippocampus of rats.

Deregulations like the loss of sensitivity to insulin (insulin resistance) and chronic inflammation are alterations very commonly found in sporadic forms of neurodegenerative pathologies. Thus, finding strategies to protect against them, may lead to a reduction in the incidence and/or affectation of these pathologies. The grape seed-derived proanthocyanidins extract (GSPE) is a mixture of compounds highly enriched in polyphenols and flavonoids that have shown to have a wide range of therapeutic benefits due to their antioxidant and anti-inflammatory properties. OBJECTIVES: This study aimed to assess the protective effects of a short pre-treatment of GSPE in the hippocampus against a prolonged feeding with cafeteria diet. METHODS: GSPE was administered for 10 days followed by 12 weeks of cafeteria diet. We analyzed transcriptional activity of genes and protein expression of key mediators of neurodegeneration in brain samples. RESULTS: Results indicated that GSPE was able to protect against cellular damage through the activation of AKT, as well as promote the maintenance of mitochondrial function by conserving the OXPHOS complexes and upregulating the antioxidant SOD. DISCUSSION: We observed that GSPE decreased inflammatory activation as observed through the downregulation of JNK, IL6 and TNFα, just like the reduction in reactive profile of astrocytes. Overall, the data presented here offers an interesting and hopeful initial step for future long-term studies on the beneficial effects of a supplementation of common diets with polyphenol and flavonoid substances for the amelioration of typical early hallmarks of neurodegeneration.

Looking for a needle in a haystack. SARS-CoV-2 variant characterization in sewage.

SARS-CoV-2 variants are emerging worldwide, and monitoring them is key in providing early warnings. Here, we summarize the different analytical approaches currently used to study the dissemination of SARS-CoV-2 variants in wastewater and discuss their advantages and disadvantages. We also provide preliminary results of two sensitive and cost-effective approaches: variant-specific reverse transcription-nested PCR assays and a nonvariant-specific amplicon deep sequencing strategy that targets three key regions of the viral spike protein. Next-generation sequencing approaches enable the simultaneous detection of signature mutations of different variants of concern in a single assay and may be the best option to explore the real picture at a particular time. Targeted PCR approaches focused on specific signature mutations will need continuous updating but are sensitive and cost-effective.

Management of acquired hemophilia A: results from the Spanish registry.

The Spanish Acquired Hemophilia A (AHA) Registry is intended to update the status of AHA in Spain. One hundred and fifty-four patients were included and retrospectively followed for a median of 12 months. Patients were predominantly male (56.3%), with median age at diagnosis of 74 years. AHA was more frequently idiopathic (44.1%) and autoimmune disorder-associated (31.7%). Thirty-four percent of patients were on antithrombotic therapy at diagnosis. Hemostatic treatment was used in 70% of patients. Recombinant activated factor VII was more frequently infused (60.3% vs 20.6% activated prothrombin complex concentrate). Only 1 patient did not achieve control of hemorrhage. Complete remission (CR) was achieved by 84.2% of cases after immunosuppressive therapy. Steroids alone were less efficient than the other strategies (68.2% vs 87.2%, P = .049), whereas no differences existed among these (steroids/cyclophosphamide, 88.5%, vs steroids/calcineurin inhibitors, 81.2%, vs rituximab-based regimens, 87.5%). Female sex and high inhibitor levels influenced CR negatively. Thirty-six deaths (23.8%) were reported. Main causes of death were infection (15 patients, 9.9%) and hemorrhage (5 patients, 3.3%). All hemorrhage-related and half the infection-related deaths occurred within 2 months of diagnosis. Prior antithrombotic therapy was inversely associated with survival, irrespective of age. Median age of nonsurvivors was significantly higher (79 vs 73 years in survivors). Patients dying of infection were older than the other nonsurvivors (85 vs 78 years). In summary, fatal infection in the first months is common in our series. Antithrombotic therapy is associated with mortality. Particular care should be taken to avoid misdiagnosis.

Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer's disease in metabolically stressed APPswe/PS1dE9 mice.

BACKGROUND: Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20 mg kg-1 d-1) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD. RESULTS: Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other alterations associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response. CONCLUSIONS: Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy.

Covid-19, hypercoagulability and risk of mortality in schizophrenia.

Covid-19 disease has been linked to a high risk of hyper- coagulability that can severely condition the evolution of this respiratory syndrome in the acute phase; and also due to the possible sequelae of a chronic thrombosis, as is the case of chronic pulmonary thromboembolism; or due to complications associated with anticoagulant treatment such as bleeding.

Daytime Neuromuscular Electrical Therapy of Tongue Muscles in Improving Snoring in Individuals with Primary Snoring and Mild Obstructive Sleep Apnea.

Study Objectives: Evaluating daytime neuromuscular electrical training (NMES) of tongue muscles in individuals with Primary Snoring and Mild Obstructive Sleep Apnea (OSA). Methods: A multicenter prospective study was undertaken in patients with primary snoring and mild sleep apnea where daytime NMES (eXciteOSA® Signifier Medical Technologies Ltd., London W6 0LG, UK) was used for 20 min once daily for 6 weeks. Change in percentage time spent snoring was analyzed using a two-night sleep study before and after therapy. Participants and their bed partners completed sleep quality questionnaires: Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI), and the bed partners reported on the nighttime snoring using a Visual Analogue Scale (VAS). Results: Of 125 patients recruited, 115 patients completed the trial. Ninety percent of the study population had some reduction in objective snoring with the mean reduction in the study population of 41% (p < 0.001). Bed partner-reported snoring reduced significantly by 39% (p < 0.001). ESS and total PSQI scores reduced significantly (p < 0.001) as well as bed partner PSQI (p = 0.017). No serious adverse events were reported. Conclusions: Daytime NMES (eXciteOSA®) is demonstrated to be effective at reducing objective and subjective snoring. It is associated with effective improvement in patient and bed partner sleep quality and patient daytime somnolence. Both objective and subjective measures demonstrated a consistent improvement. Daytime NMES was well tolerated and had minimal transient side effects.

Platelet hyperaggregability and venous thrombosis risk: results from the RETROVE project.

The aim of the study was to determine whether platelet hyperaggregability correlates with short closure times (PFA-100) and if hyperaggregability is associated with the risk of venous thrombosis in a Spanish population. Case--control study (RETROVE project) involving 400 patients with venous thrombosis and 400 healthy controls. We determined platelet aggregation in platelet-rich plasma (PRP) by light transmission aggregometry. Various concentrations of two aggregation agonists [ADP and epinephrine (EPI)] were tested to determine the percentage of maximal aggregation and the percentage area under the curve (AUC). Venous thrombosis risk associated with platelet hyperaggregability was calculated by logistic regression. We estimated the crude and adjusted (by sex and age) odds ratios (OR) for venous thrombosis risk. An agonist concentration of 0.5 µmol/l differentiated between hypo-responders and hyper-responders at the following AUC cut-off values: EPI: the 50th percentile for aggregation with 0.5 µmol/l of EPI (EPI_AUC) was 22.53% (>22.53% = hyper-EPI); the crude risk for venous thrombosis was statistically significant (OR = 1.37; 95% CI 1.03-1.82); ADP: the 75th percentile for aggregation with 0.5 µmol/l of ADP (ADP_AUC) was 29.6% (>29.6% = hyper-ADP), with a significant crude risk for venous thrombosis (OR = 1.44; 95% CI 1.05-1.98). However, after adjustment for confounders (age), the ORs for EPI or ADP aggregation were no longer significant. EPI_AUC and PFA-100 values with the EPI agonist were significantly correlated (R = -0.342, P < 0.01). Only 12% of the PFA-100 values were explained by platelet aggregation. In this case--control study, platelet hyperaggregability was not associated with the risk of developing venous thrombosis.

Comparación de los resultados de la artroplastia total de tobillo en pacientes menor o igual a 55 y mayor a 55 años / Comparison of total ankle arthroplasty outcomes between patients younger and older than 55 years

Objetivo: Comparar los resultados posoperatorios clínicos y radiográficos en dos grupos de pacientes: menor o igual a 55 años y mayor a 55 años, sometidos a una artroplastia total de tobillo de tercera generación. Materiales y Métodos: Se evaluó, en forma retrospectiva, a dos grupos de pacientes: menor o igual a 55 años (n = 13) y mayor a 55 años (n = 18), que fueron sometidos a una artroplastia total de tobillo de tercera generación. La edad promedio del grupo de menor o igual a 55 años era 42.8 (DE 6.4) y la del grupo mayor a 55 años, 65.7 (DE 8.8). Resultados: El seguimiento promedio fue de 36 meses (RIC 25-60). La etiología era principalmente postraumática en ambos grupos. El puntaje promedio de la escala AOFAS al año de la cirugía fue 76,69 (RIC 58-89) en el grupo menor o igual a 55 años y 85,22 (RIC 67-100) en el grupo mayor a 55 años. No hubo diferencias estadísticamente significativas entre ambos grupos en los ángulos alfa, beta y gamma; medidos en las radiografías con apoyo a los 2 meses y a los 2 años de la cirugía. Conclusiones: Nuestro estudio demostró que los resultados clínicos y radiográficos en pacientes más jóvenes serían comparables con los de pacientes más grandes en el seguimiento temprano. Se necesita un seguimiento a más largo plazo para determinar si el riesgo de revisión es más alto en los pacientes jóvenes, debido a la falla relacionada con el desgaste de la prótesis

Objective: To compare the clinical and radiographic postoperative outcomes in two groups of patients: younger 55 and older than 55-year patients undergoing a third-generation total ankle arthroplasty (TAA). Materials and Methods: Two groups of patients were retrospectively studied: younger 55 (n=13) and older 55-year patients (n=19) undergoing a third-generation TAA. Group younger 55 average age was 42.8 (SD, 6.4) and Group older 55 average age was 65.7 (SD, 8.8). Results: The average follow-up was 36 months (IQR, 25-60). The main etiology was post-traumatic conditions in both groups. The mean score of the AOFAS scale one year after surgery was 76.69 (IQR, 58-89) in the group younger 55 and 85.22 (IQR, 67-100) in the group older 55. There were no statistically significant differences between the two groups in the alpha, beta and gamma angles measured on weight-bearing radiographs at 2-month and 2-year postoperative controls. Conclusions: Our study shows clinical and radiographic short-term outcomes in younger patients are similar to those in older patients. Longer-term follow-up is warranted to determine if the revision risk is greater in young patients, due to failures related to prosthesis wear

[Pyridoxine-dependent epilepsy due to deficiency in the PNPO gene]. / Epilepsia dependiente de piridoxina por deficiencia en el gen PNPO.

TITLE: Epilepsia dependiente de piridoxina por deficiencia en el gen PNPO.

VAMP8 and serotonin transporter levels are associated with venous thrombosis risk in a Spanish female population. Results from the RETROVE Project.

INTRODUCTION: Platelet hyper-reactivity has been associated with thrombosis and high levels of human vesicle-associated membrane protein 8 (VAMP8) and serotonin transporter (SERT). Two polymorphisms (rs1010 of VAMP8 gene and in SERT gene (SLC6A4)) are associated with arterial thrombosis. AIM: To determine if levels of serotonin, SERT and/or VAMP8 and these polymorphisms are associated with the risk of venous thrombosis. MATERIAL AND METHODS: A total of 324 individuals were included in the RETROVE Study (Riesgo de Enfermedad TROmboembólica VEnosa). VAMP8, SERT and serotonin were determined by ELISA; polymorphisms of SLC6A4 and VAMP8 by polymerase chain reaction (PCR) and real time PCR. The venous thrombotic risk was calculated by a logistic regression method to estimate the crude and adjusted OR (adjusted for sex, age, body mass index and venous thrombosis risk co-factors). RESULTS: Statistically significant high levels of VAMP8 and SERT were found in patients, but not in controls. In contrast, serotonin showed lower levels in patients than in controls. When individuals were studied by gender, only women exhibited a statistically significant difference: the OR for VAMP8 was 3.25 (1.61-6.56 95% CI). The adjusted OR did not change. The OR for SERT was 2.76 (1.36-5.60 95% CI), the adjusted OR was maintained also. For serotonin with OR of 2.62 (1.40-4.92 95% CI), the adjusted OR was not significant. In contrast males did not show significant differences. No statistically differences between patients and controls were found for both polymorphisms. CONCLUSIONS: VAMP8 and SERT levels are associated with venous thrombosis in a female Spanish population.