Discriminant canonical analysis as a tool for genotype traceability testing based on turkey meat and carcass traits.

The present study aims to develop a statistical tool for turkey breed traceability testing based on meat and carcass quality characteristics. To this end, a comprehensive meta-analysis was performed, collecting data from a total of 75 studies approaching meat and carcass attributes of 37 turkey strains and landraces since the late 1960s. A total of 22 meat and carcass traits were considered variables, grouped in the following clusters: carcass dressing traits, muscle fiber properties, pH, colorimetry, water-capacity traits, texture-related attributes, and nutritional composition of the meat. Once the multicollinearity analysis allowed the deletion of redundant variables, cold carcass weight, slaughter weight, muscle fiber diameter, sex-female, carcass/piece weight, meat redness, ashes, pH24, meat lightness, moisture, fat, and water-holding capacity showed explanatory properties in the discriminating analysis (p < 0.05). In addition, strong positive and negative correlations were found among those variables studied. Carcass traits were positively associated, particularly slaughter weight and cold carcass weight (+0.561). Among meat physical traits, pH showed positive correlations with drip loss (+0.490) and pH24 (+0.327), and water-holding capacity was positively associated with cholesterol (+0.434) and negatively associated with collagen (-0.398). According to nutritional traits, fat and ash showed a strong correlation (+0.595), and both were negatively associated with moisture (-0.375 and -0.498, respectively). Strong negative correlations were found as well between meat protein and fat (-0.460) and between collagen and cholesterol (-0.654). Finally, the Mahalanobis distance suggested a clustering pattern based on meat and carcass characteristics that report information about interbreeding and variety proximity. This study establishes a departure point in the development of a tool for breed traceability guaranteeing aimed at enhancing distinguished, local breed-based turkey meat.

CAR Immunotherapy for the treatment of infectious diseases: a systematic review.

Immunotherapy treatments aim to modulate the host's immune response to either mitigate it in inflammatory/autoimmune disease or enhance it against infection or cancer. Among different immunotherapies reaching clinical application during the last years, chimeric antigen receptor (CAR) immunotherapy has emerged as an effective treatment for cancer where different CAR T cells have already been approved. Yet their use against infectious diseases is an area still relatively poorly explored, albeit with tremendous potential for research and clinical application. Infectious diseases represent a global health challenge, with the escalating threat of antimicrobial resistance underscoring the need for alternative therapeutic approaches. This review aims to systematically evaluate the current applications of CAR immunotherapy in infectious diseases and discuss its potential for future applications. Notably, CAR cell therapies, initially developed for cancer treatment, are gaining recognition as potential remedies for infectious diseases. The review sheds light on significant progress in CAR T cell therapy directed at viral and opportunistic fungal infections.

Circulating blood circular RNA in Parkinson's Disease; a systematic study.

We aimed to identify circRNAs associated with Parkinson's disease (PD) by leveraging 1,848 participants and 1,789 circRNA from two of the largest publicly available studies with longitudinal clinical and blood transcriptomic data. To comprehensively understand changes in circRNAs we performed a cross-sectional study utilizing the last visit of each participant, and a longitudinal (mix model) analysis that included 1,166 participants with at least two time points. We identified 192 circRNAs differentially expressed in PD participants compared to healthy controls, with effects that were consistent in the mixed models, mutation carriers, and diverse ancestry. Finally, we included the 149 circRNA in a model with a ROC AUC of 0.825, showing that have the potential to aid the diagnosis of PD. Overall, we demonstrated that circRNAs play an important role in PD and can be leveraged as biomarkers.

Inverse regulation of SOS1 and HKT1 protein localization and stability by SOS3/CBL4 in Arabidopsis thaliana.

To control net sodium (Na+) uptake, Arabidopsis plants utilize the plasma membrane (PM) Na+/H+ antiporter SOS1 to achieve Na+ efflux at the root and Na+ loading into the xylem, and the channel-like HKT1;1 protein that mediates the reverse flux of Na+ unloading off the xylem. Together, these opposing transport systems govern the partition of Na+ within the plant yet they must be finely co-regulated to prevent a futile cycle of xylem loading and unloading. Here, we show that the Arabidopsis SOS3 protein acts as the molecular switch governing these Na+ fluxes by favoring the recruitment of SOS1 to the PM and its subsequent activation by the SOS2/SOS3 kinase complex under salt stress, while commanding HKT1;1 protein degradation upon acute sodic stress. SOS3 achieves this role by direct and SOS2-independent binding to previously unrecognized functional domains of SOS1 and HKT1;1. These results indicate that roots first retain moderate amounts of salts to facilitate osmoregulation, yet when sodicity exceeds a set point, SOS3-dependent HKT1;1 degradation switches the balance toward Na+ export out of the root. Thus, SOS3 functionally links and co-regulates the two major Na+ transport systems operating in vascular plants controlling plant tolerance to salinity.

ABA INSENSITIVE 2 promotes flowering by inhibiting OST1/ABI5-dependent FLOWERING LOCUS C transcription in Arabidopsis.

The plant hormone abscisic acid (ABA) is an important regulator of plant growth and development and plays a crucial role in both biotic and abiotic stress responses. ABA modulates flowering time, but the precise molecular mechanism remains poorly understood. Here we report that ABA INSENSITIVE 2 (ABI2) is the only phosphatase from the ABA-signaling core that positively regulates the transition to flowering in Arabidopsis. Loss-of-function abi2-2 mutant shows significantly delayed flowering both under long day and short day conditions. Expression of floral repressor genes such as FLOWERING LOCUS C (FLC) and CYCLING DOF FACTOR 1 (CDF1) was significantly up-regulated in abi2-2 plants while expression of the flowering promoting genes FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) was down-regulated. Through genetic interactions we further found that ost1-3 and abi5-1 mutations are epistatic to abi2-2, as both of them individually rescued the late flowering phenotype of abi2-2. Interestingly, phosphorylation and protein stability of ABA INSENSITIVE 5 (ABI5) were enhanced in abi2-2 plants suggesting that ABI2 dephosphorylates ABI5, thereby reducing protein stability and the capacity to induce FLC expression. Our findings uncovered the unexpected role of ABI2 in promoting flowering by inhibiting ABI5-mediated FLC expression in Arabidopsis.

Endoscopic ultrasound performed by surgical approach in a patient with pancreatic lesion and stenosing esophageal adenocarcinoma.

Endoscopic retrograde cholangiopancreatography (ERCP) performed in situations of altered anatomy has been described. Thus, in cases of Roux-en-Y gastric by-pass, several approaches have been documented for performing ERCP: by enteroscopy, guided by laparoscopic approach through the gastric remnant, and direct transgastric guided by endoscopic ultrasound through a stent between the reservoir or alimentary loop and the gastric remnant. However, there are clinical situations in which the anatomy is not altered, but there may be pancreatic lesions subsidiary to study by endoscopic ultrasound in situations where the endoscope cannot pass through the esophagus. Therefore, we present the clinical case of a patient with a pancreatic lesion subsidiary to study and a distal esophageal adenocarcinoma that prevented the passage of the endoscope.

Pilot study: a detailed analysis of the timing of immuno-inflammatory indices in gastric cancer, and their assessment together with TNM as supplementary prognostic factors.

An analysis of the prognostic impact of up to 36 immuno-inflammatory indices at 3 different times during the diagnostic-therapeutic process for gastric cancer. The dependent variable was disease-free survival at 3 years. The independent factors obtained were combined with TNM to provide an improved prognostic model.

Unilateral focused ultrasound subthalamotomy in early Parkinson's disease: a pilot study.

BACKGROUND: Unilateral focused ultrasound subthalamotomy (FUS-STN) improves motor features of Parkinson's disease (PD) in moderately advanced patients. The less invasive nature of FUS makes its early application in PD feasible. We aim to assess the safety and efficacy of unilateral FUS-STN in patients with PD of less than 5 years from diagnosis (early PD). METHODS: Prospective, open-label study. Eligible patients with early PD had highly asymmetrical cardinal features. The primary outcome was safety, defined as treatment-related adverse events at 6 months. Secondary outcomes included efficacy, assessed as motor improvement in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), motor fluctuations, non-motor symptoms, daily living activities, quality of life, medication and patients' impression of change. RESULTS: Twelve patients with PD (median age 52.0 (IQR 49.8-55.3) years, median time from diagnosis 3.0 (2.1-3.9) years) underwent unilateral FUS-STN. Within 2 weeks after treatment, five patients developed dyskinesia on the treated side, all resolved after levodopa dose adjustment. One patient developed mild contralateral motor weakness which fully resolved in 4 weeks. One patient developed dystonic foot and another hand and foot dystonia. The latter impaired gait and became functionally disabling initially. Both cases were well controlled with botulinum toxin injections. The off-medication motor MDS-UPDRS score for the treated side improved at 12 months by 68.7% (from 14.5 to 4.0, p=0.002), and the total motor MDS-UPDRS improved by 49.0% (from 26.5 to 13.0, p=0.002). Eleven patients (92%) reported global improvement 12 months after treatment. CONCLUSION: Unilateral FUS-STN may be safe and effective to treat motor manifestations in patients with early PD. A larger confirmatory trial is warranted. TRIAL REGISTRATION NUMBER: NCT04692116.

Effect of a resistance exercise at acute moderate altitude on muscle health biomarkers.

The intensification of the stress response during resistance training (RT) under hypoxia conditions could trigger unwanted effects that compromise muscle health and, therefore, the ability of the muscle to adapt to longer training periods. We examined the effect of acute moderate terrestrial hypoxia on metabolic, inflammation, antioxidant capacity and muscle atrophy biomarkers after a single RT session in a young male population. Twenty healthy volunteers allocated to the normoxia (N < 700 m asl) or moderate altitude (HH = 2320 m asl) group participated in this study. Before and throughout the 30 min following the RT session (3 × 10 reps, 90 s rest, 70% 1RM), venous blood samples were taken and analysed for circulating calcium, inorganic phosphate, cytokines (IL-6, IL-10 and TNF-α), total antioxidant capacity (TAC) and myostatin. Main results displayed a marked metabolic stress response after the RT in both conditions. A large to very large proportional increase in the adjusted to pre-exercise change of inflammatory and anti-inflammatory markers favoured HH (serum TNF-α [ES = 1.10; p = 0.024] and IL-10 [ES = 1.31; p = 0.009]). The exercise produced a similar moderate increment of myostatin in both groups, followed by a moderate non-significant reduction in HH throughout the recovery (ES = - 0.72; p = 0.21). The RT slightly increased the antioxidant response regardless of the environmental condition. These results revealed no clear impact of RT under acute hypoxia on the metabolic, TAC and muscle atrophy biomarkers. However, a coordinated pro/anti-inflammatory response balances the potentiated effect of RT on systemic inflammation.

Manifestación clínica inicial de la lipomatosis epidural lumbar grado III de Naka: serie de casos / Initial clinical signs of Naka's grade III lumbar epidural lipomatosis: A case series

Introducción: La lipomatosis epidural espinal es una enfermedad infrecuente caracterizada por el sobrecrecimiento del tejido adiposo no encapsulado dentro del espacio epidural. Esto genera una estenosis del conducto espinal que puede provocar sintomatología compresiva. La presentación típica es insidiosa a lo largo de meses o años. El objetivo de este estudio fue realizar un análisis descriptivo de la manifestación clínica inicial en pacientes con lipomatosis epidural espinal grado III de Naka. Materiales y métodos: Estudio observacional retrospectivo en la Unidad de Patología Espinal de 4 instituciones, de 2010 a 2023. Se incluyó a pacientes >18 años, de ambos sexos, que acudieron por dolor lumbar con irradiación o sin irradiación, y presentaban lipomatosis lumbar Naka III en la resonancia magnética. Resultados: Se incorporó a 40 pacientes (edad promedio 62.5 años). El 75% era obeso, ninguno era fumador. El motivo de consulta más frecuente fue lumbalgia, con una mediana de evolución del dolor de 5.5 meses. Conclusiones:La lumbalgia fue la consulta más frecuente, con excepción del compromiso de L3-S1 que fue la lumbocruralgia. Los pacientes que sufrieron dolor más tiempo (>6 meses) eran más jóvenes y tenían un índice de masa corporal menor; sin embargo, no resultó estadísticamente significativo. Nivel de Evidencia: IV

Introduction: Spinal epidural lipomatosis (SEL) is a rare pathology characterized by the overgrowth of nonencapsulated adipose tissue within the epidural space. This generates spinal stenosis, which might result in compression symptoms. The typical presentation is insidious pain that lasts months or years. The objective of this study was to carry out a descriptive analysis of the initial clinical signs of patients with Naka's grade III lumbar SEL. materials and methods: Retrospective observational study in the Spinal Pathology Unit of 4 institutions, from 2010 to 2023. Patients over the age of 18, of both sexes, who consulted for low back pain with or without radiation and presented Naka's grade III lumbar lipomatosis on magnetic resonance imaging (MRI) were included. Results: We included 40 patients, with a mean age of 62.5 years; 75% were obese, there were no smokers. The most frequent reason for consultation was low back pain, with a median duration of 5.5 months. Conclusions: The most common reason for consultation was low back pain, with the exception of L3-S1 level involvement, which caused lumbar pain with radiation to the thigh. Patients with a longer period of pain (>6 months) were younger and had a lower BMI; although this was not statistically significant. Level of Evidence: IV

Frecuencia del dolor lumbar en médicos especialistas en Ortopedia y Traumatología: estudio transversal / Prevalence of low back pain in Orthopedics and Traumatology specialists: A cross-sectional study

Introducción: Hasta el 85% de la población padecerá, al menos, un episodio de dolor lumbar a lo largo de su vida. Representa una de las principales quejas del personal de salud, y tiene una prevalencia anual del 77%; los traumatólogos tenemos múltiples factores de riesgo para desarrollar este cuadro. El objetivo de este estudio fue evaluar la prevalencia de lumbalgia e identificar posibles factores asociados, en una muestra de médicos traumatólogos.materiales y métodos: Estudio analítico observacional transversal sobre el padecimiento de dolor lumbar en médicos especialistas en Ortopedia y Traumatología, miembros de la AAOT. El cuestionario se envió semanalmente durante un mes. Resultados: Se recibieron 393 respuestas, predominó el sexo masculino, y la media de la edad era de 46 años. Más del 50% de la muestra refirió sobrepeso, y el 43%, sedentarismo. La media de autopercepción de estrés laboral fue de 7. Un 86% afirmó haber sufrido, al menos, un episodio en el último año y un 38%, más de 4 episodios. Conclusiones: La prevalencia de lumbalgia fue alta. Predominaron los episodios agudos, no fueron necesarios estudios complementarios. Menos del 10% hizo reposo laboral. El hábito sedentario, el número de comorbilidades y la edad se asociaron con un riesgo más alto de sufrir >2 episodios de dolor. Nivel de Evidencia: III

Introduction: Up to 85% of the population will suffer at least one episode of low back pain throughout their lives. It is one of the most common complaints among healthcare workers, with a reported annual prevalence of 77%. Orthopedic surgeons have multiple risk factors for developing this condition. The objective of this study was to evaluate the prevalence of low back pain and identify possible contributing factors in a sample of orthopedic surgeons. Materials and methods: Across-sectional observational analytical study on low back pain in Orthopedics and Traumatology specialists who are members of the AAOT. Over the course of one month, a questionnaire was sent weekly. Results: 393 responses were received, the predominant sex was male, and the mean age was 46 years. More than 50% of the sample reported being overweight, whereas 43% reported being sedentary. The average self-perceived work stress was 7. 86% of respondents reported at least one episode in the previous year, with 38% reporting more than four. Conclusions: The prevalence of low back pain was high. Acute episodes predominated, and complementary studies were not necessary. Less than 10% took time off work. Sedentary habits, comorbidities, and age were all associated with an increased likelihood of suffering >2 episodes of pain. Level of Evidence: III

Deep-brain stimulation of the human nucleus accumbens-medial septum enhances memory formation.

Deep-brain stimulation (DBS) is a potential novel treatment for memory dysfunction. Current attempts to enhance memory focus on stimulating human hippocampus or entorhinal cortex. However, an alternative strategy is to stimulate brain areas providing modulatory inputs to medial temporal memory-related structures, such as the nucleus accumbens (NAc), which is implicated in enhancing episodic memory encoding. Here, we show that NAc-DBS improves episodic and spatial memory in psychiatric patients. During stimulation, NAc-DBS increased the probability that infrequent (oddball) pictures would be subsequently recollected, relative to periods off stimulation. In a second experiment, NAc-DBS improved performance in a virtual path-integration task. An optimal electrode localization analysis revealed a locus spanning postero-medio-dorsal NAc and medial septum predictive of memory improvement across both tasks. Patient structural connectivity analyses, as well as NAc-DBS-evoked hemodynamic responses in a rat model, converge on a central role for NAc in a hippocampal-mesolimbic circuit regulating encoding into long-term memory. Thus, short-lived, phasic NAc electrical stimulation dynamically improved memory, establishing a critical on-line role for human NAc in episodic memory and providing an empirical basis for considering NAc-DBS in patients with loss of memory function.

Human adipose tissue as a major reservoir of cytomegalovirus-reactive T cells.

Introduction: Cytomegalovirus (CMV) is a common herpesvirus with a high prevalence worldwide. After the acute infection phase, CMV can remain latent in several tissues. CD8 T cells in the lungs and salivary glands mainly control its reactivation control. White adipose tissue (WAT) contains a significant population of memory T cells reactive to viral antigens, but CMV specificity has mainly been studied in mouse WAT. Therefore, we obtained blood, omental WAT (oWAT), subcutaneous WAT (sWAT), and liver samples from 11 obese donors to characterize the human WAT adaptive immune landscape from a phenotypic and immune receptor specificity perspective. Methods: We performed high-throughput sequencing of the T cell receptor (TCR) locus to analyze tissue and blood TCR repertoires of the 11 donors. The presence of TCRs specific to CMV epitopes was tested through ELISpot assays. Moreover, phenotypic characterization of T cells was carried out through flow cytometry. Results: High-throughput sequencing analyses revealed that tissue TCR repertoires in oWAT, sWAT, and liver samples were less diverse and dominated by hyperexpanded clones when compared to blood samples. Additionally, we predicted the presence of TCRs specific to viral epitopes, particularly from CMV, which was confirmed by ELISpot assays. Remarkably, we found that oWAT has a higher proportion of CMV-reactive T cells than blood or sWAT. Finally, flow cytometry analyses indicated that most WAT-infiltrated lymphocytes were tissue-resident effector memory CD8 T cells. Discussion: Overall, these findings postulate human oWAT as a major reservoir of CMV-specific T cells, presumably for latent viral reactivation control. This study enhances our understanding of the adaptive immune response in human WAT and highlights its potential role in antiviral defense.

Cell-free RNA signatures predict Alzheimer's disease.

There is a need for affordable, scalable, and specific blood-based biomarkers for Alzheimer's disease that can be applied to a population level. We have developed and validated disease-specific cell-free transcriptomic blood-based biomarkers composed by a scalable number of transcripts that capture AD pathobiology even in the presymptomatic stages of the disease. Accuracies are in the range of the current CSF and plasma biomarkers, and specificities are high against other neurodegenerative diseases.

Síndrome post-COVID o COVID persistente, situaciones de incapacidad temporal, estudio de casos, protocolo de valoración de la incapacidad laboral / Post-covid or persistent covid syndrome, temporary disability situations, case study, work disability assessment protocol

Objetivo El Síndrome Post-COVID o COVID Persistente ha afectado más de 240.000 trabajadores causando incapacidad laboral, de duración e intensidad variable y de valoración compleja. Para una mejor capacidad decisoria para valorar la capacidad/incapacidad laboral proponemos un protocolo de valoración de los síntomas más limitantes en relación con el trabajo. Material y Métodos: Se realizaron búsquedas en PubMed/MEDLINE, SciELO, de artículos publicados en 2021, y hasta marzo 2022, así como otras fuentes que se reseñan en bibliografía. Para el estudio de casos se escogieron procesos de IT que reunieran características de SPC, de más de 90 días analizando diversas variables. Conclusiones: Síndrome Post-COVID presenta síntomas que son factores de mal pronóstico para el retorno laboral. La valoración de la capacidad laboral requiere un protocolo específico de evaluación de las limitaciones funcionales y su traslación a diversas tareas que pueden estar comprometidas (AU)

Introduction: Post-COVID Syndrome or Persistent COVID has affected more than 240,000 workers, causing work disability of variable duration and intensity and complex assessment. Material and Methods: Searches were carried out in PubMed/MEDLINE, SciELO, for articles published in 2021, and until March 2022, as well as other sources reviewed in the bibliography. For the case study, IT processes were chosen that met SPC characteristics, lasting more than 90 days, analyzing various variables. Conclusions: Post-COVID Syndrome presents symptoms that are poor prognostic factors for returning to work. The assessment of work capacity requires a specific protocol for evaluating functional limitations and their translation to various tasks that may be compromised (AU)

Carcinoma neuroendocrino de células grandes en la unión esofagogástrica. Una entidad extremadamente infrecuente / Large cell neuroendocrine carcinoma at the esophagogastric junction. An extremely rare entity

Presentamos el tercer caso descrito hasta la fecha de carcinoma neuroendocrino de células grandes localizado en la unión esofagogástrica (CNECG). Los tumores neuroendocrinos esofágicos representan el 0,03-0,05% de todos los tumores malignos esofágicos. Dentro de los TNE esofágicos. El CNECG representa el 1% de los TNE esofágicos. Este tipo tumoral se caracteriza por elevar unos marcadores determinados: sinaptofisina, cromogranina A y CD56. De hecho, el 100% de los pacientes tendrán cromogranina o sinaptofisina, o al menos uno de estos tres marcadores. A su vez, el 78% tendrán invasión linfovascular y el 26% invasión perineural. Únicamente el 11% de los pacientes tendrán un estadio I-II, circunstancia que implica un curso agresivo y un peor pronóstico.(AU)

Protocolización de estudios clínicos multicéntricos en la era digital. ¿Tiene utilidad la centralización de datos por un data-manager? / Protocolization of multicenter clinical studies in the digital era. Is useful data centralization by a data-manager?

Introducción En los estudios multicéntricos la protocolización de los datos es una fase crítica que puede generar sesgos, sobre todo en estudios clínicos con presupuesto limitado. El objetivo es analizar la concordancia y la confiabilidad de los datos obtenidos en un estudio multicéntrico clínico entre la protocolización del centro de origen y la protocolización centralizada mediante un data-manager. Método Estudio clínico multicéntrico de prevalencia nacional sobre un carcinoma familiar infrecuente, realizándose una doble protocolización de los datos: a)en el centro de origen, y b)centralizada con un data-manager. La concordancia se analiza para el global de los datos y para los dos subgrupos del proyecto: a)grupo a estudio (carcinoma familiar; protocolizan 30 investigadores) y b)grupo control (carcinoma esporádico; protocolizan 4). Las diferencias interobservador se evalúan mediante el índice de Kappa de Cohen. Resultados Se incluyen 689 pacientes: 252 del grupo a estudio y 437 del grupo control. Respecto al análisis de concordancia del estadio tumoral, se han objetivado un 2,5% de discordancias, siendo alta la concordancia entre protocolizadores (Kappa=0,931). Respecto a la valoración del riesgo de recidiva, las discordancias fueron del 7% de los casos, siendo alta la concordancia (Kappa=0,819). Respecto a la clasificación ecográfica TIRADS, las discordancias son del 6,9% y la concordancia es alta (Kappa=0,922). Se han detectado un 4,6% de errores de transcripción. Conclusiones En los estudios multicéntricos clínicos la protocolización centralizada de los datos por un data-manager parece presentar resultados similares a la protocolización directa en la base de datos en el centro de origen. (AU)

Introduction In multicenter studies, the protocolization of data is a critical phase that can generate biases. The objective is to analyze the concordance and reliability of the data obtained in a clinical multicenter study between the protocolization in the center of origin and the centralized protocolization of the data by a data-manager. Methods National multicenter clinical study about an infrequent carcinoma. A double protocolization of the data is carried out: (i)center of origin; and (ii)centralized by a data manager. The concordance between the data is analyzed for the global data and for the two groups of the project: (i)study group (familiar carcinoma, 30 researchers protocolize); (ii)control group (sporadic carcinoma, 4 people protocolize). Interobserver variability is evaluated using Cohen's kappa coefficient. Results The study includes a total of 689 patients with carcinoma: 252 in the study group and 437 in the control group. Regarding the concordance analysis of the tumor stage, 2.5% of disagreements were observed and the concordance between people who protocolize was near perfect (Kappa=0.931). Regarding the evaluation of the recurrence risk, disagreements occurred in 7% of the cases and the concordance was near perfect (Kappa=0.819). Regarding the sonography evaluation (TIRADS), the disagreements were 6.9% and the concordance was near perfect (Kappa=0.922). Also, 4.6% of transcription errors were detected. Conclusions In multicenter clinical studies, the centralized data protocolization by a data-manager seems to present similar results to the direct protocolization in the database in the center of origin. (AU)

Genome Sequencing of Consanguineous Family Implicates Ubiquitin-Specific Protease 53 (USP53) Variant in Psychosis/Schizophrenia: Wild-Type Expression in Murine Hippocampal CA 1-3 and Granular Dentate with AMPA Synapse Interactions.

Psychosis is a severe mental disorder characterized by abnormal thoughts and perceptions (e.g., hallucinations) occurring quintessentially in schizophrenia and in several other neuropsychiatric disorders. Schizophrenia is widely considered as a neurodevelopmental disorder that onsets during teenage/early adulthood. A multiplex consanguineous Pakistani family was afflicted with severe psychosis and apparent autosomal recessive transmission. The first-cousin parents and five children were healthy, whereas two teenage daughters were severely affected. Structured interviews confirmed the diagnosis of DSM-V schizophrenia. Probands and father underwent next-generation sequencing. All available relatives were subjected to confirmatory Sanger sequencing. Homozygosity mapping and directed a priori filtering identified only one rare variant [MAF < 5(10)-5] at a residue conserved across vertebrates. The variant was a non-catalytic deubiquitinase, USP53 (p.Cys228Arg), predicted in silico as damaging. Genome sequencing did not identify any other potentially pathogenic single nucleotide variant or structural variant. Since the literature on USP53 lacked relevance to mental illness or CNS expression, studies were conducted which revealed USP53 localization in regions of the hippocampus (CA 1-3) and granular dentate. The staining pattern was like that seen with GRIA2/GluA2 and GRIP2 antibodies. All three proteins coimmunoprecipitated. These findings support the glutamate hypothesis of schizophrenia as part of the AMPA-R interactome. If confirmed, USP53 appears to be one of the few Mendelian variants potentially causal to a common-appearing mental disorder that is a rare genetic form of schizophrenia.