New advances in genomics and epigenetics in antiphospholipid syndrome.

APS patients exhibit a wide clinical heterogeneity in terms of the disease's origin and progression. This diversity can be attributed to consistent aPL profiles and other genetic and acquired risk factors. Therefore, understanding the pathophysiology of APS requires the identification of specific molecular signatures that can explain the pro-atherosclerotic, pro-thrombotic and inflammatory states observed in this autoimmune disorder. In recent years, significant progress has been made in uncovering gene profiles and understanding the intricate epigenetic mechanisms and microRNA changes that regulate their expression. These advancements have highlighted the crucial role played by these regulators in influencing various clinical aspects of APS. This review delves into the recent advancements in genomic and epigenetic approaches used to uncover the mechanisms contributing to vascular and obstetric involvement in APS. Furthermore, we discuss the implementation of novel bioinformatics tools that facilitate the investigation of these mechanisms and pave the way for personalized medicine in APS.

Dopaminergic denervation and associated MRI microstructural changes in the nigrostriatal projection in early Parkinson's disease patients.

Loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and a profound reduction of striatal dopamine are two hallmarks of Parkinson's disease (PD). However, it's unclear whether degeneration starts at the neuronal soma or the striatal presynaptic terminals, and how microstructural degeneration is linked to dopaminergic loss is also uncertain. In this study, thirty de novo PD patients and twenty healthy subjects (HS) underwent 6-[18F]-fluoro-L-dopa (FDOPA) PET and MRI studies no later than 12 months from clinical diagnosis. FDOPA uptake rate (Ki), fractional volume of free-water (FW), and iron-sensitive R2* relaxometry were quantified within nigrostriatal regions. Inter-group differences (PD vs HS) were studied using non-parametric statistics and complemented with Cohen's d effect sizes and Bayesian statistics. Correlation analyses were performed exploring biomarker dependencies and their association with bradykinesia scores. PD patients exhibited a significant decline in nigrostriatal dopaminergic activity, being post-commissural putamen (-67%) and posterolateral SNc (-11.7%) the most affected subregions within striatum and SNc respectively. Microstructural alterations (FW) were restricted to the hemisphere corresponding to the most affected side and followed similar spatial gradients as FDOPA Ki (+20% in posterior putamen and +11% in posterolateral SNc). R2* revealed no relevant significant changes. FDOPA and FW were correlated within the posterolateral SNc, and clinical severity was associated with FDOPA Ki loss. The asymmetry between striatal and SNc changes for both dopaminergic depletion and microstructural degeneration biomarkers is consistent with a neurodegenerative process that begins in the striatal terminals before progressing toward the cell bodies in the SNc.

Splicing machinery is profoundly altered in systemic lupus erythematosus and antiphospholipid syndrome and directly linked to key clinical features.

OBJECTIVES: To characterize the splicing machinery (SM) of leukocytes from primary antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome with lupus (APS + SLE) patients, and to assess its clinical involvement. METHODS: Monocytes, lymphocytes and neutrophils from 80 patients (22 APS, 35 SLE and 23 APS + SLE) and 50 HD were purified, and 45 selected SM components were evaluated by qPCR-microfluidic array. Relationship with clinical features and underlying regulatory mechanisms were assessed. RESULTS: APS, SLE and APS + SLE leukocytes displayed significant and specific alterations in SM-components (SMC), associated with clinical features [autoimmune profiles, disease activity, lupus nephritis (LN), and CV-risk markers]. A remarkable relationship among dysregulated SMC in monocytes and the presence of LN in SLE was highlighted, revealing a novel pathological mechanism, which was further explored. Immunohistology analysis of renal biopsies highlighted the pathological role of the myeloid compartment in LN. Transcriptomic analysis of monocytes from SLE-LN(+) vs SLE-LN(-) identified 271 genes differentially expressed, mainly involved in inflammation and IFN-signaling. Levels of IFN-related genes correlated with those of SMC in SLE-LN(+). These results were validated in two external SLE-LN(+) datasets of whole-blood and kidney biopsies. In vitro, SLE-LN(+)-serum promoted a concomitant dysregulation of both, the IFN signature and several SMC, further reversed by JAKinibs treatment. Interestingly, IFNs, key inflammatory cytokines in SLE pathology, also altered SMC. Lastly, the over/down-expression of selected SMC in SLE-monocytes reduced the release of inflammatory cytokines and their adhesion capacity. CONCLUSION: Overall, we have identified, for the first time, a specific alteration of SMC in leukocytes from APS, SLE and APS + SLE patients that would be responsible for the development of distinctive clinical profiles.

CT findings for dental disease.

Traumatic and especially inflammatory-infectious dental lesions are very prevalent in our context. Inflammatory-infectious disease is usually discovered incidentally on imaging studies that include the orofacial region. Moreover, these conditions can result in potentially severe complications, so early diagnosis and treatment are important. Multidetector computed tomography offers good diagnostic performance for dental lesions, although the radiological findings can be subtle and can go undetected if the radiologist is not familiar with them. Likewise, invasive dental procedures are becoming increasingly common, and these can also result in complications. On the other hand, in daily practice a variety of radiolucent mandibular lesions or developmental anomalies can lead to erroneous interpretations. For these reasons, radiologists should be familiar with possible findings related with dental conditions.

Hallazgos por imagen de patología dentaria en tomografía computarizada / CT findings for dental disease

La patología dentaria traumática y en especial la inflamatorio-infecciosa son muy prevalentes en nuestro medio. Esta última suele encontrarse de forma incidental en muchos de los estudios radiológicos que incluyen la región orofacial. Además, es una potencial causa de complicaciones graves, lo que hace que su diagnóstico y tratamiento precoz sean importantes. La tomografía computarizada multidetector ofrece un buen rendimiento diagnóstico en la patología dentaria, aunque sus manifestaciones radiológicas pueden ser sutiles y si no se conocen, pasar desapercibidas. Asimismo, son cada vez más frecuentes los procedimientos dentales invasivos, no exentos de complicaciones. Por otra parte, en la práctica diaria pueden encontrarse variedad de lesiones mandibulares radiolucentes o anomalías del desarrollo que pueden llevar a interpretaciones erróneas. Por todo ello, es recomendable que el radiólogo esté familiarizado con los posibles hallazgos en la patología dentaria.(AU)

Traumatic and especially inflammatory-infectious dental lesions are very prevalent in our context. Inflammatory-infectious disease is usually discovered incidentally on imaging studies that include the orofacial region. Moreover, these conditions can result in potentially severe complications, so early diagnosis and treatment are important. Multidetector computed tomography offers good diagnostic performance for dental lesions, although the radiological findings can be subtle and can go undetected if the radiologist is not familiar with them. Likewise, invasive dental procedures are becoming increasingly common, and these can also result in complications. On the other hand, in daily practice a variety of radiolucent mandibular lesions or developmental anomalies can lead to erroneous interpretations. For these reasons, radiologists should be familiar with possible findings related with dental conditions.(AU)

Materials degradation in non-thermal plasma generators by corona discharge.

Atmospheric corona discharge devices are being studied as innovative systems for cooling, sterilization, and propulsion, in several industrial fields, from robotics to medical devices, from drones to space applications. However, their industrial scale implementation still requires additional understanding of several complex phenomena, such as corrosion, degradation, and fatigue behaviour, which may affect final system performance. This study focuses on the corrosive behaviour of wires that perform as a high-voltage electrode subject to DC positive corona discharge in atmospheric air. The experiments demonstrate that the non-thermal plasma process promotes the growth of the oxidative films and modifies the physicochemical properties of the materials chosen as corona electrodes, hence affecting device operation. Surfaces exposed to this non-thermal plasma are electrically characterized by negative exponential decay of time-depend power and analysed with SEM. Implications on performance are analysed and discussed.

CT findings for dental disease. / Hallazgos por imagen de patología dentaria en tomografía computarizada.

Traumatic and especially inflammatory-infectious dental lesions are very prevalent in our context. Inflammatory-infectious disease is usually discovered incidentally on imaging studies that include the orofacial region. Moreover, these conditions can result in potentially severe complications, so early diagnosis and treatment are important. Multidetector computed tomography offers good diagnostic performance for dental lesions, although the radiological findings can be subtle and can go undetected if the radiologist is not familiar with them. Likewise, invasive dental procedures are becoming increasingly common, and these can also result in complications. On the other hand, in daily practice a variety of radiolucent mandibular lesions or developmental anomalies can lead to erroneous interpretations. For these reasons, radiologists should be familiar with possible findings related with dental conditions.

Voriconazole-induced periostitis.

Voriconazole is a fluorinated drug from the triazole group that is widely used in the prophylaxis and treatment of fungal infections in immunosuppressed patients. Chronic use of this medication can generate, as an adverse effect, a multifocal, asymmetric, diffuse and nodular periosteal reaction, associated with severe and disabling skeletal pain and elevated alkaline phosphatase and serum fluoride. Radiography is the imaging technique of choice for periostitis diagnosis. In general, clinical manifestations and radiographic findings disappear, when the drug is discontinued. We report the clinical case of a 44 year-old woman diagnosed with acute myeloid leukemia, who developed an invasive fungal infection treated with voriconazole after a stem cell transplant. Nine months after starting antifungal treatment, she manifested symptoms and radiological signs compatible with periostitis. Due to clinical suspicion, we decided to suspend voriconazole, with consequent resolution of clinical manifestations and radiological findings.

Integrative Clinical, Molecular, and Computational Analysis Identify Novel Biomarkers and Differential Profiles of Anti-TNF Response in Rheumatoid Arthritis.

Background: This prospective multicenter study developed an integrative clinical and molecular longitudinal study in Rheumatoid Arthritis (RA) patients to explore changes in serologic parameters following anti-TNF therapy (TNF inhibitors, TNFi) and built on machine-learning algorithms aimed at the prediction of TNFi response, based on clinical and molecular profiles of RA patients. Methods: A total of 104 RA patients from two independent cohorts undergoing TNFi and 29 healthy donors (HD) were enrolled for the discovery and validation of prediction biomarkers. Serum samples were obtained at baseline and 6 months after treatment, and therapeutic efficacy was evaluated. Serum inflammatory profile, oxidative stress markers and NETosis-derived bioproducts were quantified and miRNomes were recognized by next-generation sequencing. Then, clinical and molecular changes induced by TNFi were delineated. Clinical and molecular signatures predictors of clinical response were assessed with supervised machine learning methods, using regularized logistic regressions. Results: Altered inflammatory, oxidative and NETosis-derived biomolecules were found in RA patients vs. HD, closely interconnected and associated with specific miRNA profiles. This altered molecular profile allowed the unsupervised division of three clusters of RA patients, showing distinctive clinical phenotypes, further linked to the TNFi effectiveness. Moreover, TNFi treatment reversed the molecular alterations in parallel to the clinical outcome. Machine-learning algorithms in the discovery cohort identified both, clinical and molecular signatures as potential predictors of response to TNFi treatment with high accuracy, which was further increased when both features were integrated in a mixed model (AUC: 0.91). These results were confirmed in the validation cohort. Conclusions: Our overall data suggest that: 1. RA patients undergoing anti-TNF-therapy conform distinctive clusters based on altered molecular profiles, which are directly linked to their clinical status at baseline. 2. Clinical effectiveness of anti-TNF therapy was divergent among these molecular clusters and associated with a specific modulation of the inflammatory response, the reestablishment of the altered oxidative status, the reduction of NETosis, and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.

Encephalopathy and encephalitis during acute SARS-CoV-2 infection. Spanish Society of Neurology COVID-19 Registry. / Encefalopatías y encefalitis durante la infección aguda por SARS-CoV2. Registro de la Sociedad Española de Neurología SEN COVID-19.

OBJECTIVES: Since the beginning of the COVID-19 pandemic, the Spanish Society of Neurology has run a registry of patients with neurological involvement for the purpose of informing clinical neurologists. Encephalopathy and encephalitis were among the most frequently reported complications. In this study, we analyse the characteristics of these complications. PATIENTS AND METHODS: We conducted a retrospective, descriptive, observational, multicentre study of patients with symptoms compatible with encephalitis or encephalopathy, entered in the Spanish Society of Neurology's COVID-19 Registry from 17 March to 6 June 2020. RESULTS: A total of 232 patients with neurological symptoms were registered, including 51 cases of encephalopathy or encephalitis (21.9%). None of these patients were healthcare professionals. The most frequent syndromes were mild or moderate confusion (33%) and severe encephalopathy or coma (9.8%). The mean time between onset of infection and onset of neurological symptoms was 8.02 days. Lumbar puncture was performed in 60.8% of patients, with positive PCR results for SARS-CoV-2 in only one case. Brain MRI studies were performed in 47% of patients, with alterations detected in 7.8% of these. EEG studies were performed in 41.3% of cases, detecting alterations in 61.9%. CONCLUSIONS: Encephalopathy and encephalitis are among the complications most frequently reported in the registry. More than one-third of patients presented mild or moderate confusional syndrome. The mean time from onset of infection to onset of neurological symptoms was 8 days (up to 24hours earlier in women than in men). EEG was the most sensitive test in these patients, with very few cases presenting alterations in neuroimaging studies. All patients treated with boluses of corticosteroids or immunoglobulins progressed favourably.

Coupled DSSAT-SWAT models to reduce off-site N pollution in Mediterranean irrigated watershed.

In any agricultural watershed, best management practices (BMPs) are a conservational way to reduce non-point source pollution and, soil and water resources sustainability. The objectives of this study were to calibrate and validate the modified Soil and Water Assessment Tool (SWAT) in the Violada Watershed (VW), Spain and assess the BMPs scenarios, already tested at field scale, using the Decision Support System for Agro Technology Transfer model (DSSAT), and finally, to access the BMPs impact on water quality off-site. To this end, daily streamflow discharge and NO3- concentration were measured at VW outlet from October 2015 to September 2017 for model evaluation. The SWAT-CUP was used for sensitivity analysis, calibration and validation for both measured variables after manual calibration of the main crops yield. Three management scenarios were compared to the current conditions (baseline): (i) recommended N fertilization, (ii) optimum irrigation and; (iii) combined recommended N fertilization and optimum irrigation (combined BMPs). The SWAT crop growth model calibration demonstrated that the annual average of crop yield and actual evapotranspiration estimations were satisfactory. Monthly calibration and validation results were satisfactory for streamflow discharge and NO3-N load, with Nash-Sutcliffe efficiency (NSE) according to the criteria reported in the literature. The two individual scenarios results showed difference in their environmental impact and therefore combined BMPs scenario was considered more efficient in reducing NO3-N load (51%) than the recommended N fertilization (36%) and the optimum irrigation (12%), while including all additional environment and farmers' benefits of both individual scenarios. Under this combined scenarios, all crops yields were maintained or increased, and the total irrigation water and N mineral fertilizers application reduction were about 5% and 27%, respectively. However, further work is still needed to consider additional BMPs to limit the soil N residual losses during the non-cropped period. The applied methodology can be a good alternative for improving water quality in similar irrigated watersheds.

Granular flow through an aperture: Influence of obstacles near the outlet.

We study how the presence of obstacles in a confined system of monodisperse disks affects their discharge through an aperture. The disks are driven by a horizontal conveyor belt that moves at constant velocity. The mean packing fraction at the outlet decreases as the distance between the obstacles and the aperture decreases. The obstacles organize the dynamics of the stagnant zones in two characteristic behaviors that differ mainly in the magnitude of the fluctuations of the fraction of stagnant disks in the system. It is shown that the effective aperture is reduced by the presence of obstacles.

Carcinoma papilar seroso primario de peritoneo diagnosticado por biopsia pleural / Serous papillary peritoneal carcinoma diagnosed by pleural biopsy

No disponible

Natural Enemies of the Harrisia Cactus Mealybug and Other Hypogeococcus Species (Hemiptera: Pseudococcidae) in Puerto Rico: Identification and Taxonomic Notes on Primary and Secondary Parasitoids.

Primary and secondary parasitoids of Hypogeococcus spp. (Hemiptera: Pseudococcidae) on Cactaceae, Amaranthaceae, and Portulacaceae were reported from field surveys conducted in Puerto Rico, USA, since 2009. Resident natural enemies of the Harrisia cactus mealybug (HCM), Hypogeococcus sp., which is devastating native cacti in Puerto Rico and threatening cacti in the adjacent Caribbean islands, were documented prior to the planned introductions of non-native biological control agents from South America against this pest. Two species of Encyrtidae (Hymenoptera: Chalcidoidea) were recorded as primary parasitoids of the HCM on Cactaceae: Leptomastidea hypogeococci Triapitsyn, which was the most common, and Anagyrus quilmes Triapitsyn, Logarzo & Aguirre. Another primary parasitoid, Acerophagus sp. near nubilipennis Dozier (Encyrtidae), was also reared from a different Hypogeococcus sp. on Amaranthaceae and Portulacaceae. Hyperparasitoids, usually via L. hypogeococci, included Prochiloneurus narendrani Noyes & Triapitsyn (Encyrtidae), Pachyneuron sp. (Hymenoptera: Pteromalidae), Chartocerus elongatus (Girault), and Chartocerus niger (Ashmead) (Hymenoptera: Signiphoridae). Cheiloneurus chrisiantorresi Triapitsyn sp. n. (Encyrtidae) is newly described and illustrated; its status as a suspect hyperparasitoid of Hypogeococcus sp. on Amaranthaceae and Portulacaceae, along with that of Cheiloneurus sp., will need to be verified. The recorded HCM predators include one species of Chamaemyiidae (Diptera), Leucopina bella (Loew), and three species of Coccinellidae (Coleoptera): Cryptolaemus montrouzieri Mulsant, Decadiomus austrinus (Gordon), and Scymnobius flavifrons (Melsheimer).

Expression of GnRH receptor and 3ßHSD during meiosis and foliculogénesis in Columba livia (Aves: Columbiformes): Histological and immunohistochemical analysis.

During the ovarian ontogeny in birds, five fundamental events can be recognized: migration and colonization of the primordial germ cells, differentiation and proliferation of oogonies, an organization of germinal nests, beginning of the meiotic process and folliculogenesis. The knowledge of these events is fundamental for the interpretation of the processes involved in the differentiation of female gametes. However, there are only references for some model species such as Gallus gallus domesticus and Coturnix coturnix. In a previous study, the histological structure of embryonic ovaries of Columba livia was revealed. Therefore, the objective of this work is to characterize the processes of meiosis and folliculogenesis C. livia from the analysis of the expression of the GnRH receptor, the 3ßHSD enzyme and the cell proliferation protein PCNA in embryonic and postnatal ovaries. Therefore, the expression of GnRHR, 3ßHSD, and PCNA was revealed in histological testicular and ovarian preparations in embryos (stages 41-43) and neonates (2, 5, 7, 10 and 75 days post-hatching). The present study demonstrates that the fate of germline cells is dictated by their location during gonadal development. Thus, the germline cells located in the cortex of the left gonad enter meiosis, while those in the right gonad and those in the medulla of the left ovary fail to go into meiosis. This indicates that somatic signals, instead of an autonomous cellular mechanism, regulate the entry of the germline cells into meiosis in the C. livia embryo. Future studies will be focused on the analysis of proteins associated with meiotic events and folliculogenesis in embryonic and neonatal ovaries of C. livia, to evaluate the regulation of meiosis in vitro.

Selective activation of memristive interfaces in TaO x -based devices by controlling oxygen vacancies dynamics at the nanoscale.

The development of novel devices for neuromorphic computing and non-traditional logic operations largely relies on the fabrication of well controlled memristive systems with functionalities beyond standard bipolar behavior and digital ON-OFF states. In the present work we demonstrate for Ta2O5-based devices that it is possible to selectively activate/deactivate two series memristive interfaces in order to obtain clockwise or counter-clockwise multilevel squared remanent resistance loops, just by controlling both the electroforming process and the (a)symmetry of the applied stimuli, and independently of the nature of the used metallic electrodes. Based on our thorough characterization, analysis and modeling, we show that the physical origin of this electrical behavior relies on controlled oxygen vacancies electromigration between three different nanoscopic zones of the active Ta2O5-x layer: a central one and two quasi-symmetric interfaces with reduced TaO2-h(y) layers. Our devices fabrication process is rather simple as it implies the room temperature deposition of only one CMOS compatible oxide-Ta-oxide-and one metal, suggesting that it might be possible to take advantage of these properties at low cost and with easy scability. The tunable opposite remanent resistance loops circulations with multiple-analogic-intermediate stable states allows mimicking the adaptable synaptic weight of biological systems and presents potential for non-standard logic devices.

Effect of sperm dosage transportation in stallions: Effect on sperm DNA fragmentation.

Artificial insemination programs for horses usually involve ex vivo handling and transporting of sperm. The present experiment was designed to: (i) assess the effect of transportation on sperm DNA integrity at different time post semen collection, and (ii) evaluate if sperm DNA quality deteriorates rapidly beyond 24 h of cooled storage. After collection, the ejaculates were extended using INRA 96 and semen was prepared for prompt analysis (A0) or 24 h/48 h cooled-shipping (B24 and C48 respectively). Each sample was assessed for sperm DNA fragmentation index (SDFI) at time 0 and after incubation for 2, 6 and 24 h at 37 °C. There was very little difference in SDFI between freshly extended (A0) and 24 h/48 h cooled-transported semen samples (B24/C48) at time 0. After 2 h of incubation at 37 °C, there was an increase in SDFI ranging from 2.7% to 7.5% per hour in freshly extended semen samples (A0: 5.1 ± 1.5), while cooled-transported semen samples had a much greater increase in SDFI, ranging from 5.0% to 20.5% (B24: 14.7 ± 5.6) and from 8.2% to 26.8% (C48: 18.3 ± 7.2) respectively. There were not marked differences in the sperm DNA integrity between 24 and 48 h for transported samples, thus there is the possibility of desirable fertility with use of stallion sperm after 48 h of cooled storage.