The mediating role of reflective functioning in the association between childhood trauma and suicide attempt.

BACKGROUND: Childhood trauma is intimately related with suicidal behaviour. Patients who have suffered childhood trauma develop impaired Reflective Functioning (RF), which refers to the capacity to understand ourselves and others in terms of intentional mental states. An improvement in RF has been associated with a reduction in suicidal attempts, but the mediating role of RF between childhood trauma and suicidal behaviour has not been addressed so far. OBJECTIVE: We aim to examine the potential mediating effect of RF among childhood trauma and suicide attempts. METHOD: We included 748 patients who had attempted suicide at least once. They were asked to complete the Reflective Functioning Questionnaire (RFQ-8), the Columbia-Suicide Severity Rating scale (CSSRS), and the Childhood Trauma Questionnaire-Short Form (CTQ-SF). We conducted linear regressions by simple mediating model to examine the role of RF in the indirect association between childhood trauma and the number of suicide attempts. RESULTS: Our results show significant indirect effects through hypo and hypermentalizing between Emotional Abuse (EA) and Sexual Abuse (SA) in childhood and the number of suicide attempts in lifetime. These results indicate that ineffective RF significantly mediates the association between childhood trauma and suicidality. CONCLUSION: This is the first study supporting the mediational role of RF in the relationship between EA and SA, and the number of suicide attempt in lifetime. These findings have important implications for reducing suicide rates and preventing future re-attempts. Further studies analysing this mediating role and focusing efforts on increasing RF-based interventions are required.

Consensus statement of the Spanish Society of Neurology on the treatment of multiple sclerosis and holistic patient management in 2023.

The last consensus statement of the Spanish Society of Neurology's Demyelinating Diseases Study Group on the treatment of multiple sclerosis (MS) was issued in 2016. Although many of the positions taken remain valid, there have been significant changes in the management and treatment of MS, both due to the approval of new drugs with different action mechanisms and due to the evolution of previously fixed concepts. This has enabled new approaches to specific situations such as pregnancy and vaccination, and the inclusion of new variables in clinical decision-making, such as the early use of high-efficacy disease-modifying therapies (DMT), consideration of the patient's perspective, and the use of such novel technologies as remote monitoring. In the light of these changes, this updated consensus statement, developed according to the Delphi method, seeks to reflect the new paradigm in the management of patients with MS, based on the available scientific evidence and the clinical expertise of the participants. The most significant recommendations are that immunomodulatory DMT be started in patients with radiologically isolated syndrome with persistent radiological activity, that patient perspectives be considered, and that the term "lines of therapy" no longer be used in the classification of DMTs (> 90% consensus). Following diagnosis of MS, the first DMT should be selected according to the presence/absence of factors of poor prognosis (whether epidemiological, clinical, radiological, or biomarkers) for the occurrence of new relapses or progression of disability; high-efficacy DMTs may be considered from disease onset.

COVID-19 thromboprophylaxis. New evidence.

Recent publications have questioned the efficacy of using therapeutic or intermediate doses of low molecular weight heparin (LMWH) in COVID-19 patients, especially in the most severe patients. In order to update these recommendations, a non-systematic review has been carried out in the main medical databases. A total of 14 randomized clinical trials, 14 meta-analyses and the recommendations of 12 scientific societies were selected, stratified according to the type of patient (outpatient, hospitalized, admitted to critical care or post-discharge). The efficacy of LMWH and other therapeutic approaches (rivaroxaban, apixaban, sulodexide, acetylsalicylic acid and P2Y12 inhibitors) has been analyzed. The findings recommend using standard doses of LMWH as thromboprophylaxis in critically hospitalized COVID-19 patients and therapeutic doses in non-critically hospitalized patients if the risk of bleeding is low. In outpatients and those discharged from the hospital, LMWH could be used at a prophylactic dose if there are thrombotic risk factors, and the bleeding risk is low. It is not recommended to associate antiplatelet agents with LMWH unless previously indicated.

Transdiagnostic inflammatory and oxidative biomarkers with predictive capacity of self-injurious behavior in impulsive and unstable disorders.

INTRODUCTION: Alterations in inflammatory processes have previously been reported in impulsive and unstable disorders, as well as in other psychiatric conditions. In order to investigate transdiagnostic biomarkers associated with various phenotypic features of these disorders, this study is designed to identify biomarkers of inflammatory and oxidative endophenotypes related to autolytic behavior. METHODS: Peripheral blood mononuclear cells were collected from 35 patients with borderline personality disorder (BPD), 29 patients with restrictive eating disorder (rED), 21 patients with purging eating disorder (pED) and 23 control subjects. Plasma levels of different inflammatory and oxidative factors were measured by ELISA and the expression of selected proteins was by Western Blot. Principal component analysis (PCA) was performed to categorize the different inflammatory factors. Additionally, Ancova was performed to observe the differences in the principal components among the different groups and logistic regression analysis was conducted to assess the predictive capacity of these components for autolytic behaviors. RESULTS: We found two inflammatory/oxidative components were associated with BPD, characterized by high levels of JNK and ERK and low levels of GPx, SOD and Keap1; and two other inflammatory/oxidative components were linked to pED, associated with more JNK, TBARS and TNF-α and less GPx and SOD. Two components, with more JNK and ERK and less GPx, SOD and Keap1, predicted non-suicidal self-injury and three components, with higher JNK, TBARS and TNF-α levels and lower GPx, SOD and iNOS levels, predicted suicide attempts. CONCLUSIONS: These results strongly support the endophenotypic characterization of impulsivity and the identification of transdiagnostic inflammatory/oxidative biomarkers relevant to autolytic behavior in impulsive and unstable disorders. These dates lay the groundwork for developing of screening tests for these biomarker components to rapidly detect biological risk factors for specific impulse control disorders and future self-injurious behaviors.

Decreased oxytocin plasma levels and oxytocin receptor expression associated with aggressive behavior in aggressive-impulsive disorders.

INTRODUCTION: This study aims to enhance the understanding of the association between the phenotypic and endophenotypic characteristics of impulsive-aggressive disorders, through the study of plasma oxytocin (OXT) and oxytocin receptor (OXTR) levels in patients with borderline personality disorder (BPD) and patients with eating disorders (ED), as well as to examine the relationship of OXT system with aggressive behavior in these disorders. METHODS: 68 patients with BPD, 67 patients with ED and 57 healthy control subjects were examined for plasma oxytocin levels and protein expression of OXTR in blood mononuclear cells. Aggressive behavior was assessed using the State-Trait Anger Expression Inventory (STAXI-2). Other self and hetero-aggressive behaviors were also evaluated through interviews. RESULTS: BPD and ED patients exhibited significantly lower plasma oxytocin levels than control subjects. Furthermore, BPD patients demonstrated significantly reduced expression of OXTR compared to controls. Plasma oxytocin levels negatively correlated with verbal aggression, while OXTR expression was inversely associated with the STAXI trait subscale. CONCLUSIONS: The findings validate the existence of oxytocin system dysfunction in impulsive-aggressive disorders. They also support the link between low OXT levels in plasma and OXTR expression and the impulsive-aggressive behavior that characterizes these patients in both state and trait situations.

Using birth-death processes to infer tumor subpopulation structure from live-cell imaging drug screening data.

Tumor heterogeneity is a complex and widely recognized trait that poses significant challenges in developing effective cancer therapies. In particular, many tumors harbor a variety of subpopulations with distinct therapeutic response characteristics. Characterizing this heterogeneity by determining the subpopulation structure within a tumor enables more precise and successful treatment strategies. In our prior work, we developed PhenoPop, a computational framework for unravelling the drug-response subpopulation structure within a tumor from bulk high-throughput drug screening data. However, the deterministic nature of the underlying models driving PhenoPop restricts the model fit and the information it can extract from the data. As an advancement, we propose a stochastic model based on the linear birth-death process to address this limitation. Our model can formulate a dynamic variance along the horizon of the experiment so that the model uses more information from the data to provide a more robust estimation. In addition, the newly proposed model can be readily adapted to situations where the experimental data exhibits a positive time correlation. We test our model on simulated data (in silico) and experimental data (in vitro), which supports our argument about its advantages.

Human femur fracture by mechanical compression: Towards the repeatability of bone fracture acquisition.

The increase in life expectancy combined with greater bone fragility over the years is causing a rise in the bone fracture cases. Femur fractures are the most important due to their high mortality rate. This multidisciplinary work is carried out in this context and focuses on the experimental reproduction of human femur fractures by compression. We describe a sequence of steps supervised by orthopaedic surgeons for the correct arrangement of specimens on the system set up to perform the experiment. The device applies force by compression until the human bone is fractured. All tests performed have been monitored and evaluated from different knowledge perspectives. The results obtained have demonstrated the repeatability of the fracture type in a controlled environment as well as identifying the main features involved in this process. In addition, the fractured bones have been digitized to analyze the fracture zone to recreate and evaluate future simulations.

Differences in Longevity and Temperature-Driven Extrinsic Incubation Period Correlate with Varying Dengue Risk in the Arizona-Sonora Desert Region.

Dengue transmission is determined by a complex set of interactions between the environment, Aedes aegypti mosquitoes, dengue viruses, and humans. Emergence in new geographic areas can be unpredictable, with some regions having established mosquito populations for decades without locally acquired transmission. Key factors such as mosquito longevity, temperature-driven extrinsic incubation period (EIP), and vector-human contact can strongly influence the potential for disease transmission. To assess how these factors interact at the edge of the geographical range of dengue virus transmission, we conducted mosquito sampling in multiple urban areas located throughout the Arizona-Sonora desert region during the summer rainy seasons from 2013 to 2015. Mosquito population age structure, reflecting mosquito survivorship, was measured using a combination of parity analysis and relative gene expression of an age-related gene, SCP-1. Bloodmeal analysis was conducted on field collected blood-fed mosquitoes. Site-specific temperature was used to estimate the EIP, and this predicted EIP combined with mosquito age were combined to estimate the abundance of "potential" vectors (i.e., mosquitoes old enough to survive the EIP). Comparisons were made across cities by month and year. The dengue endemic cities Hermosillo and Ciudad Obregon, both in the state of Sonora, Mexico, had higher abundance of potential vectors than non-endemic Nogales, Sonora, Mexico. Interestingly, Tucson, Arizona consistently had a higher estimated abundance of potential vectors than dengue endemic regions of Sonora, Mexico. There were no observed city-level differences in species composition of blood meals. Combined, these data offer insights into the critical factors required for dengue transmission at the ecological edge of the mosquito's range. However, further research is needed to integrate an understanding of how social and additional environmental factors constrain and enhance dengue transmission in emerging regions.

Inflammatory and oxidative endophenotypes in borderline personality disorder: A biomarker cluster analysis.

OBJECTIVES: This study is designed to search for aggrupation of inflammatory/oxidative biomarker alterations in borderline personality disorder (BPD) and their association with phenotypic features. METHODOLOGY: Inflammatory/nitrosative proteins were measures in plasma and peripheral blood mononuclear cells obtained from BPD patients. Patients were assessed on different clinical dimensions of BPD. Oxidative damage was tested by measuring TBARS, nitrites, catalase, GPx and SOD. Protein expression of IκBα, NFκB, iNOS, COX-2, PPARγ, Keap1, NQO1, Nrf2 and α7nAChR was also determined. Western blot and ELISA were used for measurements and a cluster analysis of inflammatory/oxidative biomarkers alterations was performed to investigate subgroups of patients with similar alterations and its relationship with clinical features of BPD. RESULTS: 69 patients were included in the study. Two inflammatory/nitrosative clusters of patients were found: Cluster 1 patients showed significantly higher levels of GPx, IκBα, keap1, NQO1, PPARγ, α7nAChR and Nrf2 than cluster 2 patients. These patients had significantly longer duration of illness, milder anxiety symptoms and lower prescription of antipsychotic drugs than cluster 2. CONCLUSIONS: Two clusters of BPD patients according to the inflammatory/nitrosative profiles were identified. Cluster 1 had increased antioxidant and anti-inflammatory biomarkers and was characterised by greater chronicity of illness but less acute symptomatic severity.

Severe rectus diastasis with midline hernia associated in males: high recurrence in mid-term follow-up of minimally invasive surgical technique.

PROPOSE: The present study aimed to assess clinical results, in terms of postoperative pain, functional recovery and recurrence rates of FESSA (Full Endoscopic Suprapubic Subcutaneous Access) technique compared to endoscopic anterior rectus sheaths plication and mesh, in male patients with midline ventral or incisional hernias and severe rectus diastasis (SRD) associated. Secondary aims were to identify intra- and postoperative complications associated with each technique. METHODS: Male patients with midline ventral or incisional hernia and severe rectus diastasis were included in a prospectively maintained databased and retrospectively analyzed from January 2017 to December 2020. From January 2017 to January 2019, male patients underwent to anterior rectus sheaths plication (ARSP) (Control group). From January 2019 to December 2020, male patients underwent to FESSA technique (FT) (Case group). RESULTS: 53 patients were finally included. 28 patients (52%) underwent to FT and 25 patients (48%) to ARSP. Regarding intraoperative complications, no significant differences were identified between the groups. Hospital stay was significantly improved in FT group when compared to ARSP group. No significant differences in terms of postoperative seroma or hematomas, were shown. FT group showed significantly less pain on 1st, 7th and 30th postoperative days than ARSP group. Functional recovery was significantly improved in FT group compared to ARSP group on the 30th day and no differences were observed on the 180th day after surgery. The mean follow-up was 17.3 ± 2.6 months in FT group and 24 ± 3 months in ARSP group. During the follow-up, 1(3%) and 9 (36%) diastasis recurrences were identified respectively, with significant differences in favor of FT group. CONCLUSION: In males with SRD and symptomatic midlines hernias, ARSP with onlay mesh placement shows high diastasis recurrence rate in mid-term follow-up. We propose FESSA technique in those patients, which decreases the excessive midline tension, improving the postoperative pain, functional recovery and recurrence rate, without increasing postoperative complications.

Global Distribution of Key Features of Streamer Corona Discharges in Thunderclouds.

We present nighttime worldwide distributions of key features of Blue LUminous Events (BLUEs) detected by the Modular Multispectral Imaging Array of the Atmosphere-Space Interaction Monitor. Around 10% of all detected BLUEs exhibit an impulsive single pulse shape. The rest of BLUEs are unclear (impulsive or not) single, multiple or with ambiguous pulse shapes. BLUEs exhibit two distinct populations with peak power density <25 µWm-2 (common) and ≥25 µWm-2 (rare) with different rise times and durations. The altitude (and depth below cloud tops) zonal distribution of impulsive single pulse BLUEs indicate that they are commonly present between cloud tops and a depth of ≤4 km in the tropics and ≤1 km in mid and higher latitudes. Impulsive single pulse BLUEs in the tropics are the longest (up to ∼4 km height) and have the largest number of streamers (up to ∼3 × 109). Additionally, the analysis of BLUEs has turned out to be particularly complex due to the abundance of radiation belt particles (at high latitudes and in the South Atlantic Anomaly [SAA]) and cosmic rays all over the planet. True BLUEs can not be fully distinguished from radiation belt particles and cosmic rays unless other ground-based measurements associated with the optically detected BLUEs are available. Thus, the search algorithm of BLUEs presented in Soler et al. (2021), https://doi.org/10.1029/2021gl094657 is now completed with a new additional step that, if used, can considerably smooth the SAA shadow but can also underestimate the number of BLUEs worldwide.

Endoscopic retromuscular technique (eTEP) vs conventional laparoscopic ventral or incisional hernia repair with defect closure (IPOM +) for midline hernias. A case-control study.

PURPOSE: This study aimed at clinical results in terms of postoperative pain and functional recovery of new technique (eTEP) compared to IPOM + for ventral/incisional midline hernias. Recurrence rate, intra/postoperative complications and aesthetic results are secondary aims. METHODS: Data from consecutive patients requiring minimally invasive hernia repair were collected. From January 2015 to September 2018, patients with midline ventral/incisional hernias underwent IPOM + were compared to patients underwent eTEP procedure from October 2018 to December 2019 in a case/control study. RESULTS: Thirty-nine patients in IPOM + group and 40 in eTEP group were included. No significant differences were identified when hernias types, mean defect area, mean mesh area and intraoperative/postoperative complications (except seroma rate in favor of eTEP group) were compared. Operative time and hospital stay were significantly higher in eTEP group and IPOM + group, respectively. eTEP group showed significantly less pain on 1st, 7th and 30th postoperative days than IPOM + group. Restriction of activities was significantly decreased in eTEP group on the 30th and 180th day after surgery. Significant differences were observed in terms of cosmetic results 30th and 180th days after surgery in favor of eTEP group. Average follow-up was 15 months in eTEP group and 28 months in IPOM + group. No recurrences were identified in eTEP group and one recurrence in IPOM + group with no significant differences. CONCLUSION: Endoscopic retromuscular technique shows significant lower postoperative pain, better functional recovery and cosmesis than IPOM + without differences in intra/postoperative complications (except seroma rate) or recurrences during the follow-up. eTEP requires longer operative time.

Efficacy and safety of Yttrium-90 radioembolization in the treatment of neuroendocrine liver metastases. Long-term monitoring and impact on survival. / Eficacia y seguridad de la radioembolización con 90Y en el tratamiento de metástasis hepáticas de tumores neuroendocrinos. Seguimiento a largo plazo y repercusión en la supervivencia.

INTRODUCTION AND OBJECTIVE: Neuroendocrine tumors (NETs) debut in 75% of cases with liver metastases (LMNETs), whose therapeutic approach includes surgical resection and liver transplantation, while liver radioembolization with 90 Y-microspheres (TARE) is reserved for non-operable patients usually due to high tumor burden. We present the accumulated experience of 10 years in TARE treatment of LMNETs in order to describe the safety and the effectiveness of the oncological response in terms of survival, as well as to detect the prognostic factors involved. MATERIAL AND METHODS: Of 136 TARE procedures, performed between January 2006 and December 2016, 30 LMNETs (11.1%) were retrospectively analyzed. The study variables were: Tumor response, time to liver progression, survival at 3 and 5 years, overall mortality and mortality associated with TARE. The radiological response assessment was assessed using RECIST 1.1 and mRECIST criteria. RESULTS: An average activity of 2.4 ± 1.3 GBq of 90 Y was administered. No patient presented postembolization syndrome or carcinoid syndrome. There were also no vascular complications associated with the procedure. According to RECIST 1.1 criteria at 6 months, 78.6% presented partial response and 21.4% stable disease, there was no progression or complete response (1 by mRECIST). Survival at 3 and 5 years was 73% in both cases. CONCLUSION: TARE treatment with 90 Y-microspheres in LMNETs, applied within a multidisciplinary approach, is a safe procedure, with low morbidity, capable of achieving a high rate of radiological response and achieving lasting tumor responses.

Submicrosecond Spectroscopy of Lightning-Like Discharges: Exploring New Time Regimes.

Submicrosecond (0.476 µs per frame with an exposure time of 160 ns) high-resolution (0.38 nm) time-resolved spectra of laboratory-produced lightning-like electrical discharges have been recorded for the first time within the visible spectral range (645-665 nm). The spectra were recorded with the GrAnada LIghtning Ultrafast Spectrograph (GALIUS), a high-speed imaging spectrograph recently developed for lightning research in the IAA-CSIC. Unprecedented spectral time dynamics are explored for meter long laboratory electrical discharges produced with a 2.0 MV Marx generator. The maximum electron density and gas temperature measured in a timescale of ≤0.50 µs (160 ns) were, respectively, ≃1018 cm-3 and ≃32,000 K. Overpressure in the lightning-like plasma channel, black-body dynamics, and self-absorption in spectral lines were investigated.

Influence of Elastic Scattering on Electron Swarm Distribution in Electrified Gases.

The propagation of energetic electrons through air is one key component in the generation of high-energy atmospheric phenomena such as lightning-generated X-ray bursts, terrestrial gamma ray flashes (TGFs), and gamma ray glows. We show here that models for this propagation can be considerably affected by the parameterization of the differential cross section of elastic scattering of electrons on the molecular components of air. We assess existing parameterizations and propose a more accurate one that builds upon the most up-to-date measurements. Then we conclude that by overweighting the forward scattering probability, previous works may have overestimated the production of runaway electrons under high electric fields close to the thermal runaway threshold.

On the Emergence Mechanism of Carrot Sprites.

We investigate the launch of negative upward streamers from sprite glows. This phenomenon is readily observed in high-speed observations of sprites and underlies the classification of sprites into carrot or column types. First, we describe how an attachment instability leads to a sharply defined region in the upper part of the streamer channel. This region has an enhanced electric field, low conductivity and strongly emits in the first positive system of molecular nitrogen. We identify it as the sprite glow. We then show how, in the most common configuration of a carrot sprite, several upward streamers emerge close to the lower boundary of the glow, where negative charge gets trapped and the lateral electric field is high enough. These streamers cut off the current flowing toward the glow and lead to the optical deactivation of the glow above. Finally, we discuss how our results naturally explain angel sprites.

SEDAR-SEMICYUC consensus recommendations on the management of haemostasis disorders in severely ill patients with COVID-19 infection. / Recomendaciones de consenso SEDAR-SEMICYUC sobre el manejo de las alteraciones de la hemostasia en los pacientes graves con infección por COVID-19.

The infection by the coronavirus SARS-CoV-2, which causes the disease called COVID-19, mainly causes alterations in the respiratory system. In severely ill patients, the disease often evolves into an acute respiratory distress syndrome that can predispose patients to a state of hypercoagulability, with thrombosis at both venous and arterial levels. This predisposition presents a multifactorial physiopathology, related to hypoxia as well as to the severe inflammatory process linked to this pathology, including the additional thrombotic factors present in many of the patients. In view of the need to optimise the management of hypercoagulability, the working groups of the Scientific Societies of Anaesthesiology-Resuscitation and Pain Therapy (SEDAR) and of Intensive, Critical Care Medicine and Coronary Units (SEMICYUC) have developed a consensus to establish guidelines for actions to be taken against alterations in haemostasis observed in severely ill patients with COVID-19. These recommendations include prophylaxis of venous thromboembolic disease in these patients, and in the peripartum, management of patients on long-term antiplatelet or anticoagulant treatment, bleeding complications in the course of the disease, and the interpretation of general alterations in haemostasis.

Hyaluronic acid biomaterial for human tissue-engineered skin substitutes: Preclinical comparative in vivo study of wound healing.

BACKGROUND: There is not an ideal biomaterial for tissue-engineered skin substitutes (TESSs), and most of the studies or existing therapies use xenogeneic origin natural biomaterials or biosynthetic scaffolds. OBJECTIVE: To analyse clinical, histological integration and homeostasis parameters of a human TESS manufactured with fibrin-hyaluronic acid biomaterial (HA-Skin), grafted in immunodeficient mice for 8 weeks, and compared with the gold standard treatment (Autograft), a human TESS manufactured with fibrin-agarose biomaterial (AG-Skin) and secondary wound healing dressings. METHODS: Human TESSs and autografts were implanted into BALB/c mice after surgical excision. Secondary wound healing approach was achieved with biosynthetic collagen wound dressing (Biobrane® ) and fibrin-hyaluronic acid or fibrin-agarose biomaterial without cells (Total N = 44). Clinical integration and homeostasis parameters were evaluated every two weeks for two months. Histological and immunohistochemical analyses were performed four and eight weeks after grafting. RESULTS: HA-Skin, AG-Skin and Autograft groups showed a proper clinical integration and epithelization eight weeks later. Scar evaluation revealed better results for Autograft and HA-Skin. Homeostasis analysis indicated similar values of transepidermal water loss and elasticity between HA-Skin (6.42 ± 0.75 g/h/m2 , 0.42 ± 0.08 AU), Autograft (6.91 ± 1.28 g/h/m2 , 0.40 ± 0.08 AU) and healthy mouse skin (6.40 ± 0.43 g/h/m2 , 0.35 ± 0.03 AU). Histological results showed that human TESSs and autografts presented better skin structuration and higher expression of cytokeratins. CONCLUSIONS: This study suggests that human TESS based on fibrin-hyaluronic acid biomaterial could be suitable for clinical application in the treatment of several dermatological pathologies (wound healing).