Modulable 3D-printed plantibody-laden platform enabling microscale affinity extraction and ratiometric front-face fluorescence detection of microcystin-LR in marine waters.

A 3D-printed stereolithographic platform for selective biorecognition is designed to enable convective microscale affinity extraction of microcystin-LR (MC-LR) followed by direct solid-phase optosensing exploiting ratiometric front-face fluorescence spectroscopy. For this purpose, a recombinant monoclonal plantibody (recAb) is covalently attached to a 3D-printed structure for sorptive immunoextraction, whereupon the free and unbound primary amino moieties of the recAb are derivatized with a fluorescent probe. The fluorophore-recAb-MC-LR laden device is then accommodated in the cuvette holder of a conventional fluorometer without any instrumental modification for the recording of the solid-phase fluorescence emission. Using Rodbard's four-parameter sigmoidal function, the 3D-printed bioselective platform features a limit of detection (LOD) of 28 ng L-1 using a sample volume of 500 mL, device-to-device reproducibility down to 12%, and relative recoveries ranging from 91 to 100% in marine waters. Printed prototypes are affordable, just 0.4 € per print and ≤ 10 € per device containing recAb. One of the main assets of the miniaturized immunoextraction device is that it performs comparably well in terms of analytical figures of merit with costly mass spectrometric-based analytical methodologies, such as HPLC-MS/MS. The device is readily applicable to high-matrix samples, such as seawater, as opposed to previous biosensing platforms, just applied to freshwater systems.

Effects of acute beetroot juice intake on performance, maximal oxygen uptake, and ventilatory efficiency in well-trained master rowers: a randomized, double-blinded crossover study.

BACKGROUND: Beetroot juice (BRJ) intake has been considered a practical nutritional strategy among well-trained athletes. This study aimed to assess the effects of BRJ intake on performance, cardiorespiratory and metabolic variables during a simulated 2000-meter rowing ergometer test in well-trained master rowers. METHOD: Ten well-trained male master rowers (30-48 years) participated in a randomized, double-blind, crossover design for 3 weeks. In the first week, a researcher explained all the experimental procedures to the participants. In the next two weeks, the participants were tested in 2 rowing ergometer sessions, separated from each other by a 7-day washout period. In both strictly identical sessions, the participants randomly drank BRJ or placebo (PL) 3 hours before the start of the tests. Subsequently, the participants carried out the 2000-meter rowing ergometer tests. Oxygen saturation and blood lactate measurements were performed before starting (pretest) and at the end of the test (posttest). Performance parameters and cardiorespiratory variables were recorded during the rowing ergometer test. RESULTS: An improvement in time trial performance was observed, with a mean difference of 4 seconds (90% confidence limits ± 3.10; p ≤ 0.05) compared to PL. Relative and absolute maximaloxygenuptakeV˙O2max increased (mean difference of 2.10 mL·kg-1·min-1, 90% confidence limits ± 1.80; mean difference of 0.16 L·min-1 90% confidence limits ± 0.11, respectively; p ≤ 0.05) compared to PL. No ergogenic effect was observed on ventilatory efficiency and blood lactate concentrations after BRJ intake. CONCLUSION: Acute BRJ intake may improve time trial performance as well as V˙O2max in well-trained master rowers. However, BRJ does not appear to improve ventilatory efficiency.

The impact of metronidazole on pain persistence after fertility-sparing endometriosis surgery: METROFERT randomized study.

BACKGROUND: Recent studies have shown that a disrupted microbiome is associated with endometriosis. Despite endometriosis affecting 1 in 10 reproductive-aged women, there is a lack of innovative and nonhormonal long-term effective treatments. Studies have reported an approximately 20-37.5% persistence of pain after fertility-sparing endometriosis surgery. Metronidazole has been shown to decrease inflammatory markers and the size of endometriosis lesions in animal studies. OBJECTIVE: To determine if modulating the microbiome with oral metronidazole for 14 days after fertility-sparing endometriosis surgery decreases pain persistence postoperatively. STUDY DESIGN: This was a randomized, multicenter, placebo-controlled, double-blind trial. Individuals 18-50 years old were prospectively randomized to placebo versus oral metronidazole for 14 days immediately after endometriosis fertility-sparing excision surgery. The primary outcome was binary, subjective pain persistence at six weeks postoperatively. Secondary outcomes of quality of life, sexual function, and endometriosis-associated pain scores according to the Endometriosis Health Profile-5, Female Sexual Function Index, and a visual analog scale. RESULTS: 152 participants were approached from October 2020 to October 2023 to enroll in the study. 64 participants were excluded either because they did not meet inclusion or exclusion criteria or because they declined to participate. 88 participants were randomized in a 1:1 ratio to receive either the oral placebo or metronidazole after endometriosis excision surgery. 18.2% of participants were lost to follow-up or discontinued treatment and this was not significantly different between the two arms, yielding a final cohort of 72 participants. Baseline demographics of the two study groups were similar. There was no statistically significant improvement in the primary outcome of binary subjective pain persistence between the metronidazole group compared to placebo (84% vs 88%, p=0.74) at 6 weeks postoperatively. Further, no significant differences between treatments were detected in the secondary outcomes. CONCLUSION: A postoperative 14-day regimen of oral metronidazole immediately after fertility-sparing endometriosis surgery was not associated with any significant differences between treatment groups in the in the persistence of endometriosis-related pain symptoms compared to placebo at 6 weeks.

Brassica rapa CURLY LEAF is a major H3K27 methyltransferase regulating flowering time.

MAIN CONCLUSION: In Brassica rapa, the epigenetic modifier BraA.CLF orchestrates flowering by modulating H3K27me3 levels at the floral integrator genes FT, SOC1, and SEP3, thereby influencing their expression. CURLY LEAF (CLF) is the catalytic subunit of the plant Polycomb Repressive Complex 2 that mediates the trimethylation of histone H3 lysine 27 (H3K27me3), an epigenetic modification that leads to gene silencing. While the function of CURLY LEAF (CLF) has been extensively studied in Arabidopsis thaliana, its role in Brassica crops is barely known. In this study, we focused on the Brassica rapa homolog of CLF and found that the loss-of-function mutant braA.clf-1 exhibits an accelerated flowering together with pleiotropic phenotypic alterations compared to wild-type plants. In addition, we carried out transcriptomic and H3K27me3 genome-wide analyses to identify the genes regulated by BraA.CLF. Interestingly, we observed that several floral regulatory genes, including the B. rapa homologs of FT, SOC1 and SEP3, show reduced H3K27me3 levels and increased transcript levels compared to wild-type plants, suggesting that they are direct targets of BraA.CLF and key players in regulating flowering time in this crop. In addition, the results obtained will enhance our understanding of the epigenetic mechanisms regulating key developmental traits and will aid to increase crop yield by engineering new Brassica varieties with different flowering time requirements.

Binary and Ternary Blended Portland Cements Containing Different Types of Rice Husk Ash.

Rice husk ash (RHA) is agricultural waste with high silica content that has exhibited proven technical feasibility as a pozzolanic material since the 1970s. Notwithstanding, its use in mortars and concrete is limited by the standards currently utilized in some countries where RHA production is high and the aforementioned pozzolanic material is not standardized. This is the case in Spain, one of the main rice producers in Europe. Nowadays, the high pressure placed on the Portland cement production sector to reduce its energy use and CO2 emissions has given rise to a keen interest in mineral admixtures for cement manufacturing. In this research, we intended to establish the contributions of different RHA types to the final blended Portland cement properties ("H" is used to identify RHA in standardized cements). The experimental results demonstrated that RHA with good pozzolanic properties (large specific surface and high amorphous silica content) had to be limited to 10% cement replacement because of the severe reduction in workability at higher replacement percentages. RHA with lower reactivity, such as crystalline RHA, or fly ash (FA) can be used to prepare binary and ternary blended cements with reactive RHA. It is possible to design the following cements: CEM II/A-H and CEM II/A-(H-V). It would also be possible to design cement (CEM II/B-(H-V) with replacement values of up to 30% and the same 28-day mechanical performance as observed for the Portland cement without mineral addition.

De novo TLK1 and MDM1 mutations in a patient with a neurodevelopmental disorder and immunodeficiency.

The Tousled-like kinases 1 and 2 (TLK1/TLK2) regulate DNA replication, repair and chromatin maintenance. TLK2 variants underlie the neurodevelopmental disorder (NDD) 'Intellectual Disability, Autosomal Dominant 57' (MRD57), characterized by intellectual disability and microcephaly. Several TLK1 variants have been reported in NDDs but their functional significance is unknown. A male patient presenting with ID, seizures, global developmental delay, hypothyroidism, and primary immunodeficiency was determined to have a heterozygous TLK1 variant (c.1435C>G, p.Q479E), as well as a mutation in MDM1 (c.1197dupT, p.K400∗). Cells expressing TLK1 p.Q479E exhibited reduced cytokine responses and elevated DNA damage, but not increased radiation sensitivity or DNA repair defects. The TLK1 p.Q479E variant impaired kinase activity but not proximal protein interactions. Our study provides the first functional characterization of NDD-associated TLK1 variants and suggests that, such as TLK2, TLK1 variants may impact development in multiple tissues and should be considered in the diagnosis of rare NDDs.

Telerehabilitation improves cardiorespiratory and muscular fitness and body composition in older people with post-COVID-19 syndrome.

BACKGROUND: The effects of post-coronavirus disease 2019 (COVID-19) syndrome on the cardiorespiratory and muscular fitness in older people are of utmost relevance. This study aimed to evaluate the effects of a 12-week telerehabilitation programme on cardiorespiratory and muscular fitness and body composition in older patients with post-COVID-19 syndrome. METHODS: One hundred twenty older patients with post-COVID-19 syndrome were randomly assigned to one of two groups: patients who carried out the telerehabilitation programme (n = 60; age: 65.0 ± 5.2; female: 14.2%) and a control group (n = 60; age: 64.3 ± 5.0; female: 24.5%). An incremental cardiopulmonary exercise testing, isokinetic strength test, and bioelectrical impedance analysis were performed to compare cardiorespiratory and muscle strength responses and body composition between telerehabilitation and control groups. RESULTS: A significant increase in the cardiopulmonary exercise testing duration was found in the telerehabilitation group compared to the control group (mean difference = 88.9 s, P = 0.001). Peak oxygen uptake increased in the telerehabilitation group (mean difference = 3.0 mL·kg-1·min-1, P < 0.001) and control group (mean difference = 1.9 mL·kg-1·min-1, P < 0.001). Power output in cycle ergometer (mean difference = 25.9 watts, P < 0.001), fat free mass (mean difference = 2.1 kg, P = 0.004), soft lean mass (mean difference = 2.1 kg, P = 0.003), and skeletal muscle mass (mean difference = 1.4 kg, P = 0.003) only increased in the telerehabilitation group. A significant increase in the power output was observed in the telerehabilitation group compared with the control group in both lower limbs after isokinetic strength test of the leg extension at a speed of 60° (right: mean difference = 18.7 watts, P = 0.012; left: mean difference = 15.3 watts, P = 0.010). The peak torque of right leg extension increased only in the telerehabilitation group after isokinetic strength test at a speed of 60° (mean difference = 13.1 N·m, P < 0.001). A significant increase in the power output was observed in the telerehabilitation group compared with the control group in the left leg extension after isokinetic strength test at a speed of 180° (mean difference = 30.2 watts, P = 0.003). CONCLUSIONS: The telerehabilitation programme improved cardiorespiratory and muscular fitness, and body composition in older patients with post-COVID-19 syndrome to a greater extent than a control group. The telerehabilitation programmes may be an alternative to improve the sequelae of post-COVID-19 syndrome in older patients.

Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression.

Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events and endothelial dysfunction. In spite of the efficacy demonstrated by enzyme replacement therapy or pharmacological chaperones in delaying disease progression, few studies have analyzed whether these treatments can improve the pro-inflammatory state of FD patients. Therefore, the aim of this work was to assess cytokines and cardiovascular risk-related proteins detectable in plasma from FD patients, whether treated or not with ERT, to evaluate the reliability of these markers in monitoring disease stage and treatment effects. We identified inflammatory and endothelial dysfunction markers (ADAMTS-13, TNF-α, GDF-15, MIP-1ß, VEGFA, MPO, and MIC-1) that cooperate in a common pathway and are increased in FD patients' plasma samples. As shown by the assessment of these proteins over time, they can help to evaluate the risk of higher severity in FD, as well as ERT effects. Even though the analyzed proteins cannot be considered as proper biomarkers due to their non-specificity to FD, taken together they can provide a signature of reference molecules with prognostic value for early diagnosis, and evaluation of disease progression and treatment efficacy, using blood samples.

Effect of transcutaneous neuromodulation on normalization of dermal body temperature and pain in a tender scar in the presence of low back pain: An update and case report.

Low back pain affects over 20% of individuals during their lifetime, and in some patients, it may be associated with scar tissue formation after surgery. Small-fiber neuropathy and scar tissue dysfunction can lead to localized pain by affecting signals to the thalamus. Transcutaneous neuromodulation using Tape with Magnetic Particles shows promise in relieving perceived pain, modulating vascularization and the autonomic nervous system, and reducing dermal temperature. In the present case, a 24-year-old woman with L5-S1 disk herniation experienced low back pain and leg pressure. The surgical intervention provided temporary relief, but scar restrictions caused pain recurrence. Tape with Magnetic Particles application initially induced scar hypothermia and pressure tolerance during posteroanterior tests on lumbar spinous processes increased, reducing pain perception for at least 12 h. Transcutaneous neuromodulation with Tape with Magnetic Particles modulated dermal temperature immediately and for 12 h, reducing perceived pain and sustaining improvement thereafter. This highlights the potential of Tape with Magnetic Particles in managing chronic low back pain associated with scar tissue.

The standardization of a new Explicit Pornographic Picture Set (EPPS).

Pictures with affective content have been extensively used in scientific studies of emotion and sexuality. However, only a few standardized picture sets have been developed that offer explicit images, with most lacking pornographic pictures depicting diverse sexual practices. This study aimed to fill this gap through developing a standardized affective set of diverse pornographic pictures (masturbation, oral sex, vaginal sex, anal sex, group sex, paraphilia) of same-sex and opposite-sex content, offering dimensional affective ratings of valence, arousal, and dominance, as well as co-elicited discrete emotions (disgust, moral and ethical acceptance). In total, 192 pornographic pictures acquired from online pornography platforms and 24 control IAPS images have been rated by 319 participants (Mage = 22.66, SDage = 4.66) with self-reported same- and opposite-sex sexual attraction. Stimuli were representative of the entire affective space, including positively and negatively perceived pictures. Participants showed differential affective perception of pornographic pictures according to gender and sexual attraction. Differences in affective ratings related to participants' gender and sexual attraction, as well as stimuli content (depicted sexual practices and sexes). From the stimuli set, researchers can select explicit pornographic pictures based on the obtained affective ratings and technical parameters (i.e., pixel size, luminosity, color space, contrast, chromatic complexity, spatial frequency, entropy). The stimuli set may be considered a valid tool of diverse explicit pornographic pictures covering the affective space, in particular, for women and men with same- and opposite-sex sexual attraction. This new explicit pornographic picture set (EPPS) is available to the scientific community for non-commercial use.

Accuracy and repeatability of fetal facial measurements in 3D ultrasound: A longitudinal study.

OBJECTIVE: Fetal face measurements in prenatal ultrasound can aid in identifying craniofacial abnormalities in the developing fetus. However, the accuracy and reliability of ultrasound measurements can be affected by factors such as fetal position, image quality, and the sonographer's expertise. This study assesses the accuracy and reliability of fetal facial measurements in prenatal ultrasound. Additionally, the temporal evolution of measurements is studied, comparing prenatal and postnatal measurements. METHODS: Three different experts located up to 23 facial landmarks in 49 prenatal 3D ultrasound scans from normal Caucasian fetuses at weeks 20, 26, and 35 of gestation. Intra- and inter-observer variability was obtained. Postnatal facial measurements were also obtained at 15 days and 1 month postpartum. RESULTS: Most facial landmarks exhibited low errors, with overall intra- and inter-observer errors of 1.01 mm and 1.60 mm, respectively. Landmarks on the nose were found to be the most reliable, while the most challenging ones were those located on the ears and eyes. Overall, scans obtained at 26 weeks of gestation presented the best trade-off between observer variability and landmark visibility. The temporal evolution of the measurements revealed that the lower face area had the highest rate of growth throughout the latest stages of pregnancy. CONCLUSIONS: Craniofacial landmarks can be evaluated using 3D fetal ultrasound, especially those located on the nose, mouth, and chin. Despite its limitations, this study provides valuable insights into prenatal and postnatal biometric changes over time, which could aid in developing predictive models for postnatal measurements based on prenatal data.

Efficiency assessment of follow-up methodology of patients with knee replacement to predict post-surgical functionality: a protocol for randomised control PROKnee trial.

INTRODUCTION: Even when total knee arthroplasty (TKA) is an extended treatment, most patients experience a suboptimal evolution after TKA. The objectives of this study are the following: (1) to determine the effectiveness of two different prosthesis stabilisation systems on the functionality in activities of daily life, and (2) to determine prognostic biomarkers of knee prosthesis function based on radiological information, quantification of cytokines, intra-articular markers and biomechanical functional evaluation to predict successful evolution. METHODS AND ANALYSIS: The PROKnee trial was designed as a randomised controlled patient-blinded trial with two parallel groups that are currently ongoing. The initial recruitment will be 99 patients scheduled for their first TKA, without previous prosthesis interventions in lower limbs, who will be randomly divided into two groups that differed in the stabilisation methodology incorporated in the knee prosthesis: the MEDIAL-pivot group and the CENTRAL-pivot group. The maximum walking speed will be reported as the primary outcome, and the secondary results will be patient-reported questionnaires related to physical status, cognitive and mental state, radiological test, laboratory analysis and biomechanical instrumented functional performance, such as the 6-minute walking test, timed up-and-go test, gait, sit-to-stand, step-over, and ability to step up and down stairs. All the results will be measured 1 week before TKA and at 1.5, 3, 6 and 12 months after surgery. ETHICS AND DISSEMINATION: All procedures were approved by the Ethical Committee for Research with Medicines of the University Clinical Hospital of Valencia on 8 October 2020 (order no. 2020/181). Participants are required to provide informed consent for the study and for the surgical procedure. All the data collected will be treated confidentially since they will be blinded and encrypted. The results from the trial will be published in international peer-reviewed scientific journals, regardless of whether these results are negative or inconclusive. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04850300).

[Microorganisms isolated from blood cultures and resistance profile in children with cancer and high-risk febrile neutropenia. Red PINDA, Chile, 2016-2021]. / Microorganismos aislados de hemocultivos y su perfil de resistencia en niños con cáncer y neutropenia febril de alto riesgo. Red PINDA, Chile, 2016-2021.

Bacteremia is a major cause of morbidity and mortality in patients with cancer and episodes of high-risk febrile neutropenia (HRFN). OBJECTIVE: To identify the frequency of microorganisms isolated from blood cultures (BC) and their antimicrobial resistance (R) profile in children with HRFN, compared with the same data from previous studies of the same group. METHOD: Prospective, multicenter, epidemiological surveillance study of microorganisms isolated from BC in patients under 18 years of age, from 7 PINDA network hospitals, between 2016 and 2021. RESULTS: 284 episodes of HRFN with positive BC were analyzed out of 1091 enrolled episodes (26%). Median age 7.2 years [3.0-12.3]. The main isolates were gram-negative bacilli (GNB) 49.2%, gram-positive cocci (GPC) 43.8%, and fungi 3.6%. The most frequently isolated microorganisms were viridans group Streptococci (VGS) (25.8%), Escherichia coli (19.8%), Pseudomonas spp. (11.2%), Klebsiella spp. (10.9%), and coagulase negative Staphylococci (CoNS) (10.9%). There was an increase in R to third-generation cephalosporins (p = 0.011) in GNB and to oxacillin in CoNS (p = 0.00), as well as a decrease in R to amikacin in non-fermenting GNB (p = 0.02) and to penicillin in VGS (p = 0.04). CONCLUSION: VGS is the main agent isolated in BC from pediatric patients with cancer and episodes of HRFN, followed by E. coli, Pseudomonas spp., and Klebsiella spp. Having epidemiological surveillance of microorganisms isolated from BC and their antimicrobial R profile is essential to favor the rational use of antimicrobials.

Effectiveness of mRNA booster doses in preventing infections and hospitalizations due to SARS-CoV-2 and its dominant variant over time in Valencian healthcare workers, Spain.

OBJECTIVE: This study aimed to evaluate the effectiveness of SARS-CoV-2 mRNA vaccines in preventing infection and hospitalization among healthcare workers (HCWs) in the Valencian Community (Spain), considering vaccination timing, dose number, and predominant variant. METHODS: A test-negative case-control design estimated vaccine effectiveness against symptomatic disease and hospitalization due to SARS-CoV-2. HCWs who underwent PCR or antigen testing for SARS-CoV-2 from January 2021 to March 2022 were included. Cases had a positive diagnostic test, while controls had negative tests. Adjusted vaccine effectiveness (aVE) was calculated using the formula: aVE = (1 - Odds ratio) × 100. RESULTS: During the Delta variant's predominance, aVE against infection within 12-120 days post-second dose was 64.8 % (BNT162b2) and 59.4 % (mRNA-1273), declining to 21.2 % and 42.2 %, respectively, after 120 days. For the Omicron variant, aVE within 12-120 days post-second dose was 61.1 % (BNT162b2) and 85.1 % (mRNA-1273), decreasing to 36.7 % and 24.9 %, respectively, after 120 days. After a booster dose of mRNA-1273, aVE was 64.0 % (BNT162b2 recipients) and 65.9 % (initial mRNA-1273 recipients). Regardless of variant, aVE for hospitalization prevention after 2 doses was 87.0 % (BNT162b2) and 89.0 % (mRNA-1273). CONCLUSION: The administration of two doses of Moderna-mRNA-1273 against SARS-CoV-2 in HCWs proved to be highly effective in preventing infections and hospitalizations in the first 120 days after the second dose during the predominance of the Omicron variant. The decline in VE after 120 days since the administration of the second dose was significantly restored by the booster dose administration. This increase in VE was greater for the Pfizer vaccine. COVID-19 hospitalization prevention remained stable with both mRNA vaccines throughout the study period.

Clinical Progression and Load Management For Proximal Hamstring Tendinopathy In A Long-Distance Runner: A Case Report.

Background and Purpose: The characteristics of Proximal Hamstring Tendinopathy (PHT) include deep, localized pain in the region of the ischial tuberosity. Chronic lesions are often found in long-distance runners. Compression of the tendon and shear force at its insertion at the ischial tuberosity during hip flexion/adduction is a key etiologic factor. The aim of this case report is to analyze the effectiveness of an exercise protocol with progression of tendon loading in PHT in an amateur runner, by assessing pain and functional capacity. Case Description: The subject was a 30-year-old male runner. After participating in a 10km race, he experienced an insidious onset of deep buttock pain in the right ischial tuberosity. His pain was aggravated by running on sloped roads and prolonged sitting on hard surfaces, particularly while driving. The visual analog scale (VAS) for pain, the Puranen-Orave test (PO), the Bent-Knee stretch test (BK stretch), the supine plank test, the Victorian Institute of Sport Assessment-proximal hamstring tendons (VISA-H) questionnaire, and the sciatic nerve mobility (via the Slump test) were assessed. The intervention involved a 12-week progressive loading exercise program divided into four phases. Outcomes: The initial pain was reduced at 6 weeks of intervention and further decreased at 12 weeks (VAS from 7, to 5 and to 1). Function increased at 6 weeks and at 12 weeks (VISA-H from 23, to 53, to 80). Sciatic nerve mobility was normal. Conclusion: The progression of training in a subject with PHT tendon injury based on isometric exercise, concentric/eccentric, energy storage, progressively increasing hip flexion was beneficial, increasing function and decreasing pain. Studies with a larger sample size and a more precise methodological design would be necessary to support this type of intervention in clinical practice. Level of Evidence: 5.

NRN1 epistasis with BDNF and CACNA1C: mediation effects on symptom severity through neuroanatomical changes in schizophrenia.

The expression of Neuritin-1 (NRN1), a neurotrophic factor crucial for neurodevelopment and synaptic plasticity, is enhanced by the Brain Derived Neurotrophic Factor (BDNF). Although the receptor of NRN1 remains unclear, it is suggested that NRN1's activation of the insulin receptor (IR) pathway promotes the transcription of the calcium voltage-gated channel subunit alpha1 C (CACNA1C). These three genes have been independently associated with schizophrenia (SZ) risk, symptomatology, and brain differences. However, research on how they synergistically modulate these phenotypes is scarce. We aimed to study whether the genetic epistasis between these genes affects the risk and clinical presentation of the disorder via its effect on brain structure. First, we tested the epistatic effect of NRN1 and BDNF or CACNA1C on (i) the risk for SZ, (ii) clinical symptoms severity and functionality (onset, PANSS, CGI and GAF), and (iii) brain cortical structure (thickness, surface area and volume measures estimated using FreeSurfer) in a sample of 86 SZ patients and 89 healthy subjects. Second, we explored whether those brain clusters influenced by epistatic effects mediate the clinical profiles. Although we did not find a direct epistatic impact on the risk, our data unveiled significant effects on the disorder's clinical presentation. Specifically, the NRN1-rs10484320 x BDNF-rs6265 interplay influenced PANSS general psychopathology, and the NRN1-rs4960155 x CACNA1C-rs1006737 interaction affected GAF scores. Moreover, several interactions between NRN1 SNPs and BDNF-rs6265 significantly influenced the surface area and cortical volume of the frontal, parietal, and temporal brain regions within patients. The NRN1-rs10484320 x BDNF-rs6265 epistasis in the left lateral orbitofrontal cortex fully mediated the effect on PANSS general psychopathology. Our study not only adds clinical significance to the well-described molecular relationship between NRN1 and BDNF but also underscores the utility of deconstructing SZ into biologically validated brain-imaging markers to explore their mediation role in the path from genetics to complex clinical manifestation.

Effectiveness of family metacognitive training in mothers with psychosis and their adolescent children: a multicenter study protocol.

Background: More than half of women with psychosis take care of their children despite the difficulties caused by the disease. Additionally, these kids have a higher risk of developing a mental health disorder. However, no interventions have been developed to meet these needs. Metacognitive Training (MCT) is a psychological intervention that has demonstrated its efficacy in improving cognitive insight, symptom management and social cognition in people with first-episode psychosis (FEP). Additionally, MCT has shown better results in women than men with FEP. This study aims to adapt and evaluate the efficacy of MCT-F in mothers and adolescent children in an online group context with the main purpose of improving family relationships, cognitive awareness and symptoms in women with psychosis and increase their children's knowledge of the disease and their functioning. As secondary objectives, it also aims to evaluate improvements in metacognition, social cognition, symptoms, protective factors and self-perception of stigma. Materials and methods: A quasi-experimental design with participants acting as their own control will be carried out. Forty-eight mothers with psychosis and their adolescent children (between 12 and 20 years old) recruited from a total of 11 adult mental health care centers will receive MCT-F. Participants will be evaluated 11 weeks before the intervention (T1), at baseline (T2), and post-intervention (T3) with a cognitive insight scale, as a primary outcome. Measures of metacognitive and social cognition, symptoms, cognitive functioning, family and social functioning, protective factors (self-esteem, resilience, and coping strategies) and self-perceived stigma will be addressed as secondary outcomes. Assessment will also address trauma and attachment in mothers and, lastly, the feasibility and acceptability of MCT-F in both participant groups. Discussion: This will be the first investigation of the efficacy, acceptability, and viability of the implementation of MCT-F. The results of this study may have clinical implications, contributing to improving mothers' with psychosis and adolescents' functioning and better understanding of the disease, in addition to the possible protective and preventive effect in adolescents, who are known to be at higher risk of developing severe mental disorders.Clinical trial registration:https://clinicaltrials.gov/, identifier [NCT05358457].

Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects.

Between 2.5 and 28% of people infected with SARS-CoV-2 suffer Long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in Long COVID and the potential association between them. To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy controls chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with Long COVID assessed by ACE III screening test (Overall Cognitive level - OCLz= -0.39± 0.12) was significantly below the infection recovered-controls (OCLz= +0.32± 0.16, p< 0.01). We observed that 48% of patients with Long COVID had episodic memory deficit, with 27% also impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in widespread areas of the patients' cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. This study shows that patients with neurological Long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.

Analysis of social metrics on scientific production in the field of emotion-aware education through artificial intelligence.

Research in the field of Artificial Intelligence applied to emotions in the educational context has experienced significant growth in recent years. However, despite the field's profound implications for the educational community, the social impact of this scientific production on digital social media remains unclear. To address this question, the present research has been proposed, aiming to analyze the social impact of scientific production on the use of Artificial Intelligence for emotions in the educational context. For this purpose, a sample of 243 scientific publications indexed in Scopus and Web of Science has been selected, from which a second sample of 6,094 social impact records has been extracted from Altmetric, Crossref, and PlumX databases. A dual analysis has been conducted using specially designed software: on one hand, the scientific sample has been analyzed from a bibliometric perspective, and on the other hand, the social impact records have been studied. Comparative analysis based on the two dimensions, scientific and social, has focused on the evolution of scientific production with its corresponding social impact, sources, impact, and content analysis. The results indicate that scientific publications have had a high social impact (with an average of 25.08 social impact records per publication), with a significant increase in research interest starting from 2019, likely driven by the emotional implications of measures taken to curb the COVID-19 pandemic. Furthermore, a lack of alignment has been identified between articles with the highest scientific impact and those with the highest social impact, as well as a lack of alignment in the most commonly used terms from both scientific and social perspectives, a significant variability in the lag in months for scientific research to make an impact on social media, and the fact that the social impact of the research did not emerge from the interest of Twitter users unaffiliated with the research, but rather from the authors, publishers, or scientific institutions. The proposed comparative methodology can be applied to any field of study, making it a useful tool given that current trends in accreditation agencies propose the analysis of the repercussion of scientific research in social media.