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Palaeoseismological studies play a crucial role in the seismic characterization of regions with slow-moving faults. This is the case in the central Betic Cordillera, a highly populated area for which the record of prehistoric earthquakes is very limited, despite being one of the regions with the greatest seismic hazard in Spain. We present here a palaeoseismological characterization of the Galera Fault, one of the active faults accommodating deformation in the central Betic Cordillera. We excavated and analysed several trenches along the fault trace. We quantitatively correlate the results from these trenches, resulting in a surface rupture history involving seven or eight events (accounting for the epistemic uncertainties) during the last ca. 24 000 years, with recurrence intervals ranging from 1520 to 1720 years. Further analysis of this surface rupture history seems to indicate that the Galera Fault is prone to producing earthquake clusters as we recorded five events in ∼400 years (ca. 1536–1126 BCE) and only two events in the ∼3200 years that followed. Using the fault geometry and palaeoseismological data, we also carried out a seismogenic characterization of the fault. This analysis yielded a maximum expected magnitude of 6.7 ± 0.3 and a recurrence interval of 1857 years. Furthermore, we also present a geodetic rupture scenario for the maximum expected event, involving displacements of up to 0.5 m. Finally, we discuss the possible impact of the deduced palaeoearthquakes on the development of Bronze Age human settlements located in the vicinity of the fault. In addition to their intrinsic value, our results will provide the basis for future seismic-hazard assessments carried out in the central Betic Cordillera.

Abstract This study presents new ionanofluids (INF) composed of 1-ethyl-3-methylimidazolium acetate ionic liquid (IL) and graphene oxide (GO) nanoparticles which have been assessed for the first time in an experimental flat plate solar thermal collector (FPSC). For this purpose, four types of INFs were synthesized, maintaining a constant concentration of GO nanoparticles dispersed in different base fluids: ionic liquid (IL/GO), a mixture of ionic liquid and water in varying concentrations (IL-water (75–25)%/GO and IL-water (50–50)%/GO), and water (Water/GO). These four INFs were characterized and their thermophysical and physicochemical properties were determined. The results indicated a 37.4% improvement in efficiency and up to a 2.5-fold increase in temperature within the collector when the IL was applied exclusively as the base fluid, compared to water. Furthermore, IL/GO demonstrated excellent stability, showing no signs of deterioration or nanoparticle precipitation two years after preparation and testing. These findings suggest that INFs based on IL and GO nanoparticles significantly enhance the efficiency of FPSC, presenting a promising option for solar energy applications and opening a new research avenue for INFs in the production of domestic hot water.

Abstract BackgroundMobile apps represent accessible and cost-effective tools to improve nutrition and prevent chronic diseases. However, most of these apps have been characterized as having limited functionality, raising concerns about their effectiveness, acceptability, and efficacy. ObjectiveThe aims of the study were to assess the quality of popular nutrition-related app platforms in Spain and to describe their characteristics and functionalities. MethodsWe screened apps providing information on dietary advice, food advice, and nutritional content in the Apple App Store and Google Play Store in Spain from March 2 to March 16, 2024. Apps with a star rating of ≥4 (of 5 stars), those available in Spanish, those that were free of charge, those last updated after January 2022, those with >500 reviews, and those with >500,000 downloads were included. The quality of apps was assessed using the user version of the Mobile App Rating Scale (uMARS). General characteristics and nutritional, health, and market-related functionalities of the nutrition-related apps were described. Correlations among total and uMARS sections, star ratings, and number of reviews and downloads were evaluated. ResultsAmong the 1460 apps identified in the search, 42 apps met the criteria. The majority of these (n=20, 48%) aimed at recording and analyzing food intake, followed by those providing nutritional plans or diets (n=9, 21%), advising on healthy habits (n=7, 17%), and offering recipes (n=6, 14%). The most prevalent nutritional functionalities offered were recording and monitoring body measurements (n=30, 71%), food tracking (n=26, 62%), and dietary analysis (n=25, 60%), whereas nutrition education was less common (n=16, 38%). Among market-related functionalities, advertisements were the most common among the study apps (n=30, 71%), followed by the option of sharing on social media (n=29, 69%) and customizable reminders (n=26, 62%). Sharing the recorded information in the app with health professionals was infrequent (n=1, 2%). The mean (SD) total uMARS score (maximum 5 points) was 3.78 (0.35), while the mean (SD) uMARS scores for functionality, aesthetics, engagement, and information were 4.21 (0.38), 3.94 (0.54), 3.51 (0.46), and 3.48 (0.44), respectively. Lower mean scores were observed for the subjective quality (mean 2.65, SD 0.56) and perceived impact (mean 3.06, SD 0.67). Moderate to strong positive significant correlations were mostly observed between total uMARS and section-specific uMARS scores, while the correlations between the uMARS section scores were mostly moderate positive. Total uMARS scores were very weakly correlated with user rating, number of reviews, and number of downloads. ConclusionsThe quality of popular nutrition-related app platforms in Spain was acceptable, with observed remarkable differences between sections. The majority of the apps were appealing due to their user-friendly interfaces. Only a few apps, however, provided dietary structure analysis or nutritional education. Further research is needed to assess the long-term impact of these apps on users.

Abstract Background There is little research investigating the subjective experiences of parenting young children while living in poverty and experiencing financial strain using qualitative methodologies. Therefore, the objective of this study was to employ a qualitative approach to provide a nuanced and balanced view on the topic of parenting young children under financial strain in the Canadian context. Methods We conducted a qualitative study using semi-structured interviews between July and August 2021 in Kingston, Ontario, Canada. Sixteen participants aged 20–39 self-identified as living under financial strain while parenting a child aged 2–5 years. A qualitative inductive thematic analysis was undertaken with a focus on describing the contents of the data. Results Four major themes emerged from the data: experience of being a parent, impact of financial strain on the family unit, impact of financial strain on the children, and impact of financial strain on the parent. Numerous deleterious physical, mental, and material impacts on the family unit and parent were identified, however parent-perceived impacts of financial strain on their children were minimal. Parents described striking levels of resourcefulness and resiliency in providing the necessities for their families, absorbing the most significant impacts of financial strain through the phenomenon of self-sacrifice. Conclusion The impacts of financial strain on families with young children are far reaching. Further research into the impacts of self-sacrifice on parents experiencing financial strain are needed to better understand this issue, and to inform social programming and resources that could help alleviate the deleterious impacts of poverty on parent mental, social, and physical health.

Hematological cancers are among the most common cancers in adults and children. Despite significant improvements in therapies, many patients still succumb to the disease. Therefore, novel therapies are needed. The Wiskott-Aldrich syndrome protein (WASp) family regulates actin assembly in conjunction with the Arp2/3 complex, a ubiquitous nucleation factor. WASp is expressed exclusively in hematopoietic cells and exists in two allosteric conformations: autoinhibited or activated. Here, we describe the development of EG-011, a first-in-class small molecule activator of the WASp auto-inhibited form. EG-011 possesses in vitro and in vivo anti-tumor activity as a single agent in lymphoma, leukemia, and multiple myeloma, including models of secondary resistance to PI3K, BTK, and proteasome inhibitors. The in vitro activity was confirmed in a lymphoma xenograft. Actin polymerization and WASp binding was demonstrated using multiple techniques. Transcriptome analysis highlighted homology with drugs-inducing actin polymerization.

Objective: The presented study shows a new and innovative method to determine nasal asymmetries in a simple way in patients with cleft lip and palate (CLP) in order to plan corrective surgery. Design: 86 non-syndromic patients with cleft lip and palate were divided into 2 groups: a) patients with unilateral cleft lip and palate b) patients with bilateral cleft lip and palate. Patients: follow-up of hospital records of 86 patients aged 2–18 years. Main outcome: Based on standardised photos of the nose from 3 different directions, the nose symmetry was assessed. A new digital measurement system was used, which is integrated into proven clinical programmes. These were compared with a control group. In addition, a mirror fog test and a standardised questionnaire were used. Result: The overall results showed a good symmetry of the nose postoperatively, as well as a high satisfaction of the patients and their parents. Profile and angle measurements showed a better result. Conclusio: The presented measurement system and especially the Cleft Lip Component Symmetry Index (CLCSI) allows an individual and very effective assessment of the symmetry of the nose as well as a control of the growth in patients with CLP. The method is easy to apply in daily practice, even for untrained practitioners.

Bacteria are capable of remarkable adaptations to their environment, including undesirable bacterial resistance to antibacterial agents. One of the most serious cases is an infection caused by multidrug-resistant Staphylococcus aureus, which has unfortunately also spread outside hospitals. Therefore, the development of new effective antibacterial agents is extremely important to solve the increasing problem of bacterial resistance. The bacteriolytic enzyme autolysin E (AtlE) is a promising new drug target as it plays a key role in the degradation of peptidoglycan in the bacterial cell wall. Consequently, disruption of function can have an immense impact on bacterial growth and survival. An in silico and in vitro evaluation of iminosugar derivatives as potent inhibitors of S. aureus (AtlE) was performed. Three promising hit compounds (1, 3 and 8) were identified as AtlE binders in the micromolar range as measured by surface plasmon resonance. The most potent compound among the SPR response curve hits was 1, with a KD of 19 μM. The KD value for compound 8 was 88 μM, while compound 3 had a KD value of 410 μM.

Abstract Critical care practice is constantly evolving. Pressures for bed availability in publicly funded healthcare systems have led to an increase in patients delayed in their discharge from critical care to the wards. This has resulted in more patients discharged directly home (DDH) from the intensive care unit (ICU). However, few formal pathways for DDH exist. We have performed a retrospective audit of the patients discharged home from our unit in the largest tertiary referral hospital in the Republic of Ireland from 2017 to 2022 to investigate their characteristics and the safety of this practice, given the understandable patient safety concerns raised. Results In total, 84 patients have been DDH from our unit between 2017 and 2022 from a total of 4747 patients. The overall rate of DDH increased year on year, and the vast majority of these patients were initially admitted from the emergency department or following elective major surgery. Most patients had an APACHE score of less than 11 points, and the majority were admitted for less than 3 days, with single organ failure. There was a gender divide, as greater than 60% of the patients admitted were male, with a mean age of 44. Conclusion DDH has been an important tool in improving patient flow through the hospital, avoiding unnecessary de-escalation to the ward for a select group of critical care patients. The re-admission rate in the year post-ICU discharge was very low, showing that DDH has not adversely impacted patient safety.

Introduction In the assessment of suicidal behavior, recent studies describe the great influence of an environmental component with adverse life events and stressors that can influence ideation and self-harm. Objectives -1. We propose to analyze the reasons for consultation of adolescents between 12 and 16 years old who consult for suicidal ideation/behavior. 2. Estimate the frequency of different socio-family life events. Methods -A retrospective review of emergency consultations in the last 4 months is performed. Sociodemographic data, vital events, reason for consultation and evolution in the following 40 days after the first consultation are collected. Results -Data are collected from 16 adolescents who consult due to suicidal ideation/gesture in a period of 4 months, of which 42% (7) are women and 57% (9) are men. The reasons recorded as stressful life events were: 32% unstructured family environment, 13% death of a close relative, 37% poor parental supervision, 26% end of a romantic relationship, 15% legal problems, 2% sexual or physical abuse, 68 % academic problems, 13% bullying. It was observed that in 63% of the cases they had more than one adverse experience. Conclusions -Different adverse life events frequently precede suicidal ideation and behavior that can be minimized or go unnoticed and undervalued. A meticulous clinical history can clarify some of the reasons that influence the hopelessness and clinical anguish that suicidal patients present. Its early detection provides the opportunity for an early and specialized approach Disclosure of Interest None Declared

Introduction The gut-brain axis establishes the relationships between bacteria, neurotransmitters and psychophysiological responses associated with a neuronal and behavioral correlate in autism and different mental disorders. In recent years, there has been an increase in studies on the implications of the gut microbiota (MI) in children with autism spectrum disorders (ASD). Objectives 1. To study if there is a dysbiosis or alteration of the MI can trigger the appearance of ASD symptoms. It is considered that there is a frequent comorbidity with gastro-intestinal symptoms (GS), pain and sensory reactivity in ASD, and that these are indicators of a possible alteration in the gut-brain axis. Methods In this sense, children with ASD have hypersensitivity to certain visual, olfactory, tactile, etc. stimuli. which makes them be more picky about food and have certain repetitive patterns of behavior, as a consequence they present gastrointestinal symptoms such as constipation and abdominal pain. Sensory reactivity can influence both feeding and sleep patterns in autism. Results Currently, there are measuring instruments for sensory reactivity, pain and gastro-intestinal symptoms. However, there are several limitations of these instruments and especially with sensory reactivity in autism because: (1) the items had not been developed in collaboration with interested parties (pediatricians, neuropsychologists, etc.) and (2) the lack of structural validity analysis. Thus, it appears that most validation studies do not meet the criteria of sufficient psychometric quality according to the COSMIN guidelines. Additionally, there is a lack of consensus around terminology (e.g., sensory overreactivity, hyperreactivity, SOR, etc.) and components relevant to sensory functioning. Conclusions In the present work, preliminary data are presented on new measures to take into account to evaluate sensory reactivity and pain in the population with autism. This is a first step to obtain an index of the gut-brain axis for the ASD population. Keywords: ASD, gut-brain, sensory reactivity, pain Disclosure of Interest None Declared

Introduction Reviewing the histories of patients with childhood and adolescent schizophrenia, on numerous occasions, traumatic factors with great emotional and social impact are observed, such as situations of mistreatment, abuse and emotional deprivation, where help is requested but resources are scarce and the approach is limited without work in network. Objectives 1. Analysis of the consultation pathways in adolescents with severe psychiatric and socio-familial symptoms and the time delay in optimal guidance. 2. Evaluate the services involved. 3. Evaluate the clinical control of treatment with aripiprazole. Methods Retrospective observational analysis, 5 months, of prodromal symptoms of childhood psychosis and help-seeking pathways in a 13-year-old adolescent, as well as a description of the pharmacological approach and professional teams involved. Results A 13-year-old adolescent who went to the emergency room with her mother for ingesting anti-cockroaches with self-inflicted intent. Reviewing his medical history, 4 serious autolytic gestures were detected in the last 2 months. Referred to Mental Health who did not attend. On clinical examination, florid psychotic, with perplexity, self-reference, ideation of harm, language and behavioral disorganization. Auditory and kinesthetic hallucinations. A situation of neglect of the minor and abuse by the parents is detected; the risk had not been previously reported. Oral aripiprazole (up to 15 mg/day) was prescribed with good tolerance and progressive improvement in symptoms. We worked jointly with Social Services, the Juvenile Prosecutor’s Office, Education and the hospital Psychiatry unit. In some of the resources the situation was already evident, the scope of their action was limited and delaying attention for months. Conclusions Based on cases like this, we ask ourselves if psychiatrists are sensitized to the comorbidity of serious mental pathology and the existence of risk situations in minors and if they are oriented toward multiprofessional management. Networking provides us with an early diagnosis, improving the therapeutic approach. Disclosure of Interest None Declared

ABSTRACT: Uterine diseases and heat stress (HS) are major challenges for the dairy cow. Heat stress alters host immune resilience, making cows more susceptible to the development of uterine disease. Although HS increases the incidence of uterine disease, the mechanisms by which this occurs are unclear. We hypothesize that evaporative cooling (CL) to alleviate HS in prepartum cows has carry-over effects on postpartum innate immunity. Nulliparous pregnant Holstein heifers were assigned to receive either forced CL that resulted in cool conditions (shade with water soakers and fans; n = 14) or to remain under HS conditions (barn shade only; n = 16) for 60 d prepartum. Postpartum, all cows were housed in a freestall barn equipped with shade, water soakers, and fans. Respiratory rate and rectal temperature during the prepartum period were greater in HS heifers compared with CL heifers, indicative of HS. Although milk production was decreased in HS cows compared with CL cows, the incidence of uterine disease and content of total or pathogenic bacteria in vaginal mucus on d 7 or d 21 postpartum was not affected by treatment. Whole blood was collected on d 21 and subjected to in vitro stimulation with lipopolysaccharide. Lipopolysaccharide-induced accumulation of IL-1β, IL-10, and MIP-1α was greater in blood collected from HS cows compared with CL cows. Our results imply that prepartum HS during late pregnancy has carry-over effects on postpartum innate immunity, which may contribute to the increased incidence of uterine disease observed in cows exposed to prepartum HS.

Abstract Nowadays, exome sequencing is a robust and cost-efficient genetic diagnostic tool already implemented in many clinical laboratories. Despite it has undoubtedly improved our diagnostic capacity and has allowed the discovery of many new Mendelian-disease genes, it only provides a molecular diagnosis in up to 25–30% of cases. Here, we comprehensively evaluate the results of a large sample set of 4974 clinical exomes performed in our laboratory over a period of 5 years, showing a global diagnostic rate of 24.62% (1391/4974). For the evaluation we establish different groups of diseases and demonstrate how the diagnostic rate is not only dependent on the analyzed group of diseases (43.12% in ophthalmological cases vs 16.61% in neurological cases) but on the specific disorder (47.49% in retinal dystrophies vs 24.02% in optic atrophy; 18.88% in neuropathies/paraparesias vs 11.43% in dementias). We also detail the most frequent mutated genes within each group of disorders and discuss, on our experience, further investigations and directions needed for the benefit of patients.

Abstract Objective Tracheostomy tube change is a multistep skill that must be performed rapidly and precisely. Despite the critical importance of this skill, there is wide variation in teaching protocols. Methods An innovative operant conditioning teaching methodology was employed and compared to traditional educational techniques. Medical student volunteers at a tertiary care academic institution (Albert Einstein College of Medicine) were recruited and randomly distributed into 2 groups: operant vs traditional (control). Following the educational session, each group was provided with practice time and then asked to perform 10 tracheostomy tube changes. Performance was recorded and scored by blinded raters using deidentified video recordings. Results The operant learning group (OLG) demonstrated greater accuracy in performing a tracheostomy tube change than the traditional demonstration group. Twelve of 13 operant learners performed the skill accurately each time compared to 3 of 13 in the traditional group (P = 0.002). The median lesson time was longer for the OLG (535 seconds) than for the traditional group, (200 seconds P

The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5’ (n=9) and 3’ (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5’ breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3’ breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively.

Spelling ability is a key dimension of orthographic knowledge and a crucial component literacy skill that supports automatic word recognition and fluent reading. There has been substantial research on first language (child) English speakers’ spelling ability, including the effectiveness of instruction interventions for improving spelling knowledge. However, there is relatively little research on spelling in adult learners of English as a second language, and even less examining instructional interventions for improving their spelling. The current study addressed this gap by implementing an adaptation of a phonics-based instructional intervention in a university-based intensive English reading class. Compared to two different control cohorts, the cohort receiving the intervention significantly improved their ability to accurately identify whether an English word was spelled correctly or not. Analyses also considered the influence of a variety of lexical characteristics as well as participants’ L1 writing system. The results demonstrate the efficacy of this intervention in adult L2 English learners and also highlight the importance of considering word characteristics and participants’ language background when examining spelling performance.

Abstract Background Existing studies of patient-reported outcomes (PRO) following total knee arthroplasty (TKA) based on fixation methods (cemented vs cementless) are limited to single centers with small sample sizes. Using multicentered data,, we compared baseline and early post-operative global and condition-specific PROs between patients undergoing cemented versus cementless TKA. Methods With PROs prospectively collected through Comparative Effectiveness Pulmonary Embolism Prevention After Hip and Knee Replacement (PEPPER) trial (ClinicalTrials.gov: NCT02810704), we examined pre- and post-operative (1, 3, and 6-months) outcomes in 5,961 patients undergoing primary TKA enrolled by 28 medical centers between December 2016 and August 2021. Outcomes included the short-form of the Knee Injury and Osteoarthritis Outcome Score (KOOS-Jr.), the Patient-Reported Outcomes Measurement Information System Physical Health (PROMIS-PH), and the Numeric Pain Rating Scale (NPRS). To minimize selection bias, we performed a 1-to-1 propensity score matched analysis to assess relative pre- to post-operative change in outcomes within and between cemented and cementless TKA groups. Results With greater than 90% follow-up, significant pre to- post-operative improvements were observed in both groups. At 6 months, the cemented TKA group achieved a 3.3 point (55% of the Minimum Clinically Important Difference) greater improvement in the mean KOOS-Jr. (95%CI: 0.36, 6.30; P = 0.028) than did the cementless group with no significant between-group differences in PROMIS-PH and NPRS. Conclusions In a large cohort of primary TKAs, patients with cemented fixation reported early incremental benefit in KOOS-Jr. over those with cementless TKA. Future studies are warranted to capture longer follow-up of PROs.

Abstract Background Bacterial infection of the uterus in postpartum dairy cows limits ovarian follicle growth, reduces blood estradiol concentrations, and leads to accumulation of bacterial lipopolysaccharide (LPS) in ovarian follicular fluid. Although treating granulosa cells with LPS in vitro decreases the expression of the estradiol synthesis enzyme CYP19A1 and reduces estradiol secretion, the molecular mechanisms are unclear. The transcription factor CCAAT enhancer binding protein beta (CEBPβ) not only facilitates the transcription of LPS regulated cytokines, but also binds to the promoter region of CYP19A1 in humans, mice, and buffalo. We hypothesized that LPS alters CEBPβ signaling to reduce CYP19A1 expression, resulting in decreased estradiol secretion. Methods Bovine granulosa cells were isolated from small/medium or large follicles and treated with LPS in the presence of FSH and androstenedione for up to 24 h. Results Treatment with LPS increased CXCL8 and IL6 gene expression and reduced estradiol secretion in granulosa cells from both small/medium and large follicles. However, LPS only reduced CYP19A1 expression in granulosa cells from large follicles. Treatment with LPS increased CEBPB expression and reduced CEBPβ nuclear localization in granulosa cells from small/medium follicles, but not granulosa cells from large follicles. Conclusions Although LPS reduces estradiol synthesis in bovine granulosa cells, the effects of LPS on CYP19A1 and CEBPβ are dependent on follicle size.

NOTCH mutations are frequent in B cell malignancies. Here the authors use retroviral transduction of primary malignant B cells from Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL) patients to show that NOTCH1/2-mutations facilitate mechanism of immune escape.

There is still a long way ahead regarding the COVID-19 pandemic, since emerging waves remain a daunting challenge to the healthcare system. For this reason, the development of new preventive tools and therapeutic strategies to deal with the disease have been necessary, among which serological assays have played a key role in the control of COVID-19 outbreaks and vaccine development. Here, we have developed and evaluated an immunoassay capable of simultaneously detecting multiple IgG antibodies against different SARS-CoV-2 antigens through the use of Bio-PlexTM technology. Additionally, we have analyzed the antibody response in COVID-19 patients with different clinical profiles in Cadiz, Spain. The multiplex immunoassay presented is a high-throughput and robust immune response monitoring tool capable of concurrently detecting anti-S1, anti-NC and anti-RBD IgG antibodies in serum with a very high sensitivity (94.34–97.96%) and specificity (91.84–100%). Therefore, the immunoassay proposed herein may be a useful monitoring tool for individual humoral immunity against SARS-CoV-2, as well as for epidemiological surveillance. In addition, we show the values of antibodies against multiple SARS-CoV-2 antigens and their correlation with the different clinical profiles of unvaccinated COVID-19 patients in Cadiz, Spain, during the first and second waves of the pandemic.

Abstract Current somatic mutation callers are biased against repetitive regions, preventing the identification of potential driver alterations in these loci. We developed a mutation caller for repetitive regions, and applied it to study repetitive non protein-coding genes in more than 2200 whole-genome cases. We identified a recurrent mutation at position c.28 in the gene encoding the snRNA U2. This mutation is present in B-cell derived tumors, as well as in prostate and pancreatic cancer, suggesting U2 c.28 constitutes a driver candidate associated with worse prognosis. We showed that the GRCh37 reference genome is incomplete, lacking the U2 cluster in chromosome 17, preventing the identification of mutations in this gene. Furthermore, the 5′-flanking region of WDR74, previously described as frequently mutated in cancer, constitutes a functional copy of U2. These data reinforce the relevance of non-coding mutations in cancer, and highlight current challenges of cancer genomic research in characterizing mutations affecting repetitive genes.

Summary: Antibiotic resistance is reaching alarming levels, demanding for the discovery and development of antibiotics with novel chemistry and mechanisms of action. The recently discovered antibiotic cacaoidin combines the characteristic lanthionine residue of lanthipeptides and the linaridin-specific N-terminal dimethylation in an unprecedented N-dimethyl lanthionine ring, being therefore designated as the first class V lanthipeptide (lanthidin). Further notable features include the high D-amino acid content and a unique disaccharide substitution attached to the tyrosine residue. Cacaoidin shows antimicrobial activity against gram-positive pathogens and was shown to interfere with peptidoglycan biosynthesis. Initial investigations indicated an interaction with the peptidoglycan precursor lipid IIPGN as described for several lanthipeptides. Using a combination of biochemical and molecular interaction studies we provide evidence that cacaoidin is the first natural product demonstrated to exhibit a dual mode of action combining binding to lipid IIPGN and direct inhibition of cell wall transglycosylases.

Introduction In schizoaffective disorder, treatment with atypical antipsychotics is a first-line treatment option associated with treatment with mood stabilizers. One of the associated adverse effects is weight gain, which is sometimes associated with a deterioration of self-image and greater psychosocial impact. Objectives 1. To assess the personal perception and psychosocial adjustment in patients with affective psichotic disorder onset of symptoms in adolescence in current treatment with oral or IM aripiprazole. 2. To determine if there is variation in self-perception in patients with oral treatment compared to patients with long-term injectable treatment Methods Patients with affective psichotic disorder onset in adolescence come to consultation. Retrospective data collection: 9 months. Cross-sectional assessment with E-PICA scale. SPSS21.0. Results 33 patients, 60% women (mean 38.6 years) and 40% men (40.46 years). Men consulted for psychiatric symptoms earlier and their diagnosis is earlier than in women (men: onset 16.8 years, ASD diagnosis 27.15; women: symptoms onset 20.5 years, diagnosis 37.1 years). The use of ILD aripiprazole is observed in 54%, with a similar proportion in both sexes (men 53%, women 55%). In patients with oral aripiprazole, scores were obtained: mild psychosocial impact in 18%, all of them women; moderate impact 18% and severe impact in 9% of cases. While the results with ILD treatment: mild impact in 30% and moderate impact in 24% of cases, not observing severity scores in aripiprazole ILD. Conclusions We observed a better body perception and self-esteem in women diagnosed with schizoaffective disorder and with long-term injectable aripiprazole treatment, assessing the psychosocial impact as mild. In men, the impact is greater, being observed more frequently in men with oral treatment. Continuity of follow-up and future studies will be necessary to determine other associated factors, as well as comparison with the use of other treatments. Disclosure of Interest None Declared

Introduction Chronic back pain is one of the leading causes of disability and treatment is often ineffective. Approximately 85% of cases are primary, for which the peripheral etiology cannot be identified, and maintenance factors include fear, avoidance, and beliefs that pain indicates injury.Studies suggest that an excessively negative orientation towards pain (pain catastrophism) and fear of movement/(re)injury (kinesiophobia) are important in the aetiology of chronic low back pain and associated disability. Objectives The aim is to identify the psychopatological profile (including levels of movement phobia and catastrophic thinking) in patients with chronic low back pain who participate in a multidisciplinary group Comprehensive Care Program for Patients with Chronic Pain (PAINDOC) in the Pain Unit of the Hospital Clínic i Provincial de Barcelona. Methods A cross-sectional descriptive study of 75 patients aged between 28 and 68 years who participate in the treatment is carried out. A clinical interview was carried out, anxiety and depression symptoms were assessed with thHospital Anxiety and Depression Scale (HADS), Kinesiophobia was evaluated with the Tampa Scale Kinesiophobia (TSK-11SV) and catastrophism with the Pain Catastrophizing Scale (PCS). Results The results show that the patients presented a high level of catastrophic thinking, especially in the subgroup of women with a longer duration of pain.Movement phobia was observed in 27% of patients, and correlated with feelings of depression and anxiety. Conclusions Catastrophism is a multidimensional psychological construct that encompasses elements such as rumination, magnification, and incapacity.Catastrophic thinking in relation to pain is a risk factor for chronic pain. Kinesiophobia is based on the fear avoidance model and perpetuates a cycle of heightened fear of pain, disability, and depression. These constructs can be very useful to evaluate in patients to reduce the intensity of pain, the associated emotional suffering and reduce the probability that the pain will become chronic. Disclosure of Interest None Declared

Introduction Schizophrenia is a chronic disease that deteriorates the functionality of patients, especially when raising a family and caring for children. We are interested in analyzing the characteristics of mothers and fathers diagnosed with schizophrenia and their degree of global activity when switching from oral treatments to injectable treatments. Objectives 1 To evaluate the quality of life and functional level of mothers with schizophrenia treated with quarterly paliperidone palmitate. 2. To compare the quality of life and functional level when switching from oral treatment to long-acting injectables. Methods Participants were 3 mothers and 3 fathers, 33-40 years old, with a diagnosis of schizophrenia in monotherapy who changed treatment with monthly paliperidone palmitate to quarterly paliperidone palmitate LD IM (525 mg/every 12 weeks). Retrospective data collection. QLS quality of life scale. Results Six patients were included, caregivers of 1 child (80%), 2 children (20%) who met the inclusion criteria and completed the questionnaires. After its application and correction by means of non-parametric tests (N

Introduction Serious mental illness in adolescence that not only has a significant impact on the patient but also on other contexts such as their family. Caregivers assume almost all of the care. This responsibility exposes caregivers to intense overload with negative consequences. Objectives To evaluate and quantify the overload of the primary caregiver in children and adolescents with severe mental disorders. Methods A prospective study was designed using structured interviews in caregivers of patients between 11 and 18 years of age with severe mental disorders and substance use who were evaluated in the psychiatric emergency service for 2 months. The Zarit Caregiver Burden Scale was used for quantitative assessment. Diagnosis, main caregiver, socio-health resources were recorded. Results Of a total of 35 patients with serious mental illness between 11 and 16 years of age, the following was observed: intense caregiver burden in 42.2% of cases, moderate in 21%. Being the main caregiver the mother. 27.5% had adequate use of socio-health resources, while 42.7% had not requested them. The greatest need detected was economic and rehabilitation. Conclusions Serious mental disorder present since adolescence leads families to significant destabilization of the family nucleus and comorbidity of psychiatric disorders in caregivers. Good orientation and evaluation of individual cases are necessary to guide families about the resources available in the social and health network, thus avoiding a high overload of caregivers and improving the quality of life of families. Disclosure of Interest None Declared

Introduction Clinical case description. A 44-year-old male, with paranoid schizophrenia, polydrug addict and IVDU since he was 14 years old. Live alone. He is brought by the Local Police for heteroaggressiveness when he was arrested for trespassing and resisting authority. He has presented 14 hospital admissions and therapeutic communities for detoxification since 2000. Objectives 1. To analyze the causes of abandonment of treatment Methods 1. Complete medical history 2. Blood test with hormone profile 3. PRAEQ Questionnaire Absence of child psychopathology until the age of 6, at which time his parents separate and he becomes introverted, with solitary activities and distractions. On examination, the patient is restless. Psychotic contact. Delusional speech centered on ill-structured ideas of harm, persecution and grandiose, being difficult to explore due to lack of collaboration on the part of the patient, who only accepts treatment with aripiprazole 5 mg due to sexual dysfunction with the rest of the treatments. Results During his admission, he has evolved from a very unstructured delusional theme and social isolation, with lax and tangential speech and refusal to take any treatment except aripiprazole, towards a cooperative, trusting attitude, with attenuation of his delusional ideation, with appropriate, organized and releasable. Treatment with IM aripiprazole is agreed upon for discharge. Clinical judgement: Paranoid schizophrenia (F20.0) Conclusions With this case, we intend to remember that antipsychotics affect different spheres of the patient’s life that can hinder adherence to treatment, and that we often do not take into account. In this specific case, Abilify Maintena is useful because it does not cause sexual dysfunction, which facilitates treatment adherence and greater patient involvement, which gives us greater opportunities for social integration. Disclosure of Interest None Declared

Background:. Online learning platforms are a staple of orthopaedic resident education. These platforms typically address a user's knowledge base, aiming to improve OITE and AAOS Board Examination scores. Orthopaedic residents often use these platforms as their primary educational resource. However, an orthopaedic surgeon is more than an orthopaedic knowledge base; acquisition of clinical acumen is integral as well. We sought to investigate the following: From a learner's and educator's perspective, do Orthobullets (OB) and Clinical Classroom (CC) contribute to both knowledge base and clinical acumen? Methods:. Thirty residents and 16 attending surgeons at a single institution were assigned to review topics and complete questions on either the OB and CC platform. Participants then filled out surveys regarding the platform they were assigned, switched platforms, and completed a final survey. Independent-samples Student t tests and χ2 tests were used to analyze differences in continuous and categorical data. Results:. Residents and attendings reported a preference for OB for fact acquisition, relevance to the OITE, and explanation of answers. Senior residents (PGY5) and attending surgeons reported that CC had a greater impact on their clinical acumen. Junior residents (PGY1, PGY2, and PGY3) reported the opposite. Participants responded that both platforms expand a learner's knowledge base and clinical acumen. Conclusions:. Learners and educators felt both platforms addressed knowledge base and clinical acumen. Junior residents reported a preference for OB to CC to advance their knowledge base and clinical acumen, but senior residents and attendings felt the opposite was true. Based on survey responses, these platforms were found to be additive, complementary, and that their value to the learner changes during the course of residency education. Level of Evidence:. III.

Introduction Obesity is a multiorgan disorder that is caused by eating a much larger overeating that the body needs to live. Obese people tend to eat a lot and after hours, and it is hypothetised that it exists a relationship between increased impulsivity and obesity. In addition these patients tend to have more psychopathology, Objectives The aim of the study is to observe if obese people ingest impulsively and if there are differences between the sexes regarding impulsivity. Also it will be studied the relationship between impulsivity in these patients and other psychosocial factors, anxiety and depression symptoms and personality traits. Methods It was carried out an assessment of impulsivity in 30 obese population followed at the outpatient Endocrinology that attended pre-bariatric surgery groups.Patients were handed the Plutchik impulsivity questionnaire, Hospital Anxiety and Depression Scale (HADS) and The Temperament and Character Inventory (TCI). Results In our sample, 43.4% of the obese patients did not show high levels of impulsivity, while 56.6% did show markedly impulsive traits. No differences in impulsivity between sexes were found. No other significant relationships with addititional psychological factors were found. Conclusions A larger sample is needed to reach a conclusion and to extrapolate the results to the general population. People with morbid obesity have higher impulsivity and a binge eating;in addition they have more psychopathology, mainly affective, greater impulsivity and greater severity on scales that assess the core symptoms of disordered eating behavior and body dissatisfaction. Disclosure No significant relationships.

Abstract Colorectal cancer (CRC) is the second leading cause for cancer-related death globally. Clinically, there is an urgent need for non-invasive CRC detection. This study assessed the feasibility of CRC detection by analysis of tumor-derived methylated DNA fragments in urine. Urine samples, including both unfractioned and supernatant urine fractions, of 92 CRC patients and 63 healthy volunteers were analyzed for DNA methylation levels of 6 CRC-associated markers (SEPT9, TMEFF2, SDC2, NDRG4, VIM and ALX4). Optimal marker panels were determined by two statistical approaches. Methylation levels of SEPT9 were significantly increased in urine supernatant of CRC patients compared to controls (p

Abstract Postpartum uterine infection reduces fertility in dairy cattle; however, the mechanisms of uterine infection‐mediated infertility are unknown. Paradoxically, infection‐induced infertility persists after the resolution of disease. Oocytes are a finite resource, which are present at various stages of development during uterine infection. It is likely that oocyte development is influenced by uterine infection‐induced changes to the follicular microenvironment. To better understand the impact of infection on oocyte quality we employed global transcriptomics of oocytes collected from heifers after receiving intrauterine infusion of pathogenic Escherichia coli and Trueperella pyogenes. We hypothesized that the oocyte transcriptome would be altered in response to intrauterine infection. A total of 452 differentially expressed genes were identified in oocytes collected from heifers 4 days after bacteria infusion compared to vehicle infusion, while 539 differentially expressed genes were identified in oocytes collected from heifers 60 days after bacteria infusion. Only 42 genes were differentially expressed in bacteria‐infused heifers at both Day 4 and Day 60. Interferon, HMGB1, ILK, IL‐6, and TGF‐beta signaling pathways were downregulated in oocytes collected at Day 4 from bacteria‐infused heifers, while interferon, ILK, and IL‐6 signaling were upregulated in oocytes collected at Day 60 from bacteria‐infused heifers. These data suggest that bacterial infusion alters the oocyte transcriptome differently at Day 4 and Day 60, suggesting different follicle stages are susceptible to damage. Characterizing the long‐term impacts of uterine infection on the oocyte transcriptome aids in our understanding of how infection causes infertility in dairy cattle.

The geometry and kinematics of active faults have a significant impact on their seismic potential. In this work, a structural characterization of the active Baza Fault (central Betic Cordillera, southern Spain) combining surface and subsurface data is presented. Two sectors are defined based on their surface geometry: a northern sector striking N–S to NNW–SSE with a narrow damage zone and a southern sector striking NW–SE with a wide damage zone. A kinematic analysis shows pure normal fault kinematics along most of the fault. Geometric differences between the northern and southern sectors are caused by i) a heterogeneous basement controlling the fault geometry at depth and in the cover; ii) different orientations of the Baza Fault in the basement with respect to the regional extension direction and iii) interaction with other active faults. We use this structural characterization to analyse the segmentation of the Baza Fault. According to segmentation criteria, the entire Baza Fault should be considered a single fault seismogenic segment. Consequently, the seismic potential of the fault is defined for a complete rupture. Magnitude for the Mmax event is calculated using several scale relationships, obtaining values ranging between Mw 6.6 and Mw 7.1. Recurrence times range between approximately 2,000 and 2,200 years for Mmax events and between 5,300 and 5,400 years for palaeo-events. A geodetic scenario modelled for an Mmax event of Mw 6.7 shows permanent vertical displacements of more than 0.40m and an overall WSW–ENE extension during entire ruptures of the Baza Fault.

Background Several hospitals have implemented a multidisciplinary Acute Pain Service (APS) to execute surgery-specific opioid sparing analgesic pathways. Implementation of an anesthesia attending-only APS has been associated with decreased postoperative opioid consumption, time to ambulation, and time to solid food intake for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. In this study, we evaluated the impact of introducing an APS trainee on postoperative opioid consumption in patients undergoing hyperthermic intraperitoneal chemotherapy during postoperative day (POD) 0–3. Methods We performed a retrospective propensity-matched cohort study where we compared opioid consumption and hospital length of stay among two historical cohorts: attending-only APS service versus service involving a regional anesthesia fellow. Results In the matched cohorts, POD 0–3 opioid use [25%, 75% quartile] for the single attending and trainee involvement cohort were 38.5 mg morphine equivalents (MEQ) [14.1 mg, 106.3 mg] and 50.4 mg MEQ [28.4 mg, 91.2 mg], respectively. The median difference was –9.8 mg MEQ (95% CI –30.7 to 16.5 mg; P = 0.43). There was no difference in hospital length of stay between both cohorts (P = 0.67). Conclusions We found that the addition of a regional anesthesia fellow to the APS team was not associated with statistically significant differences in total opioid consumption or hospital length of stay in this surgical population. The addition of trainees to the infrastructure, with vigilant supervision, is not associated with change in outcomes.

Introduction More than 1 million elective total hip and knee replacements are performed annually in the USA with 2% risk of clinical pulmonary embolism (PE), 0.1%–0.5% fatal PE, and over 1000 deaths. Antithrombotic prophylaxis is standard of care but evidence is limited and conflicting. We will compare effectiveness of three commonly used chemoprophylaxis agents to prevent all-cause mortality (ACM) and clinical venous thromboembolism (VTE) while avoiding bleeding complications.Methods and analysis Pulmonary Embolism Prevention after HiP and KneE Replacement is a large randomised pragmatic comparative effectiveness trial with non-inferiority design and target enrolment of 20 000 patients comparing aspirin (81 mg two times a day), low-intensity warfarin (INR (International Normalized Ratio) target 1.7–2.2) and rivaroxaban (10 mg/day). The primary effectiveness outcome is aggregate of VTE and ACM, primary safety outcome is clinical bleeding complications, and patient-reported outcomes are determined at 1, 3 and 6 months. Primary data analysis is per protocol, as preferred for non-inferiority trials, with secondary analyses adherent to intention-to-treat principles. All non-fatal outcomes are captured from patient and clinical reports with independent blinded adjudication. Study design and oversight are by a multidisciplinary stakeholder team including a 10-patient advisory board.Ethics and dissemination The Institutional Review Board of the Medical University of South Carolina provides central regulatory oversight. Patients aged 21 or older undergoing primary or revision hip or knee replacement are block randomised by site and procedure; those on chronic anticoagulation are excluded. Recruitment commenced at 30 North American centres in December 2016. Enrolment currently exceeds 13 500 patients, representing 33% of those eligible at participating sites, and is projected to conclude in July 2024; COVID-19 may force an extension. Results will inform antithrombotic choice by patients and other stakeholders for various risk cohorts, and will be disseminated through academic publications, meeting presentations and communications to advocacy groups and patient participants.Trial registration NCT02810704.

Pregnancy induces changes in the transcriptome of the bovine endometrium from 15 days after insemination. However, pregnancy is less likely to occur if cows had a postpartum bacterial infection of the uterus, even after the resolution of disease. We hypothesized that uterine bacterial infection alters the endometrial transcriptomic signature of pregnancy after the resolution of disease. To examine the endometrial transcriptomic signature of pregnancy, cows were inseminated 130 days after intrauterine infusion of pathogenic Escherichia coli and Trueperella pyogenes, subsequently endometrium was collected 16 days after insemination for RNA sequencing. We found 171 pregnancy regulated genes in cows 146 days after bacterial infection. When comparing our findings with previous studies that described the endometrial transcriptomic signature of pregnancy in healthy cows, 24 genes were consistently differentially expressed in pregnancy, including MX1, MX2 and STAT1. However, 12 pregnancy regulated genes were found only in the endometrium of healthy cows, including ISG15 and TRANK1. Furthermore, 28 pregnancy regulated genes were found only in the endometrium of cows following bacterial infection and these were associated with altered iNOS, TLR, and IL-7 signaling pathways. Although 94 predicted upstream regulators were conserved amongst the studies, 14 were found only in the endometrium of pregnant healthy cows, and 5 were found only in cows following bacterial infection, including AIRE, NFKBIA, and DUSP1. In conclusion, there were both consistent and discordant features of the endometrial transcriptomic signature of pregnancy 146 days after intrauterine bacterial infusion. These findings imply that there is an essential transcriptomic signature of pregnancy, but that infection induces long-term changes in the endometrium that affect the transcriptomic response to pregnancy.