Microbial richness and air chemistry in aerosols above the PBL confirm 2,000-km long-distance transport of potential human pathogens.

The existence of viable human pathogens in bioaerosols which can cause infection or affect human health has been the subject of little research. In this study, data provided by 10 tropospheric aircraft surveys over Japan in 2014 confirm the existence of a vast diversity of microbial species up to 3,000 m height, which can be dispersed above the planetary boundary layer over distances of up to 2,000 km, thanks to strong winds from an area covered with massive cereal croplands in Northeast (NE) Asia. Microbes attached to aerosols reveal the presence of diverse bacterial and fungal taxa, including potential human pathogens, originating from sewage, pesticides, or fertilizers. Over 266 different fungal and 305 bacterial genera appeared in the 10 aircraft transects. Actinobacteria, Bacillota, Proteobacteria, and Bacteroidetes phyla dominated the bacteria composition and, for fungi, Ascomycota prevailed over Basidiomycota. Among the pathogenic species identified, human pathogens include bacteria such as Escherichia coli, Serratia marcescens, Prevotella melaninogenica, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus saprophyticus, Cutibacterium acnes, Clostridium difficile, Clostridium botulinum, Stenotrophomonas maltophilia, Shigella sonnei, Haemophillus parainfluenzae and Acinetobacter baumannii and health-relevant fungi such as Malassezia restricta, Malassezia globosa, Candida parapsilosis and Candida zeylanoides, Sarocladium kiliense, Cladosporium halotolerans, and Cladosporium herbarum. Diversity estimates were similar at heights and surface when entrainment of air from high altitudes occurred. Natural antimicrobial-resistant bacteria (ARB) cultured from air samples were found indicating long-distance spread of ARB and microbial viability. This would represent a novel way to disperse both viable human pathogens and resistance genes among distant geographical regions.

Separating Actin-Dependent Chemokine Receptor Nanoclustering from Dimerization Indicates a Role for Clustering in CXCR4 Signaling and Function.

A current challenge in cell motility studies is to understand the molecular and physical mechanisms that govern chemokine receptor nanoscale organization at the cell membrane, and their influence on cell response. Using single-particle tracking and super-resolution microscopy, we found that the chemokine receptor CXCR4 forms basal nanoclusters in resting T cells, whose extent, dynamics, and signaling strength are modulated by the orchestrated action of the actin cytoskeleton, the co-receptor CD4, and its ligand CXCL12. We identified three CXCR4 structural residues that are crucial for nanoclustering and generated an oligomerization-defective mutant that dimerized but did not form nanoclusters in response to CXCL12, which severely impaired signaling. Overall, our data provide new insights to the field of chemokine biology by showing that receptor dimerization in the absence of nanoclustering is unable to fully support CXCL12-mediated responses, including signaling and cell function in vivo.

Noncanonical function of Capicua as a growth termination signal in Drosophila oogenesis.

Capicua (Cic) proteins are conserved HMG-box transcriptional repressors that control receptor tyrosine kinase (RTK) signaling responses and are implicated in human neurological syndromes and cancer. While Cic is known to exist as short (Cic-S) and long (Cic-L) isoforms with identical HMG-box and associated core regions but distinct N termini, most previous studies have focused on Cic-S, leaving the function of Cic-L unexplored. Here we show that Cic-L acts in two capacities during Drosophila oogenesis: 1) as a canonical sensor of RTK signaling in somatic follicle cells, and 2) as a regulator of postmitotic growth in germline nurse cells. In these latter cells, Cic-L behaves as a temporal signal that terminates endoreplicative growth before they dump their contents into the oocyte. We show that Cic-L is necessary and sufficient for nurse cell endoreplication arrest and induces both stabilization of CycE and down-regulation of Myc. Surprisingly, this function depends mainly on the Cic-L-specific N-terminal module, which is capable of acting independently of the Cic HMG-box-containing core. Mirroring these observations, basal metazoans possess truncated Cic-like proteins composed only of Cic-L N-terminal sequences, suggesting that this module plays unique, ancient roles unrelated to the canonical function of Cic.

Altered CXCR4 dynamics at the cell membrane impairs directed cell migration in WHIM syndrome patients.

Chemokine receptor nanoscale organization at the cell membrane is orchestrated by the actin cytoskeleton and influences cell responses. Using single-particle tracking analysis we show that CXCR4R334X, a truncated mutant chemokine receptor linked to WHIM syndrome (warts, hypogammaglobulinemia, infections, myelokathexis), fails to nanoclusterize after CXCL12 stimulation, and alters the lateral mobility and spatial organization of CXCR4 when coexpressed. These findings correlate with multiple phalloidin-positive protrusions in cells expressing CXCR4R334X, and their inability to correctly sense chemokine gradients. The underlying mechanisms involve inappropriate actin cytoskeleton remodeling due to the inadequate ß-arrestin1 activation by CXCR4R334X, which disrupts the equilibrium between activated and deactivated cofilin. Overall, we provide insights into the molecular mechanisms governing CXCR4 nanoclustering, signaling and cell function, and highlight the essential scaffold role of ß-arrestin1 to support CXCL12-mediated actin reorganization and receptor clustering. These defects associated with CXCR4R334X expression might contribute to the severe immunological symptoms associated with WHIM syndrome.

Altered B-cell, plasma cell and antibody immune profiles in blood of systemic mastocytosis.

BACKGROUND: Systemic mastocytosis (SM) is a heterogeneous disease characterised by an expansion of KIT-mutated constitutively activated mast cells (MC) which release MC mediators that might act on the tumour microenvironment including other immune cells. OBJECTIVE: Here we investigated the blood distribution of B-cell, plasma cell (PC) and antibody-isotype compartments in SM. METHODS: We used spectral flow cytometry and the EuroFlow Immunomonitoring panel and Lymphocyte Screening Tube to quantify B-cells, PC and their subsets in blood of 108 SM patients - 35 bone marrow mastocytosis (BMM), 64 indolent SM (ISM), 9 aggressive SM (ASM)- vs 117 age-matched healthy donors (HD) and paired bone marrow (BM) samples of 31 SM vs 17 controls, respectively. In parallel, immunoglobulin (Ig) M, IgD, IgG, IgA and IgE plasma levels of were measured. RESULTS: Compared to HD, SM patients showed an increased immature B-cell production in BM (P=0.003) associated with a greater release of pre-germinal center immature (P<0.001) and naive CD5+ B-lymphocytes (P<0.001) to blood, but a pronounced decrease in PC counts of all different IgH-isotypes and subclasses (P≤0.001) together with overall increased IgM (P=0.001) and IgD (P<0.001) plasma levels. Of note, different immune profiles were found per diagnostic subtype of the disease with progressively greater counts in blood of immature B-lymphocytes together with decreased IgMD+, IgG2+, IgA1+ and IgA2+ MBC (P≤0.032) and elevated IgM (P=0.017) plasma levels in ASM cases, increased IgM (P=0.001) and IgD (P=0.001) plasma levels in ISM patients and exacerbated IgE (P<0.001) with decreased IgG (P=0.008) plasma levels in BMM cases. CONCLUSION: Our results reveal a significant dysregulation of the B-cell and PC compartments in blood of SM patients, consistent with distinctly altered antibody-isotype profiles in plasma of BMM vs ISM vs ASM patients.

Frequency and prognostic impact of blood-circulating tumor mast cells in mastocytosis.

Circulating tumor mast cells (CTMCs) have been identified in the blood of a small number of patients with advanced systemic mastocytosis (SM). However, data are limited about their frequency and prognostic impact in patients with MC activation syndrome (MCAS), cutaneous mastocytosis (CM) and nonadvanced SM. We investigated the presence of CTMCs and MC-committed CD34+ precursors in the blood of 214 patients with MCAS, CM, or SM using highly sensitive next-generation flow cytometry. CTMCs were detected at progressively lower counts in almost all patients with advanced SM (96%) and smoldering SM (SSM; 100%), nearly half of the patients (45%) with indolent SM (ISM), and a few patients (7%) with bone marrow (BM) mastocytosis but were systematically absent in patients with CM and MCAS (P < .0001). In contrast to CTMC counts, the number of MC-committed CD34+ precursors progressively decreased from MCAS, CM, and BM mastocytosis to ISM, SSM, and advanced SM (P < .0001). Clinically, the presence (and number) of CTMCs in blood of patients with SM in general and nonadvanced SM (ISM and BM mastocytosis) in particular was associated with more adverse features of the disease, poorer-risk prognostic subgroups as defined by the International Prognostic Scoring System for advanced SM (P < .0001) and the Global Prognostic Score for mastocytosis (P < .0001), and a significantly shortened progression-free survival (P < .0001) and overall survival (P = .01). On the basis of our results, CTMCs emerge as a novel candidate biomarker of disseminated disease in SM that is strongly associated with advanced SM and poorer prognosis in patients with ISM.

Clinical impact of the TPSAB1 genotype in mast cell diseases: A REMA study in a cohort of 959 individuals.

BACKGROUND: A close association between hereditary alpha-tryptasemia (HAT) and mast cell (MC) disorders has been previously reported. However, the relationship between HAT and the diagnostic subtypes and clinical features of MC disorders still remains to be established. OBJECTIVE: To determine the prevalence of HAT in healthy donors (HD) vs patients with different diagnostic subtypes of MC activation syndromes (MCAS) and mastocytosis, and its relationship with the clinical behavior of the disease. METHODS: A total of 959 subjects were studied including 346 healthy donors (HD), 464 mastocytosis, and 149 non-clonal MCAS patients. Molecular studies to assess the TPSAB1 genotype were performed, and data on serum baseline tryptase (sBT) and basal MC-mediator release episodes and triggers of anaphylaxis were collected. RESULTS: HAT was detected in 15/346 (4%) HD versus 43/149 (29%) non-clonal MCAS and 84/464 (18%) mastocytosis cases. Among mastocytosis, HAT was more frequently found in patients with MC-restricted KITD816V (21% vs. 10% among multilineage KITD816V patients; p = .008). Overall, median sBT was higher in cases presenting with HAT (28.9 vs. 24.5 ng/mL; p = .008), while no significant differences in sBT were observed among HAT+ mastocytosis patients depending on the presence of 1 vs. ≥2 extra copies of the α-tryptase gene (44.1 vs. 35.2 ng/mL, p > .05). In turn, anaphylaxis was more frequently observed in HAT+ versus HAT- mastocytosis patients (76% vs. 65%; p = .018), while HAT+ and HAT- patients who did not refer anaphylaxis as the presenting symptom (n = 308) showed a similar prevalence of subsequent anaphylaxis (35% vs. 36%, respectively). CONCLUSION: The frequency of HAT in MC disorders varies according to the diagnostic subtype of the disease. HAT does not imply a higher risk (and severity) of anaphylaxis in mastocytosis patients in whom anaphylaxis is not part of the presenting symptoms of the disease.

T-cell immune profile in blood of systemic mastocytosis: Association with disease features.

BACKGROUND: Systemic mastocytosis (SM) is a heterogeneous disease characterized by an expansion of KIT-mutated mast cells (MC). KIT-mutated MC display activated features and release MC mediators that might act on the tumour microenvironment and other immune cells. Here, we investigated the distribution of lymphocyte subsets in blood of patients with distinct subtypes of SM and determined its association with other disease features. METHODS: We studied the distribution of TCD4+ and TCD4- cytotoxic cells and their subsets, as well as total NK- and B cells, in blood of 115 SM patients-38 bone marrow mastocytosis (BMM), 67 indolent SM (ISM), 10 aggressive SM (ASM)- and 83 age-matched healthy donors (HD), using spectral flow cytometry and the EuroFlow Immunomonitoring panel, and correlated it with multilineage KITD816V, the alpha-tryptasemia genotype (HαT) and the clinical manifestations of the disease. RESULTS: SM patients showed decreased counts (vs. HD) of TCD4- cytotoxic cells, NK cells and several functional subsets of TCD4+ cells (total Th1, Th2-effector memory, Th22-terminal effector and Th1-like Tregs), together with increased T-follicular-helper and Th1/Th17-like Treg counts, associated with different immune profiles per diagnostic subtype of SM, in multilineal versus MC-restricted KITD816V and in cases with a HαT+ versus HαT- genotype. Unique immune profiles were found among BMM and ISM patients with MC-restricted KITD816V who displayed HαT, anaphylaxis, hymenoptera venom allergy, bone disease, pruritus, flushing and GI symptoms. CONCLUSION: Our results reveal altered T- and NK-cell immune profiles in blood of SM, which vary per disease subtype, the pattern of involvement of haematopoiesis by KITD816V, the HαT genotype and specific clinical manifestations of the disease.

Navigating norms and expectations: the influence of culture on Latino couples and their interpersonal communication and coping post-breast cancer diagnosis.

OBJECTIVES: Cultural norms shape expectations, care, and communication. Effective interpersonal communication is a prominent predictor of patient-partner cancer management, improving the overall quality of life for the dyad by increasing their ability to cope with cancer. However, couples-based cancer interventions often do not consider cultural factors. Additionally, although Latinas have a high incidence of breast cancer, few studies focus on Latino couples and the influence of culture in cancer care interventions. This study focuses on understanding how Latino culture's norms and expectations influence how couples communicate and cope post-breast cancer diagnosis. DESIGN: This study conducted interviews and focus groups with a purposive sample of Spanish-speaking Latina breast cancer survivors (N = 21) and intimate partners (N = 5). In the focus group and interviews, participants were asked about the influence cancer had on their relationship, with specific questions focusing on communication within the dyad. The study team used CARV: Community-Engaged Adaptation with Rapid Analysis and Visualization framework to identify cultural considerations and recurring themes. RESULTS: The cross-cutting cultural considerations and themes found were: the negative influence of gendered and social norms on managing emotions and coping; the silent struggle with physical intimacy; and the inability to discuss the topic - or even say the word 'cancer.' CONCLUSION: Understanding the role of Latino culture in how couples cope with and communicate about cancer post-diagnosis is essential. This understanding will help strengthen the dyad by assisting with positive interpersonal support, which contributes to a better quality of life. These findings will also help providers assist dyads in navigating the cancer diagnosis and journey, helping to lessen the interpersonal stress and tensions that can occur after diagnosis.

Frailty trends in Catalonia 2017-2021: An epidemiological study with 1.5 million people aged ≥65 years.

OBJECTIVES: Knowledge of frailty prevalence and incidence trends over time is essential for planning the necessary health and social resources. The objective of this study was to assess frailty prevalence, incidence, reversibility and mortality rates, and trends for the population aged ≥65 years in Catalonia over the period 2017-2021. STUDY DESIGN: Longitudinal epidemiological study. METHODS: An observational longitudinal 5-year study (1 January 2017 to 31 December 2021) of the population aged ≥65 years in Catalonia (approximately 1.5 million individuals) was performed using retrospectively collected data from different health databases. Frailty status was evaluated using the electronic Screening Index of Frailty (e-SIF) and categorised as robust, pre-frail, moderately frail or severely frail. RESULTS: Standardised frailty prevalence rates were 10.5 % (2017), 11.8 % (2018), 13.1 % (2019), 12.9 % (2020) and 14.3 % (2021) [p-value for trend = 0.010]. Standardised frailty incidence rates per 1000 non-frail persons/year were 35 (2018), 36 (2019), 28 (2020) and 33 (2021) [p-value for trend = 0.492]. Both prevalence and incidence were higher in women and increased with age. Standardised frailty reversibility rates per 1000 frail persons/year were 123 (2018), 108 (2019) and 121 (2020) [p-value for trend = 0.406], and decreased with age. Standardised mortality rates for frail individuals per 1000 frail persons/year were 93 (2018), 84 (2019) and 110 (2020) [p-value for trend = 0.555], and increased with frailty severity. CONCLUSIONS: Frailty prevalence in Catalonia increased by 36 % between 2017 and 2021; however, no clear trend was evident for frailty incidence and reversibility, while results for mortality were likely to have been influenced by the COVID-19 pandemic.

Efficacy of the Otago-Exercise-Programme to reduce falls in community-dwelling adults aged 65-80 when delivered as group or individual training: Non-inferiority-clinical-trial.

BACKGROUND: The Otago Exercise Programme is an effective intervention for falls prevention. However, there is limited evidence in relation to studies that compare efficacy for falls prevention when delivered Otago Exercise Programme in a group or individual format in a primary care context. OBJECTIVE: To compare the Otago Exercise Programme delivered as a group vs. individual format for community dwelling older adults, over a one year period. The hypothesis was that neither format would be inferior to the other. METHODS: DESIGN: A four-year multicentre, randomized, non-inferiority clinical trial, with two arms- Otago Exercise Programme group training and individual Otago exercise training. SETTING(S): 21 primary healthcare centers. PARTICIPANTS: A sample size of 728 participants was established. Participants were aged between 65 and 80 years; living in the community; able to walk independently; and agreed to take part in the study and provided signed informed consent. INTERVENTION: The Otago Exercise Programme was delivered mainly by nurses in primary care, with five face to face sessions, and a reinforcement 6 months later. Participants were encouraged to exercise at home between face to face sessions. DATA COLLECTION: at baseline and after 6 and 12 months from October 2017 to 2020. PRIMARY OUTCOME: people who reported at least one fall. SECONDARY OUTCOMES: number of falls, cause of falls, consequences and assistance, adherence and satisfaction. Group allocation was blinded to the researchers involved in analysis. Reporting: Consolidated Standards of Reporting Trials recommendations for the Statement for Randomized Trials of Nonpharmacologic Treatments. RESULTS: Eight hundred twenty-seven participants were randomized (226 were allocated in group training and 272 in individual training). The analysis of the proportion of people who reported at least one fall and number of falls showed no differences between individual and group training. Assessment of the equivalence between the interventions at 12 months showed that the confidence interval for the difference of people who reported at least one fall was found to be within the equivalence limit of 10% considered. However, in those participants with a previous history of falls, group format showed potentially greater benefit. The participants in individual training presented higher scores on the Exercise Adherence Rating Scale test. No differences were found in satisfaction between the groups. CONCLUSIONS: The group Otago Exercise Programme is equivalent to individually delivered Otago Exercise Programme in terms of prevention of falls over a 12-month follow up. Adherence was higher in individual training. IMPLICATIONS: Healthcare professionals could offer either Otago Exercise Programme format dependent on patient preference and be confident that that standardized intervention provides patient benefit. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03320668). Data registration 31/10/2017.

Dysphagia and stenosis secondary to intramural esophageal pseudodiverticulosis.

We present the case of a patient with smoking, alcoholism, cirrhosis and HIV who was endoscopically diagnosed with esophageal candidiasis due to an episode of dysphagia. After treatment with antifungals and PPIs, the patient remained asymptomatic for almost 3 years. He presented an event of food impaction that was resolved by an upper endoscopy in which an esophageal stenosis and multiple esophageal pseudodiverticulosis were visualized. The biopsies only showed chronic nonspecific esophagitis. The stenosis was dilated with a balloon and PPIs were continued, with good response. Esophageal intramural pseudodiverticulosis is rare and can lead to motor disorders and strictures. It has a doubtful association with HIV and a clearer relationship with alcoholism, smoking, diabetes, reflux and candidiasis. The endoscopic diagnosis can be difficult so in order to make an accurate diagnosis is necessary an esophagram or CT. Treatment is based on controlling risk factors and dilating stenosis. The prognosis is usually favorable.

Ephaptic Coupling as a Resolution to the Paradox of Action Potential Wave Speed and Discordant Alternans Spatial Scales in the Heart.

Previous computer simulations have suggested that existing models of action potential wave propagation in the heart are not consistent with observed wave propagation behavior. Specifically, computer models cannot simultaneously reproduce the rapid wave speeds and small spatial scales of discordant alternans patterns measured experimentally in the same simulation. The discrepancy is important, because discordant alternans can be a key precursor to the development of abnormal and dangerous rapid rhythms in the heart. In this Letter, we show that this paradox can be resolved by allowing so-called ephaptic coupling to play a primary role in wave front propagation in place of conventional gap-junction coupling. With this modification, physiological wave speeds and small discordant alternans spatial scales both occur with gap-junction resistance values that are more in line with those observed in experiments. Our theory thus also provides support to the hypothesis that ephaptic coupling plays an important role in normal wave propagation.

KITD816V mutation in blood for the diagnostic screening of systemic mastocytosis and mast cell activation syndromes.

BACKGROUND: Current diagnostic algorithms for systemic mastocytosis (SM) rely on the detection of KITD816V in blood to trigger subsequent bone marrow (BM) investigations. METHODS: Here, we correlated the KITD816V mutational status of paired blood and BM samples from 368 adults diagnosed with mast cell activation syndrome (MCAS) and mastocytosis and determined the potential utility of investigating KITD816V in genomic DNA from blood-purified myeloid cell populations to increase diagnostic sensitivity. In a subset of 69 patients, we further evaluated the kinetics of the KITD816V cell burden during follow-up and its association with disease outcome. RESULTS: Our results showed a high correlation (P < .0001) between the KITD816V mutation burden in blood and BM (74% concordant samples), but with a lower mean of KITD816V-mutated cells in blood (P = .0004) and a high rate of discordant BM+ /blood- samples particularly among clonal MCAS (73%) and BM mastocytosis (51%), but also in cutaneous mastocytosis (9%), indolent SM (15%), and well-differentiated variants of indolent SM (7%). Purification of different compartments of blood-derived myeloid cells was done in 28 patients who were BM mast cell (MC)+ /blood- for KITD816V, revealing KITD816V-mutated eosinophils (56%), basophils (25%), neutrophils (29%), and/or monocytes (31%) in most (61%) patients. Prognostically, the presence of ≥3.5% KITD816V-mutated cells (P < .0001) and an unstable KITD816V mutation cell burden (P < .0001) in blood and/or BM were both associated with a significantly shortened progression-free survival (PFS). CONCLUSIONS: These results confirm the high specificity but limited sensitivity of KITD816V analysis in whole blood for the diagnostic screening of SM and other primary MCAS, which might be overcome by assessing the mutation in blood-purified myeloid cell populations.

Paclitaxel Regulates TRPA1 Function and Expression Through PKA and PKC.

Paclitaxel (PTX) is a frequently used anticancer drug that causes peripheral neuropathy. Transient receptor potential ankyrin 1 (TRPA1), a plasma membrane calcium channel, has been associated with PTX toxicity and with other chemotherapy agents such as oxaliplatin and vincristine. However, the effect of PTX on the functional expression and calcium currents of TRPA1 has not been determined. The present study shows the effect of PTX on TRPA1 activity in a neuronal cell line (SH-SY5Y). The effect of PTX on the expression of TRPA1 was assessed through quantitative PCR and Western blot analyses to determine the relative mRNA and protein expression levels. To assess the effect on calcium flux and currents, cells were exposed to PTX; simultaneously, a specific agonist and antagonist of TRPA1 were added to evaluate the differential response in exposed versus control cells. To assess the effect of PKA, PKC and PI3K on PTX-induced TRPA1 increased activity, selective inhibitors were added to these previous experiments. PTX increased the mRNA and protein expression of TRPA1 as well as the TRPA1-mediated Ca2+ currents and intracellular Ca2+ concentrations. This effect was dependent on AITC (a selective specific agonist) and was abolished with HC-030031 (a selective specific antagonist). The inhibition of PKA and PKC reduced the effect of PTX on the functional expression of TRPA1, whereas the inhibition of PI3K had no effects. PTX-induced neuropathy involves TRPA1 activity through an increase in functional expression and is regulated by PKA and PKC signaling. These findings support the role of the TRPA1 channel in the mechanisms altered by PTX, which can be involved in the process that lead to chemotherapy-induced neuropathy.

Characteristics of single vs. multiple suicide attempters among adolescents: a systematic review and meta-analysis.

There might be differential characteristics between those who have attempted suicide once in their lifetime (single attempters) and those who have attempted suicide two or more times (multiple attempters). We aimed to identify the factors that differentiate single and multiple attempters in child and adolescents. This study was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and the review protocol was registered in PROSPERO. We conducted a systematic literature search in three databases to identify original studies exploring the characteristics of single attempters vs. multiple attempters among adolescents. We considered a wide range for the definition of adolescent, following most recent recommendations: 10-24 years. We carried out a meta-analysis. Fourteen studies were included in the systematic review and 13 in the meta-analysis with a total sample of with a total of 4286 participants. The factors statistically significantly associated with being a multiple attempter in the meta-analysis were: anxiety disorders, depression severity, alcohol abuse, substance abuse, aggressiveness, and hopelessness. Multiple attempters have a more severe clinical profile, with greater severity of symptoms. Knowledge of the risk factors associated with being a multiple attempter could help us to predict which patients are more likely to reattempt suicide and need further monitoring and a tailored treatment. Prevention programs tailored for the adolescent population, along with identification of early risk factors, could help to prevent suicidal behavior among this vulnerable population.

Diagnostic trajectories of mental disorders in children and adolescents: a cohort study.

Mental disorders in children and adolescents may follow different trajectories, such as remission, change of diagnosis, or addition of two or more comorbid diagnoses, showing a heterotypic pattern. This study aims to describe the main diagnostic trajectories across a broad range of mental disorder diagnostic categories, from childhood to adolescence and from adolescence to young adulthood in a clinical population. A prospective study was conducted among a clinical sample of children and adolescents who were aged 3-17 years at the face-to-face baseline interview. Electronic health records of these participants were reviewed 10 years later. The diagnostic stability over time was examined using the kappa coefficient, and factors associated with stability were explored using simple logistic regression. The study included a sample of 691 participants. The kappa coefficient for diagnostic stability across all diagnoses was 0.574 for the transition from childhood to adulthood, 0.614 from childhood to adolescence, and 0.733 from adolescence to adulthood. Neurodevelopmental diagnoses had the highest stability. Factors associated with higher diagnostic stability included family history of mental disorders, receiving psychopharmacological treatment, and symptom severity at baseline. We found a variable diagnostic stability across different diagnoses and age categories. The different life transitions represent complex periods that should not be overlooked from a clinical standpoint. An appropriate transition from child and adolescent mental health services to adult mental health services may have a positive impact on children and adolescents with mental disorders.

Dependence of Induced Biological Damage on the Energy Distribution and Intensity of Clinical Intra-Operative Radiotherapy Electron Beams.

The survival fraction of epithelial HaCaT cells was analysed to assess the biological damage caused by intraoperative radiotherapy electron beams with varying energy spectra and intensities. These conditions were achieved by irradiating the cells at different depths in water using nominal 6 MeV electron beams while consistently delivering a dose of 5 Gy to the cell layer. Furthermore, a Monte Carlo simulation of the entire irradiation procedure was performed to evaluate the molecular damage in terms of molecular dissociations induced by the radiation. A significant agreement was found between the molecular damage predicted by the simulation and the damage derived from the analysis of the survival fraction. In both cases, a linear relationship was evident, indicating a clear tendency for increased damage as the averaged incident electron energy and intensity decreased for a constant absorbed dose, lowering the dose rate. This trend suggests that the radiation may have a more pronounced impact on surrounding healthy tissues than initially anticipated. However, it is crucial to conduct additional experiments with different target geometries to confirm this tendency and quantify the extent of this effect.

Enhancing c-Si Solar Cell Efficiency in the UV Region: Photophysical Insights into the Use of Eu3+ Complexes for Down-Shifting Layer Applications.

[Eu(3DPIQC)3] (where DPIQC = 3-(diphenyl phosphoryl)-1-isoquinolinecarboxylate), a luminescent europium complex with antenna ligands, has been carefully embedded within a polyvinyl butyral (PVB) matrix and the resulting material was used to prepare films used as luminescent down-shifting layers (LDSLs) for crystalline Si-based solar cells. The films were characterized using photoluminescence spectroscopy, atomic force spectroscopy (AFM), UV-Vis spectroscopy, and fluorescence microscopy. The AFM analysis shows films with low surface roughness, while fluorescence microscopy revealed that the Eu complex embedded in PVB assumed a spheroidal configuration, a morphology especially beneficial for optical applications. The so-obtained LDSLs were utilized as energy converters in c-Si solar cells to enhance the utilization of high-energy photons, thereby improving their overall efficiency. The determination of photovoltaic parameters carried out before and after the deposition of the LDSLs on the c-Si cells confirms a positive effect on the efficiency of the cell. The Jsc increases from 121.6 mA/cm2 to 124.9 mA/cm2, and the open circuit voltage (Voc) is found to be unrelated to the complex concentration in the films. The fill factor (FF) remains constant with the Eu concentration. The EQE curves indicate an enhancement in the performance of the photovoltaic cells within the UV region of the spectrum for all coated devices. Electrochemical impedance spectroscopy (EIS) was also carried out in order to analyze the effect of the Eu complex in the charge transfer process of the devices.

Use of teduglutide for short bowel syndrome and Crohn's disease in a patient treated with ustekinumab and vedolizumab dual biologic therapy.

Surgery in Crohn's disease may be the cause of short bowel syndrome that may lead to kidney dysfunction. Dual biologic therapy is rarely needed to control activity. We present a case of a 61-year-old steroid dependent (A2L1B3p) female who had undergone surgery on three occasions: ileocecal resection (resection of 15 cm of terminal ileum); resection of right and left colon up to sigmoid; proctectomy with intersphincteric resection along with ileostomy due to a rectovaginal fistula. She had been previously treated with prednisone, azathioprine, methotrexate, infliximab and adalimumab but the treatment was discontinued owing to adverse effects. Vedolizumab was started, showing good control of the luminal activity but the rectovaginal fistula recurred. Treatment changed to ustekinumab, the fistula activity was controlled but the mucosa activity recurred. 11 months after commencing with ustekinumab, vedolizumab was added to the treatment and complete remission was achieved for three years. Simultaneously, the patient developed renal dysfunction derived from the short bowel syndrome that led to chronic kidney failure. In the face of potential renal replacement therapy, a new therapy with 2.5 mg/sc/d teduglutide was started achieving stable figures of creatinine and normalization of the glomerular filtration rate.