Experience of a vascular ultrasound-guided program: from the ICU to the hospital.

BACKGROUND: The use of peripherally inserted central venous catheters (PICCs) has increased worldwide in the last decade. However, PICCs are associated to catheter-related thrombosis (CRT) and central line-associated bloodstream infections (CLABSIs). We describe the characteristics of patients requiring a PICC, estimate the incidence rate, and identify potential risk factors of PICC-related complications. METHODS: All adult patients requiring a PICC at our institution (Fundación Santa Fe de Bogotá, Bogota, Colombia) from September 2022 to May 2024 were included in the analysis. The database from active PICC monitoring collected demographic and PICC-related information. The incidence rate of CLABSI and CRT, and crude odds ratios (cORs) were estimated. RESULTS: Overall, 1936 individuals were included in the study. The median age was 67 years (IQR: 50-78 years), and 51.5% were females. The median duration of PICC lines was 10 days (IQR: 4-17). Seventy-nine patients had catheter-related complications, mostly in the Intensive Care Unit (ICU). The CLABSI and CRT institutional incidence rates per 1000 catheter-days were 2.03 (2.96 in the ICU) and 0.58 (0.61 in the ICU), respectively. Prolonged catheter use (≥ 6 days), PICC insertion in the intensive care unit, and postoperative care after cardiac surgery were identified as potential risk factors for CLABSI, while a catheter insertion into the brachial vein was associated with CRT. CONCLUSION: Daily PICC assessment, particularly in patients with prolonged catheter use, PICC insertion into the brachial vein, or in postoperative care after cardiac surgery may significantly reduce CLABSI and CRT cases. Implementing Vascular Access Teams, venous catheter care bundles, and institutional insertion protocols optimize clinical outcomes.

Body condition of stranded Razorbills and Atlantic Puffins in the Western Mediterranean.

Annual mass migrations of seabirds between their breeding and wintering grounds are critical for ensuring their survival and reproductive success. It is essential to comprehend their physical condition in order to identify the causes of death and to facilitate conservation efforts. This study focuses on evaluating the age, body condition index, and metabolites in liver and muscle (triglycerides, glycerol, glycogen, cholesterol, lactate, and glucose) of stranded Razorbills (n = 84) and Atlantic puffins (n = 11). The study was conducted along the Andalusian coast of Spain during the winter season of 2022-2023. The study examined the body condition of stranded individuals and their metabolic state to determine potential factors that may have caused their deaths. The study found that the majority of stranded individuals were juveniles. Both species exhibited low levels of carbohydrate (glucose and glycogen) in their tissues and high levels of lactate in their muscles. These findings could suggest that the individuals had undergone prolonged, strenuous exercise, demanding energy on anaerobic pathways, which may have been associated with migration. The study highlights the significance of adhering to standardized protocols when assessing the body condition of stranded seabirds. Doing so can help to identify causes of death and facilitate conservation efforts. A proposed index for body condition, which incorporates biometric measurements and individual physical condition, provides a comprehensive means of understanding the health of these unique species. This study underscores the importance of further research into the conservation measures and recommendations for protecting seabird populations. It is critical to comprehend the contributing factors of mass mortality incidents to work towards safeguarding these species and preserving their vital migration patterns.

All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis.

Patients with schizophrenia receiving antipsychotic treatment present lower mortality rates than those who do not. However, the non-adherence rate is high, which can be partially addressed using long-acting injectable (LAI) antipsychotics. The impact of LAI treatments on all-cause mortality compared to oral antipsychotics remains unclear. To fill that gap, a random effects meta-analysis was conducted to analyze the odds ratio (OR) of all-cause, suicidal, and non-suicidal mortality among patients taking LAI antipsychotics compared to oral antipsychotics (PROSPERO:CRD42023391352). Individual and pooled LAI antipsychotics were analyzed against pooled oral antipsychotics. Sensitivity analyses were performed for study design, setting, and industry sponsorship. Meta-regressions were conducted for gender, age, antipsychotic dose, and race. Seventeen articles, total sample 12,042 patients (N = 5795 oral, N = 6247 LAI) were included. Lower risk of all-cause mortality for patients receiving LAI antipsychotics vs receiving oral antipsychotics was found (OR = 0.79; 95%CI = 0.66-0.95). Statistical significance was maintained when only studies comparing the same LAI and oral antipsychotic were included (OR = 0.79; 95%CI = 0.66-0.95; p = <0.01), as well as for non-suicidal mortality (OR = 0.77: 95%CI = 0.63-0.94; p = 0.01), but not for suicidal mortality (OR = 0.86; 95%CI = 0.59-1.26; p = 0.44). Mortality reduction was more pronounced for LAI antipsychotics in first-episode psychosis (FEP) (OR = 0.79; 95%CI = 0.66-0.96) compared to chronic psychosis. No individual LAI reported statistically significant differences against all pooled oral antipsychotics. LAI antipsychotics are associated with a lower risk of all-cause and non-suicidal mortality in individuals with schizophrenia compared to oral antipsychotics. Better adherence to the medication and health services may explain this difference. Whenever possible, the use of LAIs should be considered from the FEP.

Prolactin Drives Iron Release from Macrophages and Uptake in Mammary Cancer Cells through CD44.

Iron is an essential element for human health. In humans, dysregulated iron homeostasis can result in a variety of disorders and the development of cancers. Enhanced uptake, redistribution, and retention of iron in cancer cells have been suggested as an "iron addiction" pattern in cancer cells. This increased iron in cancer cells positively correlates with rapid tumor growth and the epithelial-to-mesenchymal transition, which forms the basis for tumor metastasis. However, the source of iron and the mechanisms cancer cells adopt to actively acquire iron is not well understood. In the present study, we report, for the first time, that the peptide hormone, prolactin, exhibits a novel function in regulating iron distribution, on top of its well-known pro-lactating role. When stimulated by prolactin, breast cancer cells increase CD44, a surface receptor mediating the endocytosis of hyaluronate-bound iron, resulting in the accumulation of iron in cancer cells. In contrast, macrophages, when treated by prolactin, express more ferroportin, the only iron exporter in cells, giving rise to net iron output. Interestingly, when co-culturing macrophages with pre-stained labile iron pools and cancer cells without any iron staining, in an iron free condition, we demonstrate direct iron flow from macrophages to cancer cells. As macrophages are one of the major iron-storage cells and it is known that macrophages infiltrate tumors and facilitate their progression, our work therefore presents a novel regulatory role of prolactin to drive iron flow, which provides new information on fine-tuning immune responses in tumor microenvironment and could potentially benefit the development of novel therapeutics.

First Report of Pantoea ananatis causing leaf streak disease on wheat (Triticum aestivum) in the United States of America.

Wheat (Triticum aestivum) loses 21.5% yield to pests and diseases annually (Savary et al. 2019). Among the wheat diseases, bacterial leaf streak (BLS) is a growing problem, costing $78.5 million in losses (https://cropprotectionnetwork.org/). In July 2022, we sampled winter wheat leaf samples at Volga (44.30, -96.92), South Dakota, USA with an estimated disease incidence of 40% (n=100). The typical symptoms were water-soaking with large necrotic and chlorotic streaks extending the length of the leaves and were strikingly similar to BLS. To isolate the pathogen, leaves were cut lengthwise into 1 cm pieces and surface-sterilized using a 10% NaOCl solution for 3 min, followed by 70% ethanol for 3 min, and then rinsed with sterile distilled water and placed in 500 ul of sterile distilled water for 5 min and using a sterile loop the water was streaked over a plate of Nutrient Agar (NA). Following Duveiller et al. (1997), the streaked plate was incubated in the dark at 28℃ for 48 h. Observed single colonies were sub-cultured thrice onto fresh NA plates to obtain a pure culture. We named the culture SD101. Bacteria were found to be gram-negative with a colony morphology initially raised, smooth, and white that later turned yellow. DNA was extracted using the Wizard HMW DNA Extraction Kit (Promega, Madison, WI) following the manufacturer's protocol, and sequenced using Nanopore MinION R9.4 (Oxford Nanopore Technology). We used the Rapid Annotation Using Subsystems Technology approach (Aziz eal. 2008) to extract the 16S rDNA, DNA gyrase subunit B (gyrB), and translation initiation factor IF-2 (infB) gene sequences that were deposited in GenBank under accession numbers PP329908.1 for 16S rDNA, PP496481 for infB, and PP328920.1 for gyrB. Homology analysis using CLC Genomics Workbench 22.0.2 (QIAGEN) and BLASTn against the GenBank nucleotide database resulted in a 99.74% match (1543/ 1547 bp) of the 16S sequence, 99.59% match (2674/ 2685 bp) of the infB sequence, and 99.42% match (2396/ 2410 bp) of the gyrB sequence with Pantoea ananatis strain AJ13355 (AP012032). To test pathogenicity, seeds of spring wheat breeding line SD4892 were planted in 30 cm × 30 cm pots in a greenhouse under a 16 h light photoperiod. The inoculum was prepared from 48-h-old NA plates of SD101 rinsed with 1X Phosphate Buffer Saline (PBS buffer), adjusted to an OD600 = 1.0, and amended with two drops of Tween 20 (polyoxyethylene sorbitol ester, Millipore Sigma). PBS with Tween 20 was used as a negative control. The inoculum was sprayed on 15 replicates of 15-day-old seedlings, kept at 95% relative humidity for 48 h, then moved to the greenhouse at 23 to 25°C. The symptoms appeared as water soaking that later turned to necrotic streaks with surrounding chlorosis on all 15 inoculated plants while control plants remained healthy. The pathogen was re-isolated from the leaves as described above. The 16S rDNA, infB, and gyrB sequences amplified and sequenced were identical to the gene sequences from the whole genome sequencing. The experiment was repeated with the same results, completing Koch's postulates. Although P. ananatis is pathogenic on corn, rice, and other plant species in the United States (Coutinho et al. 2009), and was reported pathogenic on wheat in Poland (Krawczyk et al. 2020), this is the first report of its pathogenicity on wheat in the United States. The prevalence, and incidence of BLS disease caused by P. ananatis in wheat is needed to estimate its threat to wheat production and to develop management strategies.

Validity of the Brazilian online version of the Sexual Desire Inventory 2.

OBJECTIVE: The Sexual Desire Inventory 2 is a self-report instrument for assessing sexual desire in men and women. In Brazil, there is no validated sexual desire self-report for the adult population. The aim of this study was to determine the evidence of validity for the content and construct of the Brazilian online version of the Sexual Desire Inventory 2. METHODS: This was a cross-sectional study with Brazilian men and women. The sample size was calculated using the criterion of more than 20 participants per item. The invitation to participate in the study was conducted online by the platform Survey Monkey®. The Sexual Desire Inventory 2 was evaluated for content, construct, reliability, and invariance. RESULTS: A total of 818 female and male adults participated in the study. The two-dimensional factorial solution represented 71% of the total variance explained by the model, and the factorial loads of the model were ≥0.40; commonalities presented values ≥0.23. Reliability was measured by the coefficients of Cronbach's alpha with a total score of 0.87, McDonald's of 0.87, Omega, and greatest lower bound with a total score of 0.95. The metric invariance was tested for the sex variables ΔCFI (comparative fit index) and ΔRMSEA (root mean square error of approximation) with a total score of 0.01. CONCLUSION: The analyses indicate evidence of robust validity in the Brazilian online version of the Sexual Desire Inventory 2.

Correction: Raiola et al. Imaging Approaches and the Quantitative Analysis of Heart Development. J. Cardiovasc. Dev. Dis. 2023, 10, 145.

In the published publication [...].

Correction: Díaz del Moral et al. Cardiomyocyte-Specific Wt1 Is Involved in Cardiac Metabolism and Response to Damage. J. Cardiovasc. Dev. Dis. 2023, 10, 211.

In the published publication [...].

PP2A-B55 phosphatase counteracts Ki-67-dependent chromosome individualization during mitosis.

Cell cycle progression is regulated by the orderly balance between kinase and phosphatase activities. PP2A phosphatase holoenzymes containing the B55 family of regulatory B subunits function as major CDK1-counteracting phosphatases during mitotic exit in mammals. However, the identification of the specific mitotic roles of these PP2A-B55 complexes has been hindered by the existence of multiple B55 isoforms. Here, through the generation of loss-of-function genetic mouse models for the two ubiquitous B55 isoforms (B55α and B55δ), we report that PP2A-B55α and PP2A-B55δ complexes display overlapping roles in controlling the dynamics of proper chromosome individualization and clustering during mitosis. In the absence of PP2A-B55 activity, mitotic cells display increased chromosome individualization in the presence of enhanced phosphorylation and perichromosomal loading of Ki-67. These data provide experimental evidence for a regulatory mechanism by which the balance between kinase and PP2A-B55 phosphatase activity controls the Ki-67-mediated spatial organization of the mass of chromosomes during mitosis.

An Efficient Transgenesis Approach for Gene Delivery in the Mouse Embryonic Heart.

The mammalian heart is a complex organ formed during development via highly diverse populations of progenitor cells. The origin, timing of recruitment, and fate of these progenitors are vital for the proper development of this organ. The molecular mechanisms that govern the morphogenesis of the heart are essential for understanding the pathogenesis of congenital heart diseases and embryonic cardiac regeneration. Classical approaches to investigate these mechanisms employed the generation of transgenic mice to assess the function of specific genes during cardiac development. However, mouse transgenesis is a complex, time-consuming process that often cannot be performed to assess the role of specific genes during heart development. To address this, we have developed a protocol for efficient electroporation and culture of mouse embryonic hearts, enabling transient transgenesis to rapidly assess the effect of gain- or loss-of-function of genes involved in cardiac development. Using this methodology, we successfully overexpressed Meis1 in the embryonic heart, with a preference for epicardial cell transfection, demonstrating the capabilities of the technique.

Gold-Catalyzed "Back-to-Front" Synthesis of 4-Silyloxyindoles.

A series of pyrrol-yn-glycol derivatives were easily prepared from simple pyrroles through a three-step sequence involving hydroxyalkylation-alkynylation-O-silylation. Their reaction with IPrAuNTf2 triggers a C2-pyrrole attack onto the activated alkyne and subsequent highly selective 1,2-migration of the oxyalkyl group in the intermediate spirocycle. This approach enables the efficient synthesis of a wide selection of regioselectively functionalized 4-hydroxyindoles, which represent important yet challenging indole scaffolds, in high yields.

Technology at the Rescue? Online Games, Adolescent Mental Health and the COVID Pandemic.

The COVID pandemic has had a major impact on the mental health of the population, especially on female adolescents. Eating disorders and gender identity problems have increased markedly. Online activities have also grown enormously during this period occupying a large portion of adolescents' time. We explore the use of social networking and online gaming by adolescent girls and boys. We discuss their possible influence on different levels of psychological distress in boys and girls in the face of the pandemic. We propose that online games, mainly used by young boys, might offer them some emotional protection through mechanisms related to the body and its experience, to the group dynamics of competition, collaboration, and hierarchy, to the possibility of expressing aggression, and to the construction of a clearer and more stable identity. An unprejudiced look at new technologies is mandatory, if we are to avoid projecting our fears and expectations onto them.

A Sample Preparation Procedure for Isobaric Labeling-Based Single-Cell Proteomics.

Mass spectrometry-based proteomics has traditionally been limited by the amount of input material for analysis. Single-cell proteomics has emerged as a challenging discipline due to the ultra-high sensitivity required. Isobaric labeling-based multiplex strategies with a carrier proteome offer an approach to overcome the sensitivity limitations. Following this as the basic strategy, we show here the general workflow for preparing cells for single-cell mass spectrometry-based proteomics. This protocol can also be applied to manually isolated cells when large cells, such as cardiomyocytes, are difficult to isolate properly with conventional fluorescence-activated cell sorting (FACS) sorter methods.

Number and nature of psychiatric emergency department visits in a tertiary hospital before, during, and after coronavirus pandemic.

Introduction: The COVID-19 pandemic has significantly impacted mental health globally, leading to a deterioration in the overall mental health of the population and changes across all healthcare levels, including emergency departments (ED). However, the evolution of the quantity and nature of psychiatric ED visits in the post-pandemic period remains uncertain. Aims: To examine changes in the number and nature of psychiatric emergencies at a general hospital before, during, and after the COVID-19 pandemic. Materials and methods: Psychiatric ED visits from a tertiary hospital in the Basque Country (Spain) between January 2019 and November 2023 were investigated. Electronical health registers detailing the number and nature of psychiatric care consultations were analyzed for the study timeframe. Three periods were then compared: pre-pandemic (from January 2019 to February 2020), pandemic (from March 2020 to January 2022), and post-pandemic (from February 2022 onwards). Results: 16,969 psychiatric ED visits were recorded for the study period. The number of psychiatric ED visits remained stable from pre-pandemic (269.93 visits/month) to pandemic (264.48 visits/month) periods but experienced a significant rise during the post-pandemic period (330.00 visits/month; t=-6.42; p<0.001), which was not reflected in medical and traumatological visits. The proportion of visits for anxiety (Z=-2.97; p=0.003), suicidal ideation (Z=-5.48; p<0.001), and administrative and social consultations (Z=-5.69; p<0.001) increased over the course of the pandemic. In contrast, visits for schizophrenia and other psychotic disorders (Z=4.85; p<0.001), as well as unspecified behavioral alterations (Z=2.51; p=0.012), significantly decreased. Conclusion: The COVID-19 pandemic and its aftermath have altered the patterns of urgent psychiatric care, characterized by a sharp increase of average monthly number of consultations and a shift in their nature. Future efforts should focus on characterizing this surge in demand and enhancing both emergency services and outpatient settings.

A comprehensive examination of mental health in patients with head and neck cancer: systematic review and meta-analysis.

BACKGROUND: Patients with head and neck cancer present particularly considerable levels of emotional distress. However, the actual rates of clinically relevant mental health symptoms and disorders among this population remain unknown. METHODS: A Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analyses of Observational Studies in Epidemiology-compliant systematic review and quantitative random-effects meta-analysis was performed to determine suicide incidence and the prevalence of depression, anxiety, distress, posttraumatic stress, and insomnia in this population. MEDLINE, Web of Science, Cochrane Central Register, KCI Korean Journal database, SciELO, Russian Science Citation Index, and Ovid-PsycINFO databases were searched from database inception to August 1, 2023 (PROSPERO: CRD42023441432). Subgroup analyses and meta-regressions were performed to investigate the effect of clinical, therapeutical, and methodological factors. RESULTS: A total of 208 studies (n = 654 413; median age = 60.7 years; 25.5% women) were identified. Among the patients, 19.5% reported depressive symptoms (95% confidence interval [CI] = 17% to 21%), 17.8% anxiety symptoms (95% CI = 14% to 21%), 34.3% distress (95% CI = 29% to 39%), 17.7% posttraumatic symptoms (95% CI = 6% to 41%), and 43.8% insomnia symptoms (95% CI = 35% to 52%). Diagnostic criteria assessments revealed lower prevalence of disorders: 10.3% depression (95% CI = 7% to 13%), 5.6% anxiety (95% CI = 2% to 10%), 9.6% insomnia (95% CI = 1% to 40%), and 1% posttraumatic stress (95% CI = 0% to 84.5%). Suicide pooled incidence was 161.16 per 100 000 individuals per year (95% CI = 82 to 239). Meta-regressions found a statistically significant higher prevalence of anxiety in patients undergoing primary chemoradiation compared with surgery and increased distress in smokers and advanced tumor staging. European samples exhibited lower prevalence of distress. CONCLUSIONS: Patients with head and neck cancer presented notable prevalence of mental health concerns in all domains. Suicide remains a highly relevant concern. The prevalence of criteria-meeting disorders is significantly lower than clinically relevant symptoms. Investigating the effectiveness of targeted assessments for disorders in highly symptomatic patients is essential.

Deep generative models in single-cell omics.

Deep Generative Models (DGMs) are becoming instrumental for inferring probability distributions inherent to complex processes, such as most questions in biomedical research. For many years, there was a lack of mathematical methods that would allow this inference in the scarce data scenario of biomedical research. The advent of single-cell omics has finally made square the so-called "skinny matrix", allowing to apply mathematical methods already extensively used in other areas. Moreover, it is now possible to integrate data at different molecular levels in thousands or even millions of samples, thanks to the number of single-cell atlases being collaboratively generated. Additionally, DGMs have proven useful in other frequent tasks in single-cell analysis pipelines, from dimensionality reduction, cell type annotation to RNA velocity inference. In spite of its promise, DGMs need to be used with caution in biomedical research, paying special attention to its use to answer the right questions and the definition of appropriate error metrics and validation check points that confirm not only its correct use but also its relevance. All in all, DGMs provide an exciting tool that opens a bright future for the integrative analysis of single-cell -omics to understand health and disease.

Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.

MYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3-megabase gene desert with multiple cis-regulatory elements. Here we use genomic rearrangements, transgenesis and targeted mutation to analyse Myc regulation in early mouse embryos and pluripotent stem cells. We identify a topologically-associated region that homes enhancers dedicated to Myc transcriptional regulation in stem cells of the pre-implantation and early post-implantation embryo. Within this region, we identify elements exclusively dedicated to Myc regulation in pluripotent cells, with distinct enhancers that sequentially activate during naive and formative pluripotency. Deletion of pluripotency-specific enhancers dampens embryonic stem cell competitive ability. These results identify a topologically defined enhancer cluster dedicated to early embryonic expression and uncover a modular mechanism for the regulation of Myc expression in different states of pluripotency.