Fasting before contrast-enhanced CT and the incidence of acute adverse reactions: a single-center randomized clinical trial.

OBJECTIVES: To evaluate the effect of eliminating the traditional preparatory fasting policy before contrast-enhanced CT on acute adverse reactions and to identify potential risk factors in a Spanish population sample, since many European patients still experience this unnecessary measure in clinical practice. METHODS: Outpatients who underwent non-emergency CT to either 6 h of solid food fasting (control group) or an unrestricted consumption of solids (intervention group). Adverse reactions during contrast media administration and up to 30 min afterward were recorded and their incidence was calculated. Using univariate and multivariate logistic regression analyses, various patient-related and technical factors were evaluated to identify risk factors for nausea and vomiting. RESULTS: One thousand one hundred three patients were evaluated, 560 patients in the control group, and 543 patients in the intervention group. Moderate and severe acute adverse reactions were not identified in either group. No statistical difference was found in the overall acute adverse reactions (hypersensitivity and chemotoxicity) incidence between groups (3.21% vs 2.30% p = 0.36). The total incidence of emetic adverse reactions (nausea and vomiting) was significantly lower in the intervention group than in the control group (0.92% vs 2.86% p = 0.02). Multivariate logistic regression analysis revealed that fasting, age, allergies, neurological diseases, and contrast media concentration were independent risk factors for nausea and vomiting. CONCLUSION: Unrestricted food intake did not increase the overall incidence of acute adverse reactions and diminished the incidence of nausea and vomiting. TRIAL REGISTRATION: ANZCTR, ACTRN12623000071628. Registered 23 January 2023-retrospectively registered, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384985&showOriginal=true&isReview=true . CRITICAL RELEVANCE STATEMENT: This randomized clinical trial carried out in adults undergoing a non-emergent CT scan demonstrates that fasting as a preparation before a contrast-enhanced CT scan should be discontinued and reserved only for certain specific imaging tests. KEY POINTS: Despite low osmolar CT contrast media becoming ubiquitous, preparatory fasting is still widely practiced. The overall incidence of acute adverse reactions was unchanged after abolishing preparative fasting. Traditional preparatory fasting should be discontinued and reserved only for certain specific imaging tests.

Novel inhibition of central carbon metabolism pathways by Rac and Cdc42 inhibitor MBQ-167 and paclitaxel.

Triple negative breast cancer (TNBC) represents a therapeutic challenge where standard chemotherapy is limited to paclitaxel. MBQ-167, a clinical stage small molecule inhibitor that targets Rac and Cdc42, inhibits tumor growth and metastasis in mouse models of TNBC. Herein, we investigated the efficacy of MBQ-167 in combination with paclitaxel in TNBC pre-clinical models, as a prelude to safety trials of this combination in advanced breast cancer patients. Individual MBQ-167 or combination therapy with paclitaxel was more effective at reducing TNBC cell viability and increasing apoptosis compared to paclitaxel alone. In orthotopic mouse models of human TNBC (MDA-MB-231 and MDA-MB-468), individual MBQ-167, paclitaxel, or the combination reduced mammary tumor growth with similar efficacy, with no apparent liver toxicity. However, paclitaxel single agent treatment significantly increased lung metastasis, while MBQ-167, single or combined, reduced lung metastasis. In the syngeneic 4T1/BALB/c model, combined MBQ-167 and paclitaxel decreased established lung metastases by ~80%. To determine the molecular basis for the improved efficacy of the combined treatment on metastasis, 4T1 tumor extracts from BALB/c mice treated with MBQ-167, paclitaxel, or the combination were subjected to transcriptomic analysis. Gene set enrichment identified specific downregulation of central carbon metabolic pathways by the combination of MBQ-167 and Paclitaxel but not individual compounds. Biochemical validation, by immunoblotting and metabolic Seahorse analysis, shows that combined MBQ-167 and paclitaxel reduces glycolysis. This study provides a strong rationale for the clinical testing of MBQ-167 in combination with paclitaxel as a potential therapeutic for TNBC and identifies a unique mechanism of action.

Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism.

Microglia, the resident immune cells of the central nervous system, are intimately involved in the brain's most basic processes, from pruning neural synapses during development to preventing excessive neuronal activity throughout life. Studies have reported both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, less is known about microglia-endothelial cell interactions in the healthy brain. To investigate the role of microglia at a healthy BBB, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed the BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for the maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism. This effect was independent from microglial depletion, suggesting that PLX5622 has off-target effects on brain vasculature.

Bronchiectasis.

Non-cystic fibrosis bronchiectasis, a condition that remains relatively underrecognized, has garnered increasing research focus in recent years. This scientific interest has catalyzed advancements in diagnostic methodologies, enabling comprehensive clinical and molecular profiling. Such progress facilitates the development of personalized treatment strategies, marking a significant step toward precision medicine for these patients. Bronchiectasis poses significant diagnostic challenges in both clinical settings and research studies. While computed tomography (CT) remains the gold standard for diagnosis, novel alternatives are emerging. These include artificial intelligence-powered algorithms, ultra-low dose chest CT, and magnetic resonance imaging (MRI) techniques, all of which are becoming recognized as feasible diagnostic tools. The precision medicine paradigm calls for refined characterization of bronchiectasis patients by analyzing their inflammatory and molecular profiles. Research into the underlying mechanisms of inflammation and the evaluation of biomarkers such as neutrophil elastase, mucins, and antimicrobial peptides have led to the identification of distinct patient endotypes. These endotypes present variable clinical outcomes, necessitating tailored therapeutic interventions. Among these, eosinophilic bronchiectasis is notable for its prevalence and specific prognostic factors, calling for careful consideration of treatable traits. A deeper understanding of the microbiome's influence on the pathogenesis and progression of bronchiectasis has inspired a holistic approach, which considers the multibiome as an interconnected microbial network rather than treating pathogens as solitary entities. Interactome analysis therefore becomes a vital tool for pinpointing alterations during both stable phases and exacerbations. This array of innovative approaches has revolutionized the personalization of treatments, incorporating therapies such as inhaled mannitol or ARINA-1, brensocatib for anti-inflammatory purposes, and inhaled corticosteroids specifically for patients with eosinophilic bronchiectasis.

Las bronquiectasias no fibrosis quística han atraído una creciente atención en investigación. Este interés científico ha catalizado avances en las metodologías de diagnóstico, permitiendo realizar perfiles clínicos y moleculares integrales. Este progreso facilita el desarrollo de estrategias de tratamiento personalizadas y marca un paso significativo hacia la medicina de precisión.Desde el punto de vista diagnóstico, las bronquiectasias plantean desafíos importantes en entornos clínicos y de investigación. Si bien la TC es el gold standard, están surgiendo nuevas alternativas. Entre ellas, algoritmos de inteligencia artificial, TC de tórax de dosis ultrabajas y técnicas de resonancia magnética.La medicina de precisión aboga por la caracterización de pacientes mediante análisis de perfiles inflamatorios y moleculares. Las investigaciones sobre mecanismos subyacentes de inflamación y la evaluación de biomarcadores como la elastasa de neutrófilos, mucinas y péptidos antimicrobianos, han llevado a la identificación de endotipos de pacientes. Estos endotipos exhiben resultados clínicos variables, requiriendo intervenciones terapéuticas personalizadas. La bronquiectasia eosinofílica destaca por su prevalencia y factores pronósticos específicos, exigiendo consideración de los rasgos tratables.Una comprensión profunda de la influencia del microbioma en la patogénesis y progresión de las bronquiectasias inspira un enfoque holístico. Considera el multibioma como una red microbiana interconectada, no entidades solitarias. El análisis del interactoma se convierte en una herramienta vital para identificar alteraciones durante fases estables y exacerbaciones.Este conjunto de enfoques innovadores revoluciona la personalización de los tratamientos, incorporando terapias como manitol inhalado o ARINA-1, brensocatib con fines antiinflamatorios y corticosteroides inhalados específicos para pacientes con bronquiectasias eosinofílicas.

Comparison of Short-Term Effects of Different Spinal Manipulations in Patients with Chronic Non-Specific Neck Pain: A Randomized Controlled Trial.

Spinal manipulations for chronic non-specific neck pain (CNNP) include cervical, cervicothoracic junction, and thoracic spine (CCT) manipulations as well as upper cervical spine (UCS) manipulations. This study aimed to compare the short-term effects of UCS manipulation versus a combination of CCT spine manipulations on pain intensity, disability, and cervical range of motion (CROM) in CNNP patients. In a private physiotherapy clinic, 186 participants with CNNP were randomly assigned to either the UCS (n = 93) or CCT (n = 93) manipulation groups. Neck pain, disability, and CROM were measured before and one week after the intervention. No significant differences were found between the groups regarding pain intensity and CROM. However, there was a statistically significant difference in neck disability, with the CCT group showing a slightly greater decrease (CCT: 16.9 ± 3.8 vs. UCS: 19.5 ± 6.8; p = 0.01). The findings suggest that a combination of manipulations in the CCT spine results in a slightly more pronounced decrease in self-perceived disability compared to UCS manipulation in patients with CNNP after one week. However, no statistically significant differences were observed between the groups in terms of pain intensity or CROM.

Quahogging in a Marine Habitat: An Extremely Rare Source of an Organism to Cause Endocarditis.

A 66-year-old man with a history of apical variant hypertrophic cardiomyopathy, heart failure with preserved ejection fraction (HFpEF), severe pulmonary hypertension, and prior Group B streptococcal mitral valve endocarditis four months before, presented with generalized body shakes and urinary incontinence. Computed tomography angiography revealed an acute left M1 occlusion. The patient underwent mechanical thrombectomy. Within 24 hours of presentation, he developed hypotension, tachycardia, and fever. Infectious workup revealed a leukocytosis. One out of two sets of blood cultures revealed bacteremia with Shewanella algae. A transthoracic echocardiogram revealed a large mitral valve vegetation with multiple mobile components portending a high thromboembolic risk, as evidenced by his acute presentation with multiple embolic infarcts. He was diagnosed with infectious endocarditis caused by Shewanella algae, a rare marine environment pathogen. He was treated with ciprofloxacin 750 mg twice daily orally and meropenem 2 g every eight hours intravenously with an initial decrease in the mitral valve vegetation size. He was discharged on ceftriaxone 2g and ciprofloxacin 750mg every 12 hours for a total of six weeks from his first negative blood cultures. He was monitored through transthoracic echocardiography as he continued medical management with levofloxacin 750 mg daily. Six months after his discharge from the hospital he developed worsening heart failure and elected to pursue comfort measures only.

Decoding viral and host microRNA signatures in airway-derived biosamples: Insights for biomarker discovery in viral respiratory infections.

The global public health crisis caused by the COVID-19 pandemic has intensified the global concern regarding viral respiratory tract infections. Despite their considerable impact on health, society and the economy, effective management of these conditions remains a significant challenge. Integrating high-throughput analyses is pivotal for early detection, prognostication of adverse outcomes, elucidating pathogenetic pathways and developing therapeutic approaches. In recent years, microRNAs (miRNAs), a subset of small noncoding RNAs (ncRNAs), have emerged as promising tools for molecular phenotyping. Current evidence suggests that miRNAs could serve as innovative biological markers, aiding in informed medical decision-making. The cost-effective quantification of miRNAs in standardized samples using techniques routinely employed in clinical laboratories has become feasible. In this context, samples obtained from the airways represent a valuable source of information due to their direct exposure to the infectious agent and host response within the respiratory tract. This review explores viral and host miRNA profiling in airway-derived biosamples as a source of molecular information to guide patient management, with a specific emphasis on SARS-CoV-2 infection.

IκBα controls dormancy in hematopoietic stem cells via retinoic acid during embryonic development.

Recent findings suggest that Hematopoietic Stem Cells (HSC) and progenitors arise simultaneously and independently of each other already in the embryonic aorta-gonad mesonephros region, but it is still unknown how their different features are established. Here, we uncover IκBα (Nfkbia, the inhibitor of NF-κB) as a critical regulator of HSC proliferation throughout development. IκBα balances retinoic acid signaling levels together with the epigenetic silencer, PRC2, specifically in HSCs. Loss of IκBα decreases proliferation of HSC and induces a dormancy related gene expression signature instead. Also, IκBα deficient HSCs respond with superior activation to in vitro culture and in serial transplantation. At the molecular level, chromatin regions harboring binding motifs for retinoic acid signaling are hypo-methylated for the PRC2 dependent H3K27me3 mark in IκBα deficient HSCs. Overall, we show that the proliferation index in the developing HSCs is regulated by a IκBα-PRC2 axis, which controls retinoic acid signaling.

Impact of OLD/Emphysema in LC Mortality Risk in Screening Programs: An Analysis of NLST and P-IELCAP.

INTRODUCTION: The impact of obstructive lung disease (OLD) and emphysema on lung cancer (LC) mortality in patients undergoing LC screening is controversial. METHODS: Patients with spirometry and LC diagnosed within the first three rounds of screening were selected from the National Lung Screening Trial (NLST) and from the Pamplona International Early Lung Cancer Detection Program (P-IELCAP). Medical and demographic data, tumor characteristics, comorbidities and presence of emphysema were collected. The effect of OLD and emphysema on the risk of overall survival was assessed using unadjusted and adjusted Cox models, competing risk regression analysis, and propensity score matching. RESULTS: Data from 353 patients with LC, including 291 with OLD and/or emphysema and 62 with neither, were analyzed. The median age was 67.3 years-old and 56.1% met OLD criteria, predominantly mild (1: 28.3%, 2: 65.2%). Emphysema was present in 69.4% of the patients. Patients with OLD and/or emphysema had worse survival on univariate analysis (HR: 1.40; 95% CI: 0.86-2.31; p=0.179). However, after adjusting for LC stage, age, and sex, the HR was 1.02 (95% CI: 0.61-1.70; p=0.952). Specific LC survival between both groups showed an adjusted HR of 0.90 (95% CI: 0.47-1.72; p=0.76). Propensity score matching found no statistically significant difference in overall survival (HR: 1.03; 95% CI: 0.59-1.9; p=0.929). CONCLUSION: The survival of LC patients diagnosed in the context of screening is not negatively impacted by the coexistence of mild OLD and/or emphysema.

Effect of motivational interviewing on preventive strategies for children receiving full-mouth dental rehabilitation under general anesthesia: A randomized controlled trial.

BACKGROUND: Motivational interviewing (MI) is an approach to increase parental compliance to follow up and recall of their children. It has proven to be successful in motivating parents to adopt and maintain preventive child oral health behaviors. AIM: To assess the effectiveness of motivational interviewing on prevention strategies for parents of children who have received full-mouth dental rehabilitation under general anesthesia (GA). DESIGN: This is a parallel-arm randomized controlled trial. Parents in the treatment arm were randomized and received a combination of motivational interviewing, individualized goal setting, visual aids, and verbal education post-GA. Those in the control arm received the same information by verbal and written education. Both groups were evaluated at 2-week follow-up and 3-month recall. Differences in attendance, oral health knowledge, readiness to change, and parental self-efficacy (PSE) were compared between groups and at return visits. RESULTS: Of 74 parents of children randomly allocated in this study, 22 (61%) and 13 (38%) from the intervention group, and 21 (55%) and 16 (46%) from the control group attended the 2-week, and 3-month follow-up, respectively. The average PSE for participants in the intervention group was significantly higher than that of the control group at the follow-up visit (p = .0050). CONCLUSION: Readiness to change dietary habits and average PSE for parents in the intervention group were significantly higher than that of the control group after receiving the modified preventive strategy.

Blast from the Past: Acute Myeloid Leukemia Presenting with Cardiac Tamponade.

Acute Myeloid Leukemia (AML) is a life-threatening illness that requires prompt diagnosis and often immediate treatment. It can present in a variety of manners but most commonly is associated with fevers, fatigue, shortness of breath, or infection. Extramedullary leukemia is a less common finding upon initial presentation, but includes dermatologic manifestations, including leukemia cutis, and rarely, large mass-like presentations known as myeloid sarcomas. While leukemic infiltration of organ systems is a well-described phenomenon, cardiac tamponade is a rare form of presentation. Herein we describe a 58-year-old man with a recent hospitalization for idiopathic cardiac tamponade who re-presented to the hospital with worsening dyspnea and fevers. He was found to have a recurrent pericardial effusion with features concerning for tamponade, as well as worsening thrombocytopenia and macrocytic anemia. Bone marrow biopsy revealed 24% myeloblasts, confirming the diagnosis of AML. Notably, his cardiac symptoms improved with treatment of his leukemia. To our knowledge, this is one of only a few cases of AML with cardiac tamponade as the initial presentation.

KRAS-mutant non-small cell lung cancer (NSCLC) therapy based on tepotinib and omeprazole combination.

BACKGROUND: KRAS-mutant non-small cell lung cancer (NSCLC) shows a relatively low response rate to chemotherapy, immunotherapy and KRAS-G12C selective inhibitors, leading to short median progression-free survival, and overall survival. The MET receptor tyrosine kinase (c-MET), the cognate receptor of hepatocyte growth factor (HGF), was reported to be overexpressed in KRAS-mutant lung cancer cells leading to tumor-growth in anchorage-independent conditions. METHODS: Cell viability assay and synergy analysis were carried out in native, sotorasib and trametinib-resistant KRAS-mutant NSCLC cell lines. Colony formation assays and Western blot analysis were also performed. RNA isolation from tumors of KRAS-mutant NSCLC patients was performed and KRAS and MET mRNA expression was determined by real-time RT-qPCR. In vivo studies were conducted in NSCLC (NCI-H358) cell-derived tumor xenograft model. RESULTS: Our research has shown promising activity of omeprazole, a V-ATPase-driven proton pump inhibitor with potential anti-cancer properties, in combination with the MET inhibitor tepotinib in KRAS-mutant G12C and non-G12C NSCLC cell lines, as well as in G12C inhibitor (AMG510, sotorasib) and MEK inhibitor (trametinib)-resistant cell lines. Moreover, in a xenograft mouse model, combination of omeprazole plus tepotinib caused tumor growth regression. We observed that the combination of these two drugs downregulates phosphorylation of the glycolytic enzyme enolase 1 (ENO1) and the low-density lipoprotein receptor-related protein (LRP) 5/6 in the H358 KRAS G12C cell line, but not in the H358 sotorasib resistant, indicating that the effect of the combination could be independent of ENO1. In addition, we examined the probability of recurrence-free survival and overall survival in 40 early lung adenocarcinoma patients with KRAS G12C mutation stratified by KRAS and MET mRNA levels. Significant differences were observed in recurrence-free survival according to high levels of KRAS mRNA expression. Hazard ratio (HR) of recurrence-free survival was 7.291 (p = 0.014) for high levels of KRAS mRNA expression and 3.742 (p = 0.052) for high MET mRNA expression. CONCLUSIONS: We posit that the combination of the V-ATPase inhibitor omeprazole plus tepotinib warrants further assessment in KRAS-mutant G12C and non G12C cell lines, including those resistant to the covalent KRAS G12C inhibitors.

In situ hydrolysis of a carbophosphazene ligand leads to one-dimensional lanthanide coordination polymers. Synthesis, structure and dynamic magnetic studies.

An in situ hydrolysis of the P-Cl bonds of the carbophosphazene [{NC(NMe2)}2{NPCl2}] (LPCl2) in the presence of hydrated lanthanide(III) nitrates in a dichloromethane and methanol (2 : 1) solvent mixture afforded a series of novel 1D coordination polymers: [{Ln(LHPO2)3(NO3)2(CH3OH)(H2O)} (Cl)]n {where Ln(III) = Gd (1), Tb (2), Dy (3), or Er (4) and LHPO2 is the hydrolyzed carbophosphazene (LPCl2) ligand}. X-ray crystallographic analysis revealed that complexes 1-4 are isostructural and crystallized in the monoclinic crystal system having P21/c space group. The coordination polymers are formed because of the involvement of the geminal P(O)(OH) moieties of the carbophosphazene ligand. Each lanthanide(III) ion is 9-coordinate (9O) in a distorted muffin geometry. Magnetic measurements revealed that both DyIII and ErIII analogues exhibit field-induced single-molecule magnet (SMM) behavior at 0.8 kOe and 2.2 k Oe, respectively. At such dc fields, the dynamic magnetic susceptibility displays complex behavior with a triple magnetic relaxation contribution for 3, while two contributions were identified for 4. The observed static and dynamic magnetic behavior for complexes 1-4 were further rationalized with the aid of BS-DFT and CASSCF/SO-RASSI/SINGLE_ANISO calculations.

Depressive symptoms and suicide attempts among farmers exposed to pesticides.

Pesticides safeguard crop health but may diminish cholinesterase activity in farmers, potentially leading to psychiatric disorders like depression and suicide attempts. This study, with 453 participants (225 pesticide-exposed farmers, 228 non-farmers) in Almería, Spain, aimed to investigate the presence of depressive symptoms and suicide attempts, the decrease acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity, and their relationship with pesticide exposure in farmers. Depressive symptoms were evaluated using the Spanish adaptation of the Beck Depression Inventory, and blood samples were analyzed for AChE and BChE activity. Farmers showed significantly increased risk of moderate/severe depression and suicide attempts compared to non-farmers (OR = 2.18; p = 0.001), with highest risks observed among mancozeb users (OR = 2.76; p = 0.001 for depression) and malathion users (OR = 3.50; p = 0.001 for suicide attempts). Findings emphasize elevated depression and suicide risks among pesticide-exposed farmers, particularly associated with chlorpyrifos, mancozeb, and malathion exposure.

Sleep and Circadian Health of Critical Survivors: A 12-Month Follow-Up Study.

OBJECTIVES: To investigate the sleep and circadian health of critical survivors 12 months after hospital discharge and to evaluate a possible effect of the severity of the disease within this context. DESIGN: Observational, prospective study. SETTING: Single-center study. PATIENTS: Two hundred sixty patients admitted to the ICU due to severe acute respiratory syndrome coronavirus 2 infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was composed of 260 patients (69.2% males), with a median (quartile 1-quartile 3) age of 61.5 years (52.0-67.0 yr). The median length of ICU stay was 11.0 days (6.00-21.8 d), where 56.2% of the patients required invasive mechanical ventilation (IMV). The Pittsburgh Sleep Quality Index (PSQI) revealed that 43.1% of the cohort presented poor sleep quality 12 months after hospital discharge. Actigraphy data indicated an influence of the disease severity on the fragmentation of the circadian rest-activity rhythm at the 3- and 6-month follow-ups, which was no longer significant in the long term. Still, the length of the ICU stay and the duration of IMV predicted a higher fragmentation of the rhythm at the 12-month follow-up with effect sizes (95% CI) of 0.248 (0.078-0.418) and 0.182 (0.005-0.359), respectively. Relevant associations between the PSQI and the Hospital Anxiety and Depression Scale (rho = 0.55, anxiety; rho = 0.5, depression) as well as between the fragmentation of the rhythm and the diffusing lung capacity for carbon monoxide (rho = -0.35) were observed at this time point. CONCLUSIONS: Our findings reveal a great prevalence of critical survivors presenting poor sleep quality 12 months after hospital discharge. Actigraphy data indicated the persistence of circadian alterations and a possible impact of the disease severity on the fragmentation of the circadian rest-activity rhythm, which was attenuated at the 12-month follow-up. This altogether highlights the relevance of considering the sleep and circadian health of critical survivors in the long term.

Addressing the unsolved challenges in microRNA-based biomarker development: Suitable endogenous reference microRNAs for SARS-CoV-2 infection severity.

Circulating cell-free microRNAs (miRNAs) are promising biomarkers for medical decision-making. Suitable endogenous controls are essential to ensure reproducibility. We aimed to identify and validate endogenous reference miRNAs for qPCR data normalization in samples from SARS-CoV-2-infected hospitalized patients. We used plasma samples (n = 170) from COVID-19 patients collected at hospital admission (COVID-Ponent project, www.clinicaltrials.gov/NCT04824677). First, 179 miRNAs were profiled using RT-qPCR. After stability assessment, candidates were validated using the same methodology. miRNA stability was analyzed using the geNorm, NormFinder and BestKeeper algorithms. Stability was further evaluated using an RNA-seq dataset derived from COVID-19 hospitalized patients, along with plasma samples from patients with critical COVID-19 profiled using RT-qPCR. In the screening phase, after strict control of expression levels, stability assessment selected eleven candidates (miR-17-5p, miR-20a-5p, miR-30e-5p, miR-106a-5p, miR-151a-5p, miR-185-5p, miR-191-5p, miR-423-3p, miR-425-5p, miR-484 and miR-625-5p). In the validation phase, all algorithms identified miR-106a-5p and miR-484 as top endogenous controls. No association was observed between these miRNAs and clinical or sociodemographic characteristics. Both miRNAs were stably detected and showed low variability in the additional analyses. In conclusion, a 2-miRNA panel composed of miR-106a-5p and miR-484 constitutes a first-line normalizer for miRNA-based biomarker development using qPCR in hospitalized patients infected with SARS-CoV-2.

The relationship between female orgasmic disorder, attention-deficit/hyperactivity disorder, and depression in Dominican women.

BACKGROUND: Female orgasmic disorder is listed in the DSM-5 and is defined as the persistent or recurrent inability to have an orgasm. Many depressed women may experience sexual dysfunction, including female orgasmic disorder. AIM: The study sought to analyze the relationship between depressive disorders and attention-deficit/hyperactivity disorder (ADHD) and their influence on the development of female orgasmic disorder. METHODS: A total of 221 Dominican women participated in this case-control study. The case group consisted of 107 women diagnosed with female orgasmic disorder, while the control group consisted of 114 women without any sexual dysfunction. OUTCOMES: The diagnosis of ADHD was obtained from the participants' medical records, previously conducted using the DSM-5-TR criteria. The Beck Depression Inventory II was used to assess the severity of depressive symptoms in both groups. RESULTS: There was a significant relationship between female orgasmic disorder and ADHD and depression. The results of multiple logistic regression indicated that the highest risk of female orgasmic disorder was observed in women with ADHD (odds ratio [OR], 4.91; 95% confidence interval [CI], 2.46-9.20; P < .001), women with severe depression (OR, 2.50; 95% CI, 1.08-6.96; P = .04), and women who had sexual intercourse that focused on penetration (OR, 2.02; 95% CI, 1.03-3.98; P = .04). CLINICAL IMPLICATIONS: These findings may have important implications for the prevention and treatment of sexual disorders in women. STRENGTHS AND LIMITATIONS: This design selected all diagnosed cases of female orgasmic disorder and did not select a specific subgroup. However, some limitations must be considered. This study was conducted in a single clinic, although it should be noted that it is the main clinic for the treatment of sexual dysfunction in the country. A further limitation could be that this type of study design does not allow for statements about causality to be made. CONCLUSION: There is an increased risk of female orgasmic disorder in women with ADHD, with severe depression, and who engage in penetrative sex.

ERS International Congress 2023: highlights from the Respiratory Intensive Care Assembly.

Early career members of Assembly 2 (Respiratory Intensive Care) attended the 2023 European Respiratory Society International Congress in Milan, Italy. The conference covered acute and chronic respiratory failure. Sessions of interest to our assembly members and to those interested in respiratory critical care are summarised in this article and include the latest updates in respiratory intensive care, in particular acute respiratory distress syndrome and mechanical ventilation.

The Natural History of Severe Chronic Obstructive Pulmonary Disease: The SPOCCAT Study Protocol.

Introduction: Patients with severe chronic obstructive pulmonary disease (COPD) are often underrepresented in cohorts, creating uncertainty about the natural history and prognostic factors of this subgroup. Our goal was to describe the SPOCCAT (Severe COPD: Prospective Observational study of COPD in Catalonia) study protocol. Material and methods: SPOCCAT is a non-interventional, multicenter, prospective cohort study of patients with severe COPD (FEV1% predicted < 50%). The study aims to: (1) establish a five-year prospective cohort; (2) identify demographic and clinical characteristics; (3) describe treatment patterns; (4) better understand the natural history of severe COPD, including lung function decline, exacerbation rates, and mortality; and (5) identify prognostic factors for poor outcomes.Recruitment began in January 2024, and the cohort will be followed for a minimum of five years (or until death or lung transplant) with follow-up visits every 12 months. Baseline data include demographics, laboratory analyses, comorbidities, lung function, respiratory symptoms, respiratory disease exacerbations and etiology, quality of life, physical activity, chest computed tomography, and treatment. Annual follow-up visits will assess changes in treatment, exacerbation frequency and severity, microbiological outcomes, complementary tests, and mortality. Participation requires written informed consent from all patients, with data collected in an anonymized electronic Case Report Form. Results: The results of the SPOCCAT study will provide relevant information about the characteristics, treatment, and prognostic factors of severe COPD. Conclusions: SPOCCAT has the potential to enhance understanding of severe COPD, exploring innovative aspects and establishing a robust research framework for future COPD-related projects.

Introducción: Los pacientes con enfermedad pulmonar obstructiva crónica (EPOC) grave a menudo están infrarepresentados en las cohortes, lo que genera incertidumbre sobre la historia natural y los factores pronósticos de este subgrupo. Nuestro objetivo fue describir el protocolo del estudio de EPOC grave: estudio observacional prospectivo de la EPOC en Cataluña (SPOCCAT). Material y método: El SPOCCAT es un estudio de cohorte prospectivo, multicéntrico y no intervencionista de pacientes con EPOC grave (volumen espiratorio forzado en un segundo [FEV1] % previsto < 50%). El estudio tiene como objetivo: 1) establecer una cohorte prospectiva de cinco años, 2) identificar características demográficas y clínicas, 3) describir patrones de tratamiento, 4) comprender mejor la historia natural de la EPOC grave, incluida la disminución de la función pulmonar, las tasas de exacerbación y la mortalidad, y 5) identificar factores de pronóstico de malos resultados. El reclutamiento comenzó en enero de 2024 y se seguirá a la cohorte durante un mínimo de cinco años (o hasta la muerte o el trasplante de pulmón) con visitas de seguimiento cada 12 meses. Los datos basales incluyen datos demográficos, análisis de laboratorio, comorbilidades, función pulmonar, síntomas respiratorios, exacerbaciones y etiología de enfermedades respiratorias, calidad de vida, actividad física, tomografía computarizada de tórax y tratamiento. Las visitas de seguimiento anuales evaluarán cambios en el tratamiento, frecuencia y gravedad de las exacerbaciones, resultados microbiológicos, pruebas complementarias y mortalidad. La participación requiere el consentimiento informado por escrito de todos los pacientes, con datos anonimizados recopilados en un cuaderno de recogida de datos electrónico. Resultados: Los resultados del estudio SPOCCAT aportarán información relevante sobre las características, el tratamiento y los factores pronósticos de la EPOC grave. Conclusiones: El estudio SPOCCAT tiene el potencial de mejorar la comprensión de la EPOC grave, explorando aspectos innovadores y estableciendo un marco de investigación sólido para futuros proyectos relacionados con la EPOC.