Nonviral CRISPR/Cas9 mutagenesis for streamlined generation of mouse lung cancer models.

Functional analysis in mouse models is necessary to establish the involvement of a set of genetic variations in tumor development. A modeling platform to facilitate and cost-effectively analyze the role of multiple genes in carcinogenesis would be valuable. Here, we present an innovative strategy for lung mutagenesis using CRISPR/Cas9 ribonucleoproteins delivered via cationic polymers. This approach allows the simultaneous inactivation of multiple genes. We validate the effectiveness of this system by targeting a group of tumor suppressor genes, specifically Rb1, Rbl1, Pten, and Trp53, which were chosen for their potential to cause lung tumors, namely small cell lung carcinoma (SCLC). Tumors with histologic and transcriptomic features of human SCLC emerged after intratracheal administration of CRISPR/polymer nanoparticles. These tumors carried loss-of-function mutations in all four tumor suppressor genes at the targeted positions. These findings were reproduced in two different pure genetic backgrounds. We provide a proof of principle for simplified modeling of lung tumorigenesis to facilitate functional testing of potential cancer-related genes.

Pilot study of an online brief mindfulness-based intervention to improve the well-being of managers and reduce their stress at work.

Objectives. The COVID-19 pandemic, remote work and new technologies have heightened workplace pressures. Effective response and essential organizational changes require business leaders to be more adaptable, with managers' presence playing a pivotal role in successful implementation. The study assesses a brief mindfulness-based emotional regulation for managers (MBERM) intervention, to reduce workplace stress and enhance managerial well-being. Methods. An 8-week non-randomized controlled trial was conducted with a waiting list control group and an intervention group. Pre-post differences were measured by Student's t test or Wilcoxon test, and effect size calculated using the Hedge's g formula. The sample included 23 managers (17 men and six women) with average age 50 years. The study assessed anxiety and depressive symptoms, psychological flexibility, perceived self-efficacy, general work-related well-being, perceived stress and mindfulness. Results. Statistically significant changes were observed in the intervention group in depression, anxiety, work-related acceptance and action, general self-efficacy, exhaustion, alienation, stress and non-reactivity. The control group showed no statistically significant changes in any of the variables. Conclusion. The MBERM intervention could improve the emotional and work-related well-being of managers and reduce stress levels and burnout. Further study of this intervention is needed to promote adherence and ensure a long-term improvement.

Proof of concept: real-time viability and metabolic profiling of probiotics with isothermal microcalorimetry.

Isothermal microcalorimetry (IMC) is a potent analytical method for the real-time assessment of microbial metabolic activity, which serves as an indicator of microbial viability. This approach is highly relevant to the fields of probiotics and Live Biotherapeutic Products (LBPs), offering insights into microbial viability and growth kinetics. One important characteristic of IMC is its ability to measure microbial metabolic activity separately from cellular enumeration. This is particularly useful in situations where continuous tracking of bacterial activity is challenging. The focus on metabolic activity significantly benefits both probiotic research and industrial microbiology applications. IMC's versatility in handling different media matrices allows for the implementation of viability assessments under conditions that mirror those found in various industrial environments or biological models. In our study, we provide a proof of concept for the application of IMC in determining viability and growth dynamics and their correlation with bacterial count in probiotic organisms. Our findings reinforce the potential of IMC as a key method for process enhancement and accurate strain characterization within the probiotic sector. This supports the broader objective of refining the systematic approach and methods used during the development process, thereby providing detailed insights into probiotics and LBPs.

Characterization and modulation of voltage-gated potassium channels in human lymphocytes in schizophrenia.

BACKGROUND: It is known that the immune system is dysregulated in schizophrenia, having a state similar to chronic neuroinflammation. The origin of this process is unknown, but it is known that T and B lymphocytes, which are components of the adaptive immune system, play an important role in the pathogenic mechanisms of schizophrenia. METHODS: We analysed the membrane of PBMCs from patients diagnosed with schizophrenia through proteomic analysis (n = 5 schizophrenia and n = 5 control). We found the presence of the Kv1.3 voltage-gated potassium channel and its auxiliary subunit ß1 (KCNAB1) and ß2 (KCNAB2). From a sample of 90 participants, we carried out a study on lymphocytes with whole-cell patch-clamp experiments (n = 7 schizophrenia and n = 5 control), western blot (n = 40 schizophrenia and n = 40 control) and confocal microscopy to evaluate the presence and function of different channels. Kv in both cells. RESULTS: We demonstrated the overexpression of Kv1.1, Kv1.2, Kv1.3, Kv1.6, Kv4.2, Kv4.3 and Kv7.2 channels in PBMCs from patients with schizophrenia. This study represents a groundbreaking exploration, as it involves an electrophysiological analysis performed on T and B lymphocytes from patients diagnosed of schizophrenia compared to healthy participants. We observed that B lymphocytes exhibited an increase in output current along with greater peak current amplitude and voltage conductance curves among patients with schizophrenia compared with healthy controls. CONCLUSIONS: This study showed the importance of the B lymphocyte in schizophrenia. We know that the immune system is altered in schizophrenia, but the physiological mechanisms of this system are not very well known. We suggest that the B lymphocyte may be relevant in the pathophysiology of schizophrenia and that it should be investigated in more depth, opening a new field of knowledge and possibilities for new treatments combining antipsychotics and immunomodulators. The limitation is that all participants received antipsychotic medication, which may have influenced the differences observed between patients and controls. This implies that more studies need to be done where the groups can be separated according to the antipsychotic drug.

In vitro activity of ozenoxacin against Staphylococcus aureus and Streptococcus pyogenes clinical isolates recovered in a worldwide multicentre study (2020-2022).

Objectives: We performed a multicentre study (2020-2022) to compare the in vitro activity of ozenoxacin and comparator agents against Staphylococcus aureus and Streptococcus pyogenes clinical isolates from skin and soft-tissue infections (SSTI). Methods: A total of 1725 isolates (1454 S. aureus and 271 S. pyogenes) were collected in 10 centres from eight countries between January 2020 and December 2022. Antimicrobial susceptibility testing was determined (microdilution-SENSITITRE). Results were interpreted following European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 (clinical breakpoints, ECOFF) and CLSI criteria. Results: Ozenoxacin exhibited high in vitro activity against S. aureus (MIC50/90 = 0.002/0.12 mg/L) and S. pyogenes (MIC50/90 = 0.015/0.03 mg/L), inhibiting 99% of the isolates at MIC ≤ 0.5 mg/L and at MIC ≤ 0.06, respectively. The most active comparators against S. aureus were retapamulin (MIC90 = 0.12 mg/L), fusidic acid (MIC90 = 0.25 mg/L) and mupirocin (MIC90 = 0.5 mg/L); and against S. pyogenes were retapamulin (MIC90 = 0.03 mg/L), clindamycin (MIC90 = 0.12 mg/L) and mupirocin (MIC90 = 0.25 mg/L). Ciprofloxacin and methicillin resistant rates for S. aureus were 31.3% (455/1454) and 41% (598/1454), respectively. Additionally, 62% (373/598) of the MRSA were also ciprofloxacin non-susceptible, whereas only 10% (23/271) of the MSSA were ciprofloxacin resistant. Ozenoxacin was more active against ciprofloxacin-susceptible S. aureus than against ciprofloxacin-resistant isolates, and showed a slightly higher MIC in MRSA isolates than in MSSA. However, ozenoxacin activity was comparable in both ciprofloxacin-resistant MSSA and MRSA subsets. On the other hand, ozenoxacin had similar activity in ciprofloxacin-susceptible and resistant S. pyogenes isolates. Conclusions: Ozenoxacin is a potent antimicrobial agent of topic use against Gram-positive bacteria causing SSTI, including MRSA isolates non-susceptible to ciprofloxacin.

Description of a new method to calculate the equator of the crystalline lens using AS-OCT images: Accuracy in non-dilated measurements.

OBJECTIVE: To establish a methodology for objectively estimating the Lens Equatorial Plane (LEP) from clinical images, comparing LEP with dilated versus non-dilated pupils. METHODS: A cohort of 91 eyes from 60 patients undergoing preoperative assessments for cataract surgery was evaluated. Anterior Segment Optical Coherence Tomography (AS-OCT) images were analysed under conditions of pharmacologically induced pupil dilation versus a non-dilated pupil. Geometrical parameters, including LEP, intersection diameter (ID), lens thickness (LT), anterior and posterior lens thickness were automatically calculated by applying standard image processing techniques to clinical AS-OCT images. RESULTS: Significant differences in lens parameters, including LEP, were observed between dilated and non-dilated conditions (all p < 0.001). A strong linear correlation was found across all geometrical variables under both conditions (r[LEP] = 0.64, r[ID] = 0.78, r[LT] = 0.99, all p < 0.001); enabling reliable correction of these differences. CONCLUSION: The study introduces an objective methodology for LEP calculation, emphasising the need to consider the eye's physiological state during preoperative measurements. Incorporating LEP into future intraocular lens (IOL) power calculation formulas and replacing the habitual effective lens position may potentially improve the accuracy of IOL power estimation and thus postoperative visual outcomes.

Humanisation in paediatric intensive care units: A narrative review.

OBJECTIVE: To identify findings in the scientific literature relevant to the strategic lines proposed by the Humanising Intensive Care Project in the context of paediatric intensive care units. DESIGN: Narrative review. METHODS: A literature search was conducted in the databases PubMed, Scopus, CINHAL, and Cochrane Library. Specific indexing terms and search strategies adapted to each database were designed. The inclusion of publications was based on two criteria: 1) related to the paediatric intensive care unit and 2) addresses at least one of the topics related to the strategic lines of the Humanising Intensive Care Project. Study selection was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the quality of the included studies was assessed using the Mixed Method Appraisal tool. RESULTS: A total of 100 articles from 19 different countries were included, covering the period between 2019 and 2021. Nineteen different design types were identified. Thirty-two studies were cross-sectional observational studies, while 15 had an experimental approach. The articles were distributed among the seven strategic lines of the Humanising Intensive Care Project. CONCLUSIONS: Synthesising the knowledge related to humanisation in paediatric intensive care units will allow progress to be made in improving quality in these units. However, there is disparity in the amount of experimental research overall. IMPLICATIONS FOR CLINICAL PRACTICE: There is a disparity in the available research related to the different strategic lines, and it is necessary to carry out more exhaustive research on topics such as the presence and participation of the family in care or the management of post-paediatric intensive care syndrome.

Plasmid-encoded insertion sequences promote rapid adaptation in clinical enterobacteria.

Plasmids are extrachromosomal genetic elements commonly found in bacteria. Plasmids are known to fuel bacterial evolution through horizontal gene transfer (HGT), but recent analyses indicate that they can also promote intragenomic adaptations. However, the role of plasmids as catalysts of bacterial evolution beyond HGT remains poorly explored. In this study, we investigate the impact of a widespread conjugative plasmid, pOXA-48, on the evolution of various multidrug-resistant clinical enterobacteria. Combining experimental and within-patient evolution analyses, we unveil that plasmid pOXA-48 promotes bacterial evolution through the transposition of plasmid-encoded insertion sequence 1 (IS1) elements. Specifically, IS1-mediated gene inactivations expedite the adaptation rate of clinical strains in vitro and foster within-patient adaptation in the gut microbiota. We decipher the mechanism underlying the plasmid-mediated surge in IS1 transposition, revealing a negative feedback loop regulated by the genomic copy number of IS1. Given the overrepresentation of IS elements in bacterial plasmids, our findings propose that plasmid-mediated IS transposition represents a crucial mechanism for swift bacterial adaptation.

Seizures in Children With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Although respiratory symptoms are the most prominent manifestations of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and especially the omicron variant, may cause neurological manifestations such as seizures. It remains unclear if specific variants of the virus increase the risk of seizures more than others. MATERIAL AND METHODS: This was a retrospective multicenter study of pediatric (zero to 16 years) patients with COVID-19 who attended five pediatric emergency departments in Madrid, Spain, between March 2020 and July 2022. An analysis of demographics, medical history, and seizure characteristics was conducted. The data obtained were correlated with the incidence of the different strains of SARS-CoV-2 in the Community of Madrid. RESULTS: A total of 2411 seizures (infectious and noninfectious) were recorded, and 35 of them (1.4%) were positive for SARS-CoV-2. Of those 35 patients, 18 (51.4%) reported a history of previous seizures. The highest percentage of cases occurred when the omicron variant was the most prevalent (28 [80%] vs 7 [20%] before omicron variant). Typical febrile seizures accounted for 52.9% of the cases. No treatment was required in more than half (57.1%) of the cases. CONCLUSION: during the emergence of the omicron variant, there has been an increase in the number of COVID-19-associated seizures. These findings highlight the need for SARS-CoV-2 screening in patients with febrile and afebrile seizures, in addition to other microbiological, biochemical, or neuroimaging tests, depending on the patient's age and clinical presentation.

Bioactivity and Antibacterial Analysis of Plasticized PLA Electrospun Fibers Reinforced with MgO and Mg(OH)2 Nanoparticles.

In this work, we focused on the bioactivity and antibacterial behavior of PLA-based electrospun fibers, efibers, reinforced with both MgO and Mg(OH)2 nanoparticles, NPs. The evolution of PLA-based efibers was followed in terms of morphology, FTIR, XRD, and visual appearance. The bioactivity was discussed in terms of hydroxyapatite growth after 28 days, considered as T28, of immersion in simulated body fluid, SBF. In particular, the biomineralization process evidenced after immersion in SBF started at T14 in both systems. The number of precipitated crystals increased by increasing the amount of both NPs. The chemical composition of the precipitated crystals was also characterized in terms of the Ca/P molar ratio after T28 of immersion in SBF, indicating the presence of hydroxyapatite on the surface of both reinforced efibers. Moreover, a reduction in the average diameter of the PLA-based efibers was observed, reaching a maximum reduction of 46 and 60% in the average diameter of neat PLA and PLA:OLA efibers, respectively, after 28 days of immersion in SBF. The antibacterial behavior of the MgO and Mg(OH)2 NPs in the PLA-based electrospun fibers was tested against Escherichia coli, E. coli, as the Gram-negative bacteria, and Staphylococcus aureus, S. aureus, as the Gram-positive bacteria, obtaining the best antibacterial activity against the Gram-negative bacteria E. coli of 21 ± 2% and 34 ± 6% for the highest concentration of MgO and Mg(OH)2 NPs, respectively.

Efficient extraction of textile dyes using reusable acrylic-based smart polymers.

Water pollution from industrial or household waste, containing dyes from the textile industry, poses a significant environmental challenge requiring immediate attention. In this study, we have developed a crosslinked-smart-polymer film based on 2-(dimethylamino)ethyl methacrylate copolymerized with other hydrophilic and hydrophobic commercial monomers, and its efficacy in removing 21 different textile dyes was assessed. The smart polymer effectively interacts with and adsorbs dyes, inducing a noticeable colour change. UV-Vis spectroscopy analysis confirmed a removal efficiency exceeding 90 % for anionic dyes, with external diffusion identified as the primary influencing factor on process kinetics, consistent with both pseudo-first-order kinetics and the Crank-Dual model. Isothermal studies revealed distinct adsorption behaviors, with indigo carmine adhering to a Freundlich isotherm while others conformed to the Langmuir model. Permeation and fluorescence analyses corroborated isotherm observations, verifying surface adsorption. Significantly, our proof-of-concept demonstrated the resilience of the smart-film to common fabric softeners and detergents without compromising adsorption capacity. Additionally, the material exhibited reusability (for at least 5 cycles), durability, and good thermal and mechanical properties, with T5 and T10 values of 265 °C and 342 °C, respectively, a Tg of 168 °C, and a water swelling percentage of 54.3 %, thus confirming its stability and suitability for industrial application. ENVIRONMENTAL IMPLICATION: Dyes released during laundry processes should be classified as "hazardous materials" owing to their significant toxicity towards aquatic organisms, with the potential to disrupt ecosystems and harm aquatic biodiversity. This paper discusses the development of a novel acrylic material in film form, engineered to extract toxic anionic dyes. This study directly contributes to mitigating the environmental impact associated with the fashion industry and the domestic use of textiles. It can be implemented on both an industrial and personal scale, thereby encouraging more sustainable practices and promoting collaborative citizen science efforts towards.

In vitro activity of cefiderocol in Pseudomonas aeruginosa isolates from people with cystic fibrosis recovered during three multicentre studies in Spain.

OBJECTIVES: Despite the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, Pseudomonas aeruginosa is still a major pathogen in people with cystic fibrosis (pwCF). We determine the activity of cefiderocol and comparators in a collection of 154 P. aeruginosa isolates recovered from pwCF during three multicentre studies performed in 17 Spanish hospitals in 2013, 2017 and 2021. METHODS: ISO broth microdilution was performed and MICs were interpreted with CLSI and EUCAST criteria. Mutation frequency and WGS were also performed. RESULTS: Overall, 21.4% were MDR, 20.8% XDR and 1.3% pandrug-resistant (PDR). Up to 17% of the isolates showed a hypermutator phenotype. Cefiderocol demonstrated excellent activity; only 13 isolates (8.4%) were cefiderocol resistant by EUCAST (none using CLSI). A high proportion of the isolates resistant to ceftolozane/tazobactam (71.4%), meropenem/vaborbactam (70.0%), imipenem/relebactam (68.0%) and ceftazidime/avibactam (55.6%) were susceptible to cefiderocol. Nine out of 13 cefiderocol-resistant isolates were hypermutators (P < 0.001). Eighty-three STs were detected, with ST98 being the most frequent. Only one isolate belonging to the ST175 high-risk clone carried blaVIM-2. Exclusive mutations affecting genes involved in membrane permeability, AmpC overexpression (L320P-AmpC) and efflux pump up-regulation were found in cefiderocol-resistant isolates (MIC = 4-8 mg/L). Cefiderocol resistance could also be associated with mutations in genes related to iron uptake (tonB-dependent receptors and pyochelin/pyoverdine biosynthesis). CONCLUSIONS: Our results position cefiderocol as a therapeutic option in pwCF infected with P. aeruginosa resistant to most recent ß-lactam/ß-lactamase inhibitor combinations.

Safe practices in Intensive Care Medicine, is zero risk possible?

Incidents related to patient safety are a problem of great impact in Intensive Care Medicine (ICM). Multiple strategies have been developed to identify them, analyze, and develop policies aim at reducing their incidence and minimizing their effects and consequences. The development of a safety culture, an adequate organizational and structural design of the ICM, which contemplates the implementation of effective safe practices, with a provision of human resources adjusted to the care activity carried out and the periodic analysis of the different events and their factors, will allow us to bring the risk of critical patient care closer to zero, as would be desirable.

Exploring albumin-sulfonephthalein dyes interactions by a chemometric-assisted and multi-technique equilibria analysis in solution.

Albumin is undoubtedly the most studied protein thanks to its widespread diffusion and biochemistry; despite its binding ability towards different dyes, provoking dye's colour change, has been exploited for decades for quantification purposes, the joint effect of working pH, ionic strength, and dye's pKa still remains only sporadically discussed. In the present study, the interaction of Bovine Serum Albumin (BSA) with five dyes belonging to the sulfonephthalein group, Bromophenol Blue (BPB, pKa = 3.75), Bromocresol Green (BCG, pKa = 4.42), Chlorophenol Red (CPR, pKa = 5.74), Bromocresol Purple (BCP, pKa = 6.05) and Bromothymol Blue (BTB, pKa = 6.72), is investigated at four working pH values (3.5, 6.0, 7.5 and 9.0) and two ionic strength conditions by UV-Vis spectroscopy. Principal Component Analysis is then applied to rationalize dye behavior upon BSA addition at each pH value and to summarize the protein effect on dyes' spectral features, identifying three general behaviors. The most relevant systems are then submitted to further characterization involving a solution equilibria study aimed at determining conditional binding constants for the selected DSA-dye adducts and fluorescence, CD, and 1H NMR spectroscopy to evaluate the binding effect on the species involved.

Prevalence and genetic diversity of azole-resistant Malassezia pachydermatis isolates from canine otitis and dermatitis: A 2-year study.

Despite previous reports on the emergence of Malassezia pachydermatis strains with decreased susceptibility to azoles, there is limited information on the actual prevalence and genetic diversity of azole-resistant isolates of this yeast species. We assessed the prevalence of azole resistance in M. pachydermatis isolates from cases of dog otitis or skin disease attended in a veterinary teaching hospital during a 2-year period and analyzed the ERG11 (encoding a lanosterol 14-α demethylase, the primary target of azoles) and whole genome sequence diversity of a group of isolates that displayed reduced azole susceptibility. Susceptibility testing of 89 M. pachydermatis isolates from 54 clinical episodes (1-6 isolates/episode) revealed low minimum inhibitory concentrations (MICs) to most azoles and other antifungals, but 11 isolates from six different episodes (i.e., 12.4% of isolates and 11.1% of episodes) had decreased susceptibility to multiple azoles (fluconazole, itraconazole, ketoconazole, posaconazole, ravuconazole, and/or voriconazole). ERG11 sequencing of these 11 azole-resistant isolates identified eight DNA sequence profiles, most of which contained amino acid substitutions also found in some azole-susceptible isolates. Analysis of whole genome sequencing (WGS) results revealed that the azole-resistant isolates from the same episode of otitis, or even different episodes affecting the same animal, were more genetically related to each other than to isolates from other dogs. In conclusion, our results confirmed the remarkable ERG11 sequence variability in M. pachydermatis isolates of animal origin observed in previous studies and demonstrated the value of WGS for disentangling the epidemiology of this yeast species.

We analyzed the prevalence and diversity of azole-resistant Malassezia pachydermatis isolates in a veterinary hospital. A low prevalence of multi-azole resistance (c.10% of isolates and cases) was found. Whole genome and ERG11 sequencing of resistant isolates revealed remarkable genetic diversity.

REFORMS: Consensus-based Recommendations for Machine-learning-based Science.

Machine learning (ML) methods are proliferating in scientific research. However, the adoption of these methods has been accompanied by failures of validity, reproducibility, and generalizability. These failures can hinder scientific progress, lead to false consensus around invalid claims, and undermine the credibility of ML-based science. ML methods are often applied and fail in similar ways across disciplines. Motivated by this observation, our goal is to provide clear recommendations for conducting and reporting ML-based science. Drawing from an extensive review of past literature, we present the REFORMS checklist (recommendations for machine-learning-based science). It consists of 32 questions and a paired set of guidelines. REFORMS was developed on the basis of a consensus of 19 researchers across computer science, data science, mathematics, social sciences, and biomedical sciences. REFORMS can serve as a resource for researchers when designing and implementing a study, for referees when reviewing papers, and for journals when enforcing standards for transparency and reproducibility.

Impact of different age ranges on the benefits and harms of the breast cancer screening programme by the EU-TOPIA tool.

BACKGROUND: The recommendation for the implementation of mammography screening in women aged 45-49 and 70-74 is conditional with moderate certainty of the evidence. The aim of this study is to simulate the long-term outcomes (2020-50) of using different age range scenarios in the breast cancer screening programme of the Valencia Region (Spain), considering different programme participation rates. METHODS: Three age range scenarios (S) were simulated with the EU-TOPIA tool, considering a biennial screening interval: S1, 45-69 years old (y); S2, 50-69 y and S3, 45-74 y. Simulations were performed for four participation rates: A = current participation (72.7%), B = +5%, C = +10% and D = +20%. Considered benefits: number (N°) of in situ and invasive breast cancers (BC) (screen vs. clinically detected), N° of BC deaths and % BC mortality reduction. Considered harms: N° of false positives (FP) and % overdiagnosis. RESULTS: The results showed that BC mortality decreased in all scenarios, being higher in S3A (32.2%) than S1A (30.6%) and S2A (27.9%). Harms decreased in S2A vs. S1A (N° FP: 236 vs. 423, overdiagnosis: 4.9% vs. 5.0%) but also benefits (BC mortality reduction: 27.9% vs. 30.6%, N° screen-detected invasive BC 15/28 vs. 18/25). In S3A vs. S1A, an increase in benefits was observed (BC mortality reduction: 32.2% vs. 30.6%), N° screen-detected in situ B: 5/2 vs. 4/3), but also in harms (N° FP: 460 vs. 423, overdiagnosis: 5.8% vs. 5.0%). Similar trends were observed with increased participation. CONCLUSIONS: As the age range increases, so does not only the reduction in BC mortality, but also the probability of FP and overdiagnosis.

Lp(a) Levels in Relatives of Patients with Acute Coronary Syndrome and Elevated Lp(a): HER(a) Study.

Background: Lipoprotein(a) [Lp(a)] is a proatherogenic particle associated with increased cardiovascular risk. It is mainly genetically determined; so, the aim of our study is to evaluate the levels of Lp(a) in the relatives of a prospective cohort of patients who have suffered from an acute coronary syndrome (ACS) with Lp(a) ≥ 50 mg/dL. Methods: We conducted a multicenter prospective study, in which consecutive patients who had suffered from an ACS and presented Lp(a) ≥ 50 mg/dL and their first-degree relatives were included. Results: We included 413 subjects, of which 56.4% were relatives of the patients. Family history of early ischemic heart disease was present in 57.5%, and only 20.6% were receiving statin treatment. The family cohort was younger (37.5 vs. 59.1 years; p < 0.001), and 4% had ischemic heart disease and fewer cardiovascular risk factors. Mean Lp(a) levels were 64.9 mg/dL, 59.4% had levels ≥ 50 mg/dL, and 16.1% had levels ≥ 100 mg/dL. When comparing the patients with respect to their relatives, the mean level of Lp(a) was lower but without significant differences regarding the levels of LDLc, ApoB, and non-HDL. However, relatives with Lp(a) ≥ 50 mg/dL, had values similar to the group of patients with ACS (96.8 vs. 103.8 mg/dL; p = 0.18). No differences were found in Lp(a) levels in relatives based on the other lipid parameters. Conclusions: Overall, 59.4% of the first-degree relatives of patients who suffered from an ACS with Lp(a) ≥ 50 mg/dL also had elevated levels. Relatives with elevated Lp(a) had similar levels as patients.

Increased Serum Levels of N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) in Mobilized Healthy Donors with G-CSF: A Cohort Study.

Limited data regarding elevation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in mobilized donors with G-CSF is available. We extended these findings by examining serum NT-proBNP in a cohort study including 35 healthy donors and 69 patients who received G-CSF for CD34+ mobilization as well as 54 patients who did not receive G-CSF but who underwent collection of CD3+ cells for chimeric antigen receptor (CAR) T-cell manufacturing. No donor in the three cohorts experienced significant cardiac adverse events. NT-proBNP levels were measured before and after G-CSF administration and after finishing apheresis procedure. NT-proBNP increase was observed in mobilized healthy donors after G-CSF administration, but was not observed in mobilized or non-mobilized patients. Only in the cohort of healthy donors, pairwise comparisons using Wilcoxon signed ranks test showed a significant increase between the mean serum NT-proBNP level after G-CSF administration and the mean serum NT-proBNP level measured before G-CSF administration (231.09 ± 156.15 pg/mL vs. 58.88 ± 26.84 pg/mL; P < .01). No correlation was observed between NT-proBNP increase and G-CSF dose (rs = 0.09; n = 32; P = .6) and no other variables contributing to predict serum NT-proBNP increase were detected. In conclusion, we observed a statistically, although not clinically, significant increase of NT-proBNP in healthy donors who received G-CSF as CD34+ cell mobilization.

Mounier-Kuhn syndrome in poorly controlled asthma.

INTRODUCTION: Mounier-Kuhn syndrome or tracheobronchomegaly, is a rare condition that consists of abnormal dilation of the trachea and main bronchi due to a pathological arrangement of smooth muscle fibers in this area. CASE REPORT: We present the case of a 46-year-old woman with poorly controlled asthma and recurrent infections, who was diagnosed with Mounier-Kuhn syndrome through a computed tomography scan revealing an unusual enlargement of the trachea with associated bronchiectasis. RESULTS: The diagnosis of Mounier-Kuhn syndrome is radiological, involving measurement of the trachea where a diameter >25 mm in men and >21 mm in women is observed. While diagnosis is sometimes incidental, there is an association with respiratory diseases such as asthma or COPD, hence clinical suspicion is important in patients with poorly controlled underlying conditions who present with recurrent infections, inadequate secretion management, or even hemoptysis. CONCLUSIONS: Despite its rarity, this syndrome significantly impacts patients' quality of life. Diagnosis and management involve comprehensive evaluations including computed tomography, with a multidisciplinary approach including pulmonologists and radiologists. Exploring its clinical features, associations with other respiratory diseases and treatment options is crucial in managing this rare respiratory condition.