Reassessing blood product irradiation in haploidentical transplantation: a single-center perspective.

OBJECTIVES: The main objective was to investigate the incidence of transfusion-associated graft-versus-host disease (TA-GVHD) in patients who underwent haploidentical hematopoietic cell transplants (HCT) and received non-irradiated leukoreduced blood components. The secondary objective was to describe our leukodepletion results in blood products obtained by the filters employed at our center. STUDY DESIGN AND METHODS: Clinical records from 2018 to 2023 were retrospectively analyzed, along with a prospective evaluation of residual leukocytes in blood components from June to November 2023 in order to confirm effectivity of our leukodepletion method. RESULTS: 150 patients were included, no cases of TA-GVHD were reported after using non-irradiated blood products. The incidence of grade 3-4 acute and moderate-severe chronic GVHD was 12.7% (n = 19) and 2.7% (n = 4), respectively. The cumulative incidence of death was 39.3% (n = 52) with a 3.7-year overall survival (CI 95%, 3.3- 4.1 years). Leukodepletion analysis showed a reduction of 99.93% in platelet concentrates and 99.98% in packed red blood cells. DISCUSSION: TA-GVHD in HCT remains a concern traditionally mitigated using blood product irradiation. Recent evidence obtained in favor of leukoreduction techniques question this need, especially in resource-limited settings. CONCLUSION: These findings support leukoreduction as a primary TA-GVHD preventive measure,along with the advantage in cost reduction.

[Validation of the JH-SEFAC Questionnaire on Knowledge on Insulin Management by Patients with Diabetes in Community Pharmacies]. / Validación del cuestionario JH-SEFAC de conocimiento sobre el manejo de insulinas por pacientes con diabetes en farmacia comunitaria.

Objective: To review and validate a questionnaire on knowledge of injectable insulin management (JH-SEFAC) by patients with diabetes for use in community pharmacies. Methods: Study design: cross-sectional observational in Spanish community pharmacies during the first half of 2023. Inclusion criteria: patients with diabetes, of legal age, on insulin treatment. Questionnaire design: a nominal group of community pharmacists reviewed and piloted the initial questionnaire to determine its feasibility. It was approved by the CEIC of Aragón (PI22/375). Content validation: by a multidisciplinary group of experts in diabetes, using an ad hoc evaluation questionnaire of 10 questions (Likert scale of 1-5). Reliability: by means of the internal consistency index (Cronbach's alpha) and the intraclass correlation coefficient (ICC). Reproducibility (test/retest): the results of the questionnaire administered twice 2-3 weeks apart to the group of patients were compared. Pharmacists members of the SEFAC Diabetes Working Group collaborated. Sample: calculated in 127 subjects (95% CI and precision of 10%). Results: 20 community pharmacies from 13 autonomous communities included 131 patients. The expert assessment was 4.52 out of 5 (90.4%). The Keiser-Meyer-Olkin test was 0.626 and Bartlett's test was significant (p<0.001). The Cronbach's alpha of the global questionnaire was 0.804 and the ICC was 0.902. The mean score of the questionnaire was 15.98 out of 31 points. Conclusions: The JH-SEFAC questionnaire was validated to evaluate the management of insulin injectables, providing community pharmacists with a valuable tool for therapeutic education.

Prediction of left ventricular thrombus after myocardial infarction: a cardiac magnetic resonance-based prospective registry.

BACKGROUND: Left ventricular thrombus (LVTh) is a severe complication after ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: We aim to predict LVTh occurrence by cardiac magnetic resonance (CMR) using clinical, echocardiographic, and electrocardiographic (ECG) variables readily available at admission. METHODS: We included 590 reperfused STEMI patients who underwent early (1-week) and/or late (6-month) CMR in our institution. Baseline clinical, echocardiographic (left ventricular ejection fraction -LVEF-) and ECG data (summatory of ST-segment elevation -sum-STE- and Q-wave and residual ST-elevation >1 mm -Q-STE-) during admission were registered. Multivariate binary logistic regression models and receiver operating characteristic curves were computed for LVTh prediction. RESULTS: LVTh was detected by CMR in 43 (7.3 %) patients and was predicted by previous chronic coronary syndrome (CCS, HR 4.74 [1.82-12.35], p = 0.001), anterior STEMI (HR 10.93 [2.47-48.31], p = 0.002), LVEF (HR 0.96 [0.93-0.99] per %, p = 0.008), maximum sum-STE (HR 1.04 [1.01-1.07] per mm, p = 0.04), and Q-STE (HR 1.31 [1.08-1.6] per lead, p = 0.008). High-risk patients with both major (anterior STEMI and Q-STE in ≥1 leads) and 1-3 minor (CCS, maximum sum-STE >10 mm, LVEF <50%) factors showed the highest LVTh risk (19.6 % within 6 months). The model showed excellent discrimination ability (area under the curve=0.85 [0.81-0.9], p < 0.001). Simplified 4-variable (excluding sum-STE) and 3-variable (also excluding CCS) risk scores showed similar discrimination ability and were externally validated. CONCLUSIONS: LVTh within 6 months post-STEMI can be predicted using pre-discharge clinical (anterior infarction and CCS), echocardiographic (LVEF), and ECG (sum-STE and Q-STE) data. Our results can help select patients who should undergo CMR after STEMI for LVTh detection.

Minimally Invasive Assessment of Peripheral Residual Disease During Maintenance or Observation in Transplant-Eligible Patients With Multiple Myeloma.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In multiple myeloma (MM), measurable residual disease (MRD) is assessed in bone marrow (BM). However, less invasive evaluation of peripheral residual disease (PRD) in blood could be advantageous and less cumbersome. We investigated the prognostic value of PRD monitoring after 24 cycles of maintenance in 138 transplant-eligible patients with MM enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. PRD was assessed using next-generation flow (NGF) and mass spectrometry (MS). Positive PRD by NGF in 16/138 (11.5%) patients was associated with a 13-fold increased risk of progression and/or death; median progression-free survival (PFS) and overall survival (OS) were 2.5 and 47 months, respectively. Considering patients' MRD status in BM as the reference, PRD detection using NGF showed positive and negative predictive values of 100% and 73%, respectively. Presence of PRD helped identifying patients at risk of imminent progression among those with positive MRD in BM. Patients with undetectable PRD according to both NGF and MS showed 2-year PFS and OS rates of 97% and 100%, respectively. In multivariate analyses including the Revised International Staging System and the complete remission status, only MRD in BM and PRD by NGF showed independent prognostic value for PFS. This study supports the use of less invasive PRD monitoring during maintenance or observation in transplant-eligible patients with MM.

A comparison of haploidentical versus HLA-identical sibling outpatient hematopoietic cell transplantation using reduced intensity conditioning in patients with acute leukemia.

Background: Hematopoietic cell transplantation (HCT) increases survival for acute leukemia. Outpatient allogeneic HCT reduces costs and increases transplant rates in developing countries. We report outcomes of outpatient HLA-identical and haploidentical HCT in acute leukemia. Methods: This single-center retrospective cohort study analyzed 121 adult patients with acute myeloblastic (AML) and acute lymphoblastic leukemia (ALL) receiving an outpatient allogeneic HCT with peripheral blood allografts after reduced-intensity conditioning (RIC) from 2012-2022. Results: There were 81 (67%) haploidentical and 40 (33%) HLA-identical transplants. Complete chimerism (CC) at day +100 was not different in HLA-identical compared to haploidentical HCT (32.5% and 38.2%, P=0.054). Post-HCT complications, including neutropenic fever (59.3% vs. 40%), acute graft-versus-host-disease (aGVHD) (46.9% vs. 25%), cytokine release syndrome (CRS) (18.5% vs. 2.5%), and hospitalization (71.6% vs 42.5%) were significantly more frequent in haploidentical HCT. Two-year overall survival (OS) was 60.6% vs. 46.9%, (P=0.464) for HLA-identical and haplo-HCT, respectively. There was no difference in the 2-year disease-free-survival (DFS) (33.3% vs. 35%, P=0.924) between transplant types. In multivariate analysis, positive measurable residual disease (MRD) at 30 days (HR 8.8, P=0.018) and 100 days (HR 28.5, P=0.022) was associated with lower OS, but not with non-relapse mortality (NRM) (P=0.252 and P=0.123, univariate). In univariate analysis, both 30-day and 100-day MRD were associated with lower DFS rates (P=0.026 and P=0.006), but only day 30 MRD was significant in multivariate analysis (P=0.050). In the case of relapse, only MRD at day 100 was associated with increased risk in the univariate and multivariate analyses (HR 4.48, P=0.003 and HR 4.67, P=0.008). Chronic graft-versus-host-disease (cGVHD) was protective for NRM (HR 0.38, P=0.015). There was no difference in cumulative incidence of relapse (CIR) between transplant types (P=0.126). Forty-four (36.4%) patients died, with no difference between HCT type (P=0.307). Septic shock was the most frequent cause of death with 17 cases, with no difference between transplant types. Conclusions: Outpatient peripheral blood allogenic HCT after RIC is a valid and effective alternative for adult patients suffering acute myeloblastic or lymphoblastic leukemia in low-income populations.

Single-use commercial bio-based plastics under environmental degradation conditions: Is their biodegradability and compostability a fact?

Evaluating compostability is increasingly essential for proving commercial bio-based cutlery or packaging since these materials must biodegrade under controlled conditions quickly. Utensils for eating represent Mexico's most popular consumer single-use materials, and Mexican regulations based on biodegradation or compostability are still vague and lack scientific evaluations. This study analyzed three bio-based polymeric materials (bags, dishes, and forks) from commercial brands following Mexican regulations and using various analytical techniques to verify their biodegradability and compostability. First, weight loss measurements, stress-strain tests, and topographic imaging were applied for preliminary observations at the macro scale up to 90 days of compostability. Besides, spectroscopy, microscopy, and thermal techniques indicate changes and behavior of the bio-based materials depending on the composition. The results suggest that bags exhibited the highest decomposition rate (80 %) compared to dishes and forks. Similarly, mechanical resistance indicates a reduction of 62 % for bags, 30 % for dishes, and almost none for forks. Texture image analysis revealed that the complexity and roughness of the materials increased over time, correlating with the physical changes observed. These results indicate minimal surface topography changes and higher stiffness for dishes and forks, indicating low biodegradability. SEM images supported these findings, showing surface degradation in bags and dishes but not in forks. FTIR and XRD analyses confirmed the presence of polyamide (bags) and polypropylene (dishes and forks). These results reduce biodegradation and differ from the claims made by manufacturers. The thermal analysis found similar results, indicating that the materials' thermal stability decreased after degradation, which is related to lower biodegradability and compostability. Overall, the study concluded only bags meet the criteria for compostability in national regulations. However, dishes and forks made of petroleum-derived polymers have higher resistance to natural and microbial degradation.

Evaluating Procedure-Linked Risk Determinants in Trichinella spp. Inspection under a Quality Management System in Southern Spain.

Trichinellosis is a major foodborne zoonotic disease responsible for 41 human cases, according to the European Union One Health Zoonoses Report. In southern Spain, a quality management system (QMS) was applied to satellite laboratories (SLs) that conduct meat inspections of Trichinella spp. ensuring excellence practices. This study aimed to determine how eventual deviations from standard procedures may influence risk levels using Canonical Discriminant Analysis (CDA). Data were collected during slaughterhouses and game handling establishments' official audits in 18 SLs located in the provinces of Cordoba and Seville during a 6-year period. Technical requirement deviations regarding technique and trial information, such as performing tests or calculations incorrectly or not following technical procedures, significantly increased risk level differences. Imminent risk levels were detected if the above-mentioned deviations arose. Quality assurance compromising deviations were responsible for 1150 times risk level differences, suggesting finding such may be critical for risk determination. A lack of significant influence of records and documents compromising deviations (incomplete forms or missing-erroneous or illegible data) was found. These results strengthen Trichinella spp. control strategies by pinpointing crucial aspects within QMS that require improvement, particularly in addressing deviations related to technique, trial information, and quality assurance procedures to mitigate associated risks effectively.

Randomized Controlled Trial to Assess the Feasibility of a Novel Clinical Decision Support System Based on the Automatic Generation of Alerts through Remote Patient Monitoring.

Background/Objectives: Early identification of complications in chronic and infectious diseases can reduce clinical deterioration, lead to early therapeutic interventions and lower morbidity and mortality rates. Here, we aimed to assess the feasibility of a novel clinical decision support system (CDSS) based on the automatic generation of alerts through remote patient monitoring and to identify the patient profile associated with the likelihood of severe medical alerts. Methods: A prospective, multicenter, open-label, randomized controlled trial was conducted. Patients with COVID-19 in home isolation were randomly assigned in a 1:1 ratio to receive either conventional primary care telephone follow-up plus access to a mobile app for self-reporting of symptoms (control group) or conventional primary care telephone follow-up plus access to the mobile app for self-reporting of symptoms and wearable devices for real-time telemonitoring of vital signs (case group). Results: A total of 342 patients were randomized, of whom 247 were included in the per-protocol analysis (103 cases and 144 controls). The case group received a more exhaustive follow-up, with a higher number of alerts (61,827 vs. 1825; p < 0.05) but without overloading healthcare professionals thanks to automatic alert management through artificial intelligence. Baseline factors independently associated with the likelihood of a severe alert were having asthma (OR: 1.74, 95% CI: 1.22-2.48, p = 0.002) and taking corticosteroids (OR: 2.28, 95% CI: 1.24-4.2, p = 0.008). Conclusions: The CDSS could be successfully implemented and enabled real-time telemonitoring of patients' clinical status, providing valuable information to physicians and public health agencies.

Entomo-virological surveillance of Flavivirus in mosquitoes in Yucatan State, Mexico.

The genus Flavivirus (Family: Flaviviridae) comprises arboviruses with the capacity to infect humans and animals. It also integrates insect-specific viruses. This study aimed to identify Flavivirus in mosquitoes captured in 17 municipalities in Yucatan State, Mexico. The mosquitoes were caught in households from November 2021 to May 2022. A total of 4,321 adult mosquitoes from five species were caught. The most abundant were Culex quinquefasciatus (n = 3,563) and Aedes aegypti (n = 734). For molecular investigations, 600 female mosquitoes were split into groups of 10, mostly for species and site location. Reverse transcriptase polymerase chain reaction (RT-PCR) amplified a region of the NS5 gene to find the Flavivirus ribonucleic acids (RNA). A total of 24 pools that were positive for Flavivirus were detected in Ae. aegypti specimens and subsequently subjected to sequencing using the Sanger method. A total of 12 sequences matched the established quality criteria and were subsequently employed for sequence homology analysis. We found that one sequence corresponded to the Zika virus (ZIKV), and 11 sequences had sequence similarity with Phlebotomus-associated flavivirus (PAFV), an insect-specific virus (ISF). In conclusion, we found ZIKV in the Merida municipality, Yucatan State, which suggests that the virus is silently circulating. Phlebotomus-associated flavivirus is distributed in five municipalities in Yucatan State, Mexico. Future studies could focus on isolating this virus and studying its biological role within Ae. aegypti.

The Relationship between Laissez-Faire Leadership and Cyberbullying at Work: The Role of Interpersonal Conflicts.

A person can experience cyberbullying at work when exposed to repetitive and intrusive negative acts facilitated by new information and communication technologies (ICTs). The incidence of workplace cyberbullying has rapidly increased following the COVID-19 pandemic. This issue does not arise in isolation; leadership plays a critical role. Leaders who fail to set clear rules and provide minimal supervision may exacerbate interpersonal conflicts among subordinates. This study explores the role of laissez-faire leadership and interpersonal conflicts on workplace cyberbullying from a gender perspective. A two-wave panel study was conducted (N = 1995; 53.6% women; M age = 42.02 years old; SD = 9.23; age range: 18-74 years old). Our findings indicate no direct relationship between laissez-faire leadership and workplace cyberbullying; however, there is a significant indirect relationship. Laissez-faire leadership is associated with a higher frequency of interpersonal conflicts, which in turn are related to cyberbullying, making interpersonal conflicts a mediator. Additionally, gender moderates the relationship between interpersonal conflicts and workplace cyberbullying. Our results suggest that interpersonal conflicts may increase exposure to cyberbullying, particularly for men under laissez-faire leadership. These findings have managerial implications for introducing tailored interventions to prevent workplace cyberbullying.

Neural Basis of Number Sense in Larval Zebrafish.

Number sense, the ability to discriminate the quantity of objects, is crucial for survival. To understand how neurons work together and develop to mediate number sense, we used two-photon fluorescence light sheet microscopy to capture the activity of individual neurons throughout the brain of larval Danio rerio, while displaying a visual number stimulus to the animal. We identified number-selective neurons as early as 3 days post-fertilization and found a proportional increase of neurons tuned to larger quantities after 3 days. We used machine learning to predict the stimulus from the neuronal activity and observed that the prediction accuracy improves with age. We further tested ethanol's effect on number sense and found a decrease in number-selective neurons in the forebrain, suggesting cognitive impairment. These findings are a significant step towards understanding neural circuits devoted to discrete magnitudes and our methodology to track single-neuron activity across the whole brain is broadly applicable to other fields in neuroscience.

Assessment of care provision integration in a community-based mental health system: balanced care model implementation in Andalusia (Spain).

BACKGROUND: Andalusia is the second largest region in Spain, and it has developed a comprehensive mental health (MH) plan that encourages the consolidation of the balanced care model. However, its geographical and socioeconomic disparity is a great challenge for a community-based MH system. Both the assessment of the implementation of the MH plan and the development of new tools to support decision-making can be considered critical. OBJECTIVES: The present study aims (i) to assess how the integration of different types of MH care may influence system performance and (ii) to check the performance evolution of the integration process geographically regarding the small MH areas of Andalusia. METHODS: The performance of the Andalusian MH system was assessed by combining Monte Carlo simulation, fuzzy inference and data envelopment analysis. The relative technical efficiency was the main performance indicator. RESULTS: A correct integration of appropriate types of MH care, according to population needs, increases the performance of the Andalusian MH system both from global and regional perspectives. The spatial representation (based on small MH areas) of the results highlights how the performance depends on specific geographical characteristics. By analyzing the identified spatial clusters, defined by different management patterns depending on user and socioeconomic characteristics, benchmark areas and areas for improvement can be studied to design evidence-informed policies and interventions. CONCLUSIONS: A global analysis of MH system performance was carried out, including both the successive integration of different types of care and its spatial evolution. Although an appropriate integration of different types of MH care has a positive effect on the Andalusian MH system, this process has different profiles depending on specific geographically based user and socioeconomic characteristics. The balanced care model can be considered the paradigm for assessing the performance of a large and populated territory such as Andalusia, which has a community-based MH system. This methodological approach (performance assessment and spatial analysis) may be used as a guide for developing future evidence-informed policies and managerial interventions.

Chemoinformatic Characterization of NAPROC-13: A Database for Natural Product 13C NMR Dereplication.

Natural products (NPs) are secondary metabolites of natural origin with broad applications across various human activities, particularly the discovery of bioactive compounds. Structural elucidation of new NPs entails significant cost and effort. On the other hand, the dereplication of known compounds is crucial for the early exclusion of irrelevant compounds in contemporary pharmaceutical research. NAPROC-13 stands out as a publicly accessible database, providing structural and 13C NMR spectroscopic information for over 25 000 compounds, rendering it a pivotal resource in natural product (NP) research, favoring open science. This study seeks to quantitatively analyze the chemical content, structural diversity, and chemical space coverage of NPs within NAPROC-13, compared to FDA-approved drugs and a very diverse subset of NPs, UNPD-A. Findings indicated that NPs in NAPROC-13 exhibit properties comparable to those in UNPD-A, albeit showcasing a notably diverse array of structural content, scaffolds, ring systems of pharmaceutical interest, and molecular fragments. NAPROC-13 covers a specific region of the chemical multiverse (a generalization of the chemical space from different chemical representations) regarding physicochemical properties and a region as broad as UNPD-A in terms of the structural features represented by fingerprints.

Haplotype-Aware Detection of SERPINA1 Variants by Nanopore Sequencing.

α-1 Antitrypsin (AAT) is an acute-phase reactant with immunomodulatory properties that mainly inhibits neutrophil elastase. Low serum levels cause AAT deficiency (AATD), an underdiagnosed condition that predisposes to pulmonary and hepatic diseases. The SERPINA1 gene, which encodes AAT, contains >500 variants. PI∗Z and PI∗S alleles are the most diagnosed causes of AATD, but the role of the SERPINA1 haplotypes in AAT function remains unknown. SERPINA1 gene was PCR amplified from 94 patients with asthma, using primers with tails for indexing. Sequencing libraries were loaded into a MinION-Mk1C, and MinKNOW was used for basecalling and demultiplexing. Nanofilt and Minimap2 were used for filtering and mapping/alignment. Variant calling/phasing were performed with PEPPER-Margin-DeepVariant. SERPINA1 gene was 100% covered for all samples, with a minimum sequencing depth of 500×. A total of 75 single-nucleotide variants (SNVs) and 4 insertions/deletions were detected, with 45 and 2 of them highly polymorphic (minor allele frequency >0.1), respectively. Nine of the SNVs showed differences in allele frequencies when compared with the overall Spanish population. More than 90% of heterozygous SNVs were phased, yielding 91 and 58 different haplotypes for each SERPINA1 amplified region. Haplotype-based linkage disequilibrium analysis suggests that a recombination hotspot could generate variation in the SERPINA1 gene. The proposed workflow enables haplotype-aware genotyping of the SERPINA1 gene by nanopore sequencing, which will allow the development of novel AATD diagnostic strategies.

Symptoms of Attention Deficit Hyperactivity Disorder and Oral Health Problems among Children in Spain.

INTRODUCTION: The aim of this study was to explore the association between symptoms of attention deficit hyperactivity disorder (ADHD) and oral health in a representative sample of the Spanish population aged 6-14 years. We also examined the contribution of several sociodemographic and behavioral determinants of children/adolescents and their family environment. METHODS: A cross-sectional study involving 3,402 subjects aged between 6 and 14 years from the Spanish National Health Survey. The presence of ADHD symptoms was determined using the self-reported hyperactivity/inattention subscale of the Strength and Difficulties Questionnaire. Oral health was assessed using five indicators: caries, extraction, restorations, gingival bleeding, and the presence of teeth in poor condition (e.g., broken or misaligned). Logistic regressions were used to examine the association between the presence of ADHD symptoms and oral health indicators. These models were adjusted for sociodemographic factors, lifestyle variables, and oral hygiene behaviors relating to both the children and their parents. RESULTS: Compared to children without ADHD symptoms, children with ADHD symptoms had a higher risk of caries (fully adjusted odds ratio: 2.16; 95% confidence interval: 1.66-2.82), extraction (1.42; 1.09-1.85), restoration (1.47; 1.19-1.82) and gingival bleeding (1.64; 1.11-2.41). The increased risk of caries was maintained when the analyses were restricted to middle/high social class families and children with low sugar intake, good oral hygiene behaviors and regular dental visits. CONCLUSIONS: Children with ADHD symptoms in Spain had worse oral health indicators than those without ADHD symptoms. Our results suggest that the association of ADHD symptoms with caries was independent of socioeconomic level, cariogenic diet, frequency of toothbrushing, and dental visits.

Spanish cardiac catheterization and coronary intervention registry. 33rd official report of the Interventional Cardiology Association of the Spanish Society of Cardiology (1990-2023).

INTRODUCTION AND OBJECTIVES: This article presents the 2023 activity report of the Interventional Cardiology Association of the Spanish Society of Cardiology (ACI-SEC). METHODS: All interventional cardiology laboratories in Spain were invited to participate in an online survey. Data analysis was carried out by an external company and subsequently reviewed and presented by the members of the ACI-SEC board. RESULTS: A total of 119 hospitals participated. The number of diagnostic studies decreased by 1.8%, while the number of percutaneous coronary interventions (PCI) showed a slight increase. There was a reduction in the number of stents used and an increase in the use of drug-coated balloons. The use of intracoronary diagnostic techniques remained stable. For the first time, data on PCI guided by intracoronary imaging was reported, showing a 10% usage rate in Spain. Techniques for plaque modification continued to grow. Primary PCI increased, becoming the predominant treatment for myocardial infarction (97%). Noncoronary structural procedures continued their upward trend. Notably, the number of left atrial appendage closures, patent foramen ovale closures, and tricuspid valve interventions grew in 2023. There was also a significant increase in interventions for acute pulmonary embolism. CONCLUSIONS: The 2023 Spanish cardiac catheterization and coronary intervention registry indicates a stabilization in coronary interventions, together with an increase in complexity. There was consistent growth in procedures for both valvular and nonvalvular structural heart diseases.

Lactate/Pyruvate Ratio as an Early Predictor of Mortality in Patients with Sepsis: A Cohort Study.

Background: The lactate/pyruvate (LP) ratio has been studied as an alternative to serum lactate to determine clinical prognosis. Despite its clinical utility, there is a paucity of evidence evaluating the role of the L/P ratio in patients with sepsis. Methods: We assessed the clinical utility of the L/P ratio in patients with sepsis. The L/P ratio was measured at baseline, 4 and 8 h after admission. Our primary outcome was to determine the prognostic utility of the L/P ratio on the 15-day mortality risk. Our secondary outcomes were to compare the L/P ratio across time and its prognostic utility against standard risk calculators such as APACHE-II and SOFA scores. Results: We had a total of 80 patients, with 18 (22.5%) survivors and 62 (77.5%) non-survivors. While we found that patients having higher L/P ratios at 8 h had an increased 30-mortality risk (OR 1.08, 95% CI 1.02-1.18), the model's performance showed no difference when compared to other measurements of the L/P ratio that showed no association with mortality (p-value: 0.45). For our secondary outcome, we found that the APACHE-II and SOFA scores have better performance and predictability than the L/P ratio (AUC 0.83 and AUC 0.80, respectively), but showed no association with mortality (OR 1.07, 95% CI 1.01-1.17 and OR 1.08, 95% CI 1.02-1.18). Conclusions: Based on our findings, the L/P ratio appears to function more effectively as an early predictor of mortality when used as an adjuvant biomarker with other clinical parameters.

Connecting high-resolution 3D chromatin maps with cell division and cell differentiation at the root apical meristem.

KEY MESSAGE: We used marker-free technologies to study chromatin at cellular resolution. Our results show asymmetric chromatin distribution, explore chromatin dynamics during mitosis, and reveal structural differences between trichoblast and atrichoblast cell. The shapes, sizes, and structural organizations of plant nuclei vary considerably among cell types, tissues, and species. This diversity is dependent on various factors, including cellular function, developmental stage, and environmental or physiological conditions. The differences in nuclear structure reflect the state of chromatin, which, in turn, controls gene expression and regulates cell fate. To examine the interrelationship between nuclear structure, cell morphology, and tissue-specific cell proliferation and differentiation processes, we conducted multiple visualizations of H3K4me1, H3K9me2, 4',6-diamidino-2-phenylindole, 5-ethynyl 2'-deoxyuridine, and SCRI Renaissance 2200, followed by subsequent quantitative analysis of individual cells and nuclei. By assigning cylindrical coordinates to the nuclei in the iRoCS toolbox, we were able to construct in situ digital three-dimensional chromatin maps for all the tissue layers of individual roots. A detailed analysis of the nuclei features of H3K4me1 and H3K9me2 in the mitotic and the elongation zones in trichoblast and atrichoblast cells at the root apical meristem revealed cell type-specific chromatin dynamics with asymmetric distribution of euchromatin and heterochromatin marks that may be associated with cell cycle and cell differentiation characteristics of specific cells. Furthermore, the spatial distribution of nuclei stained with 5-ethynyl 2'-deoxyuridine in the epidermis and cortex tissues suggests short-range coordination of cell division and nuclear migration in a linear sequence through an unknown regulatory mechanism.