Recommendations for Cardiac Point-of-Care Ultrasound Nomenclature.

Point-of-care ultrasound (POCUS) involves the acquisition, interpretation, and immediate clinical integration of ultrasonographic imaging performed by a treating clinician. The current state of cardiac POCUS terminology is heterogeneous and ambiguous, in part because it evolved through siloed specialty practices. In particular, the medical literature and colloquial medical conversation contain a wide variety of terms that equate to cardiac POCUS. While diverse terminology aided in the development and dissemination of cardiac POCUS throughout multiple specialties, it also contributes to confusion and raises patient safety concerns. This statement is the product of a diverse and inclusive Writing Group from multiple specialties, including medical linguistics, that employed an iterative process to contextualize and standardize a nomenclature for cardiac POCUS. We sought to establish a deliberate vocabulary that is sufficiently unrelated to any specialty, ultrasound equipment, or clinical setting to enhance consistency throughout the academic literature and patient care settings. This statement (1) reviews the evolution of cardiac POCUS-related terms; (2) outlines specific recommendations, distinguishing between intrinsic and practical differences in terminology; (3) addresses the implications of these recommendations for current practice; and (4) discusses the implications for novel technologies and future research.

Latent Class Analysis Reveals, in patient profiles, COVID-19-related better prognosis by calcifediol treatment than glucocorticoids.

Calcifediol and glucocorticoids have been repositioned for the treatment of COVID-19 and may reduce severity, the need for intensive care unit admission and death. OBJECTIVE: to identify class or profiles of patients hospitalized and treated with COVID-19 pneumonia using latent class clustering methods to assess the clinical and prognostic relevance of the resulting patients' profiles. Poor prognosis was defined as death or need for ICU admission, good prognosis, the opposite. With special interest in differential responses to calcifediol. SETTING: Reina Sofia University Hospital, Córdoba Spain. Patients Retrospective observational cohort study of patients admitted for COVID-19. CLINICALTRIALS: gov public database (NCT05819918). INCLUSION CRITERIA: (i) Age ≥ 18 and ≤ 90 years, (ii) Pneumonia characterized by the presence of infiltrates on chest X-ray or CT scan, (iii) SARS-CoV-2 infection, confirmed, and (iv) CURB Scale 65 >1. DESIGN: Latent class analysis, for obtaining homogeneous clusters, without specifying a priori the belonging group, and selecting the optimal number of clusters by minimizing information criteria. Evaluating the differences between groups for each variable by means of chi-square, Fisher's exact test and Kruskal-Wallis test. RESULTS: 707 patients hospitalized from 10 March 2020 until 4 March 2022 were included. For the treatment variable, differences were found between class 3 (60% treated with calcifediol only) and classes 1 (less than 1% calcifediol only vs. 82% treated with both), 2 (less than 1% calcifediol only vs. 82% treated with both) and 4 (1% calcifediol only vs. 84% treated with both). Class 3, (60% with calcifediol), had a significantly better prognosis compared to patients treated with glucocorticoids alone (OR: 15.2, 95% CI: [3.73 - 142], p<0.001) or no treatment (OR: 7.38, 95% CI: [2.63 - 30.2], p<0.001). CONCLUSIONS: our real-life study shows that calcifediol treatment significantly reduces the need for ICU admission and improved prognosis in patients hospitalized for COVID-19 pneumonia, especially in the profile of patients receiving it without glucocorticoids.

Ethion food poisoning outbreak in Pereira, Colombia, 2022.

INTRODUCTION: Ethion is an organophosphate used as an acaricide and insecticide, that is restricted worldwide. In Colombia, pesticide poisoning is the third most common cause of chemical intoxication. On 9 October 2022, an outbreak of ethion poisoning occurred in Pereira. The aim of this study was to describe the clinical and epidemiological characteristics of the outbreak. METHODS: This is a descriptive study of an outbreak of organophosphate poisoning. The onset of symptoms occurred on 9 October 2022, following the consumption of empanadas. Information was collected on sociodemographic characteristics and clinical manifestations, as well as from paraclinical examinations. Data were obtained from clinical histories, field epidemiological investigations, and inspection visits. Food samples were collected for analysis by gas chromatography-mass spectrometry. Attack rates, proportions, and measures of central tendency, dispersion, and position were calculated. RESULTS: The case definition was met by 37 individuals with a median age of 30 years; all presented with muscarinic symptoms, 29 patients presented with nicotinic symptoms, and 20 patients presented with neurological symptoms. Males were the most affected (57%), and the most common time of symptom onset was 10:00 am. Twenty-three patients (62%) required intensive care unit admission, of whom 14 (38%) required mechanical ventilation. No deaths were reported. Erythrocyte acetylcholinesterase activity was reduced in all patients. Ethion was detected in mass-prepared maize and empanadas at concentrations greater than 0.1 mg/kg. The consumption of empanadas was identified as the common source. DISCUSSION: In Colombia, pesticide poisonings are the third most common type of poisoning caused by chemical substances reported to the National Health Institute through the National Public Health Surveillance System. In the present outbreak, ethion was in empanadas, likely due to contamination of cooking oil. CONCLUSIONS: We describe a large ethion-contaminated food poisoning outbreak reported in Colombia. The main symptoms were muscarinic, and the main treatment measures employed were atropine and respiratory support. Increased awareness of pesticide poisoning and training for food handlers are needed.

Dopaminergic neurons lacking Caspase-3 avoid apoptosis but undergo necrosis after MPTP treatment inducing a Galectin-3-dependent selective microglial phagocytic response.

Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc). Apoptosis is thought to play a critical role in the progression of PD, and thus understanding the effects of antiapoptotic strategies is crucial for developing potential therapies. In this study, we developed a unique genetic model to selectively delete Casp3, the gene encoding the apoptotic protein caspase-3, in dopaminergic neurons (TH-C3KO) and investigated its effects in response to a subacute regime of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, which is known to trigger apoptotic loss of SNpc dopaminergic neurons. We found that Casp3 deletion did not protect the dopaminergic system in the long term. Instead, we observed a switch in the cell death pathway from apoptosis in wild-type mice to necrosis in TH-C3KO mice. Notably, we did not find any evidence of necroptosis in our model or in in vitro experiments using primary dopaminergic cultures exposed to 1-methyl-4-phenylpyridinium in the presence of pan-caspase/caspase-8 inhibitors. Furthermore, we detected an exacerbated microglial response in the ventral mesencephalon of TH-C3KO mice in response to MPTP, which mimicked the microglia neurodegenerative phenotype (MGnD). Under these conditions, it was evident the presence of numerous microglial phagocytic cups wrapping around apparently viable dopaminergic cell bodies that were inherently associated with galectin-3 expression. We provide evidence that microglia exhibit phagocytic activity towards both dead and stressed viable dopaminergic neurons through a galectin-3-dependent mechanism. Overall, our findings suggest that inhibiting apoptosis is not a beneficial strategy for treating PD. Instead, targeting galectin-3 and modulating microglial response may be more promising approaches for slowing PD progression.

Selection maintains a nonadaptive floral polyphenism.

Adaptive phenotypic plasticity evolves in response to the contrasting selection pressures that arise when organisms face environmental heterogeneity. Despite its importance for understanding how organisms successfully cope with environmental change, adaptive plasticity is often assumed but rarely demonstrated. We study here the adaptive nature of the extreme seasonal within-individual floral polyphenism exhibited by the crucifer Moricandia arvensis, a Mediterranean species that produces two different types of flowers depending on the season of the year. During spring, this species has large, cross-shaped, lilac flowers, while during summer, it develops small, rounded, white flowers. Although floral polyphenism was associated with increased plant fitness, selection moved floral traits away from their local optimum values during the harsh summer. This result strongly suggests that floral polyphenism is not adaptive in M. arvensis. The main factor selecting against floral polyphenism was pollinators, as they select for the same floral morph in all environments. Despite not being adaptive, floral polyphenism occurs throughout the entire distribution range of M. arvensis and has probably been present since the origin of the species. To solve this paradox, we explored the factors causing floral polyphenism, finding that floral polyphenism was triggered by summer flowering. Summer flowering was beneficial because it led to extra seed production and was favored by adaptive plasticity in leaf functional traits. Taken together, our study reveals a complex scenario in which nonadaptive floral polyphenism has been indirectly maintained over M. arvensis evolutionary history by selection operating to favor summer flowering. Our study provides thus strong evidence that nonadaptive plasticity may evolve as a byproduct of colonizing stressful environments.

No Black Holes from Light.

We show that it is not possible to concentrate enough light to precipitate the formation of an event horizon. We argue that the dissipative quantum effects coming from the self-interaction of light (such as vacuum polarization) are enough to prevent any meaningful buildup of energy that could create a black hole in any realistic scenario.

Potentially inappropriate medication on communitydwelling older adults: Longitudinal analysis using the International Mobility in Aging Study. / Medicación potencialmente inapropiada en adultos mayores de la comunidad: análisis longitudinal del estudio IMIAS

Introduction: Medications are a fundamental part of the treatment of multiple pathologies. However, despite their benefits, some are considered potentially inappropriate medications for older people given their safety profile. Epidemiological data differences related to potentially inappropriate medications make it difficult to determine their effects on elderly people. Objective: To estimate the prevalence and types of potentially inappropriate medications using the 2019 Beers Criteria® in a cohort of adults older than 65 years. Materials and methods: We performed an observational, multicenter, retrospective, longitudinal study of a four-year follow-up of potentially inappropriate medications in community-dwelling older adults. Results: We followed 820 participants from five cities for four years (2012-2016) and evaluated them in three different moments (m1 = 2012, m2 = 2014, and m3 = 2016). The average age was 69.07 years, and 50.9% were women. The potentially inappropriate medication prevalence in the participants was 40.24%. The potentially inappropriate medications' mean among the studied subjects in the first moment was 1.65 (SD = 0.963), in the second was 1.73 (SD = 1.032), and in the third was 1.62 (SD = 0.915). There were no statistical differences between measurements (Friedman test, value = 0.204). The most frequent potentially inappropriate medications categories were gastrointestinal (39.4%), analgesics (18.8%), delirium-related drugs (15.4%), benzodiazepines (15.2%), and cardiovascular (14.2%). Conclusions: About half of the population of the community-dwelling older adults had prescriptions of potentially inappropriate medications in a sustained manner and without significant variability over time. Mainly potentially inappropriate medications were gastrointestinal and cardiovascular drugs, analgesics, delirium-related drugs, and benzodiazepines.

Introducción. Los fármacos son parte fundamental del tratamiento de múltiples enfermedades. Sin embargo, a pesar de sus beneficios, algunos se consideran medicamentos potencialmente inapropiados en adultos mayores, dado su perfil de seguridad. Las diferencias en los datos epidemiológicos relacionados con los medicamentos potencialmente inapropiados dificultan el establecimiento de sus efectos en adultos mayores. Objetivo. Estimar la prevalencia longitudinal y los tipos de medicamentos potencialmente inapropiados, utilizando los criterios Beers® del 2019 en una cohorte de adultos mayores de 65 años. Materiales y métodos. Se realizó un estudio observacional, multicéntrico, retrospectivo y longitudinal, de cuatro años de seguimiento de los medicamentos potencialmente inapropiados en adultos mayores de la comunidad. Resultados. Se evaluaron 820 participantes de cinco ciudades durante cuatro años (2012 a 2016) en tres momentos (m1: 2012, m2: 2014 y m3; 2016). La edad promedio fue de 69,07 años y el 50,9 % eran mujeres. La prevalencia de medicamentos potencialmente inapropiados en los participantes fue del 40,24 %. El promedio de estos medicamentos entre los sujetos estudiados en el primer momento fue de 1,65 (DE = 0,963), en el segundo fue de 1,73 (DE = 1,032) y en el tercero fue de 1,62 (DE = 0,915). No hubo diferencias estadísticas entre las mediciones (prueba de Friedman, p = 0,204). Las categorías de los medicamentos potencialmente inapropiados más frecuentes fueron: gastrointestinales (39,4 %), analgésicos (18,8 %), relacionados con delirium (15,4 %), benzodiacepinas (15,2 %) y cardiovasculares (14,2 %). Conclusiones. En cerca de la mitad de la población de adultos mayores de la comunidad, se prescribieron medicamentos potencialmente inapropiados de manera sostenida y sin variabilidad importante en el tiempo. Los más recetados fueron aquellos para tratar malestares gastrointestinales y cardiovasculares, analgésicos, para el delirium y benzodiacepinas.

Endoscopic Characterization of Giant Choledocholithiasis and Its Correlation With Primary Choledocholithiasis.

INTRODUCTION: Gallstone disease is extremely prevalent in Western society, and the prevalence of common bile duct (CBD) stones with concomitant cholelithiasis increases significantly in the elderly. Different variants influence the treatment of this pathological entity, such as the origin of the stones, their location and quantity, comorbidities of the patient, impaction, and size of the lithos, the latter being an independent predictive factor. In most situations, choledocholithiasis can be resolved with endoscopic retrograde cholangiopancreatography (ERCP); however, in complex cases, such as giant choledocholithiasis (GC), advanced surgical, endoscopic, and percutaneous techniques are required to remove gallstones. The main objective was to determine if there is a correlation between GC and primary choledocholithiasis (PC). The secondary objective consisted of describing the endoscopic characterization of GC. METHODS:  The present study is a cross-sectional and single-center study. The study population consisted of patients of the Institute for Social Security and Services for State Workers (ISSSTE by its acronym in Spanish) Regional Hospital, León, Guanajuato, belonging directly to this center or referred, who required medical attention by the General Surgery/Endoscopy Service with the diagnosis of choledocholithiasis, during the period between January 2017 and December 2022. The Kolmogorov-Smirnov test was used as the normality test. Quantitative variables were reported as mean and standard deviation if the data distribution was normal, in contrast with the expression of data in the median and interquartile range if an abnormal distribution was found. Moreover, the qualitative variables are reported in frequencies or percentages. The Chi-square test was performed as the independence test. The significance level was a 95% confidence interval (p-value 0.05). The effect size was calculated with the odds ratio (OR). RESULTS:  Out of a total of 177 patients, 33 corresponded to PC (18.6%), and 144 belonged to the secondary choledocholithiasis (SC) group (81.4%). Likewise, regarding the dimensions of the lithos, 59 patients (33.3%) presented GC and 118 (66.7%) presented non-GC. Among the 59 patients with GC, 36 were female (61%) and 23 were male (39%). Regarding age, the distribution was as follows: mean 62 ± 12 years, with a minimum value of 29 and a maximum of 88 years. The non-parametric test used to determine the existence or not of a correlation between the variables was Pearson's Chi-square, whose value was 60.509, with a p < 0.001, demonstrating the presence of a correlation between PC and GC. The effect size was corroborated and defined with the OR, whose value was 39.6 (confidence interval (CI) 11.308-139.069). CONCLUSIONS:  There is a significant correlation between GC and PC, and it was found that mechanical lithotripsy was the most performed initial extraction method for GC; furthermore, a higher rate of complete endoscopic resolution was found, as well as no complications related to the procedure, which contrasts with the literature. It would be interesting to use the information revealed in the present study as a landmark in future research in this regard.

Electrophotocatalytic Hydroxymethylation of Azaarenes with Methanol.

The merging of electrochemistry and photocatalysis allowed the required selectivity for the hydroxymethylation of functionalized azaarenes with methanol, including bioactive substrates. The two electrophotocatalytic protocols developed in this work address this transformation, using nontoxic and readily available reagents under mild reaction conditions with electricity as the only "sacrificial oxidant".

Tracing macroplastics redistribution and fragmentation by tillage translocation.

Soil is polluted with plastic waste from macro to submicron level. Our understanding of macroplastics (> 5 mm) occurrence and behavior has remained comparatively elusive, mainly due to a lack of a tracing mechanism. This study set up a methodology to trace macroplastic displacement, which combined magnetic iron oxide-tagged soil and macroplastic pieces tagged by an adhesive passive radiofrequency identification transponder. By utilizing these techniques, a field study was carried out to analyze the effect of tillage implement and plastic sizes on plastic displacement, to understand the fate of macroplastics in arable land. Results indicated that the displacement of macroplastics did not depend upon plastic sizes but did depend upon the tillage implement used. The mean macroplastics displacement per tillage pass was 0.36 ± 0.25 m with non-inversion chisel tillage and 0.15 ± 0.13 m with inversion disk tillage, which was similar to bulk soil displacement. However, only inversion disk tillage caused fragmentation (41 %) of macroplastics and generated microplastics (< 5 mm). In contrast, both tillage implements drove to similar burial of surface macroplastics into the tilled layer (74 % on average). These results highlight that tillage is a major process for macroplastics fate in arable soils, being one of the first studies to investigate it.

Plant-based proteins: clinical and technological importance.

Healthy and sustainable diets have seen a surge in popularity in recent years, driven by a desire to consume foods that not only help health but also have a favorable influence on the environment, such as plant-based proteins. This has created controversy because plant-based proteins may not always contain all the amino acids required by the organism. However, protein extraction methods have been developed due to technological advancements to boost their nutritional worth. Furthermore, certain chemicals, such as bioactive peptides, have been identified and linked to favorable health effects. As a result, the current analysis focuses on the primary plant-based protein sources, their chemical composition, and the molecular mechanism activated by the amino acid types of present. It also discusses plant protein extraction techniques, bioactive substances derived from these sources, product development using plant protein, and the therapeutic benefits of these plant-based proteins in clinical research.

Thermoelectric Property Enhancement of Tellurium Nanowires by Surface Passivation.

The pursuit of high-performance thermoelectric materials is of paramount importance in addressing energy sustainability and environmental concerns. Here, we explore the multifaceted impact of sulfur passivation in the matrix of tellurium nanowires (TeNWs), encompassing environmental control, thermoelectric properties, and charge carrier mobility. In this study, we present the facile production of TeNWs using an aqueous solution synthesis approach. The synthesized TeNWs were subsequently subjected to surface modification involving sulfur moieties. Our findings demonstrate that sulfur passivation not only effectively safeguards the nanowires from environmental degradation but also significantly augments their thermoelectric properties. Notably, the highest recorded values were achieved at 560 K for passivated tellurium nanowires, exhibiting a Seebeck coefficient of 246 µV/K, an electrical conductivity of 14.2 S/cm, and power factors of 86.7 µW/m-K2. This strategy presents a promising avenue for the development of advanced thermoelectric materials for applications in energy harvesting, waste heat recovery, and sustainable energy conversion technologies.

cGAS Expression is Enhanced in Systemic Sclerosis Associated Interstitial Lung Disease and Stimulates Inflammatory Myofibroblast Activation.

Objective: The lungs of patients with Systemic Sclerosis Associated Interstitial Lung Disease (SSc-ILD) contain inflammatory myofibroblasts arising in association with fibrotic stimuli and perturbed innate immunity. The innate immune DNA binding receptor Cyclic GMP-AMP synthase (cGAS) is implicated in inflammation and fibrosis, but its involvement in SSc-ILD remains unknown. We examined cGAS expression, activity, and therapeutic potential in SSc-ILD using cultured fibroblasts, precision cut lung slices (PCLS), and a well-accepted animal model. Methods: Expression and localization of cGAS, cytokines, and type 1 interferons were evaluated in SSc-ILD lung tissues, bronchoalveolar lavage (BAL), and isolated lung fibroblasts. CGAS activation was assessed in a publicly available SSc-ILD single cell RNA sequencing dataset. Production of cytokines, type 1 interferons, and αSMA elicited by TGFß1 or local substrate stiffness were measured in normal human lung fibroblasts (NHLFs) via qRT-PCR, ELISA, and immunofluorescence. Small molecule cGAS inhibition was tested in cultured fibroblasts, human PCLS, and the bleomycin pulmonary fibrosis model. Results: SSc-ILD lung tissue and BAL are enriched for cGAS, cytokines, and type 1 interferons. The cGAS pathway shows constitutive activation in SSc-ILD fibroblasts and is inducible in NHLFs by TGFß1 or mechanical stimuli. In these settings, and in human PCLS, cGAS expression is paralleled by the production of cytokines, type 1 interferons, and αSMA that are mitigated by a small molecule cGAS inhibitor. These findings are recapitulated in the bleomycin mouse model. Conclusion: cGAS signaling contributes to pathogenic inflammatory myofibroblast phenotypes in SSc-ILD. Inhibiting cGAS or its downstream effectors represents a novel therapeutic approach.

Continuous Rhythm Monitoring With Implanted Loop Recorders in Children and Adolescents With Brugada Syndrome.

BACKGROUND: Young (<18 years of age) patients with Brugada syndrome (BrS) are often under-represented in BrS studies and their management, especially related to syncopal episodes, remains unclear. OBJECTIVES: This study sought to describe the arrhythmia prevalence among young patients with BrS undergoing continuous rhythm monitoring by implantable loop recorder (ILR) and to assess the etiology behind syncope of undetermined origin. METHODS: A total of 147 patients with BrS with ILR were enrolled in 12 international centers and divided into pediatric (age <12 years; n = 77, 52%) and adolescents (age 13-18 years; n = 70, 48%). RESULTS: Mean age was 11.3 years, 53 patients (36.1%) were female, and 31 (21.1%) had spontaneous type 1 electrocardiograms. Over a median follow-up of 3.6 years (Q1-Q3: 1.6-4.8 years), an arrhythmic event was recorded in 33 patients (22.4%), mainly of nonventricular origin: 15 atrial (10.2%) and 16 bradyarrhythmic events (10.9%). Ventricular arrhythmias occurred in 4 patients, all with spontaneous BrS, and were fever-related in one-half. Among all patients with recurrence of syncope during follow-up, true arrhythmic syncope was documented in 5 (17.8%), and it was due to bradyarrhythmias or atrial arrhythmias in 3 cases (60%). CONCLUSIONS: Continuous rhythm monitoring with ILRs in young patients with BrS detects a broad range of arrhythmias. Ventricular arrhythmias occur predominantly in patients with spontaneous type 1 electrocardiograms and during fever. Despite the young age, bradyarrhythmias and atrial arrhythmias are frequent and represent the cause of arrhythmic syncope in 60% of patients. Young patients with BrS with syncope of undetermined origin may benefit from ILR implant.

[Repeatability of spirometrys expiratory flows]. / Repetitividad de los flujos espiratorios de la espirometría.

Background: The quality of the spirometry is estimated with criteria of acceptability and repeatability. The repeatability criteria accepted by consensus is < 0.150 L. Objective: To know the repeatability in quality A spirometry. Material and methods: Analytical cross-sectional design. The demographic variables and the 3 best spirometry curves with normal, suggestive of restriction and bronchial obstruction profiles were obtained from consecutive subjects of both genders from 18 to 80 years of age. The repeatability was analyzed with the mean difference (bias) and the intraclass correlation coefficient. Results: 630 curves from 210 subjects were accepted. Group age 60 ± 15 years. Female predominance 113 (53.8%), occupation: domestic services 61 (29%), and diagnosed with chronic obstructive pulmonary disease: 70 (33.4%). The differences in the curves were < 0.150 L. The mean difference (bias) and the intraclass correlation coefficient (95% confidence interval, 95% CI) of the forced expiratory volume in the first second were 1 vs. 2 maneuver: -0.01 (0.13, -0.14), 0.997 (95% CI 0.996, 0.998); 2 vs. 3 maneuver: 0.00 (0.13, -0.13), 0.997 (95% CI 0.996, 0.998), and maneuver 1 vs. 3: -0.00 (0.16, -0.17), 0.995 (95% CI 0.994, 0.996). Forced vital capacity: 1 vs. 2 maneuver: -0.01 (0.17, -0.18), 0.996 (95% CI 0.995, 0.997); 2 vs. 3 maneuver: 0.01 (0.17, -0.16), 0.997 (95% CI 0.0.996, 0.998), and maneuver 1 vs. 3: -0.00 (0.18, -0.19), 0.996 (95% CI 0.995, 0.997). Conclusion: The repeatability obtained in spirometry with quality A validates the use of the repeatability criterion of 0.150 L.

Introducción: la calidad de la espirometría se estima con criterios de aceptabilidad y repetitividad. La repetitividad aceptada por consenso es < 0.150 L. Objetivo: conocer la repetitividad en espirometrías de calidad A. Material y métodos: diseño transversal analítico. Se obtuvieron las variables demográficas y las 3 mejores curvas de espirometría con perfil normal, que sugiriera restricción y obstrucción bronquial de sujetos consecutivos de ambos géneros de 18 a 80 años. La repetitividad se analizó con la diferencia de medias (sesgo) y el coeficiente de correlación intraclase. Resultados: se aceptaron 630 curvas de 210 sujetos. Edad grupal 60 ± 15 años. Predominio femenino 113 (53.8%), ocupación: servicios domésticos 61 (29%) y con enfermedad pulmonar obstructiva crónica 70 (33.4%). Las diferencias en las curvas fueron < 0.150 L. Las diferencias medias (sesgo) y el coeficiente de correlación intraclase (intervalo de confianza al 95%, IC 95%) del volumen espiratorio forzado en el primer segundo fueron: maniobra 1 frente a 2: −0.01 (0.13, −0.14), 0.997 (IC 95% 0.996, 0.998); maniobra 2 frente a 3: 0.00 (0.13, −0.13), 0.997 (IC 95% 0.996, 0.998), y maniobra 1 frente a 3: −0.00 (0.16, −0.17), 0.995 (IC 95% 0.994, 0.996). La capacidad vital forzada: maniobra 1 frente a 2: −0.01 (0.17, −0.18), 0.996 (IC 95% 0.995, 0.997); maniobra 2 frente a 3: 0.01 (0.17, −0.16), 0.997 (IC 95% 0.0.996, 0.998), y maniobra 1 frente a 3: −0.00 (0.18, −0.19), 0.996 (IC 95% 0.995, 0.997). Conclusión: la repetitividad obtenida en espirometrías con calidad A valida el uso del criterio de repetitividad de 0.150 L.

Evaluation of the Minimum Segment Width and Fluence Smoothing Tools for Intensity-modulated Techniques in Monaco Treatment Planning System.

Purpose: This study aims to minimize monitor units (MUs) of intensity-modulated treatments in the Monaco treatment planning system while preserving plan quality by optimizing the "Minimum Segment Width" (MSW) and "Fluence Smoothing" parameters. Materials and Methods: We retrospectively analyzed 30 prostate, 30 gynecological, 15 breast cancer, 10 head and neck tumor, 11 radiosurgery, and 10 hypo-fractionated plans. Original prostate plans employed "Fluence Smoothing" = Off and were reoptimized with Low, Medium, and High settings. The remaining pathologies initially used MSW = 0.5 cm and were reoptimized with MSW = 1.0 cm. Plan quality, including total MU, delivery time, and dosimetric constraints, was statistically analyzed with a paired t-test. Results: Prostate plans exhibited the highest MU variation when changing "Fluence Smoothing" from Off to High (average ΔMU = -5.1%; P < 0.001). However, a High setting may increase overall MU when MSW = 0.5 cm. Gynecological plans changed substantially when MSW increased from 0.5 cm to 1.0 cm (average ΔMU = -29%; P < 0.001). Organs at risk sparing and planning target volumes remained within 1.2% differences. Replanning other pathologies with MSW = 1.0 cm affected breast and head and neck tumor plans (average ΔMU = -168.38, average Δt = -11.74 s, and average ΔMU = -256.56, average Δt = -15.05 s, respectively; all with P < 0.004). Radiosurgery and hypofractioned highly modulated plans did not yield statistically significant results. Conclusions: In breast, pelvis, head and neck, and prostate plans, starting with MSW = 1.0 cm optimally reduces MU and treatment time without compromising plan quality. MSW has a greater impact on MU than the "Fluence Smoothing" parameter. Plans with high modulation might present divergent behavior, requiring a case-specific analysis with MSW values higher than 0.5 cm.

Addressing Reproducibility Challenges in High-Throughput Photochemistry.

Light-mediated reactions have emerged as an indispensable tool in organic synthesis and drug discovery, enabling novel transformations and providing access to previously unexplored chemical space. Despite their widespread application in both academic and industrial research, the utilization of light as an energy source still encounters challenges regarding reproducibility and data robustness. Herein we present a comprehensive head-to-head comparison of commercially available batch photoreactors, alongside the introduction of the use of batch and flow photoreactors in parallel synthesis. Hence, we aim to establish a reliable and consistent platform for light-mediated reactions in high-throughput mode. Herein, we showcase the identification of several platforms aligning with the rigorous demands for efficient and robust high-throughput experimentation screenings and library synthesis.

Oxidative refolding by Copper-catalyzed air oxidation consistently increases the homogeneity and activity of a Novel Interleukin-2 mutein.

Interleukin-2 (IL-2) has been used in cancer treatment for over 30 years. However, due to its high toxicity, new mutant variants have been developed. These variants retain some of the biological properties of the original molecule but offer other therapeutic advantages. At the Center of Molecular Immunology, the IL-2 no-alpha mutein, an IL-2 agonist with lower toxicity than wtIL-2, has been designed, produced, and is currently being evaluated in a Phase I/II clinical trial. The mutein is produced in E. coli as an insoluble material that must be refolded in vitro to yield a fully active protein. Controlled oxidation steps are essential in the purification process of recombinant proteins produced in E. coli to ensure the proper formation of the disulfide bonds in the molecules. In this case, the new purification process includes a copper-catalyzed air oxidation step to induce disulfide bond establishment. The optimal conditions of pH, copper, protein and detergent concentration for this step were determined through screening. The produced protein demonstrated a conserved 3D structure, higher purity, and greater biological activity than the obtained by established process without the oxidation step. Four batches were produced and evaluated, demonstrating the consistency of the new process.

Near infrared spectroscopy (NIRS) and machine learning as a promising tandem for fast viral detection in serum microsamples: A preclinical proof of concept.

Fast detection of viral infections is a key factor in the strategy for the prevention of epidemics expansion and follow-up. Hepatitis C is paradigmatic within viral infectious diseases and major challenges to elimination still remain. Near infrared spectroscopy (NIRS) is an inexpensive, clean, safe method for quickly detecting viral infection in transmission vectors, aiding epidemic prevention. Our objective is to evaluate the combined potential of machine learning and NIRS global molecular fingerprint (GMF) from biobank sera as an efficient method for HCV activity discrimination in serum. GMF of 151 serum biobank microsamples from hepatitis C patients were obtained with a FT-NIR spectrophotometer in reflectance mode. Multiple scatter correction, smoothing and Saviztsky-Golay second derivative were applied. Spectral analysis included Principal Component Analysis (PCA), Bootstrap and L1-penalized classification. Microsamples of 70 µl were sufficient for GMF acquisition. Bootstrap evidenced significant difference between HCV PCR positive and negative sera. PCA renders a neat discrimination between HCV PCR-positive and negative samples. PCA loadings together with L1-penalized classification allow the identification of discriminative bands. Active virus positive sera are associated to free molecular water, whereas water in solvation shells is associated to HCV negative samples. Divergences in the water matrix structure and the lipidome between HCV negative and positive sera, as well as the relevance of prooxidants and glucose metabolism are reported as potential biomarkers of viral activity. Our proof of concept demonstrates that NIRS GMF of hepatitis C patients' sera aided by machine learning allows for efficient discrimination of viral presence and simultaneous potential biomarker identification.