Development of a new definition of maternal near miss based on organ dysfunction in Latin America and the Caribbean: A prospective multicenter cohort study.

BACKGROUND: There has been debate over whether the existing World Health Organization (WHO) criteria accurately represent the severity of maternal near misses. OBJECTIVE: This study assessed the diagnostic accuracy of two WHO clinical and laboratory organ dysfunction markers for determining the best cutoff values in a Latin American setting. METHODS: A prospective multicenter cohort study was conducted in five Latin American countries. Patients with severe maternal complications were followed up from admission to discharge. Organ dysfunction was determined using clinical and laboratory data, and participants were classified according to severe maternal outcomes. This study compares the diagnostic criteria of Latin American Centre for Perinatology, Network for Adverse Maternal Outcomes (CLAP/NAMO) to WHO standards. RESULTS: Of the 698 women studied, 15.2% had severe maternal outcomes. Most measured variables showed significant differences between individuals with and without severe outcomes (all P-values <0.05). Alternative cutoff values suggested by CLAP/NAMOs include pH ≤7.40, lactate ≥2.3 mmol/L, respiratory rate ≥ 24 bpm, oxygen saturation ≤ 96%, PaO2/FiO2 ≤ 342 mmHg, platelet count ≤189 × 109 × mm3, serum creatinine ≥0.8 mg/dL, and total bilirubin ≥0.67 mg/dL. No significant differences were found when comparing the diagnostic performance of the CLAP/NAMO criteria to that of the WHO standards. CONCLUSION: The CLAP/NAMO values were comparable to the WHO maternal near-miss criteria, indicating that the WHO standards might not be superior in this population. These findings suggest that maternal near-miss thresholds can be adapted regionally, improving the identification and management of severe maternal complications in Latin America.

Real-world dosing patterns of regorafenib for patients with metastatic colorectal cancer in Spain: the RE-SEARCH study.

PURPOSE: To describe the dosing patterns of regorafenib in a real-world population of patients with metastatic colorectal cancer (mCRC) in a routine clinical practice setting in Spain, focusing on the starting dose of regorafenib. METHODS: An observational, retrospective, multicenter study that included patients ≥ 18 years old who had histologically documented mCRC and who had initiated treatment with regorafenib since January 2017. Post hoc categorization of dosing patterns revealed the following: initial dose < 160 mg and dose escalation, initial dose < 160 mg and maintenance, initial dose equal to 160 mg and maintenance, and initial dose equal to 160 mg and dose reduction. RESULTS: Most patients (152/241, 63.8%) initiated treatment with regorafenib at doses < 160 mg. There was large variation in the starting dose of regorafenib over time: in 2017, most patients (59%) initiated regorafenib at a dose of 160 mg, this proportion decreased to 6% in 2021. There were no significant differences in the median progression-free survival according to the regorafenib dose patterns during the first two cycles. The proportion of patients who reported at least one adverse event (AE), had a grade 3-4 AE or had an AE leading to dose reduction was greater in the group of patients who received an initial dose equal to 160 and reduction. CONCLUSIONS: Our results indicate that physicians in Spain have gradually adopted a dose-escalation approach during cycle 1, which is a common practice for starting treatment with a reduced dose (< 160 mg/day), a strategy that seems to improve tolerability while maintaining efficacy. TRIAL REGISTRATION: Not applicable.

Viscosity of Polyelectrolytes: Influence of Counterion and Solvent Type.

We study the viscosity of polystyrenesulfonate with sodium and tetrabutylammonium counterions in aqueous and organic solvent media. We find that at low concentrations the Fuoss law (ηsp ∼ c1/2) is approximately obeyed, but at higher concentrations, an exponential dependence on the polymer volume fraction sets in. These findings are discussed in terms of Fujita's free volume theory.

Bioimpedance analysis predicts worsening events in outpatients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) with reduced left ventricle ejection fraction (LVEF) is an entity with poor prognosis characterized by decompensations. Bioelectrical impedance analysis (BIA) is used to assess volume overload (VO) and may be useful to identify apparently stable HF outpatients at risk of decompensation. The aim of this study is to analyse whether VO assessed by BIA is associated with worsening heart failure (WHF) in stable outpatients with HF and reduced LVEF (HFrEF). METHODS AND RESULTS: This is a prospective single-centre observational study. Consecutive stable HF outpatients with LVEF below 40% underwent BIA, transthoracic echocardiography, blood sampling, and physical examination and were followed up for 3 months. VO was defined as the difference between the measured weight and the dry weight assessed by BIA. Demographic, clinical, anthropometric, echocardiographic, and analytical parameters were recorded. The primary endpoint was WHF, defined by visits to the emergency department for HF or hospitalization for HF. A total of 100 patients were included. The median VO was 0.5 L (interquartile range 0-1.6 L). Eleven patients met the primary endpoint. Univariate binary logistic regression analysis showed that left ventricle filling pressures assessed by E/e', N-terminal pro B-type natriuretic peptide, inferior vena cava dilatation (≥21 mm), signs of congestion, and VO were associated with the primary endpoint. Binary logistic regression multivariate analysis showed that VO was the only independent predictor for the primary endpoint (adjusted OR 2.7; 95% CI 1.30-5.63, P = 0.008). Multivariate Cox regression analysis also showed an adjusted hazard ratio (HR) for VO of 2.03; 95% CI 1.37-3.02, P < 0.001. Receiver-operating characteristic curve analysis showed an area under the curve for VO of 0.88 (95% CI 0.79-0.97, P < 0.001) with an optimal cut-off of 1.2 L. CONCLUSIONS: VO assessed by BIA is independently associated with WHF in stable outpatients with HFrEF at 3 months.

Transapical transcatheter mitral valve replacement for mitral valve disease: an Iberian experience.

INTRODUCTION AND OBJECTIVES: Transcatheter mitral valve replacement (TMVR) is an emerging treatment alternative for mitral valve (MV) disease in patients who were ineligible for surgical intervention or edge-to-edge repair. This study aimed to assess the short- and mid-term outcomes of this procedure. METHODS: We conducted a prospective registry to include the initial experience with symptomatic, consecutive patients who underwent TMVR using the transapical Tendyne system at 7 centers in the Iberian Peninsula. Baseline clinical and imaging data, periprocedural information, and follow-up assessments were collected at 1 month and 1 year. RESULTS: A total of 40 patients (mean age 78.5 years [76-82], 47,5% males) underwent TMVR. The majority had significant surgical risk, comorbidities, and advanced functional class. All patients had significant mitral regurgitation (MR), except for 2 with severe stenosis. Previous MV intervention and off-label indication for the procedure were present in 4 (10.0%) and 8 (20.0%) patients, respectively. Technical success was recorded in 100%, device success in 95.0%, and procedural success in 85.0% at 30-day. All-cause mortality was 2.5% and 17.5% at the 1-month and 1-year follow-up, respectively. MR reduction (≤ 1) and functional class improvement (NYHA I-II) were observed at 1 year in 93.9% and 87.9% of survivors, respectively. CONCLUSIONS: Treatment with TMVR produced enduring resolution of MV disease and notable functional enhancement at 1 year of follow-up. The procedure demonstrated a satisfactory early safety profile, although 1-year mortality remained relatively high in this high-risk population.

Impact of SGLT2 Inhibitors on Very Elderly Population with Heart Failure with Reduce Ejection Fraction: Real Life Data.

(1) Background: The validation of new lines of therapy for the elderly is required due to the progressive ageing of the world population and scarce evidence in elderly patients with HF with reduced ejection fraction (HFrEF). The purpose of our study is to analyze the effect of SGLT2 inhibitors (SGLT2i) in this subgroup of patients. (2) Methods: A single-center, real-world observational study was performed. We consecutively enrolled all patients aged ≥ 75 years diagnosed with HFrEF and for treatment with SGLT2i, and considered the theoretical indications. (3) Results: A total of 364 patients were recruited, with a mean age of 84.1 years. At inclusion, the mean LVEF was 29.8%. Median follow-up was 33 months, and there were 122 deaths. A total of 55 patients were under SGLT2i treatment. A multivariate Cox logistic regression test for all-cause mortality was performed, and only SGLT2i (HR 0.39 [0.19-0.82]) and glomerular filtration rate (HR 0.98 [0.98-0.99]) proved to be protective factors. In parallel, we conducted a propensity-score-matched analysis, where a significant reduction in all-cause mortality was associated with the use of SGLT2i treatment (HR 0.39, [0.16-0.97]). (4) Conclusions: Treatment with SGLT2i in elderly patients with HFrEF was associated with a lower rate of all-cause mortality. Our data show that SGLT2i therapy could improve prognosis in the elderly with HFrEF in a real-world study.

Glycemic control and study of lipid and bone metabolism in type 1 diabetic children / Control glucémico y estudio del metabolismo lipídico y del óseo en niños con diabetes de tipo 1

Introduction. Type 1 diabetes mellitus is considered one of the most common chronic diseases of childhood. It is a high-risk factor for developing early cardiovascular disease and it also affects bone health. Objective. To describe demographic characteristics and biochemical parameters of a population of children with type 1 diabetes, evaluated in the pediatric diabetes unit of a tertiary Spanish hospital. Materials and methods. In this retrospective study, we determined metabolic, lipid, and bone parameters in 124 children with type 1 diabetes who were monitored in the pediatric diabetes unit of the Hospital Universitario Miguel Servet in Zaragoza (Spain) from May 2020 to July 2021. Results. Children with type 1 diabetes have worse metabolic control of the disease at puberty, but their lipid control is considered acceptable. We found an inverse correlation between bone formation markers and disease duration, as well as with metabolic control. Conclusion. Bone formation markers are inversely correlated with the percentage of glycated hemoglobin and diabetes evolution time. Patients' lipid and bone profiles are more favorable when metabolic control of the disease is achieved.

Introducción. La diabetes mellitus de tipo 1 se considera una de las enfermedades crónicas más frecuentes de la infancia. Es un factor de gran riesgo de desarrollar enfermedad cardiovascular temprana y afecta también la salud ósea. Objetivo. Describir las características demográficas y los parámetros bioquímicos de una población de niños con diabetes de tipo 1, supervisados en la unidad pediátrica de diabetes de un hospital español de tercer nivel. Materiales y métodos. En este estudio retrospectivo, se determinaron los parámetros de control metabólico, lipídico y óseo en 124 niños con diabetes de tipo 1, a los que se hizo seguimiento en la Unidad Pediátrica de Diabetes del Hospital Universitario Miguel Servet de Zaragoza, desde mayo del 2020 hasta julio del 2021. Resultados. Los niños con diabetes de tipo 1 presentan peor control metabólico de la enfermedad en la pubertad, pero su control lipídico se puede considerar aceptable. Existe una correlación inversa de los marcadores de formación ósea con el tiempo de evolución de la enfermedad, así como con el control metabólico. Conclusión. Los marcadores de formación ósea se encuentran correlacionados de forma inversa con el porcentaje de hemoglobina glicosilada y con el tiempo de evolución de la diabetes. En estos pacientes, el perfil lipídico y el óseo son más favorables cuando existe un buen control metabólico de la enfermedad.

Nurses' perceptions of the performance of nurse managers and senior hospital management during the COVID-19 pandemic.

BACKGROUND: The first waves of the COVID-19 pandemic had a negative impact on health systems and health professionals, due to the high number of cases and a lack of preparation. The aim of this study was to understand how nurses working in hospital units and in intensive care perceived the performance of nurse managers and senior hospital management during the first two waves of the pandemic. METHODS: The phenomenological approach proposed by Giorgi was used to investigate perceptions of the performance of nurse managers and senior hospital management during the first two waves of the COVID-19 pandemic in Spain. Fourteen clinical nurses who worked on the front line in inpatient units or intensive care units of the Health Services of Extremadura and Madrid in the first (March-April 2020) and second (October-November 2020) waves of the COVID-19 pandemic participated in this study. The data was collected through semi-structured interviews, following a script of themes, in a theoretical sample of nurses who were worked during the pandemic. RESULTS: Two main themes emerged from the analysis of the data: (1) perceptions about the performance of nurse managers and senior hospital managers during the first and second waves of the pandemic (health system failure; belief that senior hospital management professionals could have managed the pandemic better; recognizing the efforts of middle management (nursing supervisors); insufficient institutional support) and (2) strategies employed by nurses to compensate for the weaknesses in pandemic management. CONCLUSIONS: The clinical nurses perceived that the nurse managers demonstrated better management of the pandemic than the hospital's senior management, which they attribute to their proximity, empathy, accessibility, and ability to mediate between them and the senior management. The nurses also believe that the senior management of the hospitals was to blame for organisational failures and the poor management of the pandemic.

Peripheral neuropathy in patients with gout, beyond focal nerve compression: a cross-sectional study.

Neuropathies secondary to tophus compression in gout patients are well known; however, limited data exist on other types of peripheral neuropathies (PN). Our aim was to describe PN frequency, characteristics, distribution, patterns, and associated factors in gout patients through clinical evaluation, a PN questionnaire, and nerve conduction studies (NCS). This cross-sectional descriptive study included consecutive gout patients (ACR/EULAR 2015 criteria) from our clinic. All underwent evaluation by Rheumatology and Rehabilitation departments, with IRB approval. Based on NCS, patients were categorized as PN + (presence) or PN- (absence). PN + patients were further classified as local peripheral neuropathy (LPN) or generalized somatic peripheral neuropathy (GPN). We enrolled 162 patients, 98% male (72% tophaceous gout). Mean age (SD): 49.4 (12) years; mean BMI: 27.9 (6.0) kg/m2. Comorbidities included dyslipidemia (53%), hypertension (28%), and obesity (23.5%). Abnormal NCS: 65% (n = 106); 52% LPN, 48% GPN. PN + patients were older, had lower education, and severe tophaceous gout. GPN patients were older, had lower education, and higher DN4 scores compared to LPN or PN- groups (p = 0.05); other risk factors were not significant. Over half of gout patients experienced neuropathy, with 48% having multiplex mononeuropathy or polyneuropathy. This was associated with joint damage and functional impairment. Mechanisms and risk factors remain unclear. Early recognition and management are crucial for optimizing clinical outcomes and quality of life in these patients. Key Points Peripheral neuropathies in gout patients had been scarcely reported and studied. This paper report that: • PN in gout is more frequent and more diverse than previously reported. • Mononeuropathies are frequent, median but also ulnar, peroneal and tibial nerves could be injured. • Unexpected, generalized neuropathies (polyneuropathy and multiplex mononeuropathy) are frequent and associated to severe gout. • The direct role of hyperuricemia /or gout in peripheral nerves require further studies.

Energy expenditure of international female rugby union players during a major international tournament: a doubly labelled water study.

The purpose of this study was to quantify the total energy expenditure (TEE) of international female rugby union players. Fifteen players were assessed over 14 days throughout an international multi-game tournament, which represented two consecutive one-match microcycles. Resting metabolic rate (RMR) and TEE were assessed by indirect calorimetry and doubly labelled water, respectively. Physical activity level (PAL) was estimated (TEE:RMR). Mean RMR, TEE, and PAL were 6.60 ± 0.93 MJ·day-1 (1578 ± 223 kcal·day-1), 13.51 ± 2.28 MJ·day-1 (3229 ± 545 kcal·day-1), and 2.0 ± 0.3 AU, respectively. There was no difference in TEE (13.74 ± 2.31 (3284 ± 554 kcal·day-1) vs. 13.92 ± 2.10 MJ·day-1 (3327 ± 502 kcal·day-1); p = 0.754), or PAL (2.06 ± 0.26 AU vs. 2.09 ± 0.23 AU; p = 0.735) across microcycles, despite substantial decreases in training load (total distance: -8088 m, collisions: -20 n, training duration: -252 min). After correcting for body composition, there was no difference in TEE (13.80 ± 1.74 (3298 ± 416 adj. kcal·day-1) vs. 13.16 ± 1.97 (3145 ± 471 adj. kcal·day-1) adj. MJ·day-1, p = 0.190), RMR (6.49 ± 0.81 (1551 ± 194 adj. kcal·day-1) vs. 6.73 ± 0.83 (1609 ± 198 adj. kcal·day-1) adj. MJ·day-1, p = 0.633) or PAL (2.15 ± 0.14 vs. 1.87 ± 0.26 AU, p = 0.090) between forwards and backs. For an injured participant (n = 1), TEE reduced by 1.7 MJ·day-1 (-401 kcal·day-1) from pre-injury. For participants with illness (n = 3), TEE was similar to pre-illness (+0.49 MJ·day-1 (+117 kcal·day-1)). The energy requirements of international female rugby players were consistent across one-match microcycles. Forwards and backs had similar adjusted energy requirements. These findings are critical to inform the dietary guidance provided to female rugby players.

A wound-induced differentiation trajectory for neurons.

Animals capable of whole-body regeneration can replace any missing cell type and regenerate fully functional new organs, including new brains, de novo. The regeneration of a new brain requires the formation of diverse neural cell types and their assembly into an organized structure with correctly wired circuits. Recent work in various regenerative animals has revealed transcriptional programs required for the differentiation of distinct neural subpopulations, however, how these transcriptional programs are initiated in response to injury remains unknown. Here, we focused on the highly regenerative acoel worm, Hofstenia miamia, to study wound-induced transcriptional regulatory events that lead to the production of neurons and subsequently a functional brain. Footprinting analysis using chromatin accessibility data on a chromosome-scale genome assembly revealed that binding sites for the Nuclear Factor Y (NFY) transcription factor complex were significantly bound during regeneration, showing a dynamic increase in binding within one hour upon amputation specifically in tail fragments, which will regenerate a new brain. Strikingly, NFY targets were highly enriched for genes with neuronal function. Single-cell transcriptome analysis combined with functional studies identified soxC+ stem cells as a putative progenitor population for multiple neural subtypes. Further, we found that wound-induced soxC expression is likely under direct transcriptional control by NFY, uncovering a mechanism for the initiation of a neural differentiation pathway by early wound-induced binding of a transcriptional regulator.

Data-Driven Modeling of the Spray Drying Process. Process Monitoring and Prediction of the Particle Size in Pharmaceutical Production.

Spray drying is used in the pharmaceutical industry for particle engineering of amorphous solid dispersions (ASDs). The particle size of the spray-dried (SD) powders is one of their key attributes due to its impact on the downstream processes and the drug product's functional properties. Offline and inline laser diffraction methods can be used to estimate the product's particle size; however, the final release of these ASDs is based on offline instruments. This paper presents a novel data-driven modeling approach for predicting the particle size of SD products. The model-based characterization of the process and the product's particle size, as a critical quality attribute, follows the quality by design principles. The resulting model can be used for online process monitoring, reducing the risks of out-of-specifications products and supporting their real-time release. A Tucker3 model is trained to capture and factorize the deterministic variability of the process. Subsequently, a partial least-squares regression model is calibrated to model the impact that variability in the input material properties, the process parameters, and the spray nozzle have on the products' particle size. This strategy has been calibrated and validated using large scale production data for two intermediate drug products under high sparsity of particle size data. Despite the challenges, high accuracy was obtained in predicting the median particle size (dv50) for release. The 99% confidence interval results in an error of maximum 2.5 µm, which is less than 10% of the allowed range of variation.

SEOM-GEMCAD-TTD clinical guidelines for the management of hepatocarcinoma patients (2023).

Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver and is the third cause of cancer-related death worldwide. Surveillance with abdominal ultrasound should be offered to individuals at high risk for developing HCC. Accurate diagnosis, staging, and liver function are crucial when determining the optimal therapeutic approach. The BCLC staging system is widely endorsed in Western countries. Managing this pathology requires a multidisciplinary, personalized approach, generally with a multimodal strategy. Surgery remains the only curative option, albeit local and systemic therapy may also increase survival when surgery is not suitable. In advanced disease, systemic treatment should be offered to patients with ECOG/PS 0-1 and Child-Pugh class A.

Validity, reliability, and the contributing physical characteristics of a modified 15m prone Yo-Yo Intermittent Recovery Test Level-1 test in elite female rugby league players.

This study aims to establish the validity and reliability of the prone Yo-YoIRL1 in elite female rugby league players (part one) and determine the anthropometric and physical characteristics contributing to 15m prone Yo-YoIRL1 performance (part two). Part one, 21 subjects completed one Yo-YoIRL1, one 20m and two 15m prone Yo-YoIRL1 tests over four sessions, with 7-14 days in-between. Part two, ten subjects completed a testing battery, including body mass, height, dual-energy x-ray absorptiometry, isometric mid-thigh pull, isometric bench-press, 10m and 20m sprints and an incremental treadmill test ([Formula: see text]). The 15m prone YoYoIRL1 demonstrated poor reliability with a typical error of 68m (21%) and a smallest worthwhile change of 54m (9%). Validity analysis found the prone versions of the YoYoIRL1 were not sensitive measures of intermittent running performance. Both prone YoYoIRL1 test distances demonstrated large mean bias (76% and -37% respectively) and typical error of the estimate (19% and 21%, respectively) in comparison to the YoYoIRL1. Body mass (r = -0.89), lean mass (r = -0.64), body fat % (r = -0.68), [Formula: see text] (l∙min-1) (r = -0.64), IMTP (r = -0.69), IBP (r = -0.15), 10m (r = -0.77) and 20m (r = -0.72) momentum displayed large negative relationships with 15m prone Yo-YoIRL1 performance. Due to the poor validity of the 20m prone YoYoIRL1, the poor validity and reliability of the 15m prone YoYoIRL1, and the anthropometric and physical characteristics which negatively impact performance, practitioners should reconsider the use of the prone YoYoIRL1 test to monitor high intensity intermittent running performance.

Acute effects on the psychological perception of university students after participation in the "RegulACTION" workshop for the improvement of emotional health and promotion of an active lifestyle.

Introduction: Prospective research in Health Sciences and Sports Sciences warns of the need to design and implement educational program at the different stages of human development, that promote emotional competences, interpersonal competences, an adequate level of healthy physical activity as well as adherence to the Mediterranean diet and a more active lifestyle on a physical and social level. The main objective of the study was to design an intervention program on intra-and interpersonal competences together with emotional education, nutritional education and healthy physical activity, called 'RegulACTION'. Methods: The preliminary study sample consisted of 11 participants aged 21-28 years (M = 5.00, SD = 8.76) (8 female and 3 males) university students. An ad hoc questionnaire was elaborated to evaluate the participant's perception of the usefulness of the 'RegulACTION' experience and a semi-structured interview of 5 questions to assess their perception, identification of their emotions, awareness of their cognitions, emotions and behaviors in the different areas of their lives. Results: The descriptive results show that the participants are receptive to continuing training in the regulation of cognitions (thoughts) and emotions to increase their satisfaction in different areas of their lives. Regarding the qualitative results, the participants' perception, collected verbatim, is that they feel the need to apply the knowledge about personal and social emotions, as well as healthy behavior in terms of nutrition and exercise, in their daily lives. Discussion: The 'RegulACTION' program is designed based on the assessment of the prevalence of mental illness in the young adult and adult population, in line with the literature review in the area of knowledge of the theory of emotions, motivational theories and on the occasion of the development of a workshop organized.

Exploring Genetic Silencing: RNAi and CRISPR-Cas Potential Against Drug Resistance in Malaria.

Malaria has been one of the most lethal infectious diseases throughout history, claiming a high number of human lives. The genomic plasticity of Plasmodium falciparum, the causative agent of the most severe and deadly form of malaria, gives the parasite a constant resistance to drugs developed for its control. Despite efforts to control and even eradicate the disease, these have largely been unsuccessful due to the parasite's continuous adaptations. This study aims to examine the key genes involved in parasite resistance and propose a shift in the combat strategy. Gene silencing techniques offer promise in combating malaria, yet further research is needed to harness their potential for disease control fully. Although there is still a long way to go for the implementation of gene silencing-based therapeutic strategies, this review addresses examples of the use of such techniques in various human diseases and how they could be extrapolated for malaria treatment.

Source apportionment of ambient pollution levels in Guayaquil, Ecuador.

In this study, the relative contributions of main emission sources to the typical ambient concentrations of key pollutants, such as sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matter (PM10 and PM2.5) in Guayaquil, Ecuador, were investigated. A previous urban emissions inventory for mobile sources was expanded to include other transportation means and main industrial activities using the EMEP/EEA methodology to achieve this objective. The WRF/CALMET/CALPUFF modeling system was used to simulate the annual spatiotemporal distribution of air pollution in the city. According to the model, NO2 concentrations exceed the yearly value and 1-h Ecuadorian standards (40 and 200 µg/m3) in 1 % and 6 % of the cells of the modeling domain, respectively. These hotspots related to local sources were located in the northwest center of the city. The contributions of the manufacturing sector, thermal power plants, ports, airports, and road traffic were assessed individually, and the results indicated that air quality in the study area was strongly dominated by road traffic. The contributions of NO2, CO, PM10, and PM2.5 at the city level reached 76 %, 96 %, 90 %, and 92 % of the annual mean, respectively. In the case of SO2, the manufacturing sector made the most significant contribution (75 %), followed by thermal power plants (16 %). Furthermore, an analysis at 14 specific locations across Guayaquil identified spatial variations that may support the design and development of an air quality monitoring network for the city.

Signal execution modes emerge in biochemical reaction networks calibrated to experimental data.

Mathematical models of biomolecular networks are commonly used to study cellular processes; however, their usefulness to explain and predict dynamic behaviors is often questioned due to the unclear relationship between parameter uncertainty and network dynamics. In this work, we introduce PyDyNo (Python dynamic analysis of biochemical networks), a non-equilibrium reaction-flux based analysis to identify dominant reaction paths within a biochemical reaction network calibrated to experimental data. We first show, in a simplified apoptosis execution model, that despite the thousands of parameter vectors with equally good fits to experimental data, our framework identifies the dynamic differences between these parameter sets and outputs three dominant execution modes, which exhibit varying sensitivity to perturbations. We then apply our methodology to JAK2/STAT5 network in colony-forming unit-erythroid (CFU-E) cells and provide previously unrecognized mechanistic explanation for the survival responses of CFU-E cell population that would have been impossible to deduce with traditional protein-concentration based analyses.

Exploring risk factors of severe pituitary apoplexy: Insights from a multicenter study of 71 cases.

PURPOSE: To identify clinical and radiological factors associated with a higher risk of developing a severe pituitary apoplexy (PA). METHODS: Multicenter retrospective study of patients presenting with clinical PA in three Spanish tertiary hospitals of Madrid between 2008 and 2022. We classified PA as severe when presenting with an altered level of consciousness (Glasgow Coma Scale (GCS) < 15) or visual involvement. RESULTS: A total of 71 PA cases were identified, of whom 80.28% (n = 57) were classified as severe PA. The median age was 60 (18 to 85 years old) and 67.6% (n = 48) were male. Most patients had macroadenomas, except for one patient with a microadenoma of 9 mm. Headache was the most common presenting symptom (90.1%) and anticoagulation was the most frequent predisposing risk factor, but it was not associated with a higher risk for severe PA (odds ratio [OR] 1.13 [0.21-5.90]). Severe cases were associated with male gender (OR 5.53 [1.59-19.27]), tumor size >20 mm (OR 17.67 [4.07-76.64]), and Knosp grade ≥2 (OR 9.6 [2.38-38.73]). In the multivariant analysis, the only variables associated with a higher risk for severe PA were tumor size and Knosp grade. Surgery was more common in severe PA than in non-severe (91.2% vs. 64.3%, P = 0.009). CONCLUSION: A tumor size >20 mm and cavernous sinus invasion are risk factors for developing a severe PA. These risk factors can stratify patients at a higher risk of a worse clinical picture, and subsequently, more need of decompressive surgery.