First-line PARP inhibitor maintenance treatment in ovarian carcinoma for older adult women: a review of the current literature.

Ovarian cancer (OC) is the leading cause of death in women with gynecological cancers. Its diagnosis is more likely in advanced ages, with the older population being the most seen in consultations. Poly(ADP-ribose) inhibitors (PARPi) have changed OC clinical practice and evolution, showing great benefit. However, there is a lack of evidence of PARPi in elderly population that can impact the therapeutic decision and the safety/efficacy. It is necessary to avoid age as limiting factor in PARPis prescription. We conducted a review of the most relevant randomized phase III trials of maintenance PARPi after first-line treatment of advanced OC. We observed the lack of a single criterion for considering older patients, varying among trials. There is a benefit of PARPis in different populations. However, PARPi effect on quality of life is not reported, something of great relevance considering their vulnerability. Measures are needed to benefit older patients to better adapt PARPi treatment.

Metal(loid) bioaccessibility and risk assessment of ashfall deposit from Popocatépetl volcano, Mexico.

Ash emission from volcanic eruptions affects the environment, society, and human health. This study shows the total concentration and lung bioaccessible fraction of eight potential toxic metal(loid)s in five Popocatépetl ashfall samples. Mineralogical phases and particle size distribution of the ashfall were analyzed by X-ray diffraction (XRD) and Scanning Electron Microscope (SEM) techniques, respectively. The bioaccessibility test of Gamble solution (GS) and Artificial Lysosomal Fluid (ALF) were conducted to simulate extracellular (pH 7) and intracellular (pH 4.5) conditions, respectively. The studied metal(loid)s showed the following total concentration (mg kg-1): 1.98 (As), 0.17 (Cd), 134.09 (Cr), 8.66 (Cu), 697.33 (Mn), 55.35 (Ni), 8.77 (Pb), and 104.10 (Zn). Geochemical indices suggested that some metal(loid)s are slightly enriched compared to the local soil background concentrations. Several mineralogical phases were identified in the collected ashfall deposits, such as plagioclase, pyroxene, and Fe-Ti oxide, among others. According to the risk assessment results, the non-carcinogenic risk related to ashfall exposure returns an HQ > 1 for children. In contrast, the estimation of carcinogenic risk was found to be within the tolerable limit. Metal(loid)s showed low bioaccessibility (< 30%) in GS and ALF, with the highest values found in ALF solution for As (12.18%) and Cu (7.57%). Despite their metal-bioaccessibility, our findings also showed that dominant ash particle size ranged between fine (< 2.5 µm) and extremely fine (< 1 µm), considered highly inhalable fractions. The results obtained in this work indicate that volcanic ashes are bioinsoluble and biodurable, and exhibit low bioaccessibility when in contact with lung human fluids.

Thrombosis and infections associated with PICC in onco-hematological patients, what is their relevance?

PURPOSE: Peripherally inserted central venous catheters (PICC) in the onco-hematological patients may be associated with thrombosis or infections that may have short- to medium-term repercussions. MATERIAL AND METHODS: Single-centre retrospective analysis of a prospectively collected cohort. Primary objective was to establish the PICC-thrombosis and infections incidence. Secondary objectives were to analyze profile of patients suffering from these complications and variables associated with an increased likelihood of developing these events. RESULTS: 549 patients were recruited. 58.5% (n = 321) were oncology patients and 41.5% (n = 228) hematology patients. The incidence of PICC-associated thrombosis was 3.5% (n = 19). Thrombosis was associated with progression of the underlying malignant pathology in 10.6% (n = 2) of cases. No association was found between clinical variables analysed and development of thrombosis. Incidence of PICC-associated infections was 7.65% (n = 42). In the 30 days prior to PICC infection, 57.1% (n = 24) had a febrile syndrome of another focus, 73.8% (n = 11) had been hospitalized, 49.5% (n = 25) had a neutrophil count of 0-500 cells/mm3 and 47.6% (n = 20) had an episode of neutropenic fever. Variables significantly associated with the development of infection were hematological patients, high-flow PICC, 3-lm PICC or PICC insertion because of administration of vesicant therapy. CONCLUSIONS: Incidence of PICC-associated thrombosis is low and apparently less prognostically aggressive than other forms of thrombosis associated with cancer, without identify predictive factors. Infection was more prevalent and the identification of risk factors in our series could facilitate its prevention.

Differential risk factor profile and neuroimaging markers of small vessel disease between lacunar ischemic stroke and deep intracerebral hemorrhage.

Background: Lacunar ischemic stroke (LIS) and deep intracerebral hemorrhage (dICH) are two stroke phenotypes of deep perforator arteriopathy. It is unclear what factors predispose individuals with deep perforator arteriopathy to either ischemic or hemorrhagic events. Objectives: We aimed to investigate risk factors and neuroimaging features of small vessel disease (SVD) associated with LIS versus dICH in a cross-sectional study. Methods: We included patients with clinically presenting, magnetic resonance imaging-confirmed LIS or dICH from two tertiary hospitals between 2010 and 2021. We recorded vascular risk factors and SVD markers, including lacunes, white matter hyperintensities (WMH), perivascular spaces (PVS), and cerebral microbleeds (CMB). Logistic regression modeling was used to determine the association between vascular risk factors, SVD markers, and stroke phenotype. We further created WMH probability maps to compare WMH distribution between LIS and dICH. Results: A total of 834 patients with LIS (mean age 61.7 ± 12.1 years) and 405 with dICH (57.7 ± 13.2 years) were included. Hypertension was equally frequent between LIS and dICH (72.3% versus 74.8%, p = 0.349). Diabetes mellitus, hyperlipidemia, smoking, and prior ischemic stroke were more associated with LIS [odds ratio (OR) (95% confidence interval (CI)), 0.35 (0.25-0.48), 0.32 (0.22-0.44), 0.31 (0.22-0.44), and 0.38 (0.18-0.75)]. Alcohol intake and prior ICH were more associated with dICH [OR (95% CI), 2.34 (1.68-3.28), 2.53 (1.31-4.92)]. Lacunes were more prevalent in LIS [OR (95% CI) 0.23 (0.11-0.43)], while moderate-to-severe basal-ganglia PVS and CMB were more prevalent in dICH [OR (95% CI) 2.63 (1.35-5.27), 4.95 (2.71-9.42)]. WMH burden and spatial distribution did not differ between groups. Conclusion: The microangiopathy underlying LIS and dICH reflects distinct risk profiles and SVD features, hence possibly SVD subtype susceptibility. Prospective studies with careful phenotyping and genetics are needed to clarify the mechanisms underlying this difference.

Testosterone Enhances KV Currents and Airway Smooth Muscle Relaxation Induced by ATP and UTP through P2Y4 Receptors and Adenylyl Cyclase Pathway.

Numerous studies suggest the involvement of adenosine-5'-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5'-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y2 and P2Y4 receptors and K+ channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K+ (KV) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K+ channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K+ currents, and this effect was abolished with flutamide (an androgen receptor antagonist). KV channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y2), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K+ currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y4 receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of KV1.2 and KV1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y4 signaling and KV channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males.

Non-hiatal diaphragmatic hernias: results of transabdominal and transthoracic surgical approaches at a fourth-level hospital.

OBJECTIVE: The objective of this study is to elucidate the clinical and demographic profiles, as well as perioperative outcomes, of patients undergoing surgery for non-hiatal diaphragmatic hernias. Additionally, it aims to analyse these outcomes based on the surgical approach employed (transthoracic versus transabdominal). METHODS: This retrospective, observational study was conducted at a single center and involved patients diagnosed with non-hiatal diaphragmatic hernia who underwent either emergency or elective surgery between July 2007 and March 2023. Clinical characteristics and perioperative outcomes of these patients were compared using appropriate statistical tests.The research protocol for this observational, retrospective, and comparative study followed the Declaration of Helsinki's ethical requirements. The need for Clinical Research Ethics Committee approval was waived according to our institutional law because the study was a retrospective cohort study based on anonymous data of patients. Informed consent was waived because this study involved the secondary analysis of patient medical records. Additionally, this study followed the STROBE guidelines for reporting observational studies. RESULTS: The analysis included 22 patients being 59.1% men, with median age of 61 years. The predominant clinical presentation was restrictive lung disease (40.9%). The majority of cases (68%) had traumatic aetiology with a median defect size of 4 cm (range of 3-8 cm). Elective surgery was performed in 15 cases (68.1%) and transthoracic approach was employed in 13 patients (54.5%). Postoperative major morbidity reached 27.2% and mortality within 30 days was 9.1%. Emergency surgeries accounted for 44.4% of transabdominal interventions, compared to 23% in the transthoracic subgroup (p = 0.376). There were no statistically significant differences between the transabdominal and trasnthoracic approaches in terms of global postoperative complications (88.8% vs. 84.6%, p = 1), major complications (44.4% vs 15.4%, p = 0.734), mortality (11.1% v 7.6%, p = 1) and recurrence (11.1% vs 7.6%, p = 1). Postoperative stay was significantly shorter in the transthoracic subgroup (6 days vs. 14 days, p = 0.011). CONCLUSIONS: Non-hiatal diaphragmatic hernias are characterized by significant postoperative major morbidity and mortality rates, standing at 27.2% and 9.1%, respectively, accompanied by a recurrence rate of 9.1%. Both transthoracic and transabdominal approaches demonstrate comparable short- and long-term outcomes.

Scientific Output by Latin American Women in Pediatric Surgical Sciences Over the Past 11 Years: A Bibliometric and Visual Analysis.

INTRODUCTION: This academic article discusses the historical underrepresentation of female in science, with a focus on Latin America. It highlights the importance of both technical and non-technical skills in the medical-surgical field, particularly the role of research skills. The study aims to quantify and characterize the scientific output of Latin American female researchers over the past decade, providing insights into the challenges and opportunities in low and middle-income countries. MATERIAL AND METHODS: A retrospective cross-sectional bibliometric study was conducted in 2023, focusing on pediatric surgical science journals in Scopus and PubMed. It assessed Latin American female participation, journal details, and interaction networks, using SPSS and Gephi software. The period analyzed was from January 2012 to December 2022. RESULTS: Between 2012 and 2022, 727 articles with Latin authorship in pediatric surgery were analyzed across 304 journals. Of these, 63.69% had female co-authors. The majority were original articles (53.13%), with contributions from Brazil, Mexico, and Chile. Notable journals included the Journal of Pediatric Surgery and Child's Nervous System. Keywords like Laparoscopy and Cardiac surgery were common. A growth trend in female Latin American publications was observed, despite temporary declines. CONCLUSIONS: This study highlights a growing trend in Latin American females' scientific contributions to pediatric surgery from 2012 to 2022, although a gender gap persists. The research mainly consists of primary data studies, with a focus on Brazil and Mexico from public institutions. The Journal of Pediatric Surgery featured prominently, and common topics included Laparoscopy, Cardiac surgery, Liver transplant, Congenital heart defects, and COVID-19. LEVEL OF EVIDENCE: IV.

Diagnostic support in pediatric craniopharyngioma using deep learning.

PURPOSE: We studied a pediatric group of patients with sellar-suprasellar tumors, aiming to develop a convolutional deep learning algorithm for radiological assistance to classify them into their respective cohort. METHODS: T1w and T2w preoperative magnetic resonance images of 226 Chilean patients were collected at the Institute of Neurosurgery Dr. Alfonso Asenjo (INCA), which were divided into three classes: healthy control (68 subjects), craniopharyngioma (58 subjects) and differential sellar/suprasellar tumors (100 subjects). RESULTS: The PPV among classes was 0.828±0.039, and the NPV was 0.919±0.063. Also explainable artificial intelligence (XAI) was used, finding that structures that are relevant during diagnosis and radiological evaluation highly influence the decision-making process of the machine. CONCLUSION: This is the first experience of this kind of study in our institution, and it led to promising results on the task of radiological diagnostic support based on explainable artificial intelligence (AI) and deep learning models.

Targeting IL-6 trans-signalling by sgp130Fc attenuates severity in SARS-CoV-2 -infected mice and reduces endotheliopathy.

BACKGROUND: SARS-CoV-2 infection is considered as a relapsing inflammatory process with a dysregulation of IL-6 signalling. Classic IL-6 signalling is thought to represent a defence mechanism against pathogens. In contrast, IL-6 trans-signalling has pro-inflammatory effects. In severe COVID-19, therapeutic strategies have focused on global inhibition of IL-6, with controversial results. We hypothesized that specific blockade of IL-6 trans-signalling could inhibit inflammatory response preserving the host defence activity inherent to IL-6 classic signalling. METHODS: To test the role of the specific IL-6 trans-signalling inhibition by sgp130Fc in short- and long-term consequences of COVID-19, we used the established K18-hACE2 transgenic mouse model. Histological as well as immunohistochemical analysis, and pro-inflammatory marker profiling were performed. To investigate IL-6 trans-signalling in human cells we used primary lung microvascular endothelial cells and fibroblasts in the presence/absence of sgp130Fc. FINDINGS: We report that targeting IL-6 trans-signalling by sgp130Fc attenuated SARS-CoV-2-related clinical symptoms and mortality. In surviving mice, the treatment caused a significant decrease in lung damage. In vitro, IL-6 trans-signalling induced strong and persisting JAK1/STAT3 activation in endothelial cells and lung fibroblasts with proinflammatory effects, which were attenuated by sgp130Fc. Our data also suggest that in those cells with scant amounts of IL-6R, the induction of gp130 and IL-6 by IL-6:sIL-6R complex sustains IL-6 trans-signalling. INTERPRETATION: IL-6 trans-signalling fosters progression of COVID-19, and suggests that specific blockade of this signalling mode could offer a promising alternative to mitigate both short- and long-term consequences without affecting the beneficial effects of IL-6 classic signalling. These results have implications for the development of new therapies of lung injury and endotheliopathy in COVID-19. FUNDING: The project was supported by ISCIII, Spain (COV-20/00792 to MB, PI23/01351 to MARH) and the European Commission-Next generation EU (European Union) (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global, SGL2103029 to MB). PID2019-110587RB-I00 (MB) supported by MICIN/AEI/10.13039/501100011033/and PID2022-143034OB-I00 (MB) by MICIN/AEI/10.13039/501100011033/FEDER. MAR-H acknowledges support from ISCIII, Spain and the European Commission-Next generation EU (European Union), through CSIC's Global Health PTI.

A Prospective, Observational Study of the Effect of a High-Calorie, High-Protein Oral Nutritional Supplement with HMB in an Old and Malnourished or at-Risk-of-Malnutrition Population with Hip Fractures: A FracNut Study.

BACKGROUND: Hip fractures are prevalent among older people, often leading to reduced mobility, muscle loss, and bone density decline. Malnutrition exacerbates the prognosis post surgery. This study aimed to evaluate the impact of a 12-week regimen of a high-calorie, high-protein oral supplement with ß-hydroxy-ß-methylbutyrate (HC-HP-HMB-ONS) on nutritional status, daily activities, and compliance in malnourished or at-risk older patients with hip fractures receiving standard care. SUBJECTS AND METHODS: A total of 270 subjects ≥75 years of age, residing at home or in nursing homes, malnourished or at risk of malnutrition, and post hip fracture surgery, received HC-HP-HMB-ONS for 12 weeks. Various scales and questionnaires assessed outcomes. RESULTS: During the 12 weeks of follow-up, 82.8% consumed ≥75% of HC-HP-HMB-ONS. By week 12, 62.4% gained or maintained weight (+0.3 kg), 29.2% achieved normal nutritional status (mean MNA score +2.8), and 46.8% improved nutritional status. Biochemical parameters improved significantly. Subjects reported good tolerability (mean score 8.5/10), with 87.1% of healthcare providers concurring. CONCLUSIONS: The administration of HC-HP-HMB-ONS markedly enhanced nutritional status and biochemical parameters in older hip-fracture patients, with high compliance and tolerability. Both patients and healthcare professionals expressed satisfaction with HC-HP-HMB-ONS.

Is There a Safe Alcohol Consumption Limit for the General Population and in Patients with Liver Disease?

Excessive alcohol consumption represents an important burden for health systems worldwide and is a major cause of liver- and cancer-related deaths. Alcohol consumption is mostly assessed by self-report that often underestimates the amount of drinking. While alcohol use disorders identification test - version C is the most widely used test for alcohol use screening, in patients with liver disease the use of alcohol biomarker could help an objective assessment. The amount of alcohol that leads to significant liver disease depends on gender, genetic background, and coexistence of comorbidities (i.e., metabolic syndrome factors). All patients with alcohol-associated liver disease are recommended to follow complete abstinence and they should be treated within multidisciplinary teams. Abstinence slows down and even reverses the progression of liver fibrosis and can help recompensate patients with complicated cirrhosis. Whether there is a safe amount of alcohol in the general population is a matter of intense debate. Large epidemiological studies showed that the safe amount of alcohol to avoid overall health-related risks is lower than expected even in the general population. Even one drink per day can increase cancer-related death. In patients with any kind of chronic liver disease, especially in those with metabolic-associated steatotic liver disease, no alcohol intake is recommended. This review article discusses the current evidence supporting the deleterious effects of small-to-moderate amounts of alcohol in the general population and in patients with underlying chronic liver disease.

Exploring the Nutritional and Bioactive Potential of Olive Leaf Residues: A Focus on Minerals and Polyphenols in the Context of Spain's Olive Oil Production.

Lyophilized plant-origin extracts are rich in highly potent antioxidant polyphenols. In order to incorporate them into food products, it is necessary to protect these phytochemicals from atmospheric factors such as heat, light, moisture, or pH, and to enhance their bioavailability due to their low solubility. To address these challenges, recent studies have focused on the development of encapsulation techniques for antioxidant compounds within polymeric structures. In this study, lyophilized olive leaf extracts were microencapsulated with the aim of overcoming the aforementioned challenges. The method used for the preparation of the studied microparticles involves external ionic gelation carried out within a water-oil (W/O) emulsion at room temperature. HPLC analysis demonstrates a high content of polyphenols, with 90% of the bioactive compounds encapsulated. Meanwhile, quantification by inductively coupled plasma optical emission spectroscopy (ICP-OES) reveals that the dried leaves, lyophilized extract, and microencapsulated form contain satisfactory levels of macro- and micro-minerals (calcium, potassium, sodium). The microencapsulation technique could be a novel strategy to harness the polyphenols and minerals of olive leaves, thus enriching food products and leveraging the antioxidant properties of the polyphenolic compounds found in the lyophilized extract.

Asociación entre metaplasia, displasia y cáncer de vesícula biliar en una EPS de Bogotá, Colombia / Association between metaplasia, dysplasia and gallbladder cancer in an EPS in Bogotá, Colombia

Introducción. El cáncer de vesícula biliar es el más común en el tracto biliopancreático y una importante causa de mortalidad. La metaplasia y la displasia han sido mencionados como probables precursores relacionados con la secuencia metaplasia-displasia-cáncer. El objetivo de este estudio fue establecer las posibles asociaciones entre estas alteraciones histopatológicas y su relación con la edad y el sexo de los pacientes. Métodos. Estudio observacional retrospectivo descriptivo, con un componente analítico de corte transversal. Se incluyeron los informes de patología de pacientes llevados a colecistectomía laparoscópica electiva y ambulatoria, entre enero de 2015 y diciembre de 2020, con colecistitis crónica, colelitiasis o pólipos vesiculares, mayores de 18 años. Se describieron las características demográficas por sexo y edad utilizando medias, desviaciones estándar y porcentajes. Se emplearon la prueba de chi cuadrado y la prueba exacta de Fisher para evaluar la asociación entre las variables cualitativas. Resultados. Se incluyeron 4871 informes de patología. En esta cohorte se encontró asociación estadísticamente significativa entre metaplasia, displasia y cáncer de vesícula (p<0,05), al igual que con el sexo y la edad de los pacientes. Conclusiones. Los resultados sugieren una asociación entre metaplasia, displasia y cáncer de vesícula biliar en la población estudiada. Se recomienda la realización de investigaciones complementarias para definir la posible causalidad entre metaplasia, displasia y cáncer de vesícula biliar en una población más heterogénea.

Introduction. Gallbladder cancer is the most common cancer in the biliopancreatic tract and an important cause of mortality. Metaplasia and dysplasia have been mentioned as probable precursors related to the metaplasia-dysplasia-cancer sequence. The objective of this study was to establish the possible associations between these histopathological alterations and their relationship with the age and sex of the patients. Methods. Descriptive retrospective observational study, with a cross-sectional analytical component. Pathology reports of patients undergoing elective and outpatient laparoscopic cholecystectomy were included between January 2015 and December 2020, with chronic cholecystitis, cholelithiasis, or gallbladder polyps, over 18 years of age. Demographic characteristics by sex and age was performed using means, standard deviations, and percentages. The chi2 test and Fisher's exact test were used to evaluate the association between the qualitative variables. Results. 4871 pathology reports were included. In this cohort, a statistically significant association was found between metaplasia, dysplasia, and gallbladder cancer (p<0.05), as well as with the sex and age of the patients. Conclusions. The results suggest an association between metaplasia, dysplasia and gallbladder cancer in the study population. Additional research is recommended to define the possible causality between metaplasia, dysplasia, and gallbladder cancer in a more heterogeneous population.

Combinatorial Libraries of Bipodal Binders of the Insulin Receptor.

The binding process of insulin to its transmembrane receptor entails a sophisticated interplay between two proteins, each possessing two binding sites. Given the difficulties associated with the use of insulin in the treatment of diabetes, despite its remarkable efficacy, there is interest in smaller and more stable compounds than the native hormone that would effectively activate the receptor. Our study adopts a strategy focused on synthesizing extensive combinatorial libraries of bipodal compounds consisting of two distinct peptides linked to a molecular scaffold. These constructs, evaluated in a resin bead-bound format, were designed to assess their binding to the insulin receptor. Despite notable nonspecific binding, our approach successfully generated and tested millions of compounds. Rigorous evaluations via flow cytometry and specific antibodies revealed peptide sequences with specific interactions at either receptor binding Site 1 or 2. Notably, these sequences bear similarity to peptides discovered through phage display by other researchers. This convergence of chemical and biological methods underscores nature's beauty, revealing general principles in peptide binding to the insulin receptor. Overall, our study deepens the understanding of molecular interactions in ligand binding to the insulin receptor, highlighting the challenges of targeting large proteins with small synthetic peptides.

NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence.

BACKGROUND: Luminal A tumours generally have a favourable prognosis but possess the highest 10-year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post-diagnosis. Identifying such patients is crucial as long-term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment. METHODS: We conducted a study to explore non-structural chromosome maintenance condensin I complex subunit H's (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels. RESULTS: We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)-NCAPHErbB2 double-transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10-gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression. CONCLUSIONS: The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.

Follow-up for 3 years of a pediatric population diagnosed in 2018 with mother-to-child transmission of HIV in 8 Latin American countries in the PLANTAIDS cohort.

INTRODUCTION: The frequency of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in Latin America has decreased considerably. However, new infections continue to be recorded, and the pediatric population remains one of the most vulnerable groups in this region. The main objective of the study was to describe the clinical, epidemiological and psychosocial characteristics of new diagnoses of HIV MTCT in 2018 in the PLANTAIDS network (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children) during the 3 years following diagnosis. METHODOLOGY: Retrospective, multicenter, descriptive study based on a 3-year follow-up of patients diagnosed with HIV infection due to MTCT in 2018 in 10 hospitals in 8 Latin American countries (Costa Rica, Ecuador, Mexico, Honduras, El Salvador, Panama, Guatemala and Venezuela). The hospitals belonged to the PLANTAIDS network, which is included in CYTED (Ibero-American Programme of Science and Technology for Development). RESULTS: The study population comprised 72 pediatric patients (38.9% male). The median age at diagnosis was 2.4 years (IQR: 0.8-5.4). There were 35 cases of opportunistic infections corresponding to 25 patients (34.7%), with tuberculosis being the most common. Adequate childhood vaccination coverage was achieved in 80.5%. There were 3 cases of acute SARS-CoV-2 infection, and these were asymptomatic or mildly symptomatic. According to the Centers for Disease Control and Prevention (CDC) classification, the most frequent clinical-immunological stage at all check-ups was C1. Three patients died from opportunistic infections and/or advanced HIV infection. CONCLUSIONS: It is important to diagnose HIV infection early in pediatrics, since early initiation of ART is associated with a decrease in mortality. Despite this, HIV infection has a poor prognosis in children, necessitating adequate follow-up to ensure adherence to health care and ART, although it can sometimes prove difficult in children.

Enhancing disinfection and microcontaminant removal by coupling LED driven UVC and UVA/photo-Fenton processes in continuous flow reactors.

For the first time, the sequential combination of UVC-LED (276 nm) and photo-Fenton/UVA-LED (376 nm) process has been assessed in continuous flow mode for wastewater reclamation according to the new European Regulation for reuse in agricultural irrigation (EU 2020/741). The results show that it is possible to obtain water quality class B (Escherichia coli ≤ 100 CFU/100 mL) by UVC-LED irradiation alone, operating the system with a hydraulic residence time (HRT) of 6.5 min and liquid depth of 5 cm in the case of secondary effluents with low Escherichia coli load (8.102-3.1.103 CFU/100 mL). As for high bacteria concentrations (1.2-4.2.104 CFU/100 mL), HRTs longer than 30 min are required. The bacterial load has not influenced decontamination, removing 18 ± 4 % of microcontaminants. Coupling the UVC (30-min HRT and 5.0 cm liquid depth) and the UVA/photo-Fenton (60-min and 15-cm liquid depth) systems allows 58 ± 4 % of real organic microcontaminants to be removed, in addition to achieving water quality class B.