Effectiveness and safety of XEN63 in patients with primary-open-angle glaucoma.

This paper evaluates the effectiveness and safety of XEN63 stent, either standalone or in combination with phacoemulsification, in patients with primary open-angle glaucoma (POAG). Eighty eyes from 80 patients with medically uncontrolled POAG were assigned to undergo XEN63 implant. The primary outcome was the surgical success, defined as an intraocular pressure (IOP) lowering from preoperative values ≥ 20% and an IOP absolute value between 6 and 18 mmHg, with or without antiglaucoma medications. Forty-three (53.7%) eyes underwent XEN63-standalone and 37(46.2%) eyes a XEN63 + Phacoemulsification procedure. Success rate was 68.8% (55/80) eyes in the overall study sample, 69.8% (30/43) eyes in the XEN63-standalone group; and 67.6% (25/37) eyes in the XEN63 + Phaco group (p = 0.6133). Preoperative IOP was significantly lowered from 22.1 ± 4.9 mmHg and 19.8 ± 3.7 mmHg to 14.7 ± 5.3 mmHg and 13.8 ± 3.4 mmHg in the XEN63-standalone and XEN63 + Phaco groups, respectively (p < 0.0001 each, respectively); without significant differences between them at any of the time-points measured. Preoperative number of ocular-hypotensive drugs was significantly reduced from 2.3 ± 0.8 to 0.3 ± 0.7 drugs, from 2.5 ± 0.7 to 0.3 ± 0.7 drugs; and from 2.0 ± 0.8 to 0.3 ± 0.7 drugs, in the overall, XEN63-standalone, and XEN63 + Phaco groups, respectively. Regarding safety, 3(42.5%) eyes had transient hypotony at some point during the study, although only in one (1.2%) eye was clinically significant. Four (5.0%) eyes underwent a needling, 4 (5.0%) eyes underwent surgical-bleb-revision, 1 (1.2%) eye required a device replacement and 1 (1.2%) eye a device removal due to maculopathy. XEN63, either alone or in combination with phacoemulsification, significantly lowered IOP and reduced the number of ocular hypotensive medications. The rate of ocular hypotony was relatively high, although it was clinically relevant only in one eye.

Real-World Retrospective Analysis of Alemtuzumab Outcomes in Relapsing-Remitting Multiple Sclerosis: The LEMCAM Study.

BACKGROUND: Alemtuzumab is a high-efficacy treatment approved for relapsing-remitting multiple sclerosis (RRMS). Although clinical trials and observational studies are consistent in showing its efficacy and manageable safety profile, further studies under clinical practice conditions are needed to further support its clinical use. OBJECTIVE: The aim of this observational retrospective study was to evaluate the effectiveness and safety of alemtuzumab to add to the current real-world evidence on the drug. METHODS: A cohort of 115 adult patients with RRMS treated with alemtuzumab between 2014 and 2020 was retrospectively followed up in five centers in Spain. Analysis included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW), 6-month confirmed disability improvement (CDI), radiological activity, no evidence of disease activity (NEDA-3), and safety signals. Given the different follow-up periods among participants, ARR was calculated using the person-years method. CDI was defined as a ≥ 1.0-point decrease in Expanded Disability Status Scale (EDSS) score assessed in patients with a baseline EDSS score ≥ 2.0 confirmed 6 months apart. CDW was defined as a ≥ 1.0-point increase in EDSS score assessed in patients with a baseline EDSS score ≥ 1.0 (≥ 1.5 if baseline EDSS = 0), confirmed 6 months apart. RESULTS: ARR decreased from 1.9 (95% confidence interval 1.60-2.33) in the year prior to alemtuzumab initiation to 0.28 (0.17-0.37) after 1 year of treatment (87% reduction), and to 0.22 (0.13-0.35) after the second year. Over the entire follow-up period, ARR was 0.24 (0.18-0.30). At year 1, 75% of patients showed no signs of magnetic resonance imaging (MRI) activity and 70% at year 5. One percent of patients experienced 6-month CDW at year 1, 2.6% at year 2, 7.4% at year 3, and no patients over years 4 and 5. A total of 7.7% of patients achieved 6-month CDI in year 1, 3.6% in year 2, and maintained it at years 3 and 4. Most patients achieved annual NEDA-3: year 1, 72%; year 2, 79%; year 3, 80%; year 4, 89%; year 5, 75%. Infusion-related reactions were observed in 95% of patients and infections in 74%. Thyroid disorders occurred in 30% of patients, and only three patients developed immune thrombocytopenia. No cases of progressive multifocal leukoencephalopathy were reported. CONCLUSIONS: This study shows that alemtuzumab reduced the relapse rate and disability worsening in real-world clinical practice, with many patients achieving and sustaining NEDA-3 over time. The safety profile of alemtuzumab was consistent with previous findings, and no new or unexpected safety signals were observed. As this was an observational and retrospective study, the main limitation of not having all variables comprehensively available for all patients should be considered when interpreting results.

Alteraciones genéticas asociadas a la enfermedad de Parkinson y Alzheimer: evolución y respuesta al tratamiento / Genetic Alterations Associated with Parkinson's and Alzheimer's Disease: Evolution and Response to Treatment

La enfermedad de Parkinson y Alzheimer son las enfermedades neurodegenerativas más frecuentes a nivel mundial. Tienen etiología multifactorial, entre ellas, la genética; y son motivo de interés en la investigación científica actual. Se realizó una revisión narrativa con el objetivo de determinar las alteraciones genéticas asociadas a estas patologías, además su influencia en la evolución y respuesta al tratamiento de ellas. Se consultaron artículos originales, revisiones bibliográficas, sistemáticas, metaanálisis en inglés y español, con fecha de publicación entre el 1 enero de 2018 y el 20 de mayo de 2023, en bases como PubMed y Medline. Se utilizaron los términos MeSH «Alzheimer Disease¼, «Parkinson Disease¼, «Drug Therapy¼ y «Mutations¼. El riesgo hereditario para la enfermedad de Parkinson suele ser poligenético, sin embargo, existen genes relacionados con mutaciones monogénicas. Se identifican alteraciones en genes de α-sinucleína, glucocerebrosidasa y quinasa 2 rica en leucina que se relacionan con mayor riesgo de desarrollar Parkinson, además de variaciones en el cuadro clínico y edad de inicio de síntomas. En cuanto a la enfermedad de Alzheimer, las alteraciones en los genes de la proteína precursora amiloide, presenilina 1 y 2 se relacionan con la forma familiar de la enfermedad; por otra parte, las de apolipoproteína E4 se han identificado en la forma esporádica, por lo que se consideran como el factor de riesgo genético más importante para su desarrollo

Parkinson's and Alzheimer's are the most frequent neurodegenerative diseases worldwide. They have a multifactorial etiology, including genetics, and are of interest in current scientific research. A narrative review was carried out with the aim of determining the genetic alterations associated with these pathologies, as well as their influence on their evolution and response to treatment. Original articles, literature reviews, systematic reviews, meta-analyses in English and Spanish, with publication date between January 1, 2018 and May 20, 2023, were consulted in databases such as PubMed and Medline. MeSH terms "Alzheimer Disease", "Parkinson Disease", "Drug Therapy" and "Mutation" were used. Hereditary risk for Parkinson's disease is usually polygenetic, however, there are genes related to monogenic mutations. Alterations in α-synuclein, glucocerebrosidase and leucine-rich kinase 2 genes have been identified that are related to an increased risk of developing Parkinson's disease, in addition to variations in the clinical picture and age of symptom onset. As for Alzheimer's disease, alterations in the genes of the amyloid precursor protein, presenilin 1 and 2 are related to the familial form of the disease; on the other hand, those of apolipoprotein E4 have been identified in the sporadic form, and are therefore considered to be the most important genetic risk factor for its development

Soluble galectin-3 as a microenvironment-relevant immunoregulator with prognostic and predictive value in lung adenocarcinoma.

Despite the success of therapies in lung cancer, more studies of new biomarkers for patient selection are urgently needed. The present study aims to analyze the role of galectin-3 (GAL-3) in the lung tumor microenvironment (TME) using tumorspheres as a model and explore its potential role as a predictive and prognostic biomarker in non-small cell lung cancer patients. For in vitro studies, lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) primary cultures from early-stage patients and commercial cell lines were cultured, using tumorsphere-forming assays and adherent conditions for the control counterparts. We analyzed the pattern of secretion and expression of GAL-3 using reverse transcription-quantitative real-time PCR (RTqPCR), immunoblot, immunofluorescence, flow cytometry, and immunoassay analysis. Our results using three-dimensional (3D) models of lung tumor cells revealed that soluble GAL-3 (sGAL-3) is highly expressed and secreted. To more accurately mimic the TME, a co-culture of tumorspheres and fibroblasts was used, revealing that GAL-3 could be important as an immunomodulatory molecule expressed and secreted in the TME, modulating immunosuppression through regulatory T cells (TREGS ). In the translational phase, we confirmed that patients with high expression levels of GAL-3 had more TREGS , which suggests that tumors may be recruiting this population through GAL-3. Next, we evaluated levels of sGAL-3 before surgery in LUAD and LUSC patients, hypothesizing that sGAL-3 could be used as an independent prognostic biomarker for overall survival and relapse-free survival in early-stage LUAD patients. Additionally, levels of sGAL-3 at pretreatment and first response assessment from plasma to predict clinical outcomes in advanced LUAD and LUSC patients treated with first-line pembrolizumab were evaluated, further supporting that sGAL-3 has a high efficiency in predicting durable clinical response to pembrolizumab with an area under curve of 0.801 (P = 0.011). Moreover, high levels might predict decreased progression-free survival and OS to anti-PD-1 therapy, with sGAL-3 being a prognosis-independent biomarker for advanced LUAD.

Circulating Immune Proteins: Improving the Diagnosis and Clinical Outcome in Advanced Non-Small Cell Lung Cancer.

Immunotherapy has been proven a viable treatment option for non-small cell lung cancer (NSCLC) treatment in patients. However, some patients still do not benefit. Finding new predictive biomarkers for immunocheckpoint inhibitor (ICI) response will improve treatment management in the clinical routine. In this regard, liquid biopsy is a useful and noninvasive alternative to surgical biopsies. In the present study, we evaluated the potential diagnostic, prognostic, and predictive value of seven different soluble mediators involved in immunoregulation. Fifty-two plasma samples from advanced NSCLC treated in first-line with pembrolizumab at baseline (PRE) and at first response assessment (FR) were analyzed. In terms of diagnostic value, our results revealed that sFGL1, sGAL-3, and sGAL-1 allowed for optimal diagnostic efficacy for cancer patients. Additionally, the combination of sFGL1 and sGAL-3 significantly improved diagnostic accuracy. Regarding the predictive value to assess patients' immune response, sCD276 levels at PRE were significantly higher in patients without tumor response (p = 0.035). Moreover, we observed that high levels of sMICB at PRE were associated with absence of clinical benefit (pembrolizumab treatment less than 6 months) (p = 0.049), and high levels of sMICB and sGAL-3 at FR are also related to a lack of clinical benefit (p = 0.027 and p = 0.03, respectively). Finally, in relation to prognosis significance, at PRE and FR, sMICB levels above the 75th percentile are related to poor progression-free survival (PFS) (p = 0.013 and p = 0.023, respectively) and overall survival (OS) (p = 0.001 and p = 0.011, respectively). An increase in sGAL3 levels at FR was associated with worse PFS (p = 0.037). Interestingly, high sGAL-3 at PRE was independently associated with PFS and OS with a hazard ratio (HR) of 2.45 (95% CI 1.14-5.25; p = 0.021) and 4.915 (95% CI 1.89-12.73; p = 0.001). In conclusion, plasma levels of sFGL1, sGAL-3, and sGAL-1 could serve as diagnostic indicators and sMICB, sCD276, and sGAL3 were linked to outcomes, suggesting their potential in assessing NSCLC under pembrolizumab treatment. Our results highlight the value of employing soluble immune biomarkers in advanced lung cancer patients treated with pembrolizumab at first-line.

Safe Care and Medication Intake Provided by Caregivers at Home: Reality Care Study Protocol.

JUSTIFICATION: Providing care to patients with several conditions and simultaneously taking several medications at home is inexorably growing in developed countries. This trend increases the chances of home caregivers experiencing diverse errors related with medication or care. OBJECTIVE: To determine the effectiveness of four different educational solutions compared to the natural intervention (absence of intervention) to provide a safer care at home by caregivers. METHOD: Prospective, parallel, and mixed research study with two phases. Candidates: Home-based caregivers caring a person with multiple comorbid conditions or polymedication who falls into one of the three profiles of patients defined for the study (oncology, cardiovascular, or pluripathological patients). First phase: Experts first answered an online survey, and then joined together to discuss the design and plan the content of educational solutions directed to caregivers including the identification of medication and home care errors, their causes, consequences, and risk factors. Second phase: The true experiment was performed using an inter- and intrasubject single-factor experimental design (five groups: four experimental groups against the natural intervention (control), with pre- and post-intervention and follow-up measures) with a simple random assignment, to determine the most effective educational solution (n = 350 participants). The participants will be trained on the educational solutions through 360 V, VR, web-based information, or psychoeducation. A group of professionals called the "Gold Standard" will be used to set a performance threshold for the caring or medication activities. The study will be carried out in primary care centers, hospitals, and caregivers' associations in the Valencian Community, Andalusia, Madrid, and Murcia. EXPECTED RESULTS: We expect to identify critical elements of risk management at home for caregivers and to find the most effective and optimal educational solution to reduce errors at home, increasing caregivers' motivation and self-efficacy whilst the impact of gender bias in this activity is reduced. TRIAL REGISTRATION: Clinical Trial NCT05885334.

LED-light-driven over ZnO/biochar nanocomposite for activation of peroxymonosulfate to enhanced photocatalytic removal of methyl orange dye in aqueous solutions.

ABSTRACTOrganic dyes are stable and persistent toxic compounds in the aquatic environment that are refractory to decompose by removal methods such as physico-chemical, optical and biological. Their presence in the aquatic media threatens human and wildlife. Herein, ZnO nanoparticles (NPs) due to good chemical durability, low cost and good photocatalytic performance was anchored on biochar (ZnO@biochar) nanocomposites were synthesized towards activation of peroxymonosulfate (PMS) for the photocatalytic removal of methyl orange (MO) dye. Several methods were used to characterization of the nanocomposites including FESEM, XRD, PL, EDS, FT-IR spectroscopy, and N2 adsorption/desorption. The results of the techniques demonstrated that the well-dispersed ZnO NPs were loaded onto the biochar surface. According to the particle size distribution graph, the average particle size of 64 nm was obtained for the ZnO NPs. BET analyzes showed that pore volume, the specific surface area (SSA) and average pore size of the synthesized nanocomposite increased. The survey of effective operational parameters indicated that the highest photocatalytic activity for MO removal was in the pH 3 of solution, 5 ppm initial dye concentration, 30 mg ZnO/biochar nanocomposite, and 20 mg PMS dose under LED-50W lamp irradiation (97.03% in the reaction time of 80 min). During the process, the reduction of the total organic carbon (TOC) contents and chemical oxygen demand (COD) were observed. Moreover, the MO degradation kinetics under optimal operating conditions were determined. It is concluded that the ZnO@biochar nanocomposite/PMS process was an efficient degradation method for the decomposition of the dye pollutant.

Advanced oxidation processes for phthalate esters removal in aqueous solution: a systematic review.

This study addresses a systematic review of the scientific literature to evaluate the most common advanced oxidation processes (AOP) for the removal of phthalate esters (PE) in aqueous matrices. Six AOP were reviewed for PE degradation such as processes based on photolysis, Fenton, ozonation and sulfate radicals ( SO 4 • - ), combined AOP and other processes. The PE degradation efficiencies by AOP processes ranged from 40.3 to 100%. In the reviewed literature, an initial PE concentration within 0.04-250 mg/L was applied. The H2O2 concentrations used in the UV/H2O2 process and O3 concentrations in ozonation-based processes ranged between 0.85-1,360.6 mg/L and 2-4,971 mg/L, respectively. Based on the reported results, the PE oxidation data fit well to the pseudo-first order kinetic model. A review of the studies revealed that many oxidant species are produced in the AOP, including hydroxyl radicals (•OH), SO 4 • - , superoxide radical anions ( O 2 - • ), hydroperoxyl radicals (HO2 •), hydrogen peroxide (H2O2), and singlet oxygen (O2). Among these oxidants, •OH play a key role in the degradation of PE. However, SO 4 • - are more effective and efficient than •OH since SO 4 • - has a higher oxidation power (E = 2.5-3.1 V) compared to •OH radicals (E = 1.8-2.7 V). In different AOP processes, the aromatic rings of PE are destroyed by •OH and produce intermediates such as phthalic acid (C6H4(CO2H)2), benzoic acid ethyl ester (C9H10O2), 2, 5-dihydroxybenzoic acid (C7H6O4), formic acid (CH2O2), acetic acid (CH3COOH), and oxalic acid (C2H2O4), among some others. Until now, limited data have been reported on PE toxicity assessment. The reviewed literature has shown that AOP can be used effectively to degrade PE from aqueous matrices. However, this systematic study suggests focusing more on the evaluation of the toxicity of the effluent resulting from AOP for the decomposition of PE in future studies.

Linfangiectasia intestinal primaria en síndrome de Klippel-Trénaunay. Manejo anestésico a propósito de un caso / Primary intestinal lymphagiectasia in Klippel-Trénaunay syndrome. Anesthetic management. Case report

Resumen: El síndrome de Klippel-Trénaunay con linfangiectasia intestinal primaria asociada es una entidad de aparición poco frecuente en pediatría. Se presenta con edemas por hipoproteinemia y, en algunos casos, con ascitis. El objetivo es presentar un caso clínico cuyo diagnóstico fue certificado mediante endoscopía intestinal y biopsia. Debido a la ascitis refractaria, el tratamiento fue quirúrgico y se realizó derivación peritoneo venosa. El manejo anestésico de este tipo de pacientes se ha descrito en informes limitados, por lo que en el presente caso hacemos énfasis en la terapia de soporte con perfusión de albúmina como tratamiento sintomático propuesto para pacientes con drenaje masivo de ascitis.

Abstract: Klippel-Trénaunay syndrome with associated primary intestinal lymphangiectasia is a rare entity in pediatrics. It presents with edema due to hypoproteinemia, and in some cases with ascites. The objective is to present a clinical case whose diagnosis was certified by intestinal esdoscopy and biopsy. For refractary ascities, the treatment was surgical, performing peritoneal venous bypass. The anesthetic management of this type of patients has been described in limited reports, so in the present case we emphasize supportive therapy with albumin infusion as the proposed symptomatic treatment for patients with massive drainage of ascities.

XEN Gel Stent Versus Nonpenetrating Deep Sclerectomy in Ocular Hypertension and Open Angle Glaucoma Patients.

PRCIS: XEN gel stent and nonpenetrating deep sclerectomy, both either alone or in combination with cataract surgery, significantly lowered the intraocular pressure (IOP) and reduced the number of antiglaucoma medications in patients with open angle glaucoma, with no significant differences between them. PURPOSE: To compare the surgical outcomes of XEN45 implant and nonpenetrating deep sclerectomy (NPDS), either alone or in combination with cataract surgery, in patients with ocular hypertension and open angle glaucoma (OAG). A retrospective and single-center cohort study was conducted on consecutive patients who underwent a XEN45 implant or an NPDS, either alone or in combination with phacoemulsification. The primary endpoint was the mean change in IOP from the baseline to the last follow-up visit. One hundred twenty-eight eyes, 65 (50.8%) eyes in the NPDS group and 63 (49.2%) eyes in the XEN group, were included in the study. The mean preoperative IOP was significantly lowered from 17.6±5.3 mm Hg and 17.8±6.2 mm Hg to 12.6±2.6 mm Hg and 13.8±2.8 mm Hg at month 12 in the XEN and NPDS groups, respectively; P <0.0001 each. At month 12, 70 (54.7%) eyes were classified as a success, with no significant differences between XEN (57.1%; 36/63 eyes) and NPDS (52.3%; 34/65 eyes) (mean difference: 4.8%; 95% CI: -30.5% to 20.8%; P =0.7115). The number of ocular hypotensive medications was significantly reduced in the XEN (from 2.1±0.7-0.2±0.5, P <0.0001) and in the NPDS (from 2.0±0.8 to 0.3±0.6, P <0.0001) groups, with no significant differences between them ( P =0.2629). The incidence of postoperative adverse events in the overall study population was 12.5%, with no significant differences between groups ( P =0.1275). Seven (11.1%) eyes underwent needling (XEN group) and 10 (15.4%) goniopuncture (NPDS group); P =0.4753. CONCLUSIONS: XEN45 implant and the NPDS, either alone or in combination with cataract surgery, significantly lowered IOP and reduced the number of ocular hypotensive medications in ocular hypertension and patients with open angle glaucoma.

An updated systematic review on the maternal exposure to environmental pesticides and involved mechanisms of autism spectrum disorder (ASD) progression risk in children.

Autism spectrum disorder (ASD) increased dramatically over the past 25 years because of genetic and environmental factors. This systematic review (SR) aimed to determine the association between maternal exposure during pregnancy to environmental pesticides and other associations with the risk of ASD progression in children. PubMed (MEDLINE), Scopus (Elsevier) and the Institute for Scientific Information (ISI) Web of Science were searched using appropriate keywords up to March 2021. Twenty-four studies met the inclusion/exclusion criteria and were selected. Most studies reported that ASD increases the risk of offspring after prenatal exposure to environmental pesticides in pregnant mother's residences, against offspring of women from the same region without this exposure. The main potential mechanisms inducing ASD progressions are ROS and prostaglandin E2 synthesis, AChE inhibition, voltage-gated sodium channel disruption, and GABA inhibition. According to the included studies, the highest rates of ASD diagnosis increased relative to organophosphates, and the application of the most common pesticides near residences might enhance the prevalence of ASD.

Using biomonitoring as a complementary approach in BTEX exposure assessment in the general population and occupational settings: a systematic review and meta-analysis.

Hazardous organic compounds such as benzene, toluene, ethylbenzene, o-xylene, m-xylene, and p-xylene (known as BTEX) found at work and at home can cause adverse health effects of human beings throughout their lives. Biological monitoring, an exposure assessment method, considers all exposed organic and non-organic compounds. Our goal was to perform a systematic review and a statistical analysis (meta-analysis) of peer-reviewed publications to assess urinary concentrations of BTEX biomarkers in both occupationally-exposed population and the general population. Several major electronic databases, including Scopus, Embase, Medline, Web of Science, and Google scholar (grey literature), were searched for biomonitoring studies of BTEX. Overall, 33 studies met the eligible criteria for the systematic review and six met the full inclusion criteria for meta-analysis. For meta-analysis, we included studies in which unmetabolized BTEX compounds were measured in urine samples. Due to insufficient data, studies that measured BTEX metabolites in urine samples and unmetabolized BTEX compounds in blood samples were excluded from the meta-analysis but were analyzed in the qualitative synthesis. Most studies showed increased urinary concentrations of BTEX in exposed individuals (mainly workers) compared to unexposed individuals. The results showed that the highest total BTEX concentrations were recorded in painters and policemen. This study showed that the undoubted associations between lifestyle and environmental factors and urinary levels of BTEX or its metabolites have not yet been confirmed in current biomonitoring studies. This is attributed to the few studies reported in this research area, the lack of homogeneous information, and the disagreement in the published results of the studies.

The role of polybrominated diphenyl ethers in the induction of cancer: a systematic review of insight into their mechanisms.

Environmental pollution caused by persistent organic pollutants (POPs) has increased the challenge for the scientific communities. Polybrominated diphenyl ethers (PBDEs), classified as POPs, are widely applied in various materials as brominated flame retardants (BFRs). Because of the nature of these chemical compounds including toxicity, stability, and capability to bioaccumulate and biomagnify, PBDEs have posed a great challenge and risk to human health and wildlife. Therefore, the side effects of exposure to PBDEs as ubiquitous pollutants in the environment on cancer progression were investigated using a systematic review (SR) survey. To achieve this goal, forty studies were considered after defining the search terms and inclusion criteria, and/or exclusion criteria; the eligible records were collected from the international bibliographic databases. Based on the findings of the reviewed records, environmental exposure to the BFRs including PBDEs has a positive association with different mechanisms that induce cancer progression. However, the findings of the reviewed studies were not totally consistent with the mode of action and side effects are yet to be fully elucidated. Several articles have reported that BFRs can be carcinogenic and induce epithelial to mesenchymal transition via different mechanisms. The main mode of action involved in the environmental exposure to BFRs and the risk of cancer progression is endoplasmic reticulum and oxidative stress (OS). Generally, the imbalance of antioxidant mechanisms, reactive nitrogen species (RNSs) and reactive oxygen species (ROSs), during damage in cells, and stress caused OS, which increases tumorigenesis via multiple mechanisms, such as DNA damage, inflammation, and angiogenesis.

Percepción de brechas y oportunidades en eSalud de estudiantes de último año de Medicina en Colombia

Introducción: En los últimos años la explosión de dispositivos con acceso a internet en el mundo ha presentado una oportunidad para el desarrollo de intervenciones en salud. Métodos: Se realizó un estudio observacional transversal de tipo descriptivo; se clasificaron las propuestas de innovación presentadas por estudiantes de último año de medicina como trabajo final de un curso de eSalud. Los proyectos se clasificaron en tres dimensiones: grupo poblacional, problema de salud a resolver y tipo de intervención de salud digital. Resultados: Se analizaron 86 proyectos entre los años 2017 y 2020. El 80,2 % se orienta a la población general, seguidos por la gestante (10,4 %), la infantil (8,14 %) y la geriátrica (1,2 %). El 36 % de los proyectos no mencionaban una condición particular de salud; el 12,8 % se dedicó a la salud sexual y reproductiva; el 10,4 % a las enfermedades cardiovasculares; el 9,3 % a la salud mental y el 4,65 % a aspectos de crecimiento y desarrollo. El 59,3 % de los proyectos se dirigía a apoyar las actividades del prestador de servicios de salud; el 34,9 % estaba orientado hacia las necesidades de los usuarios de los sistemas de salud y el 5,9 % se enfocó en los servicios de datos. Conclusiones: La percepción colectiva de los estudiantes refleja la oportunidad de fortalecer la atención primaria en salud mediante el uso de las tecnologías de la información y las comunicaciones, con énfasis en las poblaciones vulnerables. Los estudiantes empiezan a identificar los servicios de datos como oportunidad de intervención.

Introduction: In recent years, the explosion of devices with Internet access in the world has presented an opportunity for the development of health interventions. Methods: A descriptive cross-sectional observational study was carried out. Innovation proposals submitted by last-year medical students were classified as the final project of an eHealth course. The projects were classified into three dimensions: population group, health problem to be solved, and type of digital health intervention. Results: Eighty-six projects were analyzed from 2017 to 2020. 80.2% were aimed at the general population, followed by pregnant women (10.4%), children (8.14%) and geriatrics (1, 2 %). 36% of the projects did not mention a particular health condition; 12.8% was dedicated to sexual and reproductive health; 10.4% to cardiovascular diseases; 9.3% to mental health and 4.65% to aspects of growth and development. 59.3% of the projects were aimed at supporting the activities of the health service provider; 34.9% were oriented towards the needs of users of health systems and 5.9% focused on data services. Conclusions: The collective perception of the students reflects the opportunity to strengthen primary health care through the use of information and communication technologies, with emphasis on vulnerable populations. Students begin to identify data services as an opportunity for intervention.

Comparison of Three Comorbidity Measures for Predicting In-Hospital Death through a Clinical Administrative Nacional Database.

BACKGROUND: Various authors have validated scales to measure comorbidity. However, the prognosis capacity variation according to the comorbidity measurement index used needs to be determined in order to identify which is the best predictor. AIMS: To quantify the differences between the Charlson (CCI), Elixhauser (ECI) and van Walraven (WCI) comorbidity indices as prognostic factors for in-hospital mortality and to identify the best comorbidity measure predictor. METHODS: A retrospective observational study that included all hospitalizations of patients over 18 years of age, discharged between 2017 and 2021 in the hospital, using the Minimum Basic Data Set (MBDS). We calculated CCI, ECI, WCI according to ICD-10 coding algorithms. The correlation and concordance between the three indices were evaluated by Spearman's rho and Intraclass Correlation Coefficient (ICC), respectively. The logistic regression model for each index was built for predicting in-hospital mortality. Finally, we used the receiver operating characteristic (ROC) curve for comparing the performance of each index in predicting in-hospital mortality, and the Delong method was employed to test the statistical significance of differences. RESULTS: We studied 79,425 admission episodes. The 54.29% were men. The median age was 72 years (interquartile range [IQR]: 56-80) and in-hospital mortality rate was 4.47%. The median of ECI was = 2 (IQR: 1-4), ICW was 4 (IQR: 0-12) and ICC was 1 (IQR: 0-3). The correlation was moderate: ECI vs. WCI rho = 0.645, p < 0.001; ECI vs. CCI rho = 0.721, p < 0.001; and CCI vs. WCI rho = 0.704, p < 0.001; and the concordance was fair to good: ECI vs. WCI Intraclass Correlation Coefficient type A (ICCA) = 0.675 (CI 95% 0.665-0.684) p < 0.001; ECI vs. CCI ICCA = 0.797 (CI 95% 0.780-0.812), p < 0.001; and CCI vs. WCI ICCA = 0.731 (CI 95% 0.667-0.779), p < 0.001. The multivariate regression analysis demonstrated that comorbidity increased the risk of in-hospital mortality, with differences depending on the comorbidity measurement scale: odds ratio [OR] = 2.10 (95% confidence interval [95% CI] 2.00-2.20) p > |z| < 0 using ECI; OR = 2.31 (CI 95% 2.21-2.41) p > |z| < 0 for WCI; and OR = 2.53 (CI 95% 2.40-2.67) p > |z| < 0 employing CCI. The area under the curve [AUC] = 0.714 (CI 95% 0.706-0.721) using as a predictor of in-hospital mortality CCI, AUC = 0.729 (CI 95% 0.721-0.737) for ECI and AUC = 0.750 (CI 95% 0.743-0.758) using WCI, with statistical significance (p < 0.001). CONCLUSION: Comorbidity plays an important role as a predictor of in-hospital mortality, with differences depending on the measurement scale used, the van Walraven comorbidity index being the best predictor of in-hospital mortality.

New Ceramic Multi-Unit Dental Abutments with an Antimicrobial Glassy Coating.

The choice of suitable materials and new designs in oral implantology and the subsequent enhancement of the characteristics of the dental implant developed is an important research topic with wide scope. The present work aims to develop a new multifunctional zirconia-ceria/alumina (Ce-TZP/Al2O3) composite with an antimicrobial glass-based coating to be used in multi-unit abutments compatible with commercially available Ti implants for peri-implantitis prevention. An airbrush spraying technique was effectively applied to coat the sintered ceramic composite starting from a glass powder suspension. This deposition technique was appropriate for obtaining continuous antimicrobial glass-based coatings with homogenous thickness (~35 µm) on ceramic dental implant components. The dental implant systems with the antimicrobial glassy coating were subjected to a mechanical integrity test following ISO 14801 to determine their long-term stability. The tested implant-coating structure seems to be stable under in vitro conditions with ultimate applied forces exceeding the maximum physiological occlusal loading force. This paper also presents a pilot clinical case report that shows peri-implant tissue around the mechanically stable glass coating with no signs of inflammation 1 year after implant insertion. This result is a preliminary probe of the durability and biological tolerance of the glassy material by the gingiva, as well as the antimicrobial effect on the peri-implant microbiota displayed by the coating.

Analysis of Exosomal Cargo Provides Accurate Clinical, Histologic and Mutational Information in Non-Small Cell Lung Cancer.

Lung cancer is a malignant disease with high mortality and poor prognosis, frequently diagnosed at advanced stages. Nowadays, immense progress in treatment has been achieved. However, the present scenario continues to be critical, and a full comprehension of tumor progression mechanisms is required, with exosomes being potentially relevant players. Exosomes are membranous vesicles that contain biological information, which can be transported cell-to-cell and modulate relevant processes in the hallmarks of cancer. The present research aims to characterize the exosomes' cargo and study their role in NSCLC to identify biomarkers. We analyzed exosomes secreted by primary cultures and cell lines, grown in monolayer and tumorsphere formations. Exosomal DNA content showed molecular alterations, whereas RNA high-throughput analysis resulted in a pattern of differentially expressed genes depending on histology. The most significant differences were found in XAGE1B, CABYR, NKX2-1, SEPP1, CAPRIN1, and RIOK3 genes when samples from two independent cohorts of resected NSCLC patients were analyzed. We identified and validated biomarkers for adenocarcinoma and squamous cell carcinoma. Our results could represent a relevant contribution concerning exosomes in clinical practice, allowing for the identification of biomarkers that provide information regarding tumor features, prognosis and clinical behavior of the disease.

The cellular function of ROP GTPase prenylation is important for multicellularity in the moss Physcomitrium patens.

A complete picture of how signaling pathways lead to multicellularity is largely unknown. Previously, we generated mutations in a protein prenylation enzyme, GGB, and showed that it is essential for maintaining multicellularity in the moss Physcomitrium patens. Here, we show that ROP GTPases act as downstream factors that are prenylated by GGB and themselves play an important role in the multicellularity of P. patens. We also show that the loss of multicellularity caused by the suppression of GGB or ROP GTPases is due to uncoordinated cell expansion, defects in cell wall integrity and the disturbance of the directional control of cell plate orientation. Expressing prenylatable ROP in the ggb mutant not only rescues multicellularity in protonemata but also results in development of gametophores. Although the prenylation of ROP is important for multicellularity, a higher threshold of active ROP is required for gametophore development. Thus, our results suggest that ROP activation via prenylation by GGB is a key process at both cell and tissue levels, facilitating the developmental transition from one dimension to two dimensions and to three dimensions in P. patens.