Adverse effects of CXCR2 deficiency in mice reared under non-gnotobiotic conditions.

The family of pro-inflammatory and pro-angiogenic chemokines including Interleukin-8 (IL-8, aka CXCL8) and its homologues (CXCL1,2,3,5,6, and 7) exhibit promiscuous binding and activation of several G-protein-coupled receptors (i.e., CXCR2, CXCR1, and the atypical chemokine receptor (ACKR1)). A high proportion of their biological activity is attributed to CXCR2 activation, thus many CXCR2 inhibitors are in clinical trials for several chronic diseases. However, CXCR2 inhibition is often only investigated acutely in these trials or in Cxcr2-/- mice grown in gnotobiotic conditions. Since humans do not live in germ-free environments, our first goal is to highlight novel retinal and systemic observations in Cxcr2-/- mice grown in non-gnotobiotic conditions that suggest potential harmful consequences of long-term CXCR2 deficiency or blockade. Beyond confirmation of circulating blood/immune cell-related phenotypes, we report novel findings in Cxcr2-/- mice including: (1) delayed dye transit to the retinal vasculature, (2) alterations in the density and distribution of retinal vessels, astrocytes and microglia, (3) decreased electroretinogram a- and b-wave amplitudes, (4) reduced visual acuity, and (5) increased polymorphonuclear cell accumulation in vascular lumina abutting venular walls in the retina and in vital non-ocular tissues (lung and liver). Furthermore, PheWAS of CXCR2 CXCR1, and ACKR1 gene variants using data from UK Biobank participants suggest clinical associations with both retinal and vascular disease phenotypes. We conclude that chronic CXCR2 deficiency in mice contributes to functional damage to the retina and that the long-term safety of CXCR1/2 inhibitors designed for chronic use in humans should be explored before clinical adoption to safeguard sight and overall vascular health.

Induction, amplification, and propagation of diabetic retinopathy-associated inflammatory cytokines between human retinal microvascular endothelial and Müller cells and in the mouse retina.

Ocular levels of IL-1ß, TNFα, IL-8, and IL-6 correlate with progression of diabetic retinopathy (DR). Müller cells (MC), which are crucial to maintaining retinal homeostasis, are targets and sources of these cytokines. We explored the relative capacities of these four DR-associated cytokines to amplify inflammatory signal expression both in and between human MC (hMC) and retinal microvascular endothelial cells (hRMEC) and in the mouse retina. Of the four cytokines, IL-1ß was the most potent stimulus of transcriptomic alterations in hMC and hRMEC in vitro, as well as in the mouse retina after intravitreal injection in vivo. Stimulation with IL-1ß significantly induced expression of all four transcripts in hMC and hRMEC. TNFα significantly induced expression of some, but not all, of the four transcripts in each cell, while neither IL-8 nor IL-6 showed significant induction in either cell. Similarly, conditioned media (CM) derived from hMC or hRMEC treated with IL-1ß, but not TNFα, upregulated inflammatory cytokine transcripts in the reciprocal cell type. hRMEC responses to hMC-derived CM were dependent on IL-1R activation. In addition, we observed a correlation between cytokine expression changes following direct and CM stimulation and NFκB-p65 nuclear translocation in both hMC and hRMEC. Finally, in mice, intravitreal injections of IL-1ß, but not TNFα, induced retinal expression of Il1b and CXCL8 homologues Cxcl1, Cxcl2, Cxcl3, and Cxcl5, encoding pro-angiogenic chemokines. Our results suggest that expression of IL-1ß, TNFα, IL-8, and IL-6 may be initiated, propagated, and sustained by autocrine and paracrine signals in hRMEC and hMC through a process involving IL-1ß and NFκB. Targeting these signals may help thwart inflammatory amplification, preventing progression to vision-threatening stages and preserving sight.

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

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

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

Anatomical factors of the maxillary tuberosity that influence molar distalization.

Objective: To examine the areas of the maxillary tuberosity (MT) (coronal, apical, width, and height) with respect to the presence or absence of the third molar to establish possible anatomical limitations for molar distalization. Methods: A total of 277 tuberosities were evaluated through sagittal computed tomography (CT) images, divided for measurement into coronal (free of bone), apical (area of influence of the maxillary sinus), and tuberosity (bony area) zones, and stratified by the presence or absence of the third molar, sex, and two age subgroups. Mann-Whitney U test was used to compare the groups considering the third molar. Results: The medians of the width and height of the tuberosity decreased significantly in the absence of the third molar (P < 0.001). The apical area also showed differences, with negative values in the absence of the third molar and positive values in the presence of the third molar (P < 0.001). However, no differences were observed for the coronal area (P > 0.05). Conclusions: In the absence of the third molar, the size of the MT, represented by its width and height, was smaller and negative values (decrease) were observed for the maxillary sinus. The sagittal CT provides useful information regarding the amount of bone tissue available for distalization and relationship of the second molar with respect to the maxillary sinus, which allows individualizing each case in relation to the amount and type of movement expected.

Internalization and toxicity of polystyrene nanoplastics on inmortalized human neural stem cells.

Global plastic production has increased exponentially in recent decades, and a significant part of it persists in the environment, where it degrades into microplastics and nanoplastics (MPs and NPs). These can enter in humans by ingestion, inhalation, and dermal routes, and there is scientific evidence that they are able to reach the systemic circulation and penetrate and accumulate in various tissues and organs. Neurodevelopmental toxicity of NPs is one of the most worrying effects, as they can cross the blood-brain barrier. In the following study, we analyzed, by transmission electron microscopy, the in vitro uptake of 30-nm polystyrene nanoplastics (PS-NPs) into human neural stem cells (NSCs), their accumulation and subcellular localization within the cell. Furthermore, we studied the effects of different concentrations of PS-NPs on cell death, proliferation, and cell differentiation using immunocytochemistry and quantitative real time PCR for specific markers. This study demonstrated that PS-NPs were able to enter the cell, probably by endocytosis, accumulate, and aggregated in human NSCs, without being detected in the nucleus, causing cell death by apoptosis and decreased cell proliferation. This study provides new insights into the interaction and effects of PS-NPs in human NSC and supports the scientific evidence for the involvement of nanoplastic in neurodevelopmental disorders.

Update on the management of older patients with pancreatic adenocarcinoma: a perspective from medical oncology.

In the context of pancreatic cancer, surgical intervention is typically recommended for localized tumours, whereas chemotherapy is the preferred approach in the advanced and/or metastatic setting. However, pancreatic cancer is closely linked to ageing, with an average diagnosis at 72 years. Paradoxically, despite its increased occurrence among older individuals, this population is often underrepresented in clinical studies, complicating the decision-making process. Age alone should not determine the therapeutic strategy but, given the high comorbidity and mortality of this disease, a comprehensive geriatric assessment (CGA) is necessary to define the best treatment, prevent toxicity, and optimize older patient care. In this review, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica, SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours (Grupo Español de Tratamiento de los Tumores Digestivos, TTD), and the Multidisciplinary Spanish Group of Digestive Cancer (Grupo Español Multidisciplinar en Cáncer Digestivo, GEMCAD) have assessed the available scientific evidence and propose a series of recommendations on the management and treatment of the older population with pancreatic cancer.

Molecular effects of polystyrene nanoplastics on human neural stem cells.

Nanoplastics (NPs) have been found in many ecological environments (aquatic, terrestrial, air). Currently, there is great concern about the exposition and impact on animal health, including humans, because of the effects of ingestion and accumulation of these nanomaterials (NMs) in aquatic organisms and their incorporation into the food chain. NPs´ mechanisms of action on humans are currently unknown. In this study, we evaluated the altered molecular mechanisms on human neural stem cell line (hNS1) after 4 days of exposure to 30 nm polystyrene (PS) NPs (0.5, 2.5 and 10 µg/mL). Our results showed that NPs can induce oxidative stress, cellular stress, DNA damage, alterations in inflammatory response, and apoptosis, which could lead to tissue damage and neurodevelopmental diseases.

DNA damage and molecular level effects induced by polystyrene (PS) nanoplastics (NPs) after Chironomus riparius (Diptera) larvae.

In this work, we analyzed the early molecular effects of polystyrene (PS) nanoplastics (NPs) on an aquatic primary consumer (larvae of Chironomus riparius, Diptera) to evaluate their potential DNA damage and the transcriptional response of different genes related to cellular and oxidative stress, endocrine response, developmental, oxygen transport, and immune response. After 24-h exposures of larvae to doses of PS NPs close to those currently found in the environment, the results revealed a large genotoxic effect. This end was evidenced after significant increases in DNA strand breaks of C. riparius larvae quantified by the comet assay, together with results obtained when analyzing the expression of four genes involved in DNA repair (xrrc1, ATM, DECAY and NLK) and which were reduced in the presence of these nanomaterials. Consequently, this reduction trend is likely to prevent the repair of DNA damage caused by PS NPs. In addition, the same tendency to reduce the expression of genes involved in cellular stress, oxidative stress, ecdysone pathway, development, and oxygen transport was observed. Taken together, these results suggest that PS NPs reduce the expression of hormonal target genes and a developmental gene. We show, for the first time, effects of PS NPs on the endocrine system of C. riparius and suggest a possible mechanism of blocking ecdysteroid hormones in insects. Moreover, the NPs were able to inhibit the expression of hemoglobin (Hb C), a protein involved in oxygen transport, and activate a gene of the humoral immune system. These data reveal for the first time the genomic effects of PS NPs in the aquatic invertebrate C. riparius, at the base of the food chain.

Expert consensus to optimize the management of older adult patients with advanced EGFR-mutated non-small cell lung cancer.

Lung cancer (LC) is associated with ageing, with the average age of affected individuals being approximately 70 years. However, despite a higher incidence and prevalence among older people, the older adult population is underrepresented in clinical trials. For LC with Epidermal Growth Factor Receptor (EGFR) mutations, there is no clear association of this mutation with age. Geriatric assessments (GAs) and a multidisciplinary approach are essential for defining the optimal treatment. In this consensus, a group of experts selected from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sección de Oncogeriatría de la Sociedad Española de Oncología Médica-SEOM), the Spanish Lung Cancer Group (Grupo Español de Cáncer de Pulmón-GECP) and the Association for Research on Lung Cancer in Women (Asociación para la Investigación del Cáncer de Pulmón en Mujeres-ICAPEM) evaluate the scientific evidence currently available and propose a series of recommendations to optimize the management of older adult patients with advanced LC with EGFR mutations.

Simultaneous Surgical Approach with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients with Concurrent Peritoneal and Liver Metastases of Colon Cancer Origin.

Background: Simultaneous liver resection and peritoneal cytoreduction with hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial today. The aim of the study was to analyze the postoperative outcomes and survival of patients with advanced metastatic colon cancer (peritoneal and/or liver metastases). Methods: Retrospective observational study from a prospective maintained data base. Patients who underwent a simultaneous peritoneal cytoreduction and liver resection plus HIPEC were studied. Postoperative outcomes and overall and disease free survival were analyzed. Univariate and multivariate analyses were performed. Results: From January 2010 to October 2022, 22 patients operated with peritoneal and liver metastasis (LR+) were compared with 87 patients operated with peritoneal metastasis alone (LR-). LR+ group presented higher serious morbidity (36.4 vs. 14.9%; p: 0.034). Postoperative mortality did not reach statistical difference. Median overall and disease free survival was similar. Peritoneal carcinomatosis index was the only predictive factor of survival. Conclusions: Simultaneous peritoneal and liver resection is associated with increased postoperative morbidity and hospital stay, but with similar postoperative mortality and OS and disease free survival. These results reflect the evolution of these patients, considered inoperable until recently, and justify the trend to incorporate this surgical strategy within a multimodal therapeutic plan in highly selected patients.

Clinical, imaging, and laboratory characteristics of patients with COVID-19 according to ICU admission requirement in Cali, Colombia / Características clínicas, imagenológicas y de laboratorio de pacientes con COVID-19 según requerimiento de ingreso a UCI en Cali, Colombia

Abstract Introduction: At present, few studies conducted in Latin America have addressed the demographic, clinical, and laboratory characteristics of patients with COVID-19 and intensive care unit (ICU) admission requirement. Objective: To compare the sociodemographic, clinical, imaging, and laboratory characteristics of patients diagnosed with COVID -19 and treated in the emergency department of a hospital in Cali, Colombia, based on ICU admission requirement. Materials and methods: Retrospective and descriptive single cohort study conducted in 49 adults with COVID-19 treated in the emergency department of a quaternary care hospital in Cali (Colombia) between March and April 2020. Patients were divided into two groups: ICU admission requirement (n=24) and non-ICU admission requirement (n=25). Bivariate analyses were performed to determine differences between groups (chi-square, Fisher's exact, Student's t, and Mann-Whitney U tests), with a significance level of p<0.05. Results: Participants' mean age was 53 years (SD=13) and 29 patients were men. Significant differences were found between groups in the following variables: mean age (ICU x̅ =58 vs. Non-ICU x̅ =49; p=0.020), presence of diabetes (8 vs. 1; p=0.010); presence of respiratory distress (20 vs. 11; p=0.007) ; unilateral or bilateral presence of areas of consolidation (12 vs. 3; p=0.005); median leukocyte (Med=7 570/mm3 vs. Med=5 130/mm3; p=0.0013), neutrophil (Med=5 980/mm3 vs. Med=3 450/mm3; p=0.0001) and lymphocyte (Med=865/mm3 vs. Med=1 400/mm3; p<0.0001) count; median C-reactive protein (Med=141,25mg/L vs. Med=27.95mg/L; p<0.001), ferritin (Med=1038ng/L vs. Med=542.5ng/L; p=0.0073) and lactate dehydrogenase (Med=391U/L vs. Med=248.5U/L, p=0.0014) levels. Finally, 15 patients required invasive mechanical ventilation, 2 presented with extubation failure, and 5 died. Conclusions. Significant differences were observed in the values of several inflammatory markers, cellular damage and complete blood count parameters between patients who required admission to the ICU and those who did not, so these variables could be used to develop tools that contribute to establishing the prognosis of this disease.

Resumen Introducción. Actualmente hay pocos estudios en Latinoamérica sobre las características demográficas, clínicas y de laboratorio de pacientes con COVID-19 y con requerimiento de ingreso a la unidad de cuidados intensivos (UCI). Objetivo. Comparar las características sociodemográficas, clínicas, imagenológicas y de laboratorio de pacientes diagnosticados con COVID-19 atendidos en el servicio de urgencias de una clínica en Cali, Colombia, según requerimiento de ingreso a UCI. Materiales y métodos. Estudio retrospectivo descriptivo de cohorte única realizado en 49 adultos con COVID-19 atendidos en el servicio de urgencias de un hospital de cuarto nivel de atención de Cali entre marzo y abril de 2020, los cuales se dividieron en dos grupos: requerimiento de ingreso a UCI (n=24) y no requerimiento de ingreso a UCI (n=25). Se realizaron análisis bivariados para determinar las diferencias entre ambos grupos (pruebas de chi-cuadrado, exacta de Fisher, t de Student y U de Mann-Whitney), con un nivel de significancia de p<0.05. Resultados. La edad promedio fue 53 años (DE=13) y 29 pacientes fueron hombres. Se encontraron diferencias significativas entre ambos grupos en las siguientes variables: edad promedio (UCI x̅ =58 vs. No UCI x̅=49; p=0.020); presencia de diabetes (8 vs. 1; p=0.010); presencia de dificultad respiratoria (20 vs. 11; p=0.007); presencia uni o bilateral de áreas de consolidación (12 vs. 3; p=0.005), y mediana del conteo de leucocitos (Med=7 570/mm3 vs. Med=5 130/mm3; p=0.0013), neutrófilos (Med=5 980/mm3 vs. Med=3 450/mm3; p=0.0001), linfocitos (Med=865/mm3 vs. Med=1 400/mm3; p<0.0001), proteína C reactiva (Med=141.25 mg/L vs. Med=27.95 mg/L; p<0.001), ferritina (Med=1038 ng/L vs. Med=542.5 ng/L; p=0.0073) y lactato-deshidroge-nasa (Med=391 U/L vs. Med=248.5 U/L; p=0.0014). Finalmente, 15 pacientes requirieron ventilación mecánica invasiva, 2 presentaron extubación fallida y 5 fallecieron. Conclusiones. Se observaron diferencias significativas en los valores de varios marcadores inflamatorios, daño celular y parámetros del hemograma entre los pacientes que requirieron admisión a la UCI y los que no, por lo que estas variables podrían emplearse para desarrollar herramientas que contribuyan a establecer el pronóstico de esta enfermedad.

Graphene Oxides (GOs) with Different Lateral Dimensions and Thicknesses Affect the Molecular Response in Chironomus riparius.

Graphene oxide (GO) materials possess physicochemical properties that facilitate their application in the industrial and medical sectors. The use of graphene may pose a threat to biota, especially aquatic life. In addition, the properties of nanomaterials can differentially affect cell and molecular responses. Therefore, it is essential to study and define the possible genotoxicity of GO materials to aquatic organisms and their ecosystems. In this study, we investigated the changes in the expression of 11 genes in the aquatic organism Chironomus riparius after 96 h of exposure to small GOs (sGO), large GOs (lGO) and monolayer GOs (mlGO) at 50, 500 and 3000 µg/L. Results showed that the different genes encoding heat shock proteins (hsp90, hsp70 and hsp27) were overexpressed after exposure to these nanomaterials. In addition, ATM and NLK-the genes involved in DNA repair mechanisms-were altered at the transcriptional level. DECAY, an apoptotic caspase, was only activated by larger size GO materials, mlGO and lGO. Finally, the gene encoding manganese superoxide dismutase (MnSOD) showed higher expression in the mlG O-treated larvae. The lGO and mlGO treatments indicated high mRNA levels of a developmental gene (FKBP39) and an endocrine pathway-related gene (DRONC). These two genes were only activated by the larger GO materials. The results indicate that larger and thicker GO nanomaterials alter the transcription of genes involved in cellular stress, oxidative stress, DNA damage, apoptosis, endocrine and development in C. riparius. This shows that various cellular processes are modified and affected, providing some of the first evidence for the action mechanisms of GOs in invertebrates. In short, the alterations produced by graphene materials should be further studied to evaluate their effect on the biota to show a more realistic scenario of what is happening at the molecular level.

Neurotoxicity and endocrine disruption caused by polystyrene nanoparticles in zebrafish embryo.

Nanoplastics (NP) are present in aquatic and terrestrial ecosystems. Humans can be exposed to them through contaminated water, food, air, or personal care products. Mechanisms of NP toxicity are largely unknown and the Zebrafish embryo poses an ideal model to investigate them due to its high homology with humans. Our objective in the present study was to combine a battery of behavioral assays with the study of endocrine related gene expression, to further explore potential NP neurotoxic effects on animal behavior. Polystyrene nanoplastics (PSNP) were used to evaluate NP toxicity. Our neurobehavioral profiles include a tail coiling assay, a light/dark activity assay, two thigmotaxis anxiety assays (auditory and visual stimuli), and a startle response - habituation assay in response to auditory stimuli. Results show PSNP accumulated in eyes, neuromasts, brain, and digestive system organs. PSNP inhibited acetylcholinesterase and altered endocrine-related gene expression profiles both in the thyroid and glucocorticoid axes. At the whole organism level, we observed altered behaviors such as increased activity and anxiety at lower doses and lethargy at a higher dose, which could be due to a variety of complex mechanisms ranging from sensory organ and central nervous system effects to others such as hormonal imbalances. In addition, we present a hypothetical adverse outcome pathway related to these effects. In conclusion, this study provides new understanding into NP toxic effects on zebrafish embryo, emphasizing a critical role of endocrine disruption in observed neurotoxic behavioral effects, and improving our understanding of their potential health risks to human populations.

Molecular effects of polystyrene nanoplastics toxicity in zebrafish embryos (Daniorerio).

Plastics pose a health hazard to living beings and the environment. Plastic degradation produces nano-sized plastic particles (NPs) that end up in terrestrial and aquatic ecosystems, including oceans, rivers, and lakes. Their presence in air, drinking water, sediments, food, and personal care products leads to a variety of exposure routes for living beings, including humans. The toxicity mechanisms of these nanomaterials (NMs) in living organisms and ecosystems are currently unknown, making it a priority to understand their effects at the molecular and cellular levels. The zebrafish (Zf) (Danio rerio) is a model organism which has a high homology with humans and has been widely used to assess the hazard of different xenobiotics. In this study, the expression changes of different genes in 120 hpf Zf embryos (Zfe) after exposure to polystyrene (PS) NPs (30 nm) at concentrations of 0.1, 0.5 and 3 ppm were investigated. The results showed that the gene encoding heat shock protein (hsp70) was down-regulated in a dose-dependent manner. The genes encoding superoxide dismutase (SOD 1 and SOD 2), apoptotic genes (cas 1 and cas 8) and interleukin 1-ß (il1ß) were activated at the concentration of 3 ppm PS NP, while the anti-apoptotic gene Bcl2α was inhibited at 0.5 and 3 ppm. In addition, the neurotransmitter-related gene Acetyl-Cholinesterase (ache) was significantly inhibited and the DNA repair genes (gadd45α and rad51) were also down-regulated. In contrast, the mitochondrial metabolism-related gene cox1 did not alter its expression in any of the treatments. Most of the changes in gene expression occurred at the highest concentration of NPs. Overall, the results indicated that NPs generated cellular stress that caused certain alterations in normal gene expression (oxidative stress, apoptotic and inflammatory processes, neurotoxicity and anti-apoptotic proteins), but did not cause any mortality after 120 hpf exposure at the three concentrations assayed. These results highlight the need for further studies investigating the effects, at the molecular level, of these materials in humans and other living organisms.

Processes implemented and activities carried out by the pharmacists during the COVID­19 pandemic: A scoping review.

OBJECTIVE: To identify and summarize the processes implemented and the  activities performed by community and hospital-based pharmacists during the  COVID­19 pandemic. METHOD: A scoping review was carried out of the PubMed/Medline database  with the aim of identifying articles published until 30 June 2021. The PRISMA  recommendations for this type of review were followed. The articles included  were reviewed and classified according to their main characteristics and  outcomes, according to population, concept and context. The processes and  activities identified were grouped into three categories: those performed in  community and hospital pharmacies, those performed essentially in community  pharmacies, and those performed essentially in hospital  pharmacies. RESULTS: A total of 629 articles were identified, of which 454 were excluded  because they were unrelated to the object of the review and 81 due to meeting  the exclusion criteria. So, 94 articles were included in the analysis.  Most studies were conducted in Europe and the United States. During the  COVID­19 pandemic, the processes implemented and the activities carried out  in both community and hospital-based pharmacies included pharmaceutical  care, efficient and timely management of services, information and education,  psychological support, pharmacovigilance and telepharmacy. Processes  implemented and activities carried out essentially in community pharmacies  were those related to the detection recommendations, and drug indications.  Finally, processes and activities essentially occurring in hospital pharmacies  included those related to participation in drug treatment research, drug  evaluation and guidelines development, and to managing off-label drugs. CONCLUSIONS: During the COVID­19 crisis, pharmacists have led and implemented processes aimed at mitigating the impact of the pandemic on  the population´s health. Pharmaceutical care, efficient and  timely management of services, information and education, psychological  support, pharmacovigilance and telepharmacy, both in community and hospital pharmacies, are the main processes implemented by pharmacists  during the COVID­19 pandemic. These processes and activities, in addition to contributing to the control, prevention and effective and safe treatment of  COVID­19; have ensured the implementation of biosecurity measures, proper  dispensing of medication, the drug rational use, and the provision of evidence- based information and education.

OBJETIVO: Identificar y sintetizar los procesos y actividades realizados por el  farmacéutico en la farmacia comunitaria y hospitalaria durante la pandemia por  COVID-19.Método: Revisión sistemática exploratoria en PubMed/Medline de artículos publicados hasta el 30 de junio de 2021, siguiendo las  recomendaciones PRISMA para este tipo de revisiones. Los artículos incluidos  se clasificaron según sus principales características y resultados, acorde con la  estructura: población, concepto y contexto. Los procesos y las actividades  identificados se agruparon en tres categorías: realizados en farmacia  comunitaria y hospitalaria, llevados a cabo esencialmente en farmacia  comunitaria y realizados esencialmente en farmacia hospitalaria. RESULTADOS: Se identificaron 629 artículos, de los cuales se excluyeron 454  por no estar en relación con el objeto de la revisión y 81 por los criterios de  exclusión; por tanto, se incluyeron 94 en la revisión y análisis. La mayoría de  los estudios se desarrollaron en Europa y Estados Unidos. Entre los procesos y  actividades llevados a cabo por el farmacéutico durante la pandemia, tanto en  farmacia comunitaria como en hospitalaria, destacaron: atención farmacéutica,  gestión eficiente y oportuna de los servicios, información y  educación, apoyo psicológico, farmacovigilancia y telefarmacia. En farmacia  comunitaria destacaron también los relacionados con la detección de COVID-19  y derivación de pacientes, inmunización en farmacias, recomendaciones de  cuidados en el hogar e indicación farmacéutica. Entre los procesos  realizados esencialmente en farmacia hospitalaria destacaron los relacionados  con la participación en investigaciones de tratamientos farmacológicos,  desarrollo de guías de utilización de medicamentos basadas en evidencia y  manejo de medicamentos en indicaciones no aprobadas. CONCLUSIONES: Durante la pandemia por COVID-19, los farmacéuticos han  liderado e implantado procesos orientados a mitigar su impacto en la salud de  la población. Atención farmacéutica, gestión eficiente y oportuna de los  servicios, información y educación, apoyo psicológico, farmacovigilancia y  telefarmacia fueron los principales procesos y actividades realizados en  farmacia comunitaria y hospitalaria durante la pandemia por COVID-19. Dichos  procesos y actividades buscaron, además de contribuir al control,  prevención y tratamiento efectivo y seguro de la COVID-19, asegurar la  implantación de medidas de bioseguridad, la dispensación y uso adecuado de  los medicamentos y la información y educación basadas en la mejor evidencia  disponible.

Hospital outcomes in patients evaluated by rheumatology in a Colombian historical cohort

Introduction: Hospitalized patients with systemic autoimmune rheumatic diseases (SARDs) generate high impact in clinical terms. Objectives: To characterize the study population and estimate risk factors associated with the presence of adverse outcomes in hospitalized patients consulting rheumatology at Clínica Imbanaco between January 2013 and December 2019. Methods: We analyzed a historical cohort of hospitalized patients who were evaluated by rheumatology. The population was classified as follows: group 1, patients with new onset diagnosed SARDs; group 2, patients with known diagnosed SARDs; group 3, patients without diagnosed SARDs; and group 4, patients with unconfirmed suspicion of SARDs. A composite adverse outcome was defined if at least one of the following occurred: (1) hospital mortality, (2) admission to the intensive care unit, (3) hospital infection, or (4) readmission. Results: Information was collected from 327 hospitalization events (307 patients). The median age was 48 (34-63) years and 222 (72.3%) were women. The composite adverse outcome occurred in 136 (41.5%) hospitalization events. Group 2 had the highest number of adverse outcomes (61/128; 47.6%). The variables associated with the worst outcomes were cardiovascular diagnosis at admission (OR = 4.63; CI: 1.60-13.43; p = 0.005), longer hospital stay (OR = 1.04; CI: 1.01-1.07; p = 0.005), and a treating specialty other than internal medicine (OR = 2.79; CI: 1.26-6.17; p = 0.011). Male sex (OR = 0.29; CI: 0.12-0.66; p = 0.004), having special health coverage (OR = 0.39; CI: 0.15-.099; p = 0.047), and hemoglobin > 11.4 g/dL (OR = 0.82; CI: 0.69-0.99; p = 0.039) were the factors associated with lower odds of developing the composite outcome. Conclusions: In this historical cohort, the group of patients with known diagnosed SARDs presented a higher number in percentage terms of adverse outcomes. The most frequent adverse outcomes were admission to the ICU and hospital readmission.

Introducción: Los pacientes hospitalizados con enfermedades reumáticas o autoinmunes sistémicas (ERAS) generan gran impacto en términos clínicos. Objetivos: Caracterizar a la población y estimar factores de riesgo asociados con la presencia de desenlaces adversos en pacientes evaluados hospitalariamente por reumatología en la Clínica Imbanaco durante los arios 2013-2019. Metodología: Se analizó una cohorte histórica de pacientes hospitalizados que fueron evaluados por reumatología. La población se clasificó así: grupo 1, pacientes con ERAS diagnosticada de novo; grupo 2, pacientes con ERAS diagnosticada conocida; grupo 3, pacientes sin ERAS diagnosticada; y grupo 4, pacientes con sospecha no confirmada de ERAS. Se definió un desenlace adverso compuesto si se presentó al menos uno de los siguientes casos: 1) mortalidad hospitalaria; 2) ingreso a la unidad de cuidado intensivo; 3) infección intrahospitalaria; 4) reingreso. Resultados: En un total de 327 eventos de hospitalización (307 pacientes), la mediana de edad fue 48 (34-63) años y 222 (72,3%) fueron mujeres. El desenlace adverso compuesto se presentó en 136 (41,5%) eventos. El grupo 2 tuvo mayor número de desenlaces adversos (61/128; 47,6%). Las variables asociadas con peores resultados fueron: diagnóstico inicial cardiovascular (OR = 4,63; IC: 1,60-13,43; p = 0,005), mayor estancia hospitalaria (OR = 1,04; IC: 1,01-1,07; p = 0,005) y tener una especialidad tratante diferente a medicina interna (OR = 2,79; IC: 1,266,17; p = 0,011). El sexo masculino (OR = 0,29; IC: 0,12-0,66; p = 0,004), pertenecer a un régimen especial de salud (OR = 0,39; IC: 0,15-0,99; p = 0,047) y tener hemoglobina > 11,4 g/dL (OR = 0,82; IC: 0,69-0,99; p = 0,039) fueron factores asociados con menor oportunidad de desarrollar el desenlace compuesto. Conclusiones: En esta cohorte histórica se encontró que porcentualmente el grupo de pacientes con ERAS diagnosticadas conocidas presentó mayor número de desenlaces adversos, entre los que se destacan para el mismo grupo, el ingreso a UCI y el reingreso hospitalario.

Acknowledging and citing core facilities: Key contributions to data lifecycle should be recognised in the scientific literature: Key contributions to data lifecycle should be recognised in the scientific literature.

Core facilities play a central role in the life sciences by generating data and ensuring quality standards. Their contributions to research should be appropriately acknowledged or cited in research papers.

[Within-subject variability of the 6-minute walk test]. / Variabilidad intrasujeto de la prueba de caminata de seis minutos.

Background: The 6-minute walk test assesses the ability to perform exercise and it is widely used, of low cost, and of diverse variability. Objective: To define the usefulness of a second 6-minute walk test performed 30 minutes from the first. Material and methods. Material and methods: An observational, longitudinal and analytical study was carried out in subjects born and inhabitants from Mexico City, both genders, without cardiopulmonary disease. Their demographic variables were recorded. Differences were calculated with the t test for independent groups and variability with the Bland-Altman statistic; its magnitude, with the intraclass correlation coefficient and 95% confidence intervals (95% CI). A p < 0.05 was considered significant. Results: 200 tests from 100 subjects were studied. Average age was 36 ± 11 years. Body mass index average was 24.71 ± 3.24 kg/m2. 43 subjects were male (43%). The most frequent activity was arts and crafts in 38 (38%). Only 55 subjects (55%) increased by 24 the number of meters walked in the second test. Total of meters walked on walk 1 vs. 2 were: 437.65 ± 48.84 vs. 441.62 ± 11.49. Mean difference (bias) was of -4 (57.9, -65.9) and intraclass correlation coefficient of 0.800 (95% CI, 0.717-0.861). Conclusions: The 6-minute walk test is reproducible with wide variability. These results suggest to do only one 6-minute walk test.

Introducción: la prueba de caminata de seis minutos evalúa la capacidad para hacer ejercicio y es de amplio uso, bajo costo y variabilidad diversa. Objetivo: definir la utilidad de una segunda prueba de caminata de seis minutos realizada a 30 minutos de la primera. Material y métodos: se llevó a cabo un estudio observacional, longitudinal y analítico de sujetos nacidos y habitantes de la Ciudad de México, de ambos géneros, sin enfermedad cardiopulmonar. Se registraron sus variables demográficas. Las diferencias se calcularon con la prueba t para grupos independientes y la variabilidad con el estadístico de Bland-Altman; su magnitud, con el coeficiente de correlación intraclase e intervalos de confianza del 95% (IC 95%). Una p < 0.05 se consideró significativa. Resultados: se estudiaron 200 pruebas de 100 sujetos. La edad promedio fue de 36 ± 11 años. La media del índice de masa corporal fue 24.71 ± 3.24 kg/m2. Fueron 43 hombres (43%). La actividad más frecuente fueron las artes y los oficios en 38 (38%). Solo en 55 (55%) incrementaron en 24 los metros caminados en la segunda prueba. Los metros caminados totales de la caminata 1 frente a la 2 fueron 437.65 ± 48.84 frente a 441.62 ± 11.49. La diferencia media (sesgo) fue de −4 (57.9, −65.9) y el coeficiente de correlación intraclase de 0.800 (IC 95% 0.717-0.861). Conclusiones: la prueba de caminata de seis minutos es reproducible con variabilidad amplia. Estos resultados sugieren realizar solo una prueba de caminata de seis minutos.

Toxicological effects of three different types of highly pure graphene oxide in the midge Chironomus riparius.

Graphene oxide (GO) is a carbon nanomaterial used in electronics, biomedicine, environmental remediation and biotechnology. The production of graphene will increase in the upcoming years. The carbon nanoparticles (NPs) are released into the environment and accumulated in aquatic ecosystems. Information on the effects of GO in aquatic environments and its impact on organisms is still lacking. The aim of this study was to synthesise and characterise label-free GO with controlled lateral dimensions and thickness - small GO (sGO), large GO (lGO) and monolayer GO (mlGO) - and determine their impact on Chironomus riparius, a sentinel species in the freshwater ecosystem. Superoxide dismutase (SOD) and lipid peroxidation (LPO) was evaluated after exposures for 24 h and 96 h to 50, 500, and 3000 µg/L. GOs accumulated in the gut of C. riparius and disturbed its antioxidant metabolism. We suggest that all types of GO exposure can upregulate of SOD. Moreover, both lGO and mlGO treatments caused LPO damage in C. riparius in comparison to sGO, proving its favourable lateral size impact in this organism. Our results indicate that GOs could accumulate and induce significant oxidative stress on C. riparius. This work shows new information about the potential oxidative stress of these NMs in aquatic organisms.