Toxicological effects of solvent-extracted organic matter associated with PM2.5 on human bronchial epithelial cell line NL-20.

The heterogeneity and complexity of solvent-extracted organic matter associated with PM2.5 (SEOM-PM2.5) is well known; however, there is scarce information on its biological effects in human cells. This work aimed to evaluate the effect of SEOM-PM2.5 collected in northern Mexico City during the cold-dry season (November 2017) on NL-20 cells, a human bronchial epithelial cell line. The SEOM obtained accounted for 15.5% of the PM2.5 mass and contained 21 polycyclic aromatic hydrocarbons (PAHs). The cell viability decreased following exposure to SEOM-PM2.5, and there were noticeable morphological changes such as increased cell size and the presence of cytoplasmic vesicles in cells treated with 5-40 µg/mL SEOM-PM2.5. Exposure to 5 µg/mL SEOM-PM2.5 led to several alterations compared with the control cells, including the induction of double-stranded DNA breaks based (p < 0.001); nuclear fragmentation and an increased mitotic index (p < 0.05); 53BP1 staining, a marker of DNA repair by non-homologous end-joining (p < 0.001); increased BiP protein expression; and reduced ATF6, IRE1α, and PERK gene expression. Conversely, when exposed to 40 µg/mL SEOM-PM2.5, the cells showed an increase in reactive oxygen species formation (p < 0.001), BiP protein expression (p < 0.05), and PERK gene expression (p < 0.05), indicating endoplasmic reticulum stress. Our data suggest concentration-dependent toxicological effects of SEOM-PM2.5 on NL-20 cells, including genotoxicity, genomic instability, and endoplasmic reticulum stress.

The CB1 receptor interacts with cereblon and drives cereblon deficiency-associated memory shortfalls.

Cereblon/CRBN is a substrate-recognition component of the Cullin4A-DDB1-Roc1 E3 ubiquitin ligase complex. Destabilizing mutations in the human CRBN gene cause a form of autosomal recessive non-syndromic intellectual disability (ARNSID) that is modelled by knocking-out the mouse Crbn gene. A reduction in excitatory neurotransmission has been proposed as an underlying mechanism of the disease. However, the precise factors eliciting this impairment remain mostly unknown. Here we report that CRBN molecules selectively located on glutamatergic neurons are necessary for proper memory function. Combining various in vivo approaches, we show that the cannabinoid CB1 receptor (CB1R), a key suppressor of synaptic transmission, is overactivated in CRBN deficiency-linked ARNSID mouse models, and that the memory deficits observed in these animals can be rescued by acute CB1R-selective pharmacological antagonism. Molecular studies demonstrated that CRBN interacts physically with CB1R and impairs the CB1R-Gi/o-cAMP-PKA pathway in a ubiquitin ligase-independent manner. Taken together, these findings unveil that CB1R overactivation is a driving mechanism of CRBN deficiency-linked ARNSID and anticipate that the antagonism of CB1R could constitute a new therapy for this orphan disease.

Aluminum enhances the oxidative damage of ZnO NMs in the human neuroblastoma SH-SY5Y cell line.

Bare and doped zinc oxide nanomaterials (ZnO NMs) are of great interest as multifunctional platforms for biomedical applications. In this study, we systematically investigate the physicochemical properties of Aluminum doped ZnO (AZO) and its bio-interactions with neuroblastoma (SH-SY5Y) and red blood (RBCs) cells. We provide a comprehensive chemical and structural characterization of the NMs. We also evaluated the biocompatibility of AZO NMs using traditional toxicity assays and advanced microscopy techniques. The toxicity of AZO NMs towards SH-SY5Y cells, decreases as a function of Al doping but is higher than the toxicity of ZnO NMs. Our results show that N-acetyl cysteine protects SH-SY5Y cells against reactive oxygen species toxicity induced by AZO NMs. ZnO and AZO NMs do not exert hemolysis in human RBCs at the doses that cause toxicity (IC50) in neuroblastoma cells. The Atomic force microscopy qualitative analysis of the interaction of SH-SY5Y cells with AZO NMs shows evidence that the affinity of the materials with the cells results in morphology changes and diminished interactions between neighboring cells. The holotomographic microscopy analysis demonstrates NMs' internalization in SH-SY5Y cells, changes in their chemical composition, and the role of lipid droplets in the clearance of toxicants.

Neural Mechanisms Responsible for Vagus Nerve Stimulation-Dependent Enhancement of Somatosensory Recovery.

Impairments in somatosensory function are a common and often debilitating consequence of neurological injury, with few effective interventions. Building on success in rehabilitation for motor dysfunction, the delivery of vagus nerve stimulation (VNS) combined with tactile rehabilitation has emerged as a potential approach to enhance recovery of somatosensation. In order to maximize the effectiveness of VNS therapy and promote translation to clinical implementation, we sought to optimize the stimulation paradigm and identify neural mechanisms that underlie VNS-dependent recovery. To do so, we characterized the effect of tactile rehabilitation combined with VNS across a range of stimulation intensities on recovery of somatosensory function in a rat model of chronic sensory loss in the forelimb. Consistent with previous studies in other applications, we find that moderate intensity VNS yields the most effective restoration of somatosensation, and both lower and higher VNS intensities fail to enhance recovery compared to rehabilitation without VNS. We next used the optimized intensity to evaluate the mechanisms that underlie recovery. We find that moderate intensity VNS enhances transcription of Arc, a canonical mediator of synaptic plasticity, in the cortex, and that transcript levels were correlated with the degree of somatosensory recovery. Moreover, we observe that blocking plasticity by depleting acetylcholine in the cortex prevents the VNS-dependent enhancement of somatosensory recovery. Collectively, these findings identify neural mechanisms that subserve VNS-dependent somatosensation recovery and provide a basis for selecting optimal stimulation parameters in order to facilitate translation of this potential intervention.

Vagus Nerve Stimulation Must Occur During Tactile Rehabilitation to Enhance Somatosensory Recovery.

Chronic sensory loss is a common and undertreated consequence of many forms of neurological injury. Emerging evidence indicates that vagus nerve stimulation (VNS) delivered during tactile rehabilitation promotes recovery of somatosensation. Here, we systematically varied the timing of VNS relative to tactile rehabilitation to determine the paradigm that yields the greatest degree of somatosensory recovery after peripheral nerve injury (PNI). The medial and ulnar nerves in rats were transected, causing chronic sensory loss. Eight weeks after injury, rats were given a VNS implant followed by four weeks of tactile rehabilitation sessions consisting of repeated mechanical stimuli to the previously denervated forepaw. Rats received VNS before, during, or after tactile rehabilitation. Delivery of VNS during rehabilitative training generates robust, significant recovery compared to rehabilitative training without stimulation (56 ± 14% improvement over sham stimulation). A matched amount of VNS before training, immediately after training, or two hours after training is significantly less effective than VNS during rehabilitative training and fails to improve recovery compared to rehabilitative training alone (5 ± 10%, 4 ± 11%, and -7 ± 22% improvement over sham stimulation, respectively). These findings indicate that concurrent delivery of VNS during rehabilitative training is most effective and illustrate the importance of considering stimulation timing for clinical implementation of VNS therapy.

Effective Delivery of Vagus Nerve Stimulation Requires Many Stimulations Per Session and Many Sessions Per Week Over Many Weeks to Improve Recovery of Somatosensation.

BACKGROUND: Chronic sensory loss is a common and undertreated consequence of many forms of neurological injury. Emerging evidence indicates that vagus nerve stimulation (VNS) delivered during tactile rehabilitation promotes recovery of somatosensation. OBJECTIVE: Here, we characterize the amount, intensity, frequency, and duration of VNS therapy paradigms to determine the optimal dosage for VNS-dependent enhancement of recovery in a model of peripheral nerve injury (PNI). METHODS: Rats underwent transection of the medial and ulnar nerves in the forelimb, resulting in chronic sensory loss in the paw. Eight weeks after injury, rats were implanted with a VNS cuff and received tactile rehabilitation sessions consisting of repeated mechanical stimulation of the previously denervated forepaw paired with short bursts of VNS. Rats received VNS therapy in 1 of 6 systematically varied dosing schedules to identify a paradigm that balanced therapy effectiveness with a shorter regimen. RESULTS: Delivering 200 VNS pairings a day 4 days a week for 4 weeks produced the greatest percent improvement in somatosensory function compared to any of the 6 other groups (One Way analysis of variance at the end of therapy, F[4 70] P = .005). CONCLUSIONS: Our findings demonstrate that an effective VNS therapy dosage delivers many stimulations per session, with many sessions per week, over many weeks. These results provide a framework to inform the development of VNS-based therapies for sensory restoration.

Dysfunctional serotonergic neuron-astrocyte signaling in depressive-like states.

Astrocytes play crucial roles in brain homeostasis and are regulatory elements of neuronal and synaptic physiology. Astrocytic alterations have been found in Major Depressive Disorder (MDD) patients; however, the consequences of astrocyte Ca2+ signaling in MDD are poorly understood. Here, we found that corticosterone-treated juvenile mice (Cort-mice) showed altered astrocytic Ca2+ dynamics in mPFC both in resting conditions and during social interactions, in line with altered mice behavior. Additionally, Cort-mice displayed reduced serotonin (5-HT)-mediated Ca2+ signaling in mPFC astrocytes, and aberrant 5-HT-driven synaptic plasticity in layer 2/3 mPFC neurons. Downregulation of astrocyte Ca2+ signaling in naïve animals mimicked the synaptic deficits found in Cort-mice. Remarkably, boosting astrocyte Ca2+ signaling with Gq-DREADDS restored to the control levels mood and cognitive abilities in Cort-mice. This study highlights the important role of astrocyte Ca2+ signaling for homeostatic control of brain circuits and behavior, but also reveals its potential therapeutic value for depressive-like states.

Long-term exposure to ambient fine particulate matter and carotid intima media thickness at bilateral, left and right in adults from Mexico City: Results from GEA study.

BACKGROUND: PM2.5 exposure has been associated with intima-media thickness (cIMT) increase. However, very few studies distinguished between left and right cIMT in relation to PM2.5 exposure. AIM: To evaluate associations between chronic exposure to PM2.5 and cIMT at bilateral, left, and right in adults from Mexico City. METHODS: This study comprised 913 participants from the control group, participants without personal or family history of cardiovascular disease, of the Genetics of Atherosclerosis Disease Mexican study (GEA acronym in Spanish), recruited at the Instituto Nacional de Cardiología Ignacio Chávez from June 2008 to January 2013. To assess the associations between chronic exposure to PM2.5 (per 5 µg/m3 increase) at different lag years (1-4 years) and cIMT (bilateral, left, and right) we applied distributed lag non-linear models (DLNMs). RESULTS: The median and interquartile range for cIMT at bilateral, left, and right, were 630 (555, 735), 640 (550, 750), and 620 (530, 720) µm, respectively. Annual average PM2.5 exposure was 26.64 µg/m3, with median and IQR, of 24.46 (23.5-25.46) µg/m3. Results from DLNMs adjusted for age, sex, body mass index, low-density lipoproteins, and glucose, showed that PM2.5 exposure for year 1 and 2, were positively and significantly associated with right-cIMT [6.99% (95% CI: 3.67; 10.42) and 2.98% (0.03; 6.01), respectively]. Negative associations were observed for PM2.5 at year 3 and 4 and right-cIMT; however only year 3 was statistically significant [-2.83% (95% CI: 5.12; -0.50)]. Left-cIMT was not associated with PM2.5 exposure at any lag year. The increase in bilateral cIMT followed a similar pattern as that observed for right-cIMT, but with lower estimates. CONCLUSIONS: Our results suggest different susceptibility between left and right cIMT associated with PM2.5 exposure highlighting the need of measuring both, left and right cIMT, regarding ambient air pollution in epidemiological studies.

Genomically matched therapy in refractory colorectal cancer according to ESMO Scale for Clinical Actionability of Molecular Targets: experience of a comprehensive cancer centre network.

Efficiency of expanded genomic profiling (EGP) programmes in terms of final inclusion of patients in genomically matched therapies is still unknown. Fit patients with advanced and refractory colorectal cancer (CRC) were selected for an EGP programme. Next-generation sequencing (NGS) analysis from formalin-fixed paraffin-embedded tumour samples was performed. The purpose was to describe the prevalence of genomic alterations defined by the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT), as well as the percentage of patients finally included in genomically guided clinical trials. In total, 187 patients were recruited. Mutational profile was obtained in 177 patients (10 patients were failure due to insufficient tumour sample), copy number alterations in 41 patients and fusions in 31 patients. ESCAT-defined alterations were detected in 28.8% of the intention-to-analyse population. BRAF V600E was clustered in ESCAT I, with a prevalence of 3.7%, KRAS G12C and ERBB2 amplification were clustered in ESCAT II, whose prevalence was 4.2% and 1.6%, respectively. Most alterations were classified in ESCAT III (mutations in ERBB2, PIK3CA or FGFR genes and MET amplification) and IV (mutations in BRAF non-V600E, ERBB3, FBXW7, NOTCH, RNF43), with a single prevalence under 5%, except for PIK3CA mutation (9%). The final rate of inclusion into genomically guided clinical trials was 2.7%, including therapies targeting BRAF V600E or RNF43 mutations in two patients each, and ERBB2 mutation in one patient. In conclusion, EGP programmes in patients with advanced CRC are feasible and identify a subset of patients with potentially druggable genomic alterations. However, further efforts must be made to increase the rate of patients treated with genomically guided therapies.

Subchronic co-exposure to particulate matter and fructose-rich-diet induces insulin resistance in male Sprague Dawley rats.

Insulin resistance (IR) and metabolic disorders are non-pulmonary adverse effects induced by fine particulate matter (PM2.5) exposure. The worldwide pandemic of high fructose sweeteners and fat rich modern diets, also contribute to IR development. We investigated some of the underlying effects of IR, altered biochemical insulin action and Insulin/AKT pathway biomarkers. Male Sprague Dawley rats were subchronically exposed to filtered air, PM2.5, a fructose rich diet (FRD), or PM2.5 + FRD. Exposure to PM2.5 or FRD alone did not induce metabolic changes. However, PM2.5 + FRD induced leptin release, systemic hyperinsulinemia, and Insulin/AKT dysregulation in insulin-sensitive tissues preceded by altered AT1R levels. Histological damage and increased HOMA-IR were also observed from PM2.5 + FRD co-exposure. Our results indicate that the concomitant exposure to a ubiquitous environmental pollutant, such as PM2.5, and a metabolic disease risk factor, a FRD, can contribute to the metabolic disorder pandemic occurring in highly polluted locations.

Effect of subchronic exposure to ambient fine and ultrafine particles on rat motor activity and ex vivo striatal dopaminergic transmission.

Alterations in dopaminergic transmission are associated with neurological disorders, such as depression, autism, and Parkinson's disease. Exposure of rats to ambient fine (FP) or ultrafine (UFP) particles induces oxidative and inflammatory responses in the striatum, a neuronal nucleus with dense dopaminergic innervation and critically involved in the control of motor activity.Objectives: We used an ex vivo system to evaluate the effect of in vivo inhalation exposure to FP and UFP on motor activity and dopaminergic transmission.Materials and Methods: Male adult Wistar rats were exposed to FP, UFP, or filtered air for 8 weeks (subchronic exposure; 5 h/day, 5 days/week) in a particle concentrator. Motor activity was evaluated using the open-field test. Uptake and release of [3H]-dopamine were assessed in striatal synaptosomes, and dopamine D2 receptor (D2R) affinity for dopamine was evaluated by the displacement of [3H]-spiperone binding to striatal membranes.Results: Exposure to FP or UFP significantly reduced spontaneous motor activity (ambulatory distance: FP -25%, UFP -32%; ambulatory time: FP -24%, UFP -22%; ambulatory episodes: FP -22%, UFP -30%), decreased [3H]-dopamine uptake (FP -18%, UFP -24%), and increased, although not significantly, [3H]-dopamine release (113.3 ± 16.3 and 138.6 ± 17.3%). Neither FP nor UFP exposure affected D2R density or affinity for dopamine.Conclusions: These results indicate that exposure to ambient particulate matter reduces locomotion in rats, which could be related to altered striatal dopaminergic transmission: UFP was more potent than FP. Our results contribute to the evidence linking environmental factors to changes in brain function that could turn into neurological and psychiatric disorders.HIGHLIGHTSYoung adult rats were exposed to fine (FP) or ultrafine (UFP) particles for 40 days.Exposure to FP or UFP reduced motor activity.Exposure to FP or UFP reduced dopamine uptake by striatal synaptosomes.Neither D2R density or affinity for dopamine was affected by FP or UFP.UFP was more potent than FP to exert the effects reported.

Approximations to Diagnosis and Therapy of COVID-19 in Nervous Systems Using Extracellular Vesicles.

The SARS-CoV-2 virus was first identified at the end of December 2019, causing the disease known as COVID-19, which, due to the high degree of contagion, was declared a global pandemic as of 2020. The end of the isolation was in 2022, thanks to the global multidisciplinary work of the massive vaccination campaigns. Even with the current knowledge about this virus and the COVID-19 disease, there are many questions and challenges regarding diagnosis and therapy in the fight against this virus. One of the big problems is the so-called "long COVID", prolonged symptomatology characterized as a multiorgan disorder manifested as brain fog, fatigue, and shortness of breath, which persist chronically after the disease resolution. Therefore, this review proposes using extracellular vesicles (EVs) as a therapeutic or diagnostic option to confront the sequelae of the disease at the central nervous system level. Development: the review of updated knowledge about SARS-CoV-2 and COVID-19 is generally addressed as well as the current classification of extracellular vesicles and their proposed use in therapy and diagnosis. Through an analysis of examples, extracellular vesicles are highlighted to learn what happens in the central nervous system during and after COVID-19 and as a therapeutic option. Conclusions: even though there are limitations in the knowledge of the neurological manifestations of COVID-19, it is possible to observe the potential use of extracellular vesicles in therapy or as a diagnostic method and even the importance of their study for the knowledge of the pathophysiology of the disease.

Protocol to downregulate GABAergic-astrocyte signaling via astrocyte-selective ablation of GABAB receptor in adult mice.

Here, we present a protocol to selectively downregulate GABAB receptor (GABABR) expression in astrocytes of mouse medial prefrontal cortex (mPFC). We first describe the procedure of surgeries and viral injections. We then detail genetic, histological, and functional characterizations of astrocytic GABABR ablation using RT-PCR, imaging, and behavioral assays. The use of GABAB flox mice can be easily adapted to generate astrocyte-selective GABABR ablation in different brain areas and postnatal stages, leading to local downregulation of GABAergic-astrocyte signaling without developmental issues. For complete details on the use and execution of this protocol, please refer to Mederos et al. (2021).

New Procedure to Maintain Fecal Microbiota in a Dry Matrix Ready to Encapsulate.

Fecal microbiota transplantation (FMT) is one of the recommended treatments for recurrent Clostridioides difficile infection, but endoscopy and available oral formulations still have several limitations in their preparation, storage, and administration. The need for a viable oral formulation that facilitates the implementation of this highly effective therapy in different settings has led us to test the microcrystalline cellulose particles as an adsorbent of concentrated filtered fresh feces in comparison to lyophilized feces. This free-flowing material can provide protection to bacteria and results in a dried product able to maintain the viability of the microbiota for a long time. Adsorbate formulation showed a stabilizing effect in gut microbiota, maintaining bacteria viability and preserving its diversity, and is a competitive option for lyophilized capsules.

PM2.5 induces airway hyperresponsiveness and inflammation via the AhR pathway in a sensitized Guinea pig asthma-like model.

Exposure to fine particulate matter (PM2.5) induces airway inflammation and hyperreactivity that lead to asthma. The mechanisms involved are still under investigation. We investigated the effect of resveratrol (3,4',5-trihydroxystilbene) (RES) on airway hyperresponsiveness, inflammation and CYP1A1 protein expression (an aryl hydrocarbon receptor (AhR) target) induced by PM2.5 exposure in an allergic asthma experimental guinea pig model. The polyphenolic compound RES was used due to its antioxidant and anti-inflammatory properties and as an antagonist of the AhR; thus, providing mechanistic insights. Animals were sensitized with aluminum hydroxide and ovalbumin and exposed to filtered air or PM2.5. Exposure to PM2.5 was conducted using a whole-body chamber particle concentrator (5 h/day) for 15 days. Animals received saline solution or RES (10 mg/kg per day) orally for 21 days simultaneously to the OVA challenge or PM2.5 exposure. PM2.5 exposure (mean 433 ± 111 µg/m3 in the exposure chamber) in OVA challenged animals induced an asthma-like phenotype characterized by increased baseline lung resistance (Rrs) and central airway resistance (Rn) in response to acetylcholine (ACh) evaluated using a flexiVent system®. A parallel increase of pro-inflammatory cytokines (IL-6, IL-17, TNF-α and IFN-γ), inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid (BALF) and lung CYP1A1 increase also occurred. RES significantly inhibited airway hyperresponsiveness, inflammation, and CYP1A1 protein expression in the OVA-challenged PM2.5 exposed animals. In summary, with the use of RES we demonstrate that PM-induced airway hyperreactivity is modulated by the inflammatory response via the AhR pathway in an allergic asthma guinea pig model.

Sindrome de Down resultante de uma translocação não Robertsoniana rara t(11; 21) (p13; q22)

Introdução: A síndrome de Down (SD) é um distúrbio genético comum, ocorrendo em aproximadamente 1 em 700 nascimentos. Resulta de uma cópia extra de todo ou de parte do braço longo do cromossomo 21, causada por diferentes alterações citogenéticas: trissomia livre, translocações robertsonianas, mosaicismo, duplicação da região crítica e outros rearranjos estruturais. Translocações cromossômicas não-Robertsonianas são eventos muito raros, com poucos casos relatados. Objetivo: Descrever uma paciente com SD resultante da translocação não-Robertsoniana t(11; 21)(p13; q22). Relato de Caso: Uma menina encaminhada com diagnóstico clínico de trissomia do 21 apresentou dois cromossomos 21 e a translocação não-Robertsoniana t(11; 21)(p13; q22). A criança desenvolveu distúrbio mieloproliferativo transitório aos 17 meses. A análise citogenética foi realizada em metáfases obtidas de linfócitos e de células da medula óssea, de acordo com procedimento padrão - bandamento G e hibridização in situ fluorescente. O estudo do cariótipo dos pais revelou que sua mãe, fenotipicamente normal, é portadora da mesma translocação recíproca. Conclusão: Este é o segundo relato da translocação t(11; 21)(p13; q22), o primeiro resultando na SD. Essa descrição amplia o conhecimento sobre a variabilidade citogenética na etiologia da síndrome de Down. Estudos futuros são necessários para investigar os efeitos clínicos a longo prazo da trissomia do cromossomo 21 associada com a t(11; 21)(p13; q22).

Changes in digestive enzyme activities during the early ontogeny of the South American cichlid (Cichlasoma dimerus).

Cichlasoma dimerus is a neotropical cichlid that has been used as a biological model for neuroendocrinology studies. However, its culture is problematic in terms of larval feeding to allow having enough fry quantity and quality. Larviculture requires full knowledge about the digestive system and nutrition; therefore, this study was intended to assess the digestive enzymes' changes at different ages during the early ontogeny. Acid protease activity was detectable from the first day after hatching (dah), increasing to its maximum peaks on 9 dah. In contrast, alkaline proteases had low activity in the first days of life but reached their maximum activity on 17 dah. Chymotrypsin, L-aminopeptidase, and carboxypeptidase A activities increased at 6 dah, while trypsin activity was first detected on 13 dah and reached its maximum activity on 17 dah. Lipase and α-amylase activity were detectable at low levels in the first days of life, but the activity fluctuated and reaching its maximum activity at 21 dah. Alkaline phosphatase continued to oscillate and had two maximum activity peaks, the first at 6 dah and the second at 19 dah. Zymograms of alkaline proteases on day 6 dah six revealed four activity bands with molecular weights from 16.1 to 77.7 kDa. On 13 dah, two more activity bands of 24.4 and 121.9 kDa were detected, having a total of six proteases. The enzymatic activity analyzes indicate the digestive system shows the low activity of some enzymes in the first days after hatching, registering significant increases on 6 dah and the maximum peaks of activities around at 17 dah. Therefore, we recommend replacing live food with dry feed and only providing dry feed after day 17 dah.

Validation of an instrument to measure adherence to orthodontic treatment provided in dental clinics of dentistry schools / Validación de un instrumento para medir la adherencia al tratamiento de ortodoncia en servicios odontológicos de facultades de odontología

Abstract Introduction: Adherence to treatment is associated with the quality of health care given to the patient, especially in institutions with a high workload, such as dentistry schools. In these places, treatments are long and high adherence is required for them to be successful. Objective: To validate, by means of an exploratory factor analysis (EFA) and a confirmatory factor analysis (CFA), an instrument for measuring adherence to orthodontic treatment in dental clinics of dentistry schools, where a large number of patients are treated. Materials and methods: Quantitative study in which an instrument was validated by performing an EFA and a CFA. A 27-item questionnaire (adapted from the original 37-item instrument) was administered to 601 patients treated at a dentistry school of a Colombian university in two different periods: during the second semester of 2018 (n=202) and during the first semester of 2019 (n=399). The EFA and the CFA were performed using the SPSS and the LISREL software, respectively. Results: Factor analysis established that the instrument has six factors and 25 questions suitable for collecting information on adherence to treatment by obtaining the following adjustment values: x2 S B=420.09 with d.f.=260 and p<0.05; x2 S B divided by the degrees of freedom index (X2 SB/d.f.) = 1.62; CFI=0.99; RFI=0.98; NNFI= 0.99; RMSEA=0.039 (90%CI 0.032-0.046); and SRMR= 0.057. Conclusions: Based on the results obtained after performing the EFA and the CFA, it is possible to conclude that the instrument is valid and highly reliable to measure orthodontic treatment in this context. Consequently, its use in similar institutions will allow determining the levels of adherence in these patients accurately, and thus, when necessary, develop and implement actions that encourage greater engagement from this population to orthodontic treatment to obtain better outcomes.

Resumen Introducción. La adherencia al tratamiento está relacionada con la calidad de la atención en salud dada al paciente, especialmente en instituciones con un alto volumen de trabajo, como las facultades de odontología, donde los tratamientos son prolongados y se requiere de una alta adherencia para que estos sean exitosos. Objetivo. Validar, mediante un análisis factorial exploratorio (AFE) y un análisis factorial confirmatorio (AFC), un instrumento para medir la adherencia al tratamiento ortodóntico en clínicas odontológicas de facultades de odontología en las que se atiende un alto número de pacientes. Materiales y métodos. Estudio cuantitativo en el que se validó un instrumento mediante un AFE y un AFC. Se aplicó un cuestionario de 27 preguntas (adaptado del instrumento original de 37 preguntas) a 601 pacientes atendidos en una facultad de odontología de una universidad colombiana en dos periodos diferentes: el segundo semestre de 2018 y el primer semestre de 2019. El AFE y el AFC se realizaron mediante los programas SPSS y LISREL, respectivamente. Resultados. El análisis factorial permitió establecer un instrumento con 6 factores y 25 preguntas adecuado para recolectar información sobre la adherencia al tratamiento al obtener los siguientes valores de ajuste: B=420.09 con gl=260 y p<0.05; B/gl = 1.62; CFI=0.99; RFI=0.98; NNFI=0.99; RMSEA=0.039 (IC90%: 0.032-0.046), y SRMR=0.057. Conclusiones. El AFE y el AFC permitieron establecer un instrumento válido y con una alta con-fiabilidad para medir la adherencia al tratamiento ortodóntico en este escenario, por lo que su uso en instituciones similares permitirá determinar de manera confiable los niveles de adherencia en estos pacientes, y, de esta forma, cuando sea necesario, desarrollar e implementar acciones que fomenten un mayor compromiso de esta población con los tratamientos de ortodoncia para obtener mejores desenlaces.

Acute kidney damage by PM2.5 exposure in a rat model.

PM2.5 exposure is associated with a glomerular filtration rate (GFR) reduction, and renal tissue damage. The goal of this study was demonstrate the acute effect of PM2.5 on the kidney. Male rats were acutely exposed to PM2.5 or filtered air. Blood pressure was mesure and early kidney biomarkers were evaluated in serum and urine samples, and also IL-1ß, IL-6 and TNFα were determined. Oxidative biomarkers, angiotensin/bradykinin-related proteins, KIM-1, IL-6 and histology were determined. Blood pressure, GFR, and early kidney damage biomarkers increase together with oxidative biomarkers and angiotensin/bradykinin endocrine-related proteins increased after exposure to PM2.5. Urinary IL-6 increased after exposure to PM2.5, whereas in kidney cortex decreased. Histological changes were observed and accompanied by the induction of KIM-1. Acute exposure to PM2.5 not decline kidney function. However, it can induce early kidney damage biomarkers, oxidative stress, inflammation and angiotensin mediators, which perhabs culminates in a lose of renal function.