[Risk of epilepsy after a first epileptic seizure with unknown etiology in elderly patients]. / Riesgo de epilepsia tras una primera crisis epiléptica de etiología desconocida en pacientes de edad avanzada.

AIM: Patients whose epilepsy begins with seizures with unknown etiology in old age have been studied to a limited extent. The aim is to clinically characterise these patients, and predict their risk of developing epilepsy in the long term. MATERIALS AND METHODS: This is a retrospective observational study of patients over 55 years old experiencing a first epileptic seizure with unknown etiology. The data were collected from their clinical history, including electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) results. RESULTS: Eighty-seven patients (58.6% male; 71.5 ± 8.1 years) were included. The mean follow-up was 7.3 ± 4.9 years. The most common vascular risk factor was arterial hypertension (77%; n = 67). Focal seizures with altered consciousness were the most frequent type of seizure (44.8%; n = 39), followed by focal seizures evolving to bilateral tonic-clonic seizures (39.1%; n = 34). Brain MRI showed cortical atrophy (50%; n = 42) and signs of small-vessel vascular disease (SVVD) (67.8%; n = 57). Interictal epileptiform EEG abnormalities were observed in 43.7% (n = 38) of the patients, mostly with temporal localisations (94.7%; n = 36). 44.8% (n = 39) had mild cognitive impairment at baseline. Recurrence of seizures, which was observed in 49 patients (56.1%), occurred after a median of 12 months (interquartile range: 4.4-25.9). Finally, 71 patients (81.6%) developed epilepsy. CONCLUSION: The risk of epilepsy in the long term following a single seizure of unknown etiology in elderly patients is greater than 80%. Arterial hypertension and mild cognitive impairment at baseline are the most common clinical features. Cortical atrophy and the presence of SVVD are frequent in MRI, and routine EEGs do not usually show epileptiform alterations.

TITLE: Riesgo de epilepsia tras una primera crisis epiléptica de etiología desconocida en pacientes de edad avanzada.Objetivo. Los pacientes que comienzan con crisis de origen desconocido en la edad avanzada no están bien estudiados. El objetivo es caracterizar clínicamente a estos pacientes y predecir el riesgo de desarrollar epilepsia a largo plazo. Materiales y métodos. Es un estudio observacional retrospectivo en pacientes mayores de 55 años con una primera crisis epiléptica de causa desconocida. Se recogieron los datos desde la historia clínica, incluyendo electroencefalograma (EEG) y resonancia magnética (RM) cerebral. Resultados. Se incluyó a 87 pacientes (58,6% varones; 71,5 ± 8,1 años). El seguimiento medio fue de 7,3 ± 4,9 años. El factor de riesgo vascular más frecuente fue la hipertensión arterial (77%; n = 67). Las crisis focales con alteración de la conciencia fueron el tipo de crisis más frecuente (44,8%; n = 39), seguidas de las crisis focales con evolución a bilaterales tonicoclónicas (39,1%; n = 34). La RM cerebral mostró atrofia cortical (50%; n = 42) y signos de enfermedad vascular de pequeño vaso (EVPV) (67,8%; n = 57). Se observaron anomalías epileptiformes intercríticas en el EEG en un 43,7% (n = 38) de los pacientes, mayoritariamente con localización temporal (94,7%; n = 36). Hasta un 44,8% (n = 39) presentaba deterioro cognitivo leve basalmente. La recurrencia de crisis, observada en 49 pacientes (56,1%), sucedió con una mediana de 12 meses (rango intercuartílico: 4,4-25,9). Finalmente, 71 pacientes (81,6%) desarrollaron epilepsia. Conclusión. El riesgo de epilepsia a largo plazo tras una crisis única de etiología desconocida en pacientes de edad avanzada es superior al 80%. La hipertensión arterial y el deterioro cognitivo leve en el inicio son las características clínicas más frecuentes. En la RM, la atrofia cortical y la presencia de EVPV son frecuentes, y los EEG de rutina no suelen mostrar alteraciones epileptiformes.

Verbal episodic memory in children undergoing temporal lobe epilepsy surgery: a one-year follow-up study. / Memoria episódica verbal en pacientes pediátricos intervenidos de cirugía de la epilepsia del lóbulo temporal: un estudio de seguimiento al año.

INTRODUCTION: Verbal episodic memory (VEM) is often unimpaired in children with focal epilepsy undergoing left temporal lobe resections, unlike what we might expect in the adult brain. The latter findings suggest that epileptiform activity in early life disrupts memory system lateralization, leading to the development of bilateral memory representation. The present study aims to analyze whether the laterality of epilepsy is a major predictor for post-operative VEM prognosis in pediatric temporal lobe epilepsy (TLE) surgery. This research also pretends to provide evidence about the relationship of VEM performance with other relevant demographical and clinical factors such as sex, age at onset of seizures, age at surgery and duration of epilepsy, as well as to study the impact of presurgical VEM performance on postsurgical outcomes. PATIENTS AND METHODS: Pre-operative and one-year follow-up post-operative word-list recall scores from 25 children who underwent TLE surgery (left-sided, n = 11; right-sided, n = 14) were extracted from the Hospital Sant Joan de Deu database and were retrospectively analyzed. RESULTS: No significant presurgical intergroup differences were found when comparing VEM scores by laterality of epilepsy (p > 0.5). Looking at the left TLE group, a high negative correlation was found between the onset age and the pre-operative long-term free recall score (rho = -0.72, p = 0.01). No significant pre- to post-operative intragroup changes were found regarding VEM performance, regardless of epilepsy laterality (left TLE group, p > 0.56; right TLE group, p > 0.12). CONCLUSIONS: The laterality of epilepsy does not show to be a significant factor in and of itself regarding presurgical VEM outcome and its prognosis one year after surgery, thus supporting the bilateral memory representation hypothesis. Furthermore, a younger age at onset of seizures seems to be related with a better pre-operative VEM performance, likely due to a more efficient reorganization of memory system induced by a greater brain plasticity at lower ages; however, this relationship has been only reported for the left-sided epilepsies in our sample.

TITLE: Memoria episódica verbal en pacientes pediátricos intervenidos de cirugía de la epilepsia del lóbulo temporal: un estudio de seguimiento al año.Introducción. La memoria episódica verbal (MEV) no suele resultar alterada en niños con epilepsia focal sometidos a resecciones del lóbulo temporal izquierdo, a diferencia de lo que cabría esperar si se tratara de un cerebro adulto. Los últimos hallazgos sugieren que la actividad epileptógena en los primeros años de vida disrumpe la lateralización del sistema mnésico, lo que conduce al desarrollo de una representación bilateral de la memoria. El presente estudio pretende analizar si la lateralidad de la epilepsia es un predictor significativo de cara al pronóstico posquirúrgico de la MEV en la cirugía de la epilepsia del lóbulo temporal (ELT) en edad pediátrica. Esta investigación también pretende aportar evidencias sobre la relación de la MEV con otros factores demográficos y clínicos relevantes, como el sexo, la edad de inicio de las crisis, la edad quirúrgica y la duración de la epilepsia, así como estudiar el impacto del rendimiento prequirúrgico en la MEV sobre los resultados posquirúrgicos. Pacientes y métodos. Se extrajeron de la base de datos del Hospital Sant Joan de Déu y se analizaron retrospectivamente las puntuaciones prequirúrgicas y al año de seguimiento postoperatorio de una tarea de recuerdo de lista de palabras correspondientes a 25 niños intervenidos de ELT (ELT izquierdo, n = 11; ELT derecho, n = 14). Resultados. No se encontraron diferencias intergrupales prequirúrgicas significativas al comparar las puntuaciones en MEV sobre la base de la lateralidad de la epilepsia (p > 0,5). En cuanto al grupo de ELT izquierdo, se encontró una alta correlación negativa entre la edad de inicio y la puntuación prequirúrgica del recuerdo libre a largo plazo (rho = ­0,72; p = 0,01). No se encontraron cambios intragrupo significativos entre el pre- y el postoperatorio en relación con el rendimiento en la MEV, independientemente de la lateralidad de la epilepsia (grupo de ELT izquierdo, p > 0,56; grupo de ELT derecho, p > 0,12). Conclusiones. La lateralidad de la epilepsia no parece ser un factor significativo por sí solo en relación con el rendimiento prequirúrgico en la MEV y su pronóstico un año después de la cirugía, lo que apoya la hipótesis de una representación bilateral de la memoria. Además, una edad más temprana al inicio de las crisis parece estar relacionada con un mejor resultado preoperatorio en la MEV, probablemente debido a una reorganización más eficiente del sistema de memoria inducida por una mayor plasticidad cerebral en edades más bajas; sin embargo, esta relación sólo se ha observado en nuestra muestra para las epilepsias de lateralidad izquierda.

Reactogenicity, pregnancy outcomes, and SARS-CoV-2 infection following COVID-19 vaccination during pregnancy in Canada: A national prospective cohort study.

OBJECTIVE: To describe self-reported reactogenicity, pregnancy outcomes, and SARS-CoV-2 infection following COVID-19 vaccination during pregnancy. DESIGN: National, prospective cohort study. SETTING: Participants across Canada were enrolled from July 2021 until June 2022. POPULATION: Individuals pregnant during the COVID-19 pandemic, regardless of vaccination status, were included. METHODS: The Canadian COVID-19 Vaccine Registry for Pregnant and Lactating Individuals (COVERED) was advertised through traditional and social media. Surveys were administered at baseline, following each vaccine dose if vaccinated, pregnancy conclusion, and every two months for 14 months. Changes to pregnancy or vaccination status, SARS-CoV-2 infections, or significant health events were recorded. MAIN OUTCOME MEASURES: Reactogenicity (local and systemic adverse events, and serious adverse events) within 1 week post-vaccination, pregnancy and neonatal outcomes, and subsequent SARS-CoV-2 infection. RESULTS: Among 2868 participants who received 1-2 doses of a COVID-19 vaccine during pregnancy, adverse events described included: headache (19.5-33.9%), nausea (4.8-13.8%), fever (2.7-10.2%), and myalgia (33.4-42.2%). Reactogenicity was highest after the 2nd dose of vaccine in pregnancy. Compared to 1660 unvaccinated participants, there were no statistically significant differences in adverse pregnancy or infant outcomes, aside from an increased risk of NICU admission ≥ 24 h among the unvaccinated group. During follow-up, there was a higher rate of participant-reported SARS-CoV-2 infection in the unvaccinated compared to the vaccinated group (18[47.4%] vs. 786[27.3%]). CONCLUSIONS: Participant-reported reactogenicity was similar to reports from non-pregnant adults. There was no increase in adverse pregnancy and birth outcomes among vaccinated vs. unvaccinated participants and lower rates of SARS-CoV-2 infection were reported in vaccinated participants. TWEETABLE ABSTRACT: No significant increase in adverse pregnancy or infant outcomes among vaccinated versus unvaccinated pregnant women in Canada.

Intermittent parathyroid hormone enhances the healing of medication-related osteonecrosis of the jaw lesions in rice rats.

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event in patients treated with antiresorptives. Management of MRONJ is challenging, and no non-antibiotic, established medical treatment exists. Intermittent parathyroid hormone (iPTH) has been used off-label to treat MRONJ with favorable results. However, its medical efficacy has rarely been substantiated in clinical or preclinical experiments. Using a validated rice rat, infection-based model of MRONJ, we evaluated the effects of iPTH on established MRONJ. We hypothesize that iPTH contributes to MRONJ resolution by enhancing alveolar bone turnover and healing oral soft tissues. Eighty-four rice rats began a standard rodent chow diet at age 4 weeks to induce localized periodontitis. Rats were simultaneously randomized to receive saline (vehicle, VEH) or zoledronic acid (ZOL, 80 µg/kg IV) every 4 weeks. Oral exams were conducted bi-weekly to assign a gross quadrant grade (GQG, 0-4) to evaluate any lesion at the lingual aspect of the interdental space between maxillary molar (M2) and M3. 14 of 20 VEH-treated rice rats (70%) developed maxillary localized periodontitis with GQG 2-3 after 30 ± 10 weeks of saline. Additionally, 40 of 64 ZOL-treated rice rats with periodontitis developed MRONJ-like lesions after 30 ± 10 weeks of ZOL treatment. Rice rats with localized periodontitis or MRONJ-like lesions were treated with saline or iPTH (40 µg/kg) subcutaneously (SC) 3 times/week For 6 weeks until euthanasia. We found that iPTH -treated ZOL rats had a lower prevalence of MRONJ (p < 0.001), with lower severity extent of oral lesions (p = 0.003) and percentage of empty osteocyte lacunae (p < 0.001). ZOL rats treated with iPTH displayed a higher osteoblast surface (p < 0.001), more osteoblasts (p < 0.001), higher osteoclast surface (p < 0.001) and more osteoclasts (p = 0.002) at alveolar bone surfaces than ZOL/VEH rats. Greater gingival epithelial thickness and epithelial cell proliferation rate was found in the oral mucosa and gingiva of ZOL/PTH rats than in ZOL/VEH rats (p < 0.001). Our data suggest that iPTH is an efficacious non-operative medicinal therapy that accelerates oral healing and enhances the resolution of MRONJ lesions in ZOL-treated rice rats.

Urbanization, migration, and indigenous health in Peru.

INTRODUCTION: We compare demographic, socioeconomic, and anthropometric characteristics and blood pressure (BP), between rural and urban Peruvian indigenous women. These are preliminary results from a project on urbanization, migration, and health. METHODS: Data were collected cross-sectionally (2019) and compared between a rural (n = 92) and an urban (n = 93) community. RESULTS: Height: µ = 148.3 ± 5.0 cm (range = 137-162), weight: µ = 62.0 ± 11.5 (range = 37.5-108.7), median waist circumference = 89.0 (IQR = 15.8, range = 64.0-126.0), BMI = 28.3 (IQR = 6.2, range = 16.7-40.0), with no significant rural-urban differences. Systolic but not diastolic BP was significantly higher in urban versus rural women (median = 110, IQR = 18, range = 80-170 vs. median = 120, IQR = 10, range = 90-170, p = .002 and median = 70, IQR = 17, range = 50-100 vs. median = 70, IQR = 10, range = 60-100, p = .354), respectively. CONCLUSIONS: Despite major lifestyle differences, there were no anthropometric differences between rural and urban women. Higher systolic BP in urban women may reflect social/economic stressors rather than dietary factors.

Effectiveness of a digital application to improve stroke knowledge for kids.

INTRODUCTION: Stroke is highly prevalent in Latin America and one of the leading causes of morbidity and mortality in the world. Educating children about stroke has been established as an effective method to detect symptoms early, reduce hospital visits, and raise awareness among adults. OBJECTIVE: To analyze the effectiveness of a mobile application to improve knowledge and understanding of stroke among children. METHOD: We conducted a focus group session including 12 children in order to analyze the behavior of 6 questions previously validated by expert neurologists. Subsequently, 105 primary school students between the ages of 7 and 12 completed a questionnaire on stroke symptoms and how to contact the emergency services before and after using an application on stroke symptoms. Qualitative analyses and the Student t test were used to verify the existence of differences between pre- and post-intervention test results. RESULTS: After a single 40-min working session with the application, between 50% and 67% of the children were able to identify the signs of stroke, and 96.2% knew the national emergency services telephone number. Statistical analysis revealed statistically significant differences before and after the intervention with the digital application (t=19.54; p<0.001) and intragroup differences in the post-intervention test results (t=40.71; p<0.001). CONCLUSION: Primary school children who used our digital application increased their knowledge, understanding, and learning of stroke symptoms.

Effectiveness of a digital application to improve stroke knowledge for kids / Efectividad de una aplicación móvil para mejorar el conocimiento sobre los síntomas de ictus en una población pediátrica de Colombia

Introduction: Stroke is highly prevalent in Latin America and one of the leading causes of morbidity and mortality in the world. Educating children about stroke has been established as an effective method to detect symptoms early, reduce hospital visits, and raise awareness among adults. Objective: To analyze the effectiveness of a mobile application to improve knowledge and understanding of stroke among children. Method: We conducted a focus group session including 12 children in order to analyze the behavior of 6 questions previously validated by expert neurologists. Subsequently, 105 primary school students between the ages of 7 and 12 completed a questionnaire on stroke symptoms and how to contact the emergency services before and after using an application on stroke symptoms. Qualitative analyses and the Student t test were used to verify the existence of differences between pre- and post-intervention test results. Results: After a single 40-min working session with the application, between 50% and 67% of the children were able to identify the signs of stroke, and 96.2% knew the national emergency services telephone number. Statistical analysis revealed statistically significant differences before and after the intervention with the digital application (t = 19.54; p < 0.001) and intragroup differences in the post-intervention test results (t = 40.71; p < 0.001). Conclusion: Primary school children who used our digital application increased their knowledge, understanding, and learning of stroke symptoms.(AU)

Introducción: El ictus es muy prevalente en Latinoamérica y constituye una de las principales causas de morbimortalidad a nivel mundial. Se ha sugerido que enseñar a los niños a reconocer los primeros síntomas de ictus puede ayudar a reducir el número de ingresos por esta enfermedad y a concienciar a la población adulta. Objetivo: Analizar la efectividad de una aplicación móvil para aumentar el conocimiento del ictus en los niños. Método: Llevamos a cabo una sesión con un grupo focal de 12 niños para analizar el comportamiento de 6 preguntas previamente validadas por un grupo de neurólogos expertos. Posteriormente, administramos un cuestionario sobre síntomas de ictus y servicios de emergencias a 105 niños de entre 7 y 12 años en dos momentos diferentes: antes y después de usar la aplicación sobre síntomas de ictus. Se realizaron análisis cualitativos y se aplicó la prueba t de Student para confirmar la presencia de diferencias en las respuestas al cuestionario antes y después de la intervención. Resultados: Tras una única sesión de 40 minutos con la aplicación, entre el 50% y el 67% de los niños eran capaces de identificar los síntomas de ictus y el 96,2% se sabían el número de teléfono de emergencias. El análisis estadístico reveló diferencias estadísticamente significativas entre los resultados del cuestionario antes y después de la intervención (t = 19,54; P < 0,001), así como diferencias intragrupo en los resultados postintervención (t = 40,71; P < 0,001). Conclusión: Los niños que utilizaron nuestra aplicación acabaron sabiendo más sobre los síntomas de ictus y cómo actuar.(AU)

Rol de la cirugía endoscópica en el tratamiento de quistes odontogénicos del hueso maxilar: revisión de la literatura

Los quistes odontogénicos son lesiones óseas, de carácter benigno, la mayoría asintomáticas, que habitualmente corresponden a un hallazgo radiológico. El tratamiento es quirúrgico y está condicionado por factores como localización, tamaño y la afectación de estructuras vecinas. El objetivo es elegir la modalidad de tratamiento que conlleve el menor riesgo de recurrencia, la mínima morbilidad, y al mismo tiempo la erradicación de la lesión. Siguiendo esta premisa han sido abordados, tradicionalmente, con técnicas abiertas con buenos resultados, pero con el advenimiento y desarrollo de la cirugía endoscópica, se empezó a usar esta técnica en forma exclusiva o en forma mixta para la resección de los quistes odontogénicos, logrando similares tasas de éxito, pero con menores complicaciones y morbilidad posoperatoria. Además, presenta una ventaja respecto del seguimiento para las recurrencias, ya que se pueden controlar endoscópicamente en la consulta ambulatoria. El objetivo de esta revisión es describir el desarrollo del rol de las cirugías endoscópicas para el tratamiento de lesiones odontogénicas maxilares.

Odontogenic cysts are benign bone lesions, most of them asymptomatic, which usually constitute a radiological finding. The treatment is surgical and is conditioned by factors such as location, size and involvement of nearby structures. The objective is to choose the treatment mode that presents the lowest risk of recurrence, the minimum morbidity, and at the same time, the eradication of the lesion. Following this premise, the treatment of these lesions has traditionally been approached with open techniques with good results but, with the advent and development of endoscopic surgery, this technique began to be used exclusively or in a mixed form for the resection of odontogenic cysts, achieving similar rates of surgical success, but with fewer complications and postoperative morbidity. It also has an advantage regarding follow-up for recurrences, since patients can be controlled endoscopically in the outpatient clinic. The objective of this review is to describe the development and role of endoscopic surgery for the treatment of maxillary odontogenic lesions.

Chloroplastic pentatricopeptide repeat proteins (PPR) in albino plantlets of Agave angustifolia Haw. reveal unexpected behavior.

BACKGROUND: Pentatricopeptide repeat (PPR) proteins play an essential role in the post-transcriptional regulation of genes in plastid genomes. Although important advances have been made in understanding the functions of these genes, there is little information available on chloroplastic PPR genes in non-model plants and less in plants without chloroplasts. In the present study, a comprehensive and multifactorial bioinformatic strategy was applied to search for putative PPR genes in the foliar and meristematic tissues of green and albino plantlets of the non-model plant Agave angustifolia Haw. RESULTS: A total of 1581 PPR transcripts were identified, of which 282 were chloroplastic. Leaf tissue in the albino plantlets showed the highest levels of expression of chloroplastic PPRs. The search for hypothetical targets of 12 PPR sequences in the chloroplast genes of A. angustifolia revealed their action on transcripts related to ribosomes and translation, photosystems, ATP synthase, plastid-encoded RNA polymerase and RuBisCO. CONCLUSIONS: Our results suggest that the expression of PPR genes depends on the state of cell differentiation and plastid development. In the case of the albino leaf tissue, which lacks functional chloroplasts, it is possible that anterograde and retrograde signaling networks are severely compromised, leading to a compensatory anterograde response characterized by an increase in the expression of PPR genes.

Development, Validation, and Utility of Species-Specific Diagnostic Markers for Detection of Peronospora belbahrii.

Peronospora belbahrii is an oomycete and the cause of basil downy mildew, one of the most destructive diseases affecting basil production worldwide. Disease management is challenging due to wind-dispersed sporangia and contaminated seed; therefore, identifying P. belbahrii in seed lots before sale or planting or in the field before symptoms develop could allow for timely deployment of disease management strategies. In this study, a draft genome assembly and next-generation sequencing reads for P. belbahrii, as well as publicly available DNA-seq and RNA-seq reads of several other downy mildew pathogens, were incorporated into a bioinformatics pipeline to predict P. belbahrii-specific diagnostic markers. The specificity of each candidate marker was validated against a diverse DNA collection of P. belbahrii, host tissue, and related oomycetes using PCR. Two species-specific markers were identified and used as templates to develop a highly sensitive probe-based real-time quantitative PCR (qPCR) assay that could detect P. belbahrii in leaf tissue and seed samples. Both markers were capable of reliably detecting as low as 500 fg/µl of P. belbahrii genomic DNA and as few as 10 sporangia. The qPCR assay was then validated with seed samples collected from a basil cultivar experiment. In total, 48 seed samples were collected and tested; P. belbahrii was detected in samples of all cultivars at estimated concentrations of 600 fg/µl up to 250 pg/µl and at as few as 10 sporangia up to >1,000 sporangia. The markers and assays are valuable for diagnostics and identifying P. belbahrii-contaminated seed lots to mitigate the effects of future basil downy mildew epidemics.

Biologic and pathologic aspects of osteocytes in the setting of medication-related osteonecrosis of the jaw (MRONJ).

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe, debilitating condition affecting patients with cancer and patients with osteoporosis who have been treated with powerful antiresorptives (pARs) or angiogenesis inhibitors (AgIs). Oral risk factors associated with the development of MRONJ include tooth extraction and inflammatory dental disease (e.g., periodontitis, periapical infection). In bone tissues, osteocytes play a bidirectional role in which they not only act as the "receiver" of systemic signals from blood vessels, such as hormones and drugs, or local signals from the mineralized matrix as it is deformed, but they also play a critical role as "transmitter" of signals to the cells that execute bone modeling and remodeling (osteoclasts, osteoblasts and lining cells). When the survival capacity of osteocytes is overwhelmed, they can die. Osteocyte death has been associated with several pathological conditions. Whereas the causes and mechanisms of osteocyte death have been studied in conditions like osteonecrosis of the femoral head (ONFH), few studies of the causes and mechanisms of osteocyte death have been done in MRONJ. The three forms of cell death that affect most of the different cells in the body (apoptosis, autophagy, and necrosis) have been recognized in osteocytes. Notably, necroptosis, a form of regulated cell death with "a necrotic cell death phenotype," has also been identified as a form of cell death in osteocytes under certain pathologic conditions. Improving the understanding of osteocyte death in MRONJ may be critical for preventing disease and developing treatment approaches. In this review, we intend to provide insight into the biology of osteocytes, cell death, in general, and osteocyte death, in particular, and discuss hypothetical mechanisms involved in osteocyte death associated with MRONJ.

Pharmacokinetic and pharmacodynamic properties of aerosolized ("vaped") THC in adolescent male and female rats.

RATIONALE: Adolescent exposure to ∆9-tetrahydrocannabinol (THC), the psychotropic constituent of cannabis, might affect brain development, and in rodent models leads to long-term behavioral and physiological alterations. Yet, the basic pharmacology of this drug in adolescent rodents, especially when ingested via ecologically relevant routes like aerosol inhalation, commonly referred to as "vaping," is still poorly characterized. Moreover, sex differences exist in THC metabolism, kinetics, and behavioral effects, but these have not been rigorously examined after vapor dosing in adolescents. OBJECTIVES: We investigated the pharmacokinetics and pharmacodynamics of aerosolized THC (30 min inhalation exposure, 25 or 100 mg/ml) in adolescent Wistar rats of both sexes. METHODS: Liquid chromatography/mass spectrometry analysis of THC and its major metabolites was conducted on blood plasma and brain tissue at 5, 30, 60, and 120 min following a 30-min aerosol dosing session. Effects on activity in a novel environment for 120 min after aerosol, and temperature, were measured in separate rats. RESULTS: We found sex-dependent differences in the pharmacokinetics of THC and its active (11-OH-THC) and inactive (11-COOH-THC) metabolites in the blood and brain, along with dose- and sex-dependent effects on anxiety-like and exploratory behaviors; namely, greater 11-OH-THC levels accompanied by greater behavioral effects in females at the low dose but similar hypothermic effects in both sexes at the high dose. CONCLUSIONS: These results provide a benchmark for dosing adolescent rats with aerosolized (or "vaped") THC, which could facilitate adoption by other labs of this potentially human-relevant THC exposure model to understand cannabis effects on the developing brain.

Preclinical models of medication-related osteonecrosis of the jaw (MRONJ).

Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse event affecting patients with cancer and patients with osteoporosis who have been treated with powerful antiresorptives (pARs) or angiogenesis inhibitors (AgIs). pARs, including nitrogen-containing bisphosphonates (N-BPs; e.g., zoledronic acid, alendronate) and anti-RANKL antibodies (e.g., denosumab), are used to manage bone metastases in patients with cancer or to prevent fragility fractures in patients with osteoporosis. Though significant advances have been made in understanding MRONJ, its pathophysiology is still not fully elucidated. Multiple species have been used in preclinical MRONJ research, including the rat, mouse, rice rat, rabbit, dog, sheep, and pig. Animal research has contributed immensely to advancing the MRONJ field, particularly, but not limited to, in developing models and investigating risk factors that were first observed in humans. MRONJ models have been developed using clinically relevant doses of systemic risk factors, like N-BPs, anti-RANKL antibodies, or AgIs. Specific local oral risk factors first noted in humans, including tooth extraction and inflammatory dental disease (e.g., periodontitis, periapical infection, etc.), were then added. Research in rodents, particularly the rat, and, to some extent, the mouse, across multiple laboratories, has contributed to establishing multiple relevant and complementary preclinical models. Models in larger species produced accurate clinical and histopathologic outcomes suggesting a potential role for confirming specific crucial findings from rodent research. We view the current state of animal models for MRONJ as good. The rodent models are now reliable enough to produce large numbers of MRONJ cases that could be applied in experiments testing treatment modalities. The course of MRONJ, including stage 0 MRONJ, is characterized well enough that basic studies of the molecular or enzyme-level findings in different MRONJ stages are possible. This review provides a current overview of the existing models of MRONJ, their more significant features and findings, and important instances of their application in preclinical research.

Secuestro pulmonar en varón joven con episodio de hemoptisis / Pulmonary sequestration in a young man with hemoptisis episode

Se describe el caso de un paciente de 37 años, que a raíz de un episodio de hemoptisis diagnosticamos un secuestro pulmonar, malformación congénita infrecuente del pulmón, diagnosticada principalmente durante los primeros años de vida. Habitualmente cursa de manera asintomática, pudiendo debutar de manera puntual en forma de hemoptisis en la edad adulta (AU)

We describe a case of a 37-year-old patient who, as a result of an episode of hemoptisis, we find out a lung malformation, a rare cause of adult hemoptisis. Pulmonary sequestration is a rare congenital malformation of the lung, diagnosed mainly during the early years of life and childhood, which usually takes place asymptomatically, but which can start on time in the form of hemoptisis in adulthood (AU)

Reduced Th1 response is associated with lower glycolytic activity in activated peripheral blood mononuclear cells after metabolic and bariatric surgery.

BACKGROUND: Obesity promotes cellular immunometabolism changes that trigger the activation of macrophages and lymphocytes, leading to systemic inflammation. Activated leukocytes undergo metabolic reprogramming, increasing glycolytic activity. OBJECTIVE: To examine whether the reduction in the inflammatory state associated with bariatric surgery is associated with decreased glycolytic activity in leukocytes. Setting Single-center, prospective observational study. METHODS: This study involved 18 patients with obesity undergoing bariatric surgery. All measurements were performed preoperatively and six months postoperatively. Peripheral blood mononuclear cells and plasma were obtained to determine the glycolytic rate and mitochondrial membrane potential as surrogates of the metabolic switching and high-sensitivity C-reactive protein, adipokines, and CD69 expression as inflammatory and activation markers. RESULTS: Glycolytic activity engaged by CD3/CD28 activation was reduced six months after bariatric surgery, associated with decreased levels of T helper (Th) 1 and Th17 signature cytokines. An overall reduction in inflammatory markers was observed, which correlated with a higher adiponectin/leptin ratio. CONCLUSIONS: Metabolic and bariatric surgery-induced weight loss leads to reprogramming in T cells' metabolic machinery, resulting in reduced stimulation of glycolysis after activation, which may explain the decrease in systemic inflammation mediated by cytokines such as interferon-γ and interleukin-17A.

Preventing or controlling periodontitis reduces the occurrence of osteonecrosis of the jaw (ONJ) in rice rats (Oryzomys palustris).

INTRODUCTION: Osteonecrosis of the jaw (ONJ) is an adverse event that requires association of both systemic risk factors, such as powerful anti-resorptives (pARs; e.g. zoledronic acid [ZOL]), and local oral risk factors (e.g. tooth extraction, periodontitis). Whereas optimal oral health prior to initiate pARs is recognized as critically important for minimizing ONJ risk, the efficacy of preventive/maintenance measures in patients who are taking pARs is understudied. Rice rats fed a standard diet (STD), rich in insoluble fiber, develop localized periodontitis. STD-rats with localized periodontitis treated with ZOL for 18-24 wk develop ONJ. Hence, we hypothesized that controlling/preventing localized periodontitis in the ZOL-treated rats, reduces ONJ occurrence. METHODS: We used two approaches to attempt reducing periodontitis prevalence: 1) periodontal cleaning (PC); and 2) replacing the STD-diet with a nutritionally-equivalent diet high in soluble fiber (SF). 75 four-week-old male rats were weight-randomized into five groups (n = 15) in a 24-week experiment. Three groups ate the STD-diet and two the high SF-diet. STD-diet groups received intravenous (IV) vehicle (VEH) q4wks (STD + VEH), 80 µg/kg ZOL q4wks IV (STD + ZOL), or ZOL plus PC q2wks (STD + ZOL + PC). The SF-diet groups received VEH (SF + VEH) or ZOL (SF + ZOL). Jaws were processed for histopathology and evaluated for ONJ prevalence and tissue-level periodontitis. RESULTS: 1) 40% of STD + VEH rats developed maxillary localized periodontitis with no ONJ; 2) 50% of STD + ZOL rats developed ONJ; 3) 7% of STD + ZOL + PC rats developed ONJ (p < 0.01 vs. STD + ZOL); and 4) one SF + ZOL rat developed localized periodontitis, and no SF + VEH or SF + ZOL rats developed ONJ (p < 0.001 vs. STD + ZOL). CONCLUSIONS: 1) Periodontal cleaning in ZOL-treated rats decreases localized periodontitis severity and reduces ONJ prevalence; and 2) feeding a SF-diet to ZOL-treated rats reduces both incidence of localized periodontitis and ONJ. Our data indicates strong oral microbial community shifts according to oral health condition and trends in the shifts associated with diet.

Modelling of Chaotic Processes with Caputo Fractional Order Derivative.

Chaotic dynamical systems are studied in this paper. In the models, integer order time derivatives are replaced with the Caputo fractional order counterparts. A Chebyshev spectral method is presented for the numerical approximation. In each of the systems considered, linear stability analysis is established. A range of chaotic behaviours are obtained at the instances of fractional power which show the evolution of the species in time and space.