Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects.

Between 2.5 and 28% of people infected with SARS-CoV-2 suffer Long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in Long COVID and the potential association between them. To address these objectives, 83 patients with persistent neurological symptoms after COVID-19 were recruited, and 22 now healthy controls chosen because they had suffered COVID-19 but did not experience persistent neurological symptoms. Patients and controls were matched for age, sex and educational level. All participants were assessed by clinical interview, comprehensive standardized neuropsychological tests and structural MRI. The mean global cognitive function of patients with Long COVID assessed by ACE III screening test (Overall Cognitive level - OCLz= -0.39± 0.12) was significantly below the infection recovered-controls (OCLz= +0.32± 0.16, p< 0.01). We observed that 48% of patients with Long COVID had episodic memory deficit, with 27% also impaired overall cognitive function, especially attention, working memory, processing speed and verbal fluency. The MRI examination included grey matter morphometry and whole brain structural connectivity analysis. Compared to infection recovered controls, patients had thinner cortex in a specific cluster centred on the left posterior superior temporal gyrus. In addition, lower fractional anisotropy (FA) and higher radial diffusivity (RD) were observed in widespread areas of the patients' cerebral white matter relative to these controls. Correlations between cognitive status and brain abnormalities revealed a relationship between altered connectivity of white matter regions and impairments of episodic memory, overall cognitive function, attention and verbal fluency. This study shows that patients with neurological Long COVID suffer brain changes, especially in several white matter areas, and these are associated with impairments of specific cognitive functions.

Molecular Detection and Characterization of Ehrlichia canis Isolates from Three Geographic Regions in Mexico: A Retrospective Study.

Canine monocytic ehrlichiosis (CME) is the most common tick-borne disease affecting domestic dogs and other wild canids. It has a worldwide distribution and is associated with the presence of the brown dog tick. Few studies have been conducted in Mexico to identify and characterize Ehrlichia canis genetic variability. In the present study, 111 dogs of different sex, breed, and age from three geographic regions in Mexico were included. All of them had a previous history of tick infestation and/or the presence of one or more clinical signs compatible with CME. All dogs were tested by a commercial ELISA and nested PCR assay for the detection of E. canis. In addition, we analyzed the E. canis genetic diversity from the 16S rRNA gene sequences obtained in this study, along with 15 additional sequences described for E. canis in Mexico and obtained from GeneBank. Serological detection by commercial ELISA results showed overall infection rates of 85.58% (95/111), including 73.1% (30/41) in samples from Guerrero state; 75% (15/20) in Morelos; and 100% (50/50) in Chihuahua. On the other hand, molecular detection (nPCR assay) showed 31.5% (35/111) overall infection rate, with 41.4% (17/41) in Guerrero state; 55% (11/20) in Morelos; and 14% (7/50) in Chihuahua. We observed a high 16S rRNA gene sequence conservancy in most of the E. canis isolates in the three geographical areas from Mexico, including those analyzed in this research, suggesting a common geographic origin among isolates.

Analysis of the Pediatric Radiotherapy Landscape in Mexico and a Subsequent Educational e-Contouring Intervention.

PURPOSE: Mexico and Central America have the highest childhood cancer incidence in the West. Pediatric-specific oncology knowledge contributes to the disparity. We sought to (1) determine the self-identified treatment patterns and needs of Mexican pediatric radiation oncologists and (2) pilot a workshop to improve contouring accuracy. MATERIALS AND METHODS: Partnering with local experts and the Sociedad Mexicana de Radioterapeutas (SOMERA), a 35-question survey was designed to ascertain pediatric radiotherapy capacity and distributed through the SOMERA listserv. The most challenging malignancies were selected for workshop. Participants received precontouring and postcontouring homework to assess improvement per the Dice metric. The Wilcoxon sign-rank test was used for comparative statistics. RESULTS: Ninety-four radiation oncologists attempted and 79 completed the survey. Forty-four (76%) felt comfortable treating a pediatric patient, and 36 (62%) were familiar with national protocols for pediatric treatment. Most had access to nutrition, rehabilitation, endocrinology, and anesthesia; 14% had access to fertility services and 27% to neurocognitive support; 11% noted no support, and only one respondent had child-life support. The postsurvey contouring workshop was conducted for high-grade glioma, medulloblastoma, and Hodgkin lymphoma. Significant improvements were seen in all target volumes. CONCLUSION: We present the first national survey of Mexico's pediatric radiotherapy capacity and Latin American e-contouring educational intervention with preworkshop and postworkshop Dice metrics, noting statistically significant improvement in all target volumes. Participation improved compared with prior experience through SOMERA partnership and Continuing Medical Education incentivization.

Possible Association between Selected Tick-Borne Pathogen Prevalence and Rhipicephalus sanguineus sensu lato Infestation in Dogs from Juarez City (Chihuahua), Northwest Mexico-US Border.

Tick-borne bacterial pathogens (TBBPs) show a worldwide distribution and represent a great impact on public health. The brown dog tick (Rhipicephalus sanguineus) is a vector of several pathogens that affect dogs and sometimes humans as well. In addition, TBBPs represent a diagnostic challenge and imply financial resources and medical treatment for long periods of time. In the present study, R. sanguineus s. l. was identified as the main tick species naturally parasitizing dogs that inhabit. Juárez City, Chihuahua, in the Paso del Norte region, Mexico-US Border, representing 99.8% of the cases. Additionally, an end-point PCR was performed to search for whether pathogens in R. sanguineus s. l. can transmit in DNA extracted from ticks and dog blood samples. This is the first molecular detection of Rickettsia rickettsi infecting domestic dogs in Mexico; however, other pathogens were also identified, such as Ehrlichia canis and Anaplasma platys in both ticks and dog blood samples, while Anaplasma phagocytophilum was identified only in dog blood samples. Moreover, co-detection in tick pools and co-infection in the analyzed dog blood samples could be found. Similarly, this research showed that dogs were found mostly parasitized by adult female ticks, increasing the possibility of transmission of E. canis.

A novel telencephalon-opto-hypothalamic morphogenetic domain coexpressing Foxg1 and Otp produces most of the glutamatergic neurons of the medial extended amygdala.

Deficits in social cognition and behavior are a hallmark of many psychiatric disorders. The medial extended amygdala, including the medial amygdala and the medial bed nucleus of the stria terminalis, is a key component of functional networks involved in sociality. However, this nuclear complex is highly heterogeneous and contains numerous GABAergic and glutamatergic neuron subpopulations. Deciphering the connections of different neurons is essential in order to understand how this structure regulates different aspects of sociality, and it is necessary to evaluate their differential implication in distinct mental disorders. Developmental studies in different vertebrates are offering new venues to understand neuronal diversity of the medial extended amygdala and are helping to establish a relation between the embryonic origin and molecular signature of distinct neurons with the functional subcircuits in which they are engaged. These studies have provided many details on the distinct GABAergic neurons of the medial extended amygdala, but information on the glutamatergic neurons is still scarce. Using an Otp-eGFP transgenic mouse and multiple fluorescent labeling, we show that most glutamatergic neurons of the medial extended amygdala originate in a distinct telencephalon-opto-hypothalamic embryonic domain (TOH), located at the transition between telencephalon and hypothalamus, which produces Otp-lineage neurons expressing the telencephalic marker Foxg1 but not Nkx2.1 during development. These glutamatergic cells include a subpopulation of projection neurons of the medial amygdala, which activation has been previously shown to promote autistic-like behavior. Our data open new venues for studying the implication of this neuron subtype in neurodevelopmental disorders producing social deficits.

Involvement of N-methylpurine DNA glycosylase in resistance to temozolomide in patient-derived glioma cells.

Chemotherapy for high-grade astrocytic tumors is mainly based on the use of temozolomide (TMZ), whose efficacy is limited by resistance mechanisms. Despite many investigations pointing to O6-methylguanine-DNA-methyltransferase (MGMT) as being responsible for tumor chemo-resistance, its expression does not predict an accurate response in most gliomas, suggesting that MGMT is not the only determinant of response to treatment. In this sense, several reports indicate that N-methylpurine-DNA-glycosylase (MPG) may be involved in that resistance. With that in mind, we evaluated for the first time the degree of resistance to TMZ treatment in 18 patient-derived glioma cells and its association with MGMT and MPG mRNA levels. Viability cell assays showed that TMZ treatment hardly caused growth inhibition in the patient-derived cells, even in high concentrations, indicating that all primary cultures were chemo-resistant. mRNA expression analyses showed that the TMZ-resistant phenotype displayed by cells is associated with an elevated expression of MPG to a greater extent than it is with transcript levels of MGMT. Our findings suggest that not only is MGMT implicated in resistance to TMZ but MPG, the first enzyme in base excision repair processing, is also involved, supporting its potential role as a target in anti-resistance chemotherapy for astrocytoma and glioblastoma.

Isolation and Quantification of Blood Apoptotic Bodies, a Non-invasive Tool to Evaluate Apoptosis in Patients with Ischemic Stroke and Neurodegenerative Diseases.

BACKGROUND: Improper regulation of apoptosis has been postulated as one of the main factors that contributes to the etiology and/or progression of several prevalent diseases, including ischemic stroke and neurodegenerative pathologies. Consequently, in the last few years, there has been an ever-growing interest in the in vivo study of apoptosis. The clinical application of the tissue sampling and imaging approaches to analyze apoptosis in neurological diseases is, however, limited. Since apoptotic bodies are membrane vesicles that are released from fragmented apoptotic cells, it follows that the presence of these vesicles in the bloodstream is likely due to the apoptotic death of cells in tissues. We therefore propose to use circulating apoptotic bodies as biomarkers for measuring apoptotic death in patients with ischemic stroke and neurodegenerative diseases. RESULTS: Since there is no scientific literature establishing the most appropriate method for collecting and enumerating apoptotic bodies from human blood samples. Authors, here, describe a reproducible centrifugation-based method combined with flow cytometry analysis to isolate and quantify plasma apoptotic bodies of patients with ischemic stroke, multiple sclerosis, Parkinson's disease and also in healthy controls. Electron microscopy, dynamic light scattering and proteomic characterization in combination with flow cytometry studies revealed that our isolation method achieves notable recovery rates of highly-purified intact apoptotic bodies. CONCLUSIONS: This easy, minimally time consuming and effective procedure for isolating and quantifying plasma apoptotic bodies could help physicians to implement the use of such vesicles as a non-invasive tool to monitor apoptosis in patients with cerebrovascular and neurodegenerative diseases for prognostic purposes and for monitoring disease activity.

Sex-related differences in the distance of the mental foramen to the cementoenamel junction in adults: a study using cone beam computed tomography.

Injury to the contents of the mental foramen (MF) can be minimized by using cone beam computed tomography (CBCT) to determine the exact location of the MF prior to surgical procedures. In this retrospective study, variations in the vertical position of the MF between adult men and women older than 18 years were investigated using CBCT. The distance between the superior border of the MF and the most apical aspect of the cementoenamel junction (CEJ) of the mandibular second premolar was measured. Among the randomly accessed CBCT records of 200 patients, 176 MF-CEJ measurements met the inclusion criteria. There was a statistically significant difference (P < 0.001) between the sexes in the location of the MF. The distance in women was shorter by an average of 2.00 mm, irrespective of the side of the mandible. Additionally, a within-sex asymmetry between right and left sides was observed; the asymmetry was significantly greater in men than in women (P < 0.05). Clinicians should be cognizant of the influence of the patient's sex on the vertical position of the MF and the presence of asymmetry in the position of the MF between the right and left sides of the mandible within the sex groups.

Probabilistic Prognosis of Environmental Radioactivity Concentrations due to Radioisotopes Discharged to Water Bodies from Nuclear Power Plants.

Due to their very low values, the complexity of comparing the contribution of nuclear power plants (NPPs) to environmental radioactivity with modeled values is recognized. In order to compare probabilistic prognosis of radioactivity concentrations with environmental measurement values, an exercise was performed using public data of radioactive routine discharges from three representative Spanish nuclear power plants. Specifically, data on liquid discharges from three Spanish NPPs: Almaraz, Vandellós II, and Ascó to three different aquatic bodies (river, lake, and coast) were used. Results modelled using generic conservative models together with Monte Carlo techniques used for uncertainties propagation were compared with values of radioactivity concentrations in the environment measured in the surroundings of these NPPs. Probability distribution functions were inferred for the source term, used as an input to the model to estimate the radioactivity concentrations in the environment due to discharges to the water bodies. Radioactivity concentrations measured in bottom sediments were used in the exercise due to their accumulation properties. Of all the radioisotopes measured in the environmental monitoring programs around the NPPs, only Cs-137, Sr-90, and Co-60 had positive values greater than their respective detection limits. Of those, Sr-90 and Cs-137 are easily measured in the environment, but significant contribution from the radioactive fall-out due to nuclear explosions in the atmosphere exists, and therefore their values cannot be attributed to the NPPs. On the contrary, Co-60 is especially useful as an indicator of the radioactive discharges from NPPs because its presence in the environment can solely be attributed to the impact of the closer nuclear facilities. All the modelled values for Co-60 showed a reasonable correspondence with measured environmental data in all cases, being conservative in two of them. The more conservative predictions obtained with the models were the activity concentrations in the sediments of a lake (Almaraz) where, on average, values two times higher were obtained. For the case of rivers (Ascó), calculated results were adequately conservative-up to 3.4 times on average. However, the results for coasts (Vandellos II) were in the same range as the environmental measurements, obtaining predictions that are only-at maximum-1.1 times higher than measured values. Only for this specific case of coasts could it be established that the models are not conservative enough, although the results, on average, are relatively close to the real values.

Assessment for the management of NORM wastes in conventional hazardous and nonhazardous waste landfills.

Naturally Occurring Radioactive Materials (NORM) wastes are generated in huge quantities in several industries and their management has been carried out under considerations of industrial non-radioactive wastes, before the concern on the radioactivity content was included in the legislation. Therefore these wastes were conditioned using conventional methods and the waste disposals were designed to isolate toxic elements from the environment for long periods of time. Spanish regulation for these conventional toxic waste disposals includes conditions that assure adequate isolation to minimize the impact of the wastes to the environment in present and future conditions. After 1996 the radiological impact of the management of NORM wastes is considered and all the aspects related with natural radiations and the radiological control regarding the management of residues from NORM industries were developed in the new regulation. One option to be assessed is the disposal of NORM wastes in hazardous and non-hazardous waste disposals, as was done before this new regulation. This work analyses the management of NORM wastes in these landfills to derive the masses that can be disposed without considerable radiological impact. Generic dose assessments were carried out under highly conservative hypothesis and a discussion on the uncertainty and variability sources was included to provide consistency to the calculations.

Regionalized differentiation of CRH, TRH, and GHRH peptidergic neurons in the mouse hypothalamus.

According to the updated prosomeric model, the hypothalamus is subdivided rostrocaudally into terminal and peduncular parts, and dorsoventrally into alar, basal, and floor longitudinal zones. In this context, we examined the ontogeny of peptidergic cell populations expressing Crh, Trh, and Ghrh mRNAs in the mouse hypothalamus, comparing their distribution relative to the major progenitor domains characterized by molecular markers such as Otp, Sim1, Dlx5, Arx, Gsh1, and Nkx2.1. All three neuronal types originate mainly in the peduncular paraventricular domain and less importantly at the terminal paraventricular domain; both are characteristic alar Otp/Sim1-positive areas. Trh and Ghrh cells appeared specifically at the ventral subdomain of the cited areas after E10.5. Additional Ghrh cells emerged separately at the tuberal arcuate area, characterized by Nkx2.1 expression. Crh-positive cells emerged instead in the central part of the peduncular paraventricular domain at E13.5 and remained there. In contrast, as development progresses (E13.5-E18.5) many alar Ghrh and Trh cells translocate into the alar subparaventricular area, and often also into underlying basal neighborhoods expressing Nkx2.1 and/or Dlx5, such as the tuberal and retrotuberal areas, becoming partly or totally depleted at the original birth sites. Our data correlate a topologic map of molecularly defined hypothalamic progenitor areas with three types of specific neurons, each with restricted spatial origins and differential migratory behavior during prenatal hypothalamic development. The study may be useful for detailed causal analysis of the respective differential specification mechanisms. The postulated migrations also contribute to our understanding of adult hypothalamic complexity.

[Gastrointestinal stromal tumors in the pediatric population. Report of two cases and a review of the literature]. / Tumores estromales del tracto gastrointestinal en población pediátrica. Informe de dos casos y revisión de la literatura.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal (GI) tract that occur predominantly in adults. GISTs in pediatric patients are rare and not well characterized. We reviewed the presentation, diagnostic work-up, pathological specimens, and outcomes of two children with GIST that originated from the stomach. Literature pertaining to pediatric GISTs was also reviewed. CLINICAL CASES: Both patients presented with upper GI bleeding from a gastric tumor. The first patient was a 10-year-old male who underwent partial gastrectomy but had recurrence 26 years later requiring surgical exploration due to extensive infiltration into the surrounding organs; the tumor was not resected. The patient is currently being treated with imatinib mesylate. The second patient was a 12-year-old female who had a pedunculated mass originating from the stomach and requiring resection. She subsequently had a local recurrence 2 years later requiring partial gastrectomy. Adjuvant imatinib mesylate was recommended because of the large size of the tumor (8 cm). CONCLUSIONS: Pediatric GISTs represent a distinct subset of sarcomas with a strong predominance for females and gastric location, with 56 cases reported in the English-language literature.

Tumores estromales del tracto gastrointestinal en población pediátrica: informe de dos casos y revisión de la literatura / Gastrointestinal stromal tumors in the pediatric population: report of two cases and a review of the literature

Introducción: El tumor estromal del tracto gastrointestinal es una neoplasia rara que se presentan por lo general en la quinta a séptima década de la vida; en pacientes pediátricos es menos frecuente que en adultos y no está bien caracterizado. En esta descripción se evalúa presentación, diagnóstico clínicopatológico y evolución de dos niños con tumor estromal del tracto gastrointestinal originado en el estómago; también se revisa la literatura respecto a la experiencia mundial que se tiene con este tipo de tumor en la población pediátrica. Casos clínicos: Ambos pacientes iniciaron con hematemesis debido a un tumor gástrico. El primer paciente tenía 10 años de edad cuando se le practicó gastrectomía parcial; después de 26 años experimentó recurrencia local de la enfermedad, por lo que se le practicó laparotomía exploradora que mostró neoplasia con extensa infiltración a órganos vecinos. La neoplasia fue irresecable; se prescribió tratamiento con mesilato de imatinib. El segundo caso correspondió a una niña quien a los 12 años de edad presentó una masa unida a la pared gástrica por un pedículo, la cual fue resecada. Dos años después por recurrencia local se le practicó gastrectomía parcial. Se recomendó mesilato de imatinib como tratamiento adyuvante debido a que el tumor tenía 8 cm de diámetro mayor. Conclusiones: El tumor estromal del tracto gastrointestinal de presentación en la edad pediátrica representa un subgrupo distintivo de sarcomas que predomina en niñas y que por lo general afecta el estómago. En una revisión de la literatura solo se encontraron 56 casos de dicha neoplasia. El pronóstico es variable y heterogéneo. La resección completa de la neoplasia es indispensable y el tratamiento adyuvante con mesilato de imatinib se recomienda para los casos con alto riesgo.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal (GI) tract that occur predominantly in adults. GISTs in pediatric patients are rare and not well characterized. We reviewed the presentation, diagnostic work-up, pathological specimens, and outcomes of two children with GIST that originated from the stomach. Literature pertaining to pediatric GISTs was also reviewed. CLINICAL CASES: Both patients presented with upper GI bleeding from a gastric tumor. The first patient was a 10-year-old male who underwent partial gastrectomy but had recurrence 26 years later requiring surgical exploration due to extensive infiltration into the surrounding organs; the tumor was not resected. The patient is currently being treated with imatinib mesylate. The second patient was a 12-year-old female who had a pedunculated mass originating from the stomach and requiring resection. She subsequently had a local recurrence 2 years later requiring partial gastrectomy. Adjuvant imatinib mesylate was recommended because of the large size of the tumor (8 cm). CONCLUSIONS: Pediatric GISTs represent a distinct subset of sarcomas with a strong predominance for females and gastric location, with 56 cases reported in the English-language literature.

Efecto del clenbuterol en el asma inducido por ejercicio en niños / Effect of clenbuterol in asthma induced by exercise in children

Se evalúa el efecto protector del broncoespasmo inducido por ejercicio, de Clenbuterol inhalador, en 14 niños asmáticos lábiles. Se concluye que constituye un medicamento útil en la profilaxis del Asma Inducido por Ejercicio. Se requiere de nuevos estudios para demostrar si tiene alguna ventaja sobre otros betamiméticos en uso en nuestro medio

Evolución conductual de niños recuperados de una desnutrición grave / Conductual evolution of children recovered from severe malnutrition

Con el propósito de conocer la evolución conductual de niños lactantes tratados por desnutrición proteinoenergética, una vez que éstos son reintegrados a su medio familiar, se investigaron 56 niños con edades comprendidas entre 6 y 29 meses, cinco de ellos durante 675 días. El grupo se dividió de acuerdo a la mediana global de desarrollo (67.1%) obtenida al egresar los niños de la institución en que fueron tratados. Entre aquellos que registraron más de 67.1%, el cociente medio se mantuvo, durante el lapso de estudio, entre 80 y 90%. Los niños que tuvieron cocientes por debajo de la mediana mostraron mayor incremento a partir del segundo año de su seguimiento, encontrándose al término de la investigación con un cociente medio dentro de lo normal. La conducta del lenguaje fue la que presentó mayor deterioro. Los hallazgos hacen suponer que en ciertos niños el retraso conductal generado por la desnutrición es reversible a largo plazo