Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.

Quantitative ultrasonography reveals skeletal muscle abnormalities in carriers of DMD pathogenic variants.

INTRODUCTION/AIMS: Carriers of DMD pathogenic variants may become symptomatic and develop muscle-related manifestations. Despite that, few studies have attempted to characterize changes in the muscles of these carriers using imaging tools, particularly muscle ultrasound (MUS). The aim of this study was to compare lower limb MUS findings in carriers of DMD pathogenic variants (cDMD) vs healthy controls. METHODS: Twenty-eight women (15 cDMD and 13 controls) underwent clinical evaluation and MUS. We collected information about muscle-related symptoms and assessed muscle strength. MUS was performed by a single physician (blind to the genetic status of subjects). The following muscles were assessed: rectus femoris, sartorius, tibialis anterior, and medial gastrocnemius. For each site, we computed data on muscle thickness, cross-sectional area, sound attenuation index, and elastography. Between-group comparisons were assessed using nonparametric tests and p-values <.05 were deemed significant. RESULTS: None of the subjects had objective muscle weakness, but exercise intolerance/fatigue was reported by four cDMDs and only one control. Regarding MUS, sound attenuation indices were significantly higher among carriers for all muscles tested. Longitudinal and axial deep echo intensities for the rectus femoris and tibialis anterior were also higher in the cDMD group compared with controls. No significant between-group differences were noted for elastography values, muscle area, or mean echo intensities. DISCUSSION: cDMD have skeletal muscle abnormalities that can be detected using quantitative MUS. Further studies are needed to determine whether such abnormalities are related to muscle symptoms in these patients.

Carvacrol-Loaded Nanoemulsion Promotes Tocolytic and Anti-Dysmenorrhea Effects in Rodents.

INTRODUCTION: Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities. METHOD: This study aimed to evaluate the in vitro spasmolytic and in vivo anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV). RESULTS: In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes. CONCLUSIONS: These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.

Tract-Specific Spinal Cord Diffusion Tensor Imaging in Friedreich's Ataxia.

BACKGROUND: Spinal cord (SC) damage is a hallmark in Friedreich's ataxia (FRDA). Neuroimaging has been able to capture some SC macroscopic changes, but no study has evaluated microstructural SC white matter (WM) damage in vivo. OBJECTIVES: We designed a cross-sectional study to evaluate microstructural integrity in SC WM tracts of FRDA patients using diffusion tensor imaging (DTI) with an automated analysis pipeline. METHODS: Thirty patients and 30 matched healthy controls underwent 3 Tesla (T) magnetic resonance imaging (MRI). We obtained cervical SC T2 and diffusion-weighted imaging (DWI) acquisitions. Images were processed using the Spinal Cord Toolbox v.4.3.0. For levels C2-C5, we measured cross-sectional area (CSA) and WM DTI parameters (axial diffusivity [AD], fractional anisotropy [FA], radial diffusivity [RD], and mean diffusivity [MD]). Age, duration, and FARS scores were also obtained. RESULTS: Mean age and disease duration of patients were 31 ± 10 and 11 ± 9 years, respectively. There was CSA reduction in FRDA amongst all levels. Between-group differences in FA, MD, and RD in total white matter (TWM), dorsal columns (DC), fasciculus gracilis (FG), fasciculus cuneatus (FC), and corticospinal tracts (CST) were present in all levels. FA and RD from TWM, DC, FC, and CST correlated with FARS scores, and in CST they also correlated with disease duration. CONCLUSION: DTI uncovered abnormalities in SC WM tracts, which correlated with clinical features in FRDA. CSA and CST FA in C2 correlated best with disease severity, whereas DC FA showed the largest effect size to differentiate patients and healthy controls. SC WM microstructure is a potential neuroimaging biomarker to be explored in the disease. © 2021 International Parkinson and Movement Disorder Society.

RFC1-Related Disorder: In Vivo Evaluation of Spinal Cord Damage.

BACKGROUND: RFC1-related disorder is a novel heredodegenerative condition with a broad phenotypic spectrum. Its neuropathological bases are not yet fully understood, particularly regarding the pattern, extent, and clinical relevance of spinal cord (SC) damage. OBJECTIVES: The objectives were to determine the SC structural signature in RFC1-related disorder in vivo and to identify potential clinical correlates for these imaging abnormalities. METHODS: We enrolled 17 subjects with biallelic RFC1 (AAGGG)n expansions and 11 age- and sex-matched healthy controls that underwent multimodal magnetic resonance imaging SC acquisitions in a 3T Philips Achieva scanner. Both global morphometry and tract-specific analyses were then performed across all cervical levels. Between-group comparisons were assessed using nonparametric tests. RESULTS: In the patient group, mean age and disease duration were 62.9 ± 9.3 and 9.3 ± 4.0, respectively. Compared to controls, patients had remarkable SC cross-sectional area reduction along all cervical levels but anteroposterior flattening only in the lower cervical levels. There was also prominent SC gray matter atrophy. Diffusivity abnormalities were identified in the dorsal columns but not in the lateral corticospinal tracts. Disease severity did not correlate with these imaging parameters. CONCLUSION: SC damage is a hallmark of RFC1-related disorder and characterized by gray as well as white matter involvement. In particular, dorsal columns are severely and diffusely affected. The clinical correlates of these imaging abnormalities still deserve additional investigations. © 2022 International Parkinson and Movement Disorder Society.

NOBLADS-External Validation of a Risk Scoring System for Severe Acute Lower Gastrointestinal Bleeding.

BACKGROUND: Acute lower gastrointestinal bleeding is a common cause of hospital admission. NOBLADS is a lower gastrointestinal bleeding clinical risk score. OBJECTIVE: This study aimed to externally validate NOBLADS in predicting severe acute lower gastrointestinal bleeding and clinical outcome. DESIGN: Observational retrospective study. SETTING: This study was performed in a single large tertiary hospital. PATIENTS: Patients who were admitted with acute lower gastrointestinal bleeding during a 15-month period and underwent endoscopic evaluation were included. Patients with chronic lower gastrointestinal bleeding or acute lower gastrointestinal bleeding who were admitted for other conditions were excluded. MAIN OUTCOME MEASURES: Primary outcome was acute severe lower gastrointestinal bleeding (classified as severe if requires transfusion of >2 units of packed red blood cells and/or produces a >20% hematocrit fall). Secondary outcomes: red blood cells requirement, therapeutic intervention and hospital stay duration. NOBLADS score was applied to all patients. Its accuracy to predict acute severe bleeding and secondary outcomes were studied using receiver operating characteristic analysis. RESULTS: A total of 173 patients (50.3% males, age 69 ± 17 years) were included. The most common lower gastrointestinal bleeding etiologies were diverticular bleeding (18.5%) and ischemic colitis (15.6%). Fifty patients (28.9%) presented criteria for severe bleeding and 33 patients required instrumental intervention: endoscopic (n = 28), surgical (n = 4), and radiologic (n = 1) therapy. NOBLADS score was significantly different according with acute lower gastrointestinal bleeding causes (p < 0.001) and accurately predicted severe bleeding (area under the receiver operating characteristic curve 0.923 ± 0.018 (p < 0.001)). NOBLADS ≥2 detected acute severe lower gastrointestinal bleeding with 100% sensitivity/62.4% specificity, identifying the need for higher red blood cells requirement (3.6 vs 0.08, p < 0.001), therapeutic intervention (38% vs 13%, p < 0.001), and longer hospital stay (12.8 vs 3 days, p < 0.001). LIMITATIONS: Unicenter retrospective study; number of unprepared sigmoidoscopies/left side colonoscopies; comparison between NOBLADS and other scoring systems was not performed. CONCLUSION: NOBLADS is a practical, highly accurate tool and predicts the need of in-hospital management, early colonoscopy, red blood cells transfusion, and longer hospital stay in patients admitted with acute lower gastrointestinal bleeding. See Video Abstract at http://links.lww.com/DCR/B748.NOBLADS: VALIDACIÓN EXTERNA DE UN SISTEMA DE PUNTUACIÓN DE RIESGO PARA HEMORRAGIA DIGESTIVA BAJA AGUDA GRAVE. ANTECEDENTES: La hemorragia digestiva baja aguda es causa común de admisión hospitalaria. NOBLADS es una puntuación de riesgo clínico de hemorragia gastrointestinal baja. OBJETIVO: Este estudio tuvo como objetivo validar externamente NOBLADS en la predicción de hemorragia digestiva baja aguda grave y sus resultados clínicos. DISEO: Estudio observacional retrospectivo. AJUSTE: Realizado en un gran hospital terciario. PACIENTES: Se incluyeron todas aquellas personas ingresados con hemorragia digestiva baja aguda durante un período de 15 meses y que fueron sometidos a evaluación endoscópica. Se excluyó la hemorragia digestiva baja crónica o la hemorragia digestiva baja aguda en pacientes ingresados por otras afecciones. PRINCIPALES MEDIDAS DE RESULTADO: El resultado pricipal fue la hemorragia digestiva baja grave aguda (clasificada como grave si requiere >2 transfusiones de glóbulos rojos y / o produce una caída del hematocrit >20%). Las medidas de resultados secundarias fueron: requerimiento de glóbulos rojos, intervención terapéutica y duración de la estancia hospitalaria. Se aplicó la puntuación NOBLADS a todos los pacientes. Se estudió su precisión para predecir la hemorragia aguda grave y los resultados secundarios mediante análisis ROC. RESULTADOS: Se incluyeron 173 pacientes (50,3% varones, edad 69 ± 17 años). La etiología de hemorragia digestiva baja más frecuentes fueron: la hemorragia de orígen diverticular (18,5%) y la colitis isquémica (15,6%). 50 pacientes (28,9%) presentaron criterios de sangrado severo y 33 pacientes requirieron intervención instrumental: terapia endoscópica (n = 28), quirúrgica (n = 4), radiológica (n = 1). La puntuación NOBLADS fue significativamente diferente según las causas de hemorragia digestiva baja aguda (p <0,001), siendo precisa para predecir hemorragia grave (AUC 0,923 ± 0,018 (p <0,001). NOBLADS ≥2 detectó hemorragia digestiva baja aguda grave con 100% de sensibilidad / 62,4 % de especificidad, identificando la necesidad de mayor requerimiento de glóbulos rojos (3.6 vs 0.08, p <0.001), intervención terapéutica (38% vs 13%, p <0.001) y estadía hospitalaria más prolongada (12.8 vs 3 días, p <0.001). LIMITACIONES: Estudio retrospectivo Unicentrico; número de sigmoidoscopias / colonoscopias del lado izquierdo no preparadas; no se realizó comparación entre NOBLADS y otros sistemas de puntuación. CONCLUSIN: NOBLADS es una herramienta práctica y altamente precisa que predice la necesidad de manejo hospitalario, colonoscopia precoz, transfusión de glóbulos rojos y estadía hospitalaria más prolongada en pacientes ingresados con hemorragia digestiva baja aguda. Consulte Video Resumen en http://links.lww.com/DCR/B748. (Traducción-Dr. Xavier Delgadillo).

Chemical Analysis by LC-MS of Cannabis sativa Root Samples from Northeast Brazil and Evaluation of Antitussive and Expectorant Activities.

Cannabis sativa is a millenary medicinal plant. However, contrary to worldwide paradigm-shifting, countries like Brazil still prohibit C. sativa cultivation and its medicinal use, even though many populations use aerial parts and roots of this plant for healthcare. As such, the objective of this work was to identify substances in the samples of the C. sativa roots, tracing a correlation with antitussive and expectorant effects. Therefore, samples of C. sativa roots were donated by the Polícia Federal Brasileira, and its aqueous extract (AECsR) was prepared with subsequent lyophilization, to maintain the material stability. After that, the material was analyzed by LC-MS to observe its chemical profile. Four samples (AECsR-A, B, C, and D) were tested in animal models of citric acid-induced cough (0.4 M) and phenol red expectoration (500 mg/kg). Using LC-MS it was possible to identify 5 molecules in C. sativa roots: p-coumaroyltyramine, tetrahydrocannabinol-C4, feruoiltyramine, anhydrocanabisativine, and cannabisativine. In experimental protocols, male mice (Mus musculus) were treated with samples of AECsR at doses of 12.5, 25, or 50 mg/kg regardless of the pharmacological test. In these tests, all samples showed the potential to treat cough and promote fluid expectoration, differing only in the dose at which these effects were observed. Therefore, the data showed that the C. sativa roots of the Brazilian Northeast showed antitussive and expectorant effects, even with intense secondary metabolites' variation, which alters its potency, but not its effect. This highlights the importance of this medicinal plant for future therapy and corroborates to traditional use.

Identifying barriers for nature-based solutions in flood risk management: An interdisciplinary overview using expert community approach.

The major event that hit Europe in summer 2021 reminds society that floods are recurrent and among the costliest and deadliest natural hazards. The long-term flood risk management (FRM) efforts preferring sole technical measures to prevent and mitigate floods have shown to be not sufficiently effective and sensitive to the environment. Nature-Based Solutions (NBS) mark a recent paradigm shift of FRM towards solutions that use nature-derived features, processes and management options to improve water retention and mitigate floods. Yet, the empirical evidence on the effects of NBS across various settings remains fragmented and their implementation faces a series of institutional barriers. In this paper, we adopt a community expert perspective drawing upon LAND4FLOOD Natural flood retention on private land network (https://www.land4flood.eu) in order to identify a set of barriers and their cascading and compound interactions relevant to individual NBS. The experts identified a comprehensive set of 17 barriers affecting the implementation of 12 groups of NBS in both urban and rural settings in five European regional environmental domains (i.e., Boreal, Atlantic, Continental, Alpine-Carpathian, and Mediterranean). Based on the results, we define avenues for further research, connecting hydrology and soil science, on the one hand, and land use planning, social geography and economics, on the other. Our suggestions ultimately call for a transdisciplinary turn in the research of NBS in FRM.

Multiple bezoars causing small bowel obstruction: a unique case of resolution with upper and low GI endoscopy.

Reports of obstructing foreign bodies in the small bowel are rare and the majority describe surgical resolution. We report a case of successful endoscopic treatment of a small bowel obstruction (SBO) caused by multiple bezoars. A 92-year-old female presented to the Emergency Department with a history of persistent vomiting. Computed tomography (CT) showed gastric distension and an intraluminal ovaloid foreign body with a heterogenous density in the second portion of the duodenum, suggestive of bezoar.

Histologic Features of Colon Biopsies (Geboes Score) Associated With Progression of Ulcerative Colitis for the First 36 Months After Biopsy.

BACKGROUND & AIMS: In addition to findings from endoscopy, histologic features of colon biopsies have been associated with outcomes of patients with ulcerative colitis (UC). We investigated associations between Geboes scores (a system to quantify structural changes and inflammatory activity in colon biopsies) and UC progression, and the time period over which this association is valid. METHODS: We analyzed data from 399 asymptomatic patients with UC enrolled in the ACERTIVE study, followed at 13 inflammatory bowel disease (IBD) centers in Portugal through 31 December 2019. Blood and stool samples were collected and analyzed, and all patients underwent sigmoidoscopy within 24 h of sample collection. We assessed baseline endoscopic status (Mayo endoscopic subscore), histologic features of 2 sigmoid and 2 rectal biopsies (Geboes score), and concentration of fecal calprotectin (FC). The primary outcome was UC progression (surgical, pharmacologic, and clinical events). We generated survival curves for 36 months or less and more than 36 months after biopsy according to Geboes score using the Kaplan-Meier method and compared findings with those from a log rank test. Cox regression was adjusted for Mayo endoscopic subscore, Geboes score, and level of FC; results were expressed as adjusted hazard ratios (HR) with 95% CIs. RESULTS: Patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 had a higher frequency of, and a shorter time to UC progression, than patients with Geboes scores ≤2B.0, Geboes scores ≤3.0, or Geboes score ≤4.0 (P < .001). Disease progression occurred earlier in patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 compared with patients with Geboes scores ≤2B.0 (HR, 2.021; 95% CI, 1.158-3.526), Geboes scores ≤3.0 (HR, 2.007; 95% CI, 1.139-3.534), or Geboes scores ≤4.0 (HR, 2.349; 95% CI, 1.269-4.349), respectively, in the first 36 months after biopsy. Similar results were found for patients with concentrations of FC below 150 µg/g. CONCLUSIONS: We found histologic features of colon biopsies (Geboes score) to be an independent risk factor for progression of UC in the first 36 months after biopsy.

Brain Damage and Gene Expression Across Hereditary Spastic Paraplegia Subtypes.

BACKGROUND: Spinal cord has been considered the main target of damage in hereditary spastic paraplegias (HSPs), but mounting evidence indicates that the brain is also affected. Despite this, little is known about the brain signature of HSPs, in particular regarding stratification for specific genetic subtypes. OBJECTIVE: We aimed to characterize cerebral and cerebellar damage in five HSP subtypes (9 SPG3A, 27 SPG4, 10 SPG7, 9 SPG8, and 29 SPG11) and to uncover the clinical and gene expression correlates. METHODS: We obtained high-resolution brain T1 and diffusion tensor image (DTI) datasets in this cross-sectional case-control study (n = 84). The MRICloud, FreeSurfer, and CERES-SUIT pipelines were employed to assess cerebral gray (GM) and white matter (WM) as well as the cerebellum. RESULTS: Brain abnormalities were found in all but one HSP group (SPG3A), but the patterns were gene-specific: basal ganglia, thalamic, and posterior WM involvement in SPG4; diffuse WM and cerebellar involvement in SPG7; cortical thinning at the motor cortices and pallidal atrophy in SPG8; and widespread GM, WM, and deep cerebellar nuclei damage in SPG11. Abnormal regions in SPG4 and SPG8 matched those with higher SPAST and WASHC5 expression, whereas in SPG7 and SPG11 this concordance was only noticed in the cerebellum. CONCLUSIONS: Brain damage is a conspicuous feature of HSPs (even for pure subtypes), but the pattern of abnormalities is genotype-specific. Correlation between brain structural damage and gene expression maps is different for autosomal dominant and recessive HSPs, pointing to distinct pathophysiological mechanisms underlying brain damage in these subgroups of the disease. © 2021 International Parkinson and Movement Disorder Society.

Therapeutic Effect of Diminazene Aceturate on Parasitic Blood Fluke Schistosoma mansoni Infection.

Praziquantel is currently the only drug available to treat schistosomiasis, a disease of enormous public health significance caused by a blood fluke of the genus Schistosoma Diminazene, a drug approved by the FDA, has been successfully used to treat diseases caused by blood protozoan parasites. In this study, we evaluated the antiparasitic properties of diminazene against Schistosoma mansoniex vivo and in mice harboring either chronic or early S. mansoni infections. In vitro, we monitored phenotypic and tegumental changes as well as the effects of the drug on pairing and egg production. In mice infected with either adult (chronic infection) or immature (early infection) worms, diminazene was administered intraperitoneally (10 to 100 mg/kg of body weight) or by oral gavage (100 to 400 mg/kg), and we studied the influence of the drug on worm burden and egg production. Liver and spleen pathologies and serum aminotransferase levels were also analyzed. In vitro, 50% effective concentrations (EC50) and EC90 revealed that diminazene is able to kill both immature and adult parasites, and its effect was time and concentration dependent. In addition, confocal laser scanning microscopy showed morphological alterations in the teguments of schistosomes. In an animal model, the influence of the drug on worm burden, egg production, hepatomegaly, and splenomegaly depended on the dosing regimen applied and the route of administration. Diminazene also caused a significant reduction in aminotransferase levels. Comparatively, diminazene treatment was more effective in chronic infection than in early infection. In tandem, our study revealed that diminazene possesses anthelmintic properties and inhibits liver injury caused by Schistosoma eggs.

Somatic growth in the first six months of life of infants exposed to maternal smoking in pregnancy.

BACKGROUND: Some studies suggest a relationship between maternal smoking during pregnancy and not only intrauterine fetal growth restriction or low birth weight, but also with changes in the postnatal growth and development. The objective of the present study was to investigate the effects of smoking during pregnancy on infants growth in the first 6 months of life compared with a control group and a group with idiopathic intrauterine growth restriction. METHODS: Longitudinal observational study using a convenience sample of newborns divided into three groups: infants of smoking mothers (tobacco), with idiopathic intrauterine growth restriction (IUGR) and a control group. The sample was selected from two hospitals in Porto Alegre, located in southern Brazil, between 2011 and 2015. Newborns were evaluated at birth, 7 and 15 days, and in the first, third, and sixth month. Anthropometric measures were weight, length and head circumference. The growth indicators used were expressed as z-scores. The analyses were performed using the generalized estimating equation method. RESULTS: The sample included 273 mother/newborn pairs: 86 tobacco group, 34 IUGR group, and 153 control group. In terms of weight at birth, all groups differed significantly (p < 0.001). The birth length of tobacco and control groups were similar, but the IUGR group was lower than both (p < 0.001). We found no differences in growth trajectory between tobacco and control group, but there were differences in the growth of the IUGR group when compared with the other groups. At 6 months of age, all groups had similar anthropometric measurements. CONCLUSION: Intrauterine growth restriction had major impact on the growth trajectory of the infants studied, regardless of other factors, such as smoking and diet.

Caffeine Intake During Pregnancy in Different Intrauterine Environments and its Association with Infant Anthropometric Measurements at 3 and 6 Months of Age.

Objective To investigate the association between maternal caffeine intake during pregnancy and infant anthropometric measurements at age 3 and 6 months. Methods Longitudinal observational study of mother-child pairs stratified into five groups: diabetic women (DM), hypertensive women (HYP), smoking mothers (SMO), mothers of infants small for gestational age (SGA), and controls (CTL). Pairs were recruited from three public hospitals in Porto Alegre, Brazil, from 2011 to 2015, using a convenience sampling strategy. The Food Frequency Questionnaire (FFQ) was administered on postpartum day 7 to evaluate maternal caffeine intake during pregnancy. The anthropometric measurements of interest (weight, length, and skinfold thickness) were assessed at birth and at age 3 and 6 months. Linear regression was used to analyze the interaction between caffeine intake and skinfold thickness. Results Overall, 272 mother-child pairs were investigated (41 DM, 26 HYP, 68 SMO, 25 SGA, and 112 CTL). There were no differences in anthropometric measurements between infants born to mothers who had and had not consumed caffeine during pregnancy (P > 0.05). Children of mothers in the DM group had the highest adjusted average skinfold thicknesses at 3 months. An interaction between maternal caffeine intake during pregnancy and the sum of skinfolds at age 3 months was found in the DM and CTL groups (P < 0.05). However, significant differences were not observed at 6 months. Conclusions Maternal caffeine intake influenced infants skinfold thickness measurements at 3 months of age. This parameter was reduced in infants born to mothers with DM and increased in those born to healthy control mothers.

Microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19.

Although some studies have shown neuroimaging and neuropsychological alterations in post-COVID-19 patients, fewer combined neuroimaging and neuropsychology evaluations of individuals who presented a mild acute infection. Here we investigated cognitive dysfunction and brain changes in a group of mildly infected individuals. We conducted a cross-sectional study of 97 consecutive subjects (median age of 41 years) without current or history of psychiatric symptoms (including anxiety and depression) after a mild infection, with a median of 79 days (and mean of 97 days) after diagnosis of COVID-19. We performed semi-structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. For MRI analyses, we included a group of non-infected 77 controls. The MRI study included white matter (WM) investigation with diffusion tensor images (DTI) and functional connectivity with resting-state functional MRI (RS-fMRI). The patients reported memory loss (36%), fatigue (31%) and headache (29%). The quantitative analyses confirmed symptoms of fatigue (83% of participants), excessive somnolence (35%), impaired phonemic verbal fluency (21%), impaired verbal categorical fluency (13%) and impaired logical memory immediate recall (16%). The WM analyses with DTI revealed higher axial diffusivity values in post-infected patients compared to controls. Compared to controls, there were no significant differences in the functional connectivity of the posterior cingulum cortex. There were no significant correlations between neuropsychological scores and neuroimaging features (including DTI and RS-fMRI). Our results suggest persistent cognitive impairment and subtle white matter abnormalities in individuals mildly infected without anxiety or depression symptoms. The longitudinal analyses will clarify whether these alterations are temporary or permanent.

Completeness of notifications of accidents involving venomous animals in the Information System for Notifiable Diseases: a descriptive study, Brazil, 2007-2019.

OBJECTIVE: to describe the completeness of notifications of accidents involving venomous animals held on the Notifiable Health Conditions Information System (SINAN), in Brazil and its macro-regions, from 2007 to 2019. METHODS: we analyzed essential and non-mandatory fields for snakebite, spider bite and scorpion sting notifications, considering the following completeness categories: Excellent (≤5.0% incompleteness), Good (5.0% to 10.0%), Regular (10.0% to 20.0%), Poor (20.0% to ≤50.0%) and Very Poor (>50.0%). Proportional change in completeness between 2007 and 2019 was estimated. RESULTS: 1,871,462 notifications were investigated. The "localized manifestations", "systemic manifestations", "case classification", "case progression" and "zone of occurrence" fields had excellent or good completeness. Completeness was regular or poor for the "schooling" and "race/color" fields. The "occupation" field was predominantly poorly or very poorly filled in. There was a proportional worsening in completeness (PC<0) in most regions for the "zone of occurrence", "case progression" and "schooling" fields. CONCLUSION: completeness of most fields improved, although socioeconomic and occupational fields require more attention.

Niti-S Esophageal Mega-Stent: An Emerging Endoscopic Tool with Different Applications in the Management of Surgical Anastomotic Leaks.

Introduction: Anastomotic leak (AL) is a dangerous complication in the early postoperative period after total gastrectomy or esophagectomy being associated with high mortality. Self-expandable metal stents (SEMS) play a significant role in AL management. Only one case report described the use of Mega-Stent in AL setting. The authors report a two-case series with different applications of a Niti-S esophageal Mega-Stent in AL management. Case Report: Case 1 is a 67-year-old male who underwent an esophagectomy due to a squamous cell carcinoma of the distal esophagus. The early postoperative period was complicated with AL and gastropleural fistula. Initially, an OTSC was deployed in the dehiscence but failed to resolve AL. The esophageal Mega-Stent was further placed in-between the esophagus and the bulbus. Post-stenting contrast studies confirmed no further AL.Case 2 is an 86-year-old woman who underwent total gastrectomy with roux-en-y esophagojejunostomy due to a gastric adenocarcinoma, complicated with AL. A partially covered metal stent (PCMS) was placed to cover the anastomosis. Computed tomography confirmed leakage persistence and a second PCMS was deployed, resolving the AL. Several weeks later, both PCMSs presented ingrowth from granulation tissue. An esophageal Mega-Stent was placed (stent-in-stent technique) and 2 weeks later, all stents were removed, with no AL recurrence. Discussion/Conclusion: SEMS placement for AL is a safe, well-established therapeutic technique. Limitations include stent migration and incomplete cover of large AL. Mega-Stent can be an emerging tool for endoscopic AL management.

Introdução: A deiscência anastomótica (DA) é uma complicação grave no pós-operatório precoce da esofagectomia e gastrectomia total, pela sua elevada mortalidade. As próteses metálicas autoexpansíveis (PMAE) desempenham um papel fundamental no tratamento das DA. Na literatura, há apenas um caso descrito sobre a utilização de um Mega-Stent no contexto de DA, que não complicação bariátrica. Os autores reportam uma série de dois casos com diferente aplicação do Mega-Stent esofágico no tratamento de DA. Descrição do caso: Caso 1: Homem de 67 anos, submetido a esofagectomia por carcinoma epidermóide do esófago distal. O período pós-operatório precoce foi complicado de DA com fístula gastro-pleural. Inicialmente foi colocado um clip OTSC no orifício da deiscência com insucesso técnico e clínico, sendo posteriormente utilizado o Mega-Stent, posicionado desde o esófago até ao bulbo duodenal. Estudos contrastados posteriores confirmaram resolução da DA. Caso 2: Mulher de 86 anos, submetida a gastrectomia total com reconstrução em Y-Roux e esofagojejunostomia por adenocarcinoma gástrico, complicada de DA. Neste contexto foi colocada uma PMAE parcialmente coberta (PMAE-PC) sobre a área da anastomose. A tomografia computorizada subsequente demonstrou persistência de extravasamento. Foi colocada uma segunda PMAE-PC, com posterior resolução da DA. Semanas depois, ambas as PMAE-PC apresentavam tecido de granulação nos topos, tendo sido colocado o Mega-Stent (técnica stent-in-stent) e decorridas duas semanas, todas as próteses foram facilmente extraídas, confirmando-se sucesso no tratamento da DA. Discussão/conclusão: A utilização de PMAE nas DA constitui uma técnica terapêutica segura e bem estabelecida, contudo passível de apresentar limitações tais como a migração ou incapacidade de cobrir totalmente DA de maiores dimensões. O Mega-Stent esofágico pode constituir uma ferramenta útil na terapêutica endoscópica destes doentes.

Long-Term Intestinal Failure and Home Parenteral Support: A Single Center Experience.

Introduction: Home parenteral nutrition (HPN) and/or home parenteral hydration (HPH) are the gold-standard treatment for patients with long-term intestinal failure (IF). The authors aimed to assess the impact of HPN/HPH on nutritional status and survival of long-term IF patients, as well as HPN/HPH-related complications. Methods: This was a retrospective study including IF patients under HPN/HPH followed in a single large tertiary Portuguese hospital. The data collected included demographics, underlying conditions, anatomical characteristics, type and duration of parenteral support, IF functional, pathophysiological, and clinical classifications, body mass index (BMI) at the beginning and end of follow-up, complications/hospitalizations, current patient status (deceased, alive with HPN/HPH, and alive without HPN/HPH), and cause of death. Survival after HPN/HPH beginning, until death or August 2021, was recorded in months. Results: Overall 13 patients were included (53.9% female, mean age 63.46 years), and 84.6% of patients presented type III IF and 15.4% type II. Short bowel syndrome caused 76.9% of IF. Nine patients received HPN and 4 HPH. Eight patients (61.5%) were underweight at the beginning of HPN/HPH. At the end of follow-up, 4 patients were alive without HPN/HPH, 4 maintained HPN/HPH, and 5 died. All patients improved their BMI (mean initial BMI 18.9 vs. 23.5 at the end, p < 0.001). Eight patients (61.5%) were hospitalized due to catheter-related complications, mainly infectious (mean hospitalization episodes 2.25, mean hospital stay of 24.5 days). No deaths were related to HPN/HPH. Conclusion: HPN/HPH significantly improved IF patients' BMI. HPN/HPH-related hospitalizations were common, however causing no deaths, reinforcing that HPN/HPH is an adequate and safe therapy for long-term IF patients.

Introdução: A nutrição parentérica domiciliária (NPD) e/ou a hidratação parentérica domiciliária (HPD) constituem o tratamento gold-standard para doentes com falência intestinal (FI) crónica. O objetivo do presente estudo foi avaliar o impacto da NPD/HPD no status nutricional e sobrevivência dos doentes com FI crónica, bem como as complicações relacionadas à NPD/HPD. Métodos: Estudo retrospetivo, incluindo doentes com FI sob NPD/HPD, seguidos num hospital terciário em Portugal. Informação recolhida para cada doente: dados demográficos, patologia de base, características anatómicas, tipo e duração do suporte parentérico, classificação funcional, fisiopatológica e clínica da FI, índice de massa corporal (IMC) no início e final do seguimento, complicações/hospitalizações, estado atual do doente (falecido, vivo sob NPD/HPD e vivo sem NPD/HPD) e causa de morte. A sobrevida após início da NPD/HPD foi calculada em meses, até à data da morte ou agosto de 2021. Resultados: Incluídos 13 doentes (53.9% do sexo feminino, idade média 63.46 anos), 84.6% com FI tipo III e 15.4% com FI tipo II. A síndrome do intestino curto foi causa de 76.9% das FI. Nove doentes foram tratados com NPD e 4 com HPD. Oito doentes (61.5%) apresentavam IMC baixo no início da NPD/HPD. No final do seguimento, 4 doentes estavam vivos sem NPD/HPD, 4 mantinham NPD/HPD e 5 faleceram. Todos os doentes melhoraram significativamente o seu IMC (IMC médio no início do seguimento 18.9kg/m2 vs 23.5kg/m2 no final, p<0.001). Oito doentes (61.5%) tiveram de ser hospitalizados devido a complicações relacionadas com o cateter, sobretudo de causa infeciosa (número médio de hospitalizações por doente 2.25, duração média de internamento 24.5 dias). Não houve mortes relacionadas com a NPD/ HPD. Conclusão: A NPD/HPD melhorou significativamente o IMC dos doentes com FI. As hospitalizações relacionadas com a NPD/HPD foram comuns, contudo não causaram mortes, reforçando o facto que a NPD/HPD é uma terapêutica segura e adequada para doentes com FI crónica.

Case report: Granzyme-B expression by T- and B- cells during severe AQP4-positive Neuromyelitis Optica spectrum disorder with fatal venous thromboembolism outcome.

Background: The expression of serine protease granzyme-B (GzmB) by circulating CD8+ T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis. Case presentation: Here, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment. Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8+GzmB+ T, CD4+GzmB+ T lymphocytes, and residual CD19+GzmB+ B cells. Conclusions: Fatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity.

Rabies outbreak in Brazil: first case series in children from an indigenous village.

BACKGROUND: Human rabies outbreak transmitted by bats continues to be a relevant public health problem not only in the Amazon region. The disease has affected one of the areas with the greatest poverty in southeastern Brazil, a region inhabited by the Maxakali indigenous people. CASE PRESENTATION: We describe four cases of rabies among indigenous children that occurred in the indigenous village of Pradinho, municipality of Bertópolis, Minas Gerais, Brazil. Cases were notified between April and May 2022, all of whom died on average eight days after the first symptoms. All cases were observed in rural residents under 12 years of age. The probable form of exposure was through bat bites. The predominant symptoms were prostration, fever, dyspnea, sialorrhea, tachycardia, and altered level of consciousness. Half of the cases underwent late and/or incomplete post-exposure rabies prophylaxis, however, the other half underwent pre-exposure rabies prophylaxis, with only one case completing the scheme and another undergoing the adapted Milwaukee Protocol (Recife Protocol). All cases ended in death. CONCLUSIONS: This was the first rabies outbreak among indigenous people in Brazil. Among the manifested clinical forms in the series, there was a disease atypical presentation in at least one case. We suggest active surveillance and an intercultural educational campaign to prevent new cases.