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Methamphetamine (Meth) use is known to induce complex neuroinflammatory responses, particularly involving astrocytes and microglia. Building upon our previous research, which demonstrated that Meth stimulates astrocytes to release tumor necrosis factor (TNF) and glutamate, leading to microglial activation, this study investigates the role of the anti-inflammatory cytokine interleukin-10 (IL-10) in this process. Our findings reveal that the presence of recombinant IL-10 (rIL-10) counteracts Meth-induced excessive glutamate release in astrocyte cultures, which significantly reduces microglial activation. This reduction is associated with the modulation of astrocytic intracellular calcium (Ca2+) dynamics, particularly by restricting the release of Ca2+ from the endoplasmic reticulum to the cytoplasm. Furthermore, we identify the small Rho GTPase Cdc42 as a crucial intermediary in the astrocyte-to-microglia communication pathway under Meth exposure. By employing a transgenic mouse model that overexpresses IL-10 (pMT-10), we also demonstrate in vivo that IL-10 prevents Meth-induced neuroinflammation. These findings not only enhance our understanding of Meth-related neuroinflammatory mechanisms, but also suggest IL-10 and Cdc42 as putative therapeutic targets for treating Meth-induced neuroinflammation.
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Astrocitos , Interleucina-10 , Metanfetamina , Ratones Transgénicos , Microglía , Proteína de Unión al GTP cdc42 , Animales , Metanfetamina/toxicidad , Metanfetamina/farmacología , Interleucina-10/metabolismo , Interleucina-10/farmacología , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Proteína de Unión al GTP cdc42/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Ratones , Ratones Endogámicos C57BL , Estimulantes del Sistema Nervioso Central/toxicidad , Estimulantes del Sistema Nervioso Central/farmacología , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/inducido químicamente , Células Cultivadas , Ácido Glutámico/metabolismo , Ácido Glutámico/toxicidadRESUMEN
Pleiotropy occurs when a genetic variant influences more than one trait. This is a key property of the genomic architecture of psychiatric disorders and has been observed for rare and common genomic variants. It is reasonable to hypothesize that the microscale genetic overlap (pleiotropy) across psychiatric conditions and cognitive traits may lead to similar overlaps at the macroscale brain level such as large-scale brain functional networks. We took advantage of brain connectivity, measured by resting-state functional MRI to measure the effects of pleiotropy on large-scale brain networks, a putative step from genes to behaviour. We processed nine resting-state functional MRI datasets including 32 726 individuals and computed connectome-wide profiles of seven neuropsychiatric copy-number-variants, five polygenic scores, neuroticism and fluid intelligence as well as four idiopathic psychiatric conditions. Nine out of 19 pairs of conditions and traits showed significant functional connectivity correlations (rFunctional connectivity), which could be explained by previously published levels of genomic (rGenetic) and transcriptomic (rTranscriptomic) correlations with moderate to high concordance: rGenetic-rFunctional connectivity = 0.71 [0.40-0.87] and rTranscriptomic-rFunctional connectivity = 0.83 [0.52; 0.94]. Extending this analysis to functional connectivity profiles associated with rare and common genetic risk showed that 30 out of 136 pairs of connectivity profiles were correlated above chance. These similarities between genetic risks and psychiatric disorders at the connectivity level were mainly driven by the overconnectivity of the thalamus and the somatomotor networks. Our findings suggest a substantial genetic component for shared connectivity profiles across conditions and traits, opening avenues to delineate general mechanisms-amenable to intervention-across psychiatric conditions and genetic risks.
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Conectoma , Trastornos Mentales , Humanos , Pleiotropía Genética , Imagen por Resonancia Magnética , Trastornos Mentales/diagnóstico por imagen , Trastornos Mentales/genética , Encéfalo/diagnóstico por imagenRESUMEN
Objective. This paper aims to investigate the possibility of detecting tonic-clonic seizures (TCSs) with behind-the-ear, two-channel wearable electroencephalography (EEG), and to evaluate its added value to non-EEG modalities in TCS detection.Methods. We included 27 participants with a total of 44 TCSs from the European multicenter study SeizeIT2. The wearable Sensor Dot (Byteflies) was used to measure behind-the-ear EEG, electromyography (EMG), electrocardiography, accelerometry (ACC) and gyroscope. We evaluated automatic unimodal detection of TCSs, using sensitivity, precision, false positive rate (FPR) and F1-score. Subsequently, we fused the different modalities and again assessed performance. Algorithm-labeled segments were then provided to two experts, who annotated true positive TCSs, and discarded false positives.Results. Wearable EEG outperformed the other single modalities with a sensitivity of 100% and a FPR of 10.3/24 h. The combination of wearable EEG and EMG proved most clinically useful, delivering a sensitivity of 97.7%, an FPR of 0.4/24 h, a precision of 43%, and an F1-score of 59.7%. The highest overall performance was achieved through the fusion of wearable EEG, EMG, and ACC, yielding a sensitivity of 90.9%, an FPR of 0.1/24 h, a precision of 75.5%, and an F1-score of 82.5%.Conclusions. In TCS detection with a wearable device, combining EEG with EMG, ACC or both resulted in a remarkable reduction of FPR, while retaining a high sensitivity.Significance. Adding wearable EEG could further improve TCS detection, relative to extracerebral-based systems.
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Acelerometría , Electroencefalografía , Electromiografía , Convulsiones , Procesamiento de Señales Asistido por Computador , Dispositivos Electrónicos Vestibles , Humanos , Electroencefalografía/instrumentación , Electroencefalografía/métodos , Electromiografía/instrumentación , Acelerometría/instrumentación , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto JovenRESUMEN
Spinal cord injury without radiological abnormality (SCIWORA) was first reported in 1974. The term was used to define "clinical symptoms of traumatic myelopathy without signs of fracture or spine instability on X-ray or CT scan." With the emergence of MRI, the gold standard method to identify spinal cord injuries, about two-thirds of former SCIWORA cases were found to have pathological findings, and, as such, the term has taken on an ambiguous meaning in the literature. We describe the clinical case of a 17-year-old boy who was admitted to the emergency department of a tertiary hospital after a fall during a soccer game. He suffered spinal and cranioencephalic trauma. A few minutes later, the boy began to show decreased strength in the right upper limb and lower limbs, as well as changes in sensation in the right hemibody. On objective examination, the boy presented a Glasgow Coma Scale score of 15 and the American Spinal Injury Association Impairment Scale D, with partial improvement of initial symptoms of monoparesis of the right lower limb. There were no other changes, specifically at the sensory level. The patient underwent a CT and MRI of the spine that showed no fractures, instability, or appreciable medullary signal changes. Electromyography was normal. Based on the clinical history and imaging findings, real SCIWORA was diagnosed. The patient was admitted to an inpatient rehabilitation program. At a follow-up visit two months later, a complete reversal of signs and symptoms was confirmed. The prognosis of this pathology depends on the extent of the spinal cord injury, as evidenced by MRI. Although neurological improvement when severe deficit is present at initial presentation is unlikely, most patients with incomplete neurological damage show good recovery. The absence of visible changes on MRI is associated with a better prognosis.
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OBJECTIVE: The aim of the study is to characterize pressure injuries, identify risk factors, and develop a predictive model for pressure injuries at intensive care unit admission for critical COVID-19 patients. DESIGN: This study was a retrospective analysis of a consecutive sample of patients admitted to intensive care unit between May 2020 and September 2021. Inclusion criteria encompassed the diagnosis of acute respiratory distress syndrome due to SARS-CoV-2, requiring invasive mechanical ventilation more than 48 hrs. The following predictors were evaluated: sociodemographic characteristics, comorbidities, as well as clinical and laboratory findings at intensive care unit admission. The primary outcome was the presence of pressure injuries. RESULTS: Two hundred five patients were included, mostly males (73%) with a mean age of 62 yrs. Pressure injury prevalence was 58%. On multivariable analysis, male sex, hypertension, hemoglobin, and albumin at intensive care unit admission were independently associated with pressure injuries, constituting the PRINCOVID model. The model reached an area under the receiver operating characteristic curve of 0.71, surpassing the Braden scale ( P = 0.0015). The PRINCOVID score ranges from 0 to 15, with two risk groups: "at risk"(≤7 points) and "high risk"(>7 points). CONCLUSIONS: This study proposes PRINCOVID as a multivariable model for developing pressure injuries in critical COVID-19 patients. Based on four parameters (sex, hypertension, hemoglobin, and albumin at intensive care unit admission), this model fairly predicts the development of pressure injuries. The PRINCOVID score allows patients' classification into two groups, facilitating early identification of high-risk patients.
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COVID-19 , Hipertensión , Úlcera por Presión , Humanos , Masculino , Persona de Mediana Edad , Femenino , COVID-19/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Úlcera por Presión/epidemiología , Unidades de Cuidados IntensivosRESUMEN
PURPOSE: To analyze the long-term consequences of critical COVID-19, regarding physical, mental, cognitive and functional impairments, and to describe its evolution through time. METHODS: Prospective cohort study, with consecutive inclusion of patients admitted due to SARS-CoV-2 to intensive care units(ICU) of a tertiary-care center, between May/2020 and September/2021. All included patients were included in Physical and Rehabilitation Medicine(PRM) inpatient programs during ICU stay. Eligible patients were evaluated on PRM appointments 6 and 12 months after ICU discharge. In each visit, physical examination and a predefined set of scales were applied, aiming to comprehensively evaluate the three domains (physical, mental and cognitive) of post-intensive care syndrome and the patients' functionality. Statistical analysis encompassed descriptive and univariate analysis. RESULTS: A total of 42 patients were included: 66.7% males, mean age of 62 yo. In the physical domain, 6 months after ICU discharge, there was a significant reduction in quality of life (p-value = 0.034), muscle strength (p-value = 0.002), gait ability (p-value<0.001) and balance (p-values<0.001) and increased fatigue levels (p-value = 0.009), in comparison with reference values. Yet, a significative positive evolution was observed in all referred subdomains (p-values<0.05). Nevertheless, 12 months after discharge, muscle strength (p-value = 0.001), gait (p-value<0.001) and balance (p-value<0.001) were still significantly compromised. Regarding the mental domain, both at 6 and 12 months after discharge, the levels of anxiety and depression were significantly increased (p-values<0.001). Nonetheless, a positive evolution was also found (p-values<0.02). Cognitive performance was significantly impaired in comparison with reference values, both at 6 and 12 months (p-value<0.001). Yet, a global improvement was also depicted (p-value = 0.003). Six months after ICU discharge, 54.8% were autonomous in activities of daily living, a value that improved to 74.0% in the subsequent 6 months (p-value = 0.002). CONCLUSION: Critical COVID-19 survivors present significant physical, mental and cognitive impairments 6 and 12 months after ICU discharge, despite their positive evolution through time.
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COVID-19 , Calidad de Vida , Masculino , Humanos , Persona de Mediana Edad , Femenino , Estudios Prospectivos , Actividades Cotidianas , SARS-CoV-2 , Unidades de Cuidados Intensivos , Fuerza Muscular , Cognición , Cuidados CríticosRESUMEN
BACKGROUND: Polygenicity and genetic heterogeneity pose great challenges for studying psychiatric conditions. Genetically informed approaches have been implemented in neuroimaging studies to address this issue. However, the effects on functional connectivity of rare and common genetic risks for psychiatric disorders are largely unknown. Our objectives were to estimate and compare the effect sizes on brain connectivity of psychiatric genomic risk factors with various levels of complexity: oligogenic copy number variants (CNVs), multigenic CNVs, and polygenic risk scores (PRSs) as well as idiopathic psychiatric conditions and traits. METHODS: Resting-state functional magnetic resonance imaging data were processed using the same pipeline across 9 datasets. Twenty-nine connectome-wide association studies were performed to characterize the effects of 15 CNVs (1003 carriers), 7 PRSs, 4 idiopathic psychiatric conditions (1022 individuals with autism, schizophrenia, bipolar conditions, or attention-deficit/hyperactivity disorder), and 2 traits (31,424 unaffected control subjects). RESULTS: Effect sizes on connectivity were largest for psychiatric CNVs (estimates: 0.2-0.65 z score), followed by psychiatric conditions (0.15-0.42), neuroticism and fluid intelligence (0.02-0.03), and PRSs (0.01-0.02). Effect sizes of CNVs on connectivity were correlated to their effects on cognition and risk for disease (r = 0.9, p = 5.93 × 10-6). However, effect sizes of CNVs adjusted for the number of genes significantly decreased from small oligogenic to large multigenic CNVs (r = -0.88, p = 8.78 × 10-6). PRSs had disproportionately low effect sizes on connectivity compared with CNVs conferring similar risk for disease. CONCLUSIONS: Heterogeneity and polygenicity affect our ability to detect brain connectivity alterations underlying psychiatric manifestations.
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Heterogeneidad Genética , Psiquiatría , Humanos , Predisposición Genética a la Enfermedad , Herencia Multifactorial/genética , Encéfalo/diagnóstico por imagen , Variaciones en el Número de Copia de ADN/genética , Estudio de Asociación del Genoma CompletoRESUMEN
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and effective technique for the sampling of mediastinal and hilar adenopathies. We describe the first reported case of pulmonary artery intramural hematoma after EBUS-TBNA puncture of this artery. The complication was visualized by ultrasound and resolved spontaneously.
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Biopsia con Aguja Fina/efectos adversos , Endosonografía/efectos adversos , Hematoma/etiología , Hemoneumotórax/etiología , Neoplasias Pulmonares/diagnóstico por imagen , Arteria Pulmonar/lesiones , Angiografía/métodos , Broncoscopía/efectos adversos , Broncoscopía/métodos , Endosonografía/métodos , Estudios de Seguimiento , Hematoma/diagnóstico por imagen , Hemoneumotórax/diagnóstico por imagen , Hemoneumotórax/fisiopatología , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Remisión Espontánea , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X/métodosRESUMEN
Aneurysmal bone cysts are rare lesions, comprising one to six percent of primary bone tumors. Despite benign, those may be locally aggressive. We report a pediatric case with an atypical presentation. The patient was a seven-year-old boy, admitted to an emergency room due to right inguinal pain, without a history of trauma. The symptoms had acute onset and worsened gradually for five days. Radiographs revealed a cystic lesion on the proximal right femur and two longitudinal fractures. After further diagnostic work-up and given the probable diagnosis of an aneurysmal bone cyst, surgical treatment was performed. The diagnosis was then confirmed by histopathological analysis. After surgery, the patient maintained severe pain, having an important range of motion (ROM) and muscular strength reduction on the affected limb. As so, the patient engaged in a daily tailored Physical Medicine and Rehabilitation (PMR) program, for four months. After concluding the treatment plan, the patient was asymptomatic: recovery of both ROM and muscular strength was achieved, as well as the ability to return to previous daily-life activities. This is a paradigmatic case in which a rare condition with a rare presentation was displayed after several others were ruled out, requiring a multidisciplinary approach.
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OBJECTIVES: We aimed to evaluate the effect of previous cerebrovascular disease (CVD) on mortality rates of critically ill COVID-19 patients. MATERIALS & METHODS: A prospective cohort study was performed between May/2020 and May/2021, at a tertiary-care-center. We consecutively included adult patients admitted to intensive care units (ICU) having as primary diagnosis Acute Respiratory Distress Syndrome due to SARS-CoV-2, requiring invasive mechanical ventilation for >48 h. We considered as exposure the diagnosis of previous CVD and as main outcome the in-ICU mortality. RESULTS: The study sample included 178 patients: 74.2% were males, with a mean age of 63 ± 12.4 years-old(yo). Previous CVD was documented in 17 patients (9.6%). During the study period, the mortality rate at ICU was of 33.1% (n = 59). The proportion of mortality at ICU was higher in patients with prior CVD (58.8% vs 30.4%; p = 0.02). Also, older patients (66 ± 11.4 yo vs. 62 ± 12.7 yo, p = 0.04) and those with higher score at SAPSII at ICU admission (47.8 ± 15.4 vs. 40.7 ± 15.9; p = 0.01) had a higher ICU deathrate. Patients with previous CVD had a 2.70 (95%CI = 1.36-5.39) higher likelihood of dying compared to those who had no previous CVD. After adjustment (for gender, age, SAPSII and total length of stay), multivariate Cox analysis revealed that previous CVD remained a strong predictor for in-ICU death in critically ill COVID-19 patients (HR = 2.51; 95%CI = 1.15-5.51). CONCLUSIONS: Previous CVD was significantly associated to higher mortality in critical COVID-19 patients. We suggest that, in patients with previous CVD, prioritization of vaccination strategies should be implemented alongst with higher surveillance when infected with SARS-CoV-2.
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COVID-19 , Enfermedades Cardiovasculares , Trastornos Cerebrovasculares , Adulto , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , SARS-CoV-2 , Enfermedad Crítica , Estudios Prospectivos , Unidades de Cuidados Intensivos , Respiración Artificial , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate whether critical SARS-CoV-2 infection is more frequently associated with signs of corticospinal tract dysfunction and other neurological signs, symptoms, and syndromes, than other infectious pathogens. METHODS: This was a prospective cohort study with consecutive inclusion of patients admitted to intensive care units due to primary infectious acute respiratory distress syndrome requiring invasive mechanical ventilation > 48 hours. Eligible patients were randomly assigned to three investigators for clinical evaluation, which encompassed the examination of signs of corticospinal tract dysfunction. Clinical data, including other neurological complications and possible predictors, were independently obtained from clinical records. RESULTS: We consecutively included 54 patients with acute respiratory distress syndrome, 27 due to SARS-CoV-2 and 27 due to other infectious pathogens. The groups were comparable in most characteristics. COVID-19 patients presented a significantly higher risk of neurological complications (RR = 1.98; 95%CI 1.23 - 3.26). Signs of corticospinal tract dysfunction tended to be more prevalent in COVID-19 patients (RR = 1.62; 95%CI 0.72 - 3.44). CONCLUSION: Our study is the first comparative analysis between SARS-CoV-2 and other infectious pathogens, in an intensive care unit setting, assessing neurological dysfunction. We report a significantly higher risk of neurological dysfunction among COVID-19 patients. As such, we suggest systematic screening for neurological complications in severe COVID-19 patients.
OBJETIVO: Avaliar se a infecção grave pelo SARS-CoV-2 está mais comumente associada a sinais de disfunção do trato corticoespinhal e outros sinais, sintomas e síndromes neurológicas, em comparação com outros agentes infecciosos. MÉTODOS: Este foi um estudo de coorte prospectivo com inclusão consecutiva de doentes admitidos a unidades de cuidados intensivos devido a síndrome do desconforto respiratório agudo infeccioso primário, com necessidade de ventilação mecânica invasiva por > 48 horas. Os doentes incluídos foram atribuídos aleatoriamente a três investigadores para a avaliação clínica, a qual incluía a pesquisa de sinais de disfunção do trato corticoespinhal. Os dados clínicos, incluindo outras complicações neurológicas e possíveis preditores, foram obtidos independentemente a partir dos registros clínicos. RESULTADOS: Foram incluídos consecutivamente 54 doentes com síndrome do desconforto respiratório agudo, 27 devido a SARS-CoV-2 e 27 devido a outros agentes infecciosos. Os grupos eram comparáveis na maioria das características. Os doentes com COVID-19 apresentavam risco significativamente superior de complicações neurológicas (RR = 1,98; IC95% 1,23 - 3,26). Os sinais de disfunção do trato corticoespinhal tendiam a ser mais prevalentes em doentes com COVID-19 (RR = 1,62; IC95% 0,72 - 3,44). CONCLUSÃO: Este estudo foi a primeira análise comparativa visando avaliar disfunção neurológica, entre doentes com infecção SARS-CoV-2 e outros agentes infecciosos, em um contexto de unidade de cuidados intensivos. Reportamos um risco significativamente superior de disfunção neurológica em doentes com COVID-19. Como tal, sugere-se o rastreio sistemático de complicações neurológicas em doentes com COVID-19 crítico.
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COVID-19 , Enfermedades del Sistema Nervioso , Síndrome de Dificultad Respiratoria , Humanos , SARS-CoV-2 , COVID-19/complicaciones , Estudios Prospectivos , Enfermedades del Sistema Nervioso/epidemiologíaRESUMEN
Anti-glomerular basement membrane (anti-GBM) disease and anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis are the main causes of pulmonary-renal syndrome (PRS). The concurrence of both ANCA - myeloperoxidase (MPO) and proteinase 3 (PR3) - and anti-GBM antibodies has been described, although positivity for all three antibodies has rarely been reported. The natural history of triple-positive patients as well as the best therapeutic approach remains unknown. We describe a case of an 80-year-old woman that presented to the emergency department with a 3-month history of progressive fatigue, malaise and anorexia, and 5 weeks of cough with blood-streaked sputum and progressive peripheral edema. Through the complementary study, a rare diagnosis of PRS with triple-seropositive for both ANCA (MPO and PR3) and anti-GBM antibodies was made in a patient with untreated chronic hepatitis B virus infection. She was treated with glucocorticoid, cyclophosphamide, plasma exchange and entecavir, with pulmonary recovery. Renal function did not improve. After 2 years, the patient is still in dialysis, but did not have relapse of alveolar hemorrhage and ANCA and anti-GBM antibody titers remain negative. The authors intend to warn to PRS, in particular this rare cause, since delaying diagnosis can lead to significant morbidity and mortality for patients.
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Neurological complications are frequently reported in an intensive care unit (ICU), as a manifestation of a critical systemic illness or of its treatment. On the specific setting of COVID-19 patients, peripheral nerve lesions can have a multiplicity of causes, such as post-infectious neuropathy, positioning-related neuropathy or iatrogeny. An unusual but potentially disabling complication of any peripheral nerve lesion is Complex Regional Pain Syndrome (CRPS). Although there have been no mechanistic studies assessing how SARS-CoV-2 might directly impact nociception, it is hypothesized that the systemic hyperinflammation seen in severe COVID-19 may contribute to peripheral and central neuronal sensitization, possibly increasing the risk of developing CRPS. This case report highlights the potential hazards and consequences of peripheral nerve injuries on an ICU setting in COVID-19 patients, as well as the importance of a multidisciplinary approach for an early diagnosis and treatment, which are directly related to a better prognosis.
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Double-stranded RNAs (dsRNAs) represent a promising class of biosafe insecticidal compounds. We examined the ability to induce RNA interference (RNAi) in the pollen beetle Brassicogethes aeneus via anther feeding, and compared short-term (3 d) to chronic (17 d) feeding of various concentrations of dsRNA targeting αCOP (dsαCOP). In short-term dsαCOP feeding, only the highest concentration resulted in significant reductions in B. aeneus survival; whereas in chronic dsαCOP feeding, all three concentrations resulted in significant mortality. Chronic dsαCOP feeding also resulted in significantly greater mortality compared to short-term feeding of equivalent dsαCOP concentrations. Our results have implications for the economics and development of dsRNA spray approaches for managing crop pests, in that multiple lower-concentration dsRNA spray treatments across crop growth stages may result in greater pest management efficacy, compared to single treatments using higher dsRNA concentrations. Furthermore, our results highlight the need for research into the development of RNAi cultivars for oilseed rape protection, given the enhanced RNAi efficacy resulting from chronic, compared to short-term, dsRNA feeding in B. aeneus.
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Escarabajos/fisiología , Polen , Interferencia de ARN/fisiología , ARN Bicatenario/metabolismo , Alimentación Animal/análisis , Animales , Escarabajos/genética , Dieta , Conducta AlimentariaRESUMEN
Pheochromocytoma (PHEO) is a rare tumour that arises from adreno-medullary chromaffin cells and secretes catecholamines. These hormones are also secreted by paragangliomas, which derive from extra-adrenal cells of the sympathetic paravertebral ganglia. At least one-third of PHEOs are familial. Neurofibromatosis type 1 (NF1), or von Recklinghausen's disease, is diagnosed upon clinical criteria, and the study of PHEO is advised if hypertension is present. The incidence of PHEO in NF1 is 0.1-5.7% and explains hypertension in 20-50% of these patients. Recent advances in the treatment of this condition and preoperative preparation allow us to reduce its high cardiovascular morbimortality. Here we present the case of a 31-year-old female with known NF1 who presented with 5 months' history of non-specific symptoms and an episode of intraoperative hypertensive crisis. The workup detected a left sided PHEO, which was treated surgically. Our case illustrates the high prevalence of hereditary PHEO and how its presentation can go unnoticed. It reinforces the significance of screening for PHEO in patients with NF1.
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Methamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation, contributing to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders triggered by neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in individuals who abuse Meth), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a process dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production, or suppressing astrocytic calcium mobilization, prevented Meth-elicited microglia reactivity and re-established risk assessment behavior as tested by elevated plus maze (EPM). Overall, our data indicate that glial crosstalk is critical to relay alterations caused by acute Meth exposure.
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Estimulantes del Sistema Nervioso Central , Metanfetamina , Factor de Necrosis Tumoral alfa , Animales , Astrocitos , Estimulantes del Sistema Nervioso Central/toxicidad , Ácido Glutámico , Metanfetamina/toxicidad , Ratones , MicroglíaRESUMEN
Spray-induced gene silencing (SIGS) is a potential strategy for agricultural pest management, whereby nucleotide sequence-specific double-stranded RNA (dsRNA) can be sprayed onto a crop; the desired effect being a consumption of dsRNA by the target pest, and subsequent gene silencing-induced mortality. Nucleotide sequence-specificity is the basis for dsRNA's perceived biosafety. A biosafe approach to pollen beetle (Brassicogethes aeneus) management in oilseed rape (Brassica napus) agroecosystems is needed. We examined the potential for SIGS in B. aeneus, via bud feeding, a field-relevant dsRNA exposure route. Oilseed rape buds were uniformly treated with dsRNA designed to target αCOP in B. aeneus. Our model control dsRNA (dsGFP) remained detectable on buds throughout the entire 3 d exposure period. When applied at 5 µg/µL, dsαCOP induced significant αCOP silencing 3 d after dietary exposure to buds treated with this dsαCOP concentration. We also observed a trend of increased αCOP silencing with increasing concentrations of dsαCOP at both 3 and 6 d. Furthermore, we observed a marginally significant and significant reduction in B. aeneus survival at 10 and 15 d, respectively. Our results suggest potential for developing a SIGS approach to B. aeneus management-though further experiments are needed to more fully understand this potential.
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BACKGROUND: The congenital muscular torticollis is characterized by a persistent lateral flexion of the head to the affected side and cervical rotation to the opposite side due to unilateral shortening of the sternocleidomastoid muscle. The majority of the cases resolve with conservative management, with parents/caregivers education and physical therapy.The aim of this study was to assess demographic and clinical characteristics, treatment options, and outcome, amongst infants referred to pediatric rehabilitation consultation due to congenital muscular torticollis. METHODS: Retrospective cohort study of infants diagnosed with congenital muscular torticollis between January 2012 and December 2014. Obstetric and perinatal data, clinical presentation, comorbidities, treatment, and outcome were abstracted from clinical records. RESULTS: One hundred six infants were included. There was no sex predominance and mean age at first pediatric rehabilitation consultation was 11.6 (10.4) weeks. Most women were primiparous (76.4%), dystocic labor predominated (73.6%), and pelvic fetal presentation occurred in 20.8%. At examination, 49.1% of the infants had abnormalities, beyond the tilt cervical, mainly range of motion restrictions and palpable nodule in sternocleidomastoid muscle. Among the 87 children who performed the cervical ultrasound, 29 (27.4%) had anomalies. Associated clinical conditions such as hip dysplasia were identified. The majority (71.7%) were submitted to conservative treatment, 30.2% in the Pediatric Rehabilitation Department. Most infants (97.2%) showed a complete resolution of the torticollis. CONCLUSIONS: Congenital muscular torticollis is the most common cause of torticollis in the infants. Early diagnosis, parent/caregivers education, and conservative treatment are crucial to achieving good results.
RESUMEN
OBJECTIVE: To access the benefits or harms of an exercise program, based on the current American College of Obstetricians and Gynecologists guidelines, on the mode of delivery, duration and onset of labor. METHODS: A study performed at the Hospital Senhora da Oliveira between October 2015 and February 2017. This was a quasi-experimental study involving 255 women divided into two groups: an intervention group engaged in a controlled and supervised exercise program during pregnancy (n = 99), and a control group that did not participate in the exercise program (n = 156). Data were collected in two stages: during the 1st trimester biochemical screening (before the beginning of the program), through a written questionnaire, and after delivery, from the medical files of the patients. The significance level in the present study was 5% (p = 0.05). RESULTS: The control group had higher odds of induced labor (odds ratio [OR] 2.71; 95% confidence interval [CI]: 1.42-5.17; p = 0.003), when compared with women who underwent the intervention. No differences were found between the groups in instrumental vaginal deliveries, cesarean rate, time until the beginning of the active phase, duration of the active phase, and duration of the second stage of labor. CONCLUSION: The implementation of a controlled and supervised exercise program in pregnancy was associated with significantly lower odds of induced deliveries.
OBJETIVO: Avaliar o efeito de um programa de exercícios na gravidez (baseado nas recomendações do American College of Obstetricians and Gynecologists) na via, duração e início do trabalho de parto. MéTODOS: Estudo realizado no Hospital Senhora da Oliveira entre outubro de 2015 e fevereiro de 2017. Trata-se de um estudo quasi-experimental com 255 grávidas, divididas em dois grupos: grupo de intervenção, constituído por mulheres que participaram de um programa controlado e supervisionado de exercícios físicos (n = 99), e um grupo de controle, formado por grávidas que não participaram do programa de exercícios (n = 156). Os dados foram colhidos em dois momentos: durante o rastreio bioquímico do primeiro trimestre (antes do início do programa), através de um questionário escrito, e após o parto, através da consulta do processo clínico da paciente. O nível de significância estatística adotado neste projeto foi de 5% (p = 0,05). RESULTADOS: O grupo controle apresentou maior probabilidade de indução do trabalho de parto (razão de chances [RC] 2,71; intervalo de confiança [IC] 95%: 1,425,17; p = 0,003) quando comparado com o grupo de intervenção. Não foram encontradas diferenças estatisticamente significativas entre os dois grupos em relação à via de parto, tempo até início da fase ativa, duração da fase ativa e duração do segundo estadio do trabalho de parto. CONCLUSãO: A implementação de um programa de exercícios controlado e supervisionado na gravidez foi associada a uma probabilidade significativamente menor de indução do trabalho de parto.