Five-Year Outcome in Stroke Patients Submitted to Thrombolysis.

BACKGROUND AND PURPOSE: Little is known on long-term follow-up after thrombolysis in ischemic stroke patients because the majority of studies evaluated outcome at 3 to 12 months. We aimed to assess 5-year outcome after intravenous thrombolysis (IVT). METHODS: Cohort study based on the prospective registry of all consecutive ischemic stroke patients submitted to IVT in our Stroke Unit. Five-year outcome, including living settings, functional outcome, stroke recurrence, and mortality, was ascertained by telephonic interviews and additional review of clinical records. Multivariate analyses were performed to identify predictors of outcome and mortality. Excellent outcome was defined as modified Rankin scale 0 to 1. RESULTS: Five-year outcome was available for 155/164 patients submitted to IVT. At 5 years, 32.9% of patients had an excellent outcome (95% confidence interval (CI) =25.5-43.3) and mortality was 43.9% (95%CI=36.1-51.7). Increasing age (odds ratio =0.93, 95% CI =0.90-0.97) and increasing National Institute of Health Stroke Scale (NIHSS) 24 h after thrombolysis (odds ratio =0.81, 95% CI =0.74-0.90) were independently associated with a lower likelihood of an excellent 5-year outcome. Age (hazards ratio =1.07, 95% CI =1.03-1.11) and excellent functional outcome 3 months after thrombolysis (hazards ratio =0.28, 95%CI=0.12-0.66) were independently associated with mortality during follow-up. CONCLUSIONS: One third of ischemic stroke patients have excellent 5-year outcome after IVT. Younger age, lower NIHSS 24 h after IVT, and excellent 3-month functional outcome are independent predictors of excellent 5-year outcome.

Atrial ectopic activity in cryptogenic ischemic stroke and TIA: a risk factor for recurrence.

BACKGROUND: To characterize atrial ectopic activity in patients with cryptogenic ischemic stroke (CIS) or transient ischemic attack (TIA) and determine its prognostic significance. METHODS: Retrospective cohort study, in which 184 patients with CIS or TIA who had performed 24-hour Holter electrocardiogram were included. The median follow-up was 27.5 months. Baseline clinical and imagiologic characteristics, etiologic investigation results, and ischemic stroke and TIA recurrences information were collected. Number of atrial premature complexes (APCs) per hour was categorized as less than 10 APCs/hour, 10-30 APCs/hour, and more than 30 APCs/hour. RESULTS: Most of the patients had less than 10 APCs/hour (82.6%), 8.2% had 10-30 APCs/hour, and 9.2% had more than 30 APCs/hour. Patients with more than 30 APCs/hour had a greater median left atrium diameter than patients with 30 APCs/hour or less (42 mm vs. 38 mm; 95% confidence interval [CI], .50-7.00; P = .003). Annual recurrence rate of CIS or TIA was 2.9% in patients with less than 10 APCs/hour, 11.0% in 10-30 APCs/hour, and 22.6% in more than 30 APCs/hour (P = .001). More than 30 APCs/hour were independently associated with recurrence risk in multivariate survival analysis (hazard ratio, 3.40; 95% CI, 1.12-10.32; P = .030). CONCLUSIONS: In patients with CIS or TIA, frequent atrial ectopic activity (>30 APCs/h) was independently associated with increased risk of stroke or TIA recurrence. Further studies need to validate frequent atrial ectopic activity as a risk factor for recurrence in cryptogenic stroke and confirm its role as a predictor of occult atrial fibrillation.

Hypertrophic olivary degeneration and cerebrovascular disease: movement in a triangle.

Hypertrophic olivary degeneration is a rare kind of trans-synaptic degeneration that occurs after lesions of the dentatorubro-olivary pathway. The lesions, commonly unilateral, may result from hemorrhage due to vascular malformation, trauma, surgical intervention or hypertension, tumor, or ischemia. Bilateral cases are extremely rare. This condition is classically associated with development of palatal tremor, but clinical manifestations can include other involuntary movements. We describe 2 cases: unilateral hypertrophic olivary degeneration in a 60-year-old man with contralateral athetosis and neurologic worsening developing several years after a pontine hemorrhage and bilateral hypertrophic olivary degeneration in a 77-year-old woman with development of palatal tremor, probably secondary to pontine ischemic lesions (small vessel disease).

Molecular energetics of alkyl pyrrolecarboxylates: calorimetric and computational study.

The pyrrole subunit plays an important role in material science as the building block of polypyrroles, an important representative class of conducting polymers, which found widely applications in the area of new materials due to their chemical, thermal, and electrical properties associated with their easiness and low cost of production, making them especially promising for commercial applications. The energetic characterization of this kind of molecules provides information concerning stability, reactivity, and biodegrability of chemical compounds in environment being, for example, helpful in choosing the most adequate method for their elimination by converting the waste into harmless compounds or even decreasing the production of toxic substances in industrial processes. This work reports a combination of calorimetric and computational determinations of several alkyl pyrrolecarboxylates (alkyl = methyl or ethyl) whose main purpose is the calculation of their standard (p° = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at T = 298.15 K. Experimentally, for methyl 1-pyrrolecarboxylate (M1PC), methyl 2-pyrrolecarboxylate (M2PC), and ethyl 2-pyrrolecarboxylate (E2PC), these values were derived from the standard (p° = 0.1 MPa) molar enthalpies of formation, in the condensed phase, ΔfHm° (cr,l), at T = 298.15 K, obtained by static bomb combustion calorimetry, and from the standard molar enthalpies of phase transition, Δcr,l(g)Hm°, at T = 298.15 K, determined by high-temperature Calvet microcalorimetry. Standard ab initio molecular calculations, at the G3(MP2)//B3LYP level, were performed, and the standard enthalpies of formation of these three compounds were estimated. A very good agreement between the calculated and the experimental data was obtained. Thereby, we have extended these calculations to other alkyl pyrrolecarboxylates, namely, ethyl 1-pyrrolecarboxylate (E1PC), methyl 3-pyrrolecarboxylate (M3PC), and ethyl 3-pyrrolecarboxylate (E3PC), whose study was not performed experimentally. The computational analysis, at the B3LYP/6-31G(d) level of theory, of the six molecules allowed a detailed inspection and a better knowledge about their molecular structure and geometrical parameters.

Reversible Bilateral Basal Ganglia Lesions Due to Multifactorial Toxic-Metabolic Disorders.

Bilateral basal ganglia lesions can include a wide variety of etiologies, including metabolic, toxic, degenerative, vascular, inflammatory, infectious, and neoplastic etiology. We present a case of a 78-year-old man who was hospitalized with acute behavioral changes and psychomotor slowing. His medical history included diabetes mellitus, arterial hypertension, and prostate adenocarcinoma. In his spare time, he was a pigeon fancier and regularly burned waste (including diapers) outside his home. In the initial evaluation, he was hypertensive, drowsy, disoriented in time and space, dysarthric, and with global bradykinesia. From the research carried out, we stand out the following: brain magnetic resonance imaging showing bilateral hyperintensity of the basal ganglia on T2/fluid-attenuated inversion recovery, with foci of hypersignal on T1 without diffusion restriction or contrast enhancement; CSF presenting 15 cells/uL, without other alterations; analytical results presenting hypernatremia (171 mEq/L), creatinine at 3.5 mg/dL, hyperglycemia (always <300 mg/dL), and slightly elevated C-reactive protein and anticardiolipin antibodies in addition to thrombocytopenia (107,000). After correcting the metabolic disturbances and evading the identified toxic substances, magnetic resonance imaging showed regression of the lesions, and the patient returned to a normal state. The functions of the basal ganglia are complex, requiring increased use of glucose and oxygen, therefore presenting a high metabolic activity, which makes them vulnerable to various metabolic changes. We report a rare case affected by symmetrical lesions in the basal ganglia and presenting an acute onset of altered mental status with behavioral alterations, related to hyperglycemia, acute kidney injury, hypertension, and exposure to toxic substances (smoke from bonfires and/or toxic chemical components). Complete clinical recovery, remaining negative investigation, and regression of the lesions support our diagnosis.

Clinical Worsening of Charcot-Marie-Tooth Disease Due to Overlapping Acute Inflammatory Polyneuropathy.

We report a case of a six-year-old male with Charcot-Marie-Tooth disease (CMT) type 1B due to MPZ gene mutation who experienced an acute worsening of his symptoms a few years after the diagnosis. He was not able to walk without assistance and had transitory paresthesia in his hands, 10 days after suffering from an upper respiratory and diarrheal illness. The investigation revealed elevated cerebrospinal fluid (CSF) protein levels with no pleocytosis, and sensory and motor chronic demyelinating neuropathy without active denervation findings on electrophysiological studies. The patient completely recovered following treatment with intravenous immunoglobulin. We describe the patient's history and engage in a review of the literature to find similar clinical cases. It has been proposed that MPZ gene mutations can change the myelin structure and result in abnormal exposure of the nervous cell components to immune cells. Hence, patients with this type of CMT would be predisposed to concurrent inflammatory forms of neuropathy.

Associations between Emotion Regulation, Feeding Practices, and Preschoolers' Food Consumption.

Previous research identified emotion dysregulation, non-responsive feeding practices, and unhealthy food consumption as risk factors for childhood obesity. However, little is known about the relationships between these factors. This study examined associations between children's emotion regulation, parental feeding practices, and children's food consumption. The sample consisted of 163 mothers of children aged 3-5 years. Mothers completed the Emotion Regulation Checklist, the Child Feeding Questionnaire, and the Child Health Section from the Parent Interview of the Early Childhood Longitudinal Study-B to assess model variables. Results showed that healthy food consumption was associated with higher emotion regulation abilities, higher monitoring, and lower pressure to eat. For unhealthy food consumption, the associations were in opposite directions. Higher emotion regulation abilities were also associated with higher monitoring, lower pressure to eat, and lower restriction. For lability, the associations were in opposite directions. Regression analyses revealed that children's lability, pressure to eat, and monitoring were significant predictors of children's food consumption. These findings suggest that children's emotion regulation and feeding practices are important determinants of children's food consumption. Future longitudinal studies that examine bidirectional associations between children's emotion regulation, parental feeding practices, children's food consumption, and potential mechanisms accounting for these associations are needed.

Cerebral Venous Thrombosis Due to Overdrainage in a Patient With Normal Pressure Hydrocephalus: A Case Report.

Mechanical shunting of cerebrospinal fluid (CSF) is an effective treatment for hydrocephalus but is not exempt from complications. A 67-year-old male with a history of normal pressure hydrocephalus (NPH) and ventriculoperitoneal shunting (VPS) one year ago presented with gait disturbance and memory impairment. His head computed tomography (CT) was normal, and the shunting pressure was reduced from 110 to 70 mmH20 with gait and memory improvement. One week later, he reported persistent pressure headaches, which worsen when lying down, accompanied by nausea and vomiting. His neurological examination was notable for a short-stepped wide-based gait. Two generalized seizures were observed. CT cerebral venography revealed sinus venous thrombosis (SVT). After two days, a new CT was performed, and bilateral subdural hygromas were found. The shunting pressure was readjusted to 110 mmH20, and symptom improvement was noted. One week later, CT showed enlargement and bleeding of subdural collections. The drainage system was closed, and the patient continue to recover. The temporal association between pressure adjustment and symptom onset and the evidence of progressive subdural effusions suggest that the decrease of CSF volume by overdrainage led to an increase in cerebral blood volume and the dilatation of the venous sinus, which precipitated thrombus formation.

Attachment and the Development of Moral Emotions in Children and Adolescents: A Systematic Review.

In recent years, the development of social and moral emotions (often associated to pro-social behaviors) has become the subject of increased research interest. However, the relation between these emotions and attachment is less studied. The present systematic literature review (PROSPERO: CRD42021247210) was designed to synthesize current empirical contributions that explore the link between attachment and the development of moral emotions (e.g., empathy, sympathy, altruism, and guilt) during childhood and adolescence. Article exclusion criteria included: studies with participants not living in natural contexts (e.g., institutionalized); studies on mental illness; qualitative research; research that does not reliably evaluate attachment or moral emotions; research on intervention programs; and non-peer-reviewed articles. Only 10 studies were found eligible. Results highlight a present focus on empathy and guilt and gaps regarding sympathy and altruism. The mediator role and positive effect of emotion regulation was noted. Significant positive correlations between attachment security and guilt, shame and forgiveness were emphasized. Limitations of the eligible studies included: representativeness of the participants; causality of the results; and the validity and significance of the instruments (e.g., lack of results reported by various parties involved). The present review aims to contribute to the understanding of an empathic, healthy development, in contrast to the alienation and bullying affecting the youth's emotional, relational and academic lives.

Primary Progressive Multiple Sclerosis in a Portuguese Patient With Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a frequent genetic neurocutaneous syndrome and multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system. The association of both these diseases is rare. In this case report, we describe a 25-year-old man with gait impairment, upper limbs tremor, slurred speech, and urinary symptoms in the form of urinary urgency and incontinence. These symptoms started a year earlier and had a progressive course. Examination revealed scattered café-au-lait spots, right ptosis, bilateral horizontal and vertical nystagmus, mild dysarthria, quadriparesis with generalized hyperreflexia and bilateral Babinski signs, upper limb tremor, bilateral proprioceptive errors, bilateral appendicular dysmetria, and severe gait ataxia. Brain MRI showed lesions involving the deep and subcortical white matter, as well as thalami, with no enhancement after administration of gadolinium, suggestive of focal areas of signal intensity (FASI) in the setting of NF1. There were also oval lesions in the periventricular white matter, perpendicular to the ventricles and involving the corpus callosum, which were atypical for FASI. Spinal MRI also demonstrated several lesions, which mildly enhance after administration of gadolinium. Cerebrospinal fluid (CSF) examination revealed mild lymphocytic pleocytosis (18/µL), mildly elevated protein (0.53 g/L), normal glucose, and positive oligoclonal IgG bands. Extensive laboratory workup, including microbiological CSF studies, aquaporin-4-IgG, myelin-oligodendrocyte glycoprotein-IgG, autoimmune screening, and viral serology, was negative. The genetic study revealed a new mutation in the NF1 gene that was not previously reported. We intend to discuss the genetic and autoimmune mechanisms by which MS and NF1 appear to be related and draw attention to this association because a timely diagnosis of MS is important to prevent further disability in NF1 patients.

Target-induced clustering activates Trim-Away of pathogens and proteins.

Trim-Away is a recently developed technology that exploits off-the-shelf antibodies and the RING E3 ligase and cytosolic antibody receptor TRIM21 to carry out rapid protein depletion. How TRIM21 is catalytically activated upon target engagement, either during its normal immune function or when repurposed for targeted protein degradation, is unknown. Here we show that a mechanism of target-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce virus neutralization or drive Trim-Away. We harness this mechanism for selective degradation of disease-causing huntingtin protein containing long polyglutamine tracts and expand the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can also be controlled optogenetically. This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

Experimental and computational study on the molecular energetics of 2-pyrrolecarboxylic acid and 1-methyl-2-pyrrolecarboxylic acid.

This paper reports a combined thermochemical experimental and computational study of 2-pyrrolecarboxylic acid and 1-methyl-2-pyrrolecarboxylic acid. Static bomb combustion calorimetry and Knudsen mass-loss effusion technique were used to determine the standard (p degrees = 0.1 MPa) molar enthalpies of combustion, Delta(c)H(m) degrees, and sublimation, Delta(cr)(g)H(m) degrees, respectively, from which the standard (p degrees = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at T = 298.15 K, were derived. The values obtained were -(286.3 +/- 1.7) and -(291.6 +/- 1.7) kJ x mol for 2-pyrrolecarboxylic acid and 1-methyl-2-pyrrolecarboxylic acid, respectively. For comparison purposes, the gas-phase enthalpies of formation of these two compounds were estimated by G3(MP2)//B3LYP and MP2 approaches, using a set of gas-phase working reactions; the results are in excellent agreement with experimental data. G3(MP2)//B3LYP computations were also extended to the calculation of N-H bond dissociation enthalpies, gas-phase acidities and basicities, proton and electron affinities and adiabatic ionization enthalpies. Moreover, the results are also discussed in terms of the energetic effects of the addition of a carboxylic and of a methyl groups to the pyrrole ring and compared with structurally similar compounds.

2- and 3-acetylpyrroles: a combined calorimetric and computational study.

A combined experimental and computational study on the thermochemistry of 2- and 3-acetylpyrroles was performed. The enthalpies of combustion and sublimation were measured by static bomb combustion calorimetry and Knudsen effusion mass-loss technique, respectively, and the standard (p(o) = 0.1 MPa) molar enthalpies of formation, in the gaseous phase, at T = 298.15 K, were determined. Additionally, the gas-phase enthalpies of formation were estimated by G3(MP2)//B3LYP calculations, using several gas-phase working reactions, and were compared with the experimental ones. N-H bond dissociation enthalpies, gas-phase acidities and basicities, proton and electron affinities and ionization enthalpies were also calculated. Experimental and theoretical results are in good agreement and show that 2-acetylpyrrole is thermodynamically more stable than the 3-isomer. The substituent effects of the acetyl group in pyrrole, thiophene and pyridine rings were also analyzed.

Thermochemistry of bithiophenes and thienyl radicals. A calorimetric and computational study.

The relative stabilities of 2,2'- and 3,3'-bithiophenes were evaluated by experimental thermochemistry and the results compared with data obtained from state of the art calculations, which were also extended to 2,3'-bithiophene. The standard (p degrees = 0.1 MPa) molar enthalpies of formation of crystalline 2,2'-bithiophene and 3,3'-bithiophene were calculated from the standard molar energies of combustion, in oxygen, to yield CO(2) (g) and H(2)SO(4) x 115 H(2)O, measured by rotating-bomb combustion calorimetry at T = 298.15 K. The vapor pressures of these two compounds were measured as a function of temperature by Knudsen effusion mass-loss technique. The standard molar enthalpies of sublimation, at T = 298.15 K, were derived from the Clausius-Clapeyron equation. The experimental values were used to calculate the standard (p(o) = 0.1 MPa) enthalpies of formation of the title compounds in the gaseous phase; the results were analyzed and interpreted in terms of enthalpic increments and molecular structure. Standard ab initio molecular orbital calculations at the G3(MP2)//B3LYP level were performed. Enthalpies of formation, using homodesmotic reactions, were calculated and compared with experimental data. The computational study was also extended to the isomeric compound 2,3'-bithiophene. Detailed inspections of the molecular and electronic structures of the compounds studied were carried out. Finally, bond dissociation enthalpies (BDE) and enthalpies of formation of thienyl radicals were also computed.

Whipple's disease: a rare case of malabsorption.

Whipple's disease is a chronic, rare, multisystemic, infectious entity, described for the first time in 1907. Its aetiological agent is the Gram-negative rod, Tropheryma whipplei, which was isolated for the first time in 2001 from a cardiac valve of a patient with endocarditis. We present the case of a 71-year-old man, who came into the emergency room complaining of anorexia, weakness, abdominal pain and diarrhoea with haematochezia and presented disseminated palpable purpuric lesions, predominantly in the lower limbs. The upper endoscopy showed a duodenal vasculitis and the biopsy of that location revealed aspects suggestive of Whipple's disease. We started him on antibiotics according to the recent orientations with progressive clinical and analytical improvement, although he developed an immune reconstitution syndrome, which lasted for 2 weeks.

Orolingual angioedema after thrombolysis is not associated with insular cortex ischemia on pre-thrombolysis CT.

OBJECTIVE: Orolingual angioedema (OA) is a well known early complication of treatment with alteplase in ischemic stroke patients. Our aim was to study risk factors for OA in these patients, namely insular cortex ischemia. METHODS: Retrospective case-cohort study using the prospective registry of all consecutive ischemic stroke patients submitted to intravenous thrombolysis with alteplase. Clinical data was retrieved from the registry and medical records. Two independent observers evaluated early signs of insular cortex ischemia on pre-thrombolysis computed tomography (CT) and of insular cortex infarct on early follow-up imaging. Univariate and multivariate analysis were performed to identify predictors of OA. RESULTS: Of the 659 patients with acute ischemic stroke treated with alteplase, 32 developed OA (4.9%, 95%CI=3.3-6.6). Frequency of early signs of insular cortex ischemia on pre-thrombolysis CT and of insular cortex infarct on follow-up imaging was similar in patients with and without OA (p=0.241 and p=0.145, respectively). The only independent predictors of OA occurrence were female sex (OR=5.47, 95%CI=1.98-15.10) and angiotensin-converting enzyme inhibitor (ACE-I) use (OR=3.87, 95%CI=1.71-8.75). CONCLUSIONS: Female sex and ACE-I use are independent risk factors for OA occurrence in ischemic stroke patients treated with alteplase. Early signs of insular cortex ischemia on pre-thrombolysis CT were not significantly associated with OA.

Vapor pressures, thermodynamic stability, and fluorescence properties of three 2,6-alkyl naphthalenes.

This work reports the experimental determination of relevant thermodynamic properties and the characterization of luminescence properties of the following polycyclic aromatic hydrocarbons (PAHs): 2,6-diethylnaphthalene, 2,6-diisopropylnaphthalene and 2,6-di-tert-butylnaphthalene. The standard (p(o) = 0.1 MPa) molar enthalpies of combustion, ΔcHm(o), of the three compounds were determined using static bomb combustion calorimetry. The vapor pressures of the crystalline phase of 2,6-diisopropylnaphthalene and 2,6-di-tert-butylnaphthalene were measured at different temperatures using the Knudsen effusion method and the vapor pressures of both liquid and crystalline phases of 2,6-diethylnaphthalene were measured by means of a static method. The temperatures and the molar enthalpies of fusion of the three compounds were determined using differential scanning calorimetry. The gas-phase molar heat capacities and absolute entropies of the three 2,6-dialkylnaphthalenes studied were determined computationally. The thermodynamic stability of the compounds in both the crystalline and gaseous phases was evaluated by the determination of the Gibbs energies of formation and compared with the ones reported in the literature for 2,6-dimethylnaphthalene. From fluorescence spectroscopy measurements, the optical properties of the compounds studied and of naphthalene were evaluated in solution and in the solid state.