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Background Autism spectrum disorder (ASD) requires trained professionals for its adequate diagnosis. There is a shortage of such professionals in Brazil. Screening tools could identify priority cases. The only instrument for that in Brazilian Portuguese is employed for toddlers up to 2.5 years old.

Background The prevalence of pain in patients with multiple sclerosis is remarkable. Fibromyalgia has been considered as one of the forms of chronic pain encompassed in multiple sclerosis, but data are restricted to studies from Europe and North America.

A definição de corrupção é extensa, relacionada a qualquer ação humana que compreenda alguma espécie de desonestidade, porém no presente artigo restará limitada e associada às atividades do Estado, de seus cidadãos e de seus governantes. A corrupção é derivada de práticas socioculturais bem balizadas, com destaque para o patrimonialismo, o clientelismo, o personalismo e o nepotismo, que surgem no bojo de ações egoístas dos indivíduos. Conclui-se que a corrupção é sistêmica porque envolve, normalmente, um padrão persistente, não episódico, de relacionamentos, abrangendo um conjunto recorrente de interações, obedecendo a um ciclo que se retroalimenta indefinidamente. O método utilizado constituiu-se em um exercício jusfilosófico qualitativo e interpretativo de todo o material acadêmico compilado.

ABSTRACT Cognitive decline can be screened by the clock drawing test (CDT), which has several versions. Objective: This survey aimed to analyze the correlation between two simple methods for scoring the CDT. Methods: This cross-sectional study was nested in the Elo-Creati cohort from Passo Fundo, Brazil and comprised 404 subjects. Two raters underwent previous training and scored the subjects’ CDT according to both the Pfizer and Shulman systems. The inter-observer and intra-observer concordance within each method was analyzed with the Spearman’s rank correlation coefficient, as well as the concordance of the scores between the two methods. Age and scholarity were also correlated with the scores. Results: Most of the participants were women (93.8%) and Caucasian (84.6%), with a mean age of 66.9 (±7.8) years and a scholarity of 10.9 years (±5.6). There was significant inter-observer (Pfizer: r=0.739, p£0.001; Shulman: r=0.727, p£0.001) and intra-observer correlation (Pfizer: rater 1, r=0.628, p≤0.001; rater 2, r=0.821, p≤0.001; Shulman: rater 1, r=0.843, p≤0.001; rater 2: r=0.819; p≤0.001). Intra-observer correlation was also observed comparing Pfizer and Shulman methods (rater 1: r=0.744; p≤0.001; rater 2: r=0.702; p≤0.001). There was weak correlation of the scores with scholarity (Pfizer: r=0.283, p£0.001; Shulman: r=0.244, p£0.001) and age (Pfizer: r=-0.174, p£0.001; Shulman: r=-0.170, p£0.001). More participants were classified with decreased cognition through the Pfizer system (rater 1: 44.3 vs. 26.5%; rater 2: 42.1 vs. 16.3%; p≤0.001). Conclusions: For this population, our results suggest that the Pfizer system of scoring CDT is more suitable for screening cognitive decline.

Abstract Trypanosoma cruzi—the causative agent of Chagas disease—like other kinetoplastids, relies mostly on post-transcriptional mechanisms for regulation of gene expression. However, trypanosomatids undergo drastic changes in nuclear architecture and chromatin structure along their complex life cycle which, combined with a remarkable set of reversible histone post-translational modifications, indicate that chromatin is also a target for control of gene expression and differentiation signals in these organisms. Chromatin-modifying enzymes have a direct impact on gene expression programs and DNA metabolism. In this work, we have investigated the function of T. cruzi histone deacetylase 4 (TcHDAC4). We show that, although TcHDAC4 is not essential for viability, metacyclic trypomastigote TcHDAC4 null mutants show a thin cell body and a round and less condensed nucleus located very close to the kinetoplast. Sixty-four acetylation sites were quantitatively evaluated, which revealed H2AT85ac, H4K10ac and H4K78ac as potential target sites of TcHDAC4. Gene expression analyses identified three chromosomes with overrepresented regions of differentially expressed genes in the TcHDAC4 knockout mutant compared with the wild type, showing clusters of either up or downregulated genes. The adjacent chromosomal location of some of these genes indicates that TcHDAC4 participates in gene expression regulation during T. cruzi differentiation.

Objective: Obstructive Sleep Apnea (OSA) is linked to classical symptoms of snoring and excessive sleepiness. However, many women with OSA may present with a diverse profile. The influence of age on the clinical differences between genders is unclear. This survey aimed to compare the clinical and polysomnographic findings of OSA between adult males and females, but considering different age groups. Methods: This cross-sectional study comprised a sample of 472 consecutive adult patients with OSA who underwent full-night polysomnography. Data from the medical and polysomnographic records was obtained, as well as the score on Portuguese validated version of the Epwoth Sleepiness Scale (ESS). Comparisons of main clinical aspects of OSA between genders were stratified according to three groups: young (< 30 years old), middle-aged (30 - 50 y.o.), and older patients (> 50 y.o.). Results: Men comprised the majority of the sample (male/female ratio of 1.6). Apnea-Hypopnea Index (AHI) was higher in men than women (median [interquartile range]: 29.7 [18.1-47.8] vs. 21.9 [11.5-36.1]; p < 0.0001), and body mass index alike (mean ± standard deviation: 29.0±4.9 vs. 27.6±5.2; p = 0.004). Snoring was more common in male than in female patients (92% vs. 84.7%; p = 0.015). In the subset of subjects younger than 30 years-old the differences between genders were prominent (male/female; AHI: 19.6 [13.1-28.1] vs. 11.8 [7.7-18.8], p = 0.012; sno ring: 89.7% vs. 55.2%, p = 0.007), accompanied by a trend to lower score in ESS in male patients (7.1 ± 4.3 vs. 9.2 ± 4.3; p = 0.066). Discussion: Results suggest that a classical clinical picture of snoring and severe daytime sleepiness is lacking in a considerable proportion of OSA sufferers, particularly young women, who tend to be sleepier than male patients. The awareness of OSA in young women should be based more in mild excessive daily sleepiness than in other typical OSA symptoms.

Abstract Background The palmitate analogue 2-bromopalmitate (2-BP) is a non-selective membrane tethered cysteine alkylator of many membrane-associated enzymes that in the last years emerged as a general inhibitor of protein S-palmitoylation. Palmitoylation is a post-translational protein modification that adds palmitic acid to a cysteine residue through a thioester linkage, promoting membrane localization, protein stability, regulation of enzymatic activity, and the epigenetic regulation of gene expression. Little is known on such important process in the pathogenic protozoan Trypanosoma cruzi, the etiological agent of Chagas disease. Results The effect of 2-BP was analyzed on different developmental forms of Trypanosoma cruzi. The IC50/48 h value for culture epimastigotes was estimated as 130 μM. The IC50/24 h value for metacyclic trypomastigotes was 216 nM, while for intracellular amastigotes it was 242 μM and for cell derived trypomasigotes was 262 μM (IC50/24 h). Our data showed that 2-BP altered T. cruzi: 1) morphology, as assessed by bright field, scanning and transmission electron microscopy; 2) mitochondrial membrane potential, as shown by flow cytometry after incubation with rhodamine-123; 3) endocytosis, as seen after incubation with transferrin or albumin and analysis by flow cytometry/fluorescence microscopy; 4) in vitro metacyclogenesis; and 5) infectivity, as shown by host cell infection assays. On the other hand, lipid stress by incubation with palmitate did not alter epimastigote growth, metacyclic trypomastigotes viability or trypomastigote infectivity. Conclusion Our results indicate that 2-BP inhibits key cellular processes of T. cruzi that may be regulated by palmitoylation of vital proteins and suggest a metacyclic trypomastigote unique target dependency during the parasite development.

Dynamic S-palmitoylation of proteins is the addition of palmitic acid by zDHHC palmitoyl transferases (PATs) and depalmitoylation by palmitoyl protein thioesterases (PPTs). A putative PAT (TcPAT1) has been previously identified in Trypanosoma cruzi, the etiological agent of Chagas disease. Here we analyse other 14 putative TcPATs and 2 PPTs in the parasite genome. T. cruzi cell lines expressing TcPATs and TcPPTs plus a FLAG tag at the C terminus were produced for most enzymes, with positive detection by indirect immunofluorescence. Overexpressed TcPATs were mostly found as single spots at the parasite anterior end, while the TcPPTs were dispersed throughout the parasite body.

The AP-1 Adaptor Complex assists clathrin-coated vesicle assembly in the trans-Golgi network (TGN) of eukaryotic cells. However, the role of AP-1 in the protozoan Trypanosoma cruzi-the Chagas disease parasite-has not been addressed. Here, we studied the function and localization of AP-1 in different T. cruzi life cycle forms, by generating a gene knockout of the large AP-1 subunit gamma adaptin (TcAP1-γ), and raising a monoclonal antibody against TcAP1-γ. Co-localization with a Golgi marker and with the clathrin light chain showed that TcAP1-γ is located in the Golgi, and it may interact with clathrin in vivo, at the TGN. Epimastigote (insect form) parasites lacking TcAP1-γ (TcγKO) have reduced proliferation and differentiation into infective metacyclic trypomastigotes (compared with wild-type parasites). TcγKO parasites have also displayed significantly reduced infectivity towards mammalian cells. Importantly, TcAP1-γ knockout impaired maturation and transport to lysosome-related organelles (reservosomes) of a key cargo-the major cysteine protease cruzipain, which is important for parasite nutrition, differentiation and infection. In conclusion, the defective processing and transport of cruzipain upon AP-1 ablation may underlie the phenotype of TcγKO parasites.

Atypical teratoid/rhabdoid (AT/RT) of the brain is a rare malignant pediatric neoplasm that usually affects children around age two. This report is about a male patient, six months of age, who presented with seizures and decreased level of consciousness, progressing to numbness, oculomotor nerve palsy and tetra-spasticity. CT scan showed left cerebellopontine angle tumor. Magnetic resonance imaging (MRI) showed a solid lesion, hypointense on T1W and heterogeneous hyperintense on T2W, enhanced after contrast infusion, accompanied by three solid lesions, rounded and irregular in the left cerebellar hemisphere, occipito-parietal transition and right occipital lobe with no evidence of leptomeningeal spread, forming secondary implants. We conducted a biopsy, which confirmed AT/ RT. Chemotherapic treatment was ineffective and the patient passed away quickly. In the literature review we found about 300 cases reported, as it is, therefore, extremely rare tumor with a mean age at diagnosis of 29 months. It can affect any area of the central nervous system, mainly infratentorial, being its main differential diagnosis medulloblastomas. The findings of secondary implantation without leptomeningeal spread seen in this patient are described in only one other case in literature. The clinical features usually are neurological deficits, seizures and coma. Its genesis stems from mutations in the gene hSNF5/INI1 on chromosome 22. Neuroimaging studies don’t reveal radiological pattern suggesting AT/RT and the diagnosis is possible only through a biopsy with immunohistochemical analysis. The available treatments are ineffective, and death is the outcome, with 84% in six months.

Epimastigote forms of Trypanosoma cruzi (the etiologic agent of Chagas disease) internalize and store extracellular macromolecules in lysosome-related organelles (LROs) called reservosomes, which are positive for the cysteine protease cruzipain. Despite the importance of endocytosis for cell proliferation, macromolecule internalization remains poorly understood in the most clinically relevant proliferative form, the intracellular amastigotes found in mammalian hosts. The main obstacle was the lack of a simple method to isolate viable intracellular amastigotes from host cells. In this work we describe the fast and efficient isolation of viable intracellular amastigotes by nitrogen decompression (cavitation), which allowed the analysis of amastigote endocytosis, with direct visualization of internalized cargo inside the cells. The method routinely yielded 5x10(7) amastigotes--with typical shape and positive for the amastigote marker Ssp4--from 5x10(6) infected Vero cells (48 h post-infection). We could visualize the endocytosis of fluorescently-labeled transferrin and albumin by isolated intracellular amastigotes using immunofluorescence microscopy; however, only transferrin endocytosis was detected by flow cytometry (and was also analyzed by western blotting), suggesting that amastigotes internalized relatively low levels of albumin. Transferrin binding to the surface of amastigotes (at 4°C) and its uptake (at 37°C) were confirmed by binding dissociation assays using acetic acid. Importantly, both transferrin and albumin co-localized with cruzipain in amastigote LROs. Our data show that isolated T. cruzi intracellular amastigotes actively ingest macromolecules from the environment and store them in cruzipain-positive LROs functionally related to epimastigote reservosomes.

Fasciculations are symptoms present in a broad spectrum of conditions, ranging from normal manifestations to motor neuron diseases. They also represent the main picture of benign fasciculation syndrome. We report a case of such syndrome: a 48-years-old woman complaining about fasciculations for three decades who remained with the symptoms even after the compensation of a disclosed hyperthyroidism. The introduction of gabapentin rendered control of her fasciculations. The available data in the literature about the therapeutic approaches for fasciculations are revised, as long as the rare reports of evolution from patients with "benign" fasciculations to cases of amyotrophic lateral sclerosis, underlining the importance of following the patients with fasciculations.Fasciculações são sintomas presentes em um amplo espectro de condições, desde manifestações normais até doenças do neurônio motor. Elas representam também o principal aspecto da síndrome de fasciculações benignas. Relatamos um caso desta síndrome: uma paciente de 48 anos com queixas de fasciculações por três décadas que, mesmo após a compensação de um quadro de hipertireoidismo, permaneceu com os sintomas. A introdução de gabapentina levou a controle das fasciculações. Os dados disponíveis na literatura sobre as abordagens terapêuticas para fasciculações são revisados, assim como os raros relatos de evolução de pacientes com fasciculações "benignas" para casos de esclerose lateral amiotrófica, salientando a importância do seguimento dos pacientes com fasciculações.

Down syndrome is the most frequent genetic cause of mental retardation. Although usually presenting dysmorphic features and organ malformations, it is rarely associated with congenital hydrocephalus. The case of male neonate whose hydrocephalus was detected since the pregnancy and was discovered to have the syndrome at birth is reported. Chromosomal analysis confirmed the genetic disorder, and hydrocephalus was treated with ventriculoperitoneal shunt because of abnormal increase of head circumference. The patient has been accompanied and his development is considered normal when compared to the expected for those affected by the syndrome.A síndrome de Down é a causa genética mais freqüente de retardo mental. Embora comumente apresentando dismorfias e malformações de órgãos, raramente está associada à hidrocefalia congênita. O caso de um recém-nascido masculino cuja hidrocefalia foi detectada desde a gravidez e que se descobriu ser portadora da síndrome ao nascimento é relatado. O cariótipo confirmou a anormalidade genética, e a hidrocefalia foi tratada com derivação ventriculoperitoneal devido ao aumento anormal do perímetro cefálico. O paciente está sendo acompanhado e seu desenvolvimento é considerado normal quando comparado ao esperado para os portadores da síndrome.

ABSTRACT Migraine is a common condition in the pediatric population and causes a significant impact on the quality of life. Atopic disorders are some of the migraine comorbidities. Objective We hypothesized that allergic rhinitis could aggravate migraine in the pediatric population. Methods This cross-sectional study consecutively evaluated 90 pediatric outpatients (46 children 6–12 years of age; 44 adolescents up to 18 years of age) who sought medical assistance because of migraine at a general neurology clinic in Passo Fundo, RS, Brazil. They, and their parents, were given three questionnaires, to evaluate the diagnosis of current allergic rhinitis, allergic rhinoconjunctivitis and seasonal allergic rhinitis, as well as the disability caused by headache (ISAAC - International Study of Asthma and Allergies in Childhood; CARATkids - Control of Allergic Rhinitis and Asthma Test for Children; PedMIDAS - Pediatric Migraine Disability Assessment). The study was approved by the local ethics committee. Results According to the ISAAC questionnaire, children with current allergic rhinoconjunctivitis in the last year showed higher scores on the PedMIDAS than those patients without atopy (median and interquartile range 26 [10–58] vs. 5 [1–13], p = 0.008). A significant positive correlation of CARATkids scores with PedMIDAS scores was found (p = 0.007, rho = 0.39). After including other putative predictors of migraine disability (age, body mass index, time since onset of migraine) in a multiple regression analysis, only the scores on the CARATkids remained a significant independent variable correlated with PedMIDAS scores (p = 0.001; R = 0.55; R2 = 0.30). Conclusions Current allergic rhinoconjunctivitis is related to enhanced disability caused by headache in childhood migraine.

ABSTRACT Migraine is a chronic condition with complex pathophysiology. Although immunologic disturbances have been linked to migraine, only few attempts have been made to assess the possibility of allergic rhinitis as a worsening factor of migraine in adults. Objective This survey aimed to compare migraine disability between adult migraineurs with and without current allergic rhinitis. Methods This cross-sectional study comprised 118 adult migraineurs who were consecutively assisted at an outpatient clinic. After ordinary neurological evaluation, participants were evaluated for headache disability using the Migraine Disability Assessment (MIDAS). The presence of current allergic rhinitis, allergic rhinoconjunctivitis and seasonal allergic rhinitis was scored for each participant according to the International Study of Asthma and Allergies in questionnaire. Results There was no significant difference between the MIDAS scores of those with current allergic rhinitis, allergic rhinoconjunctivitis, or seasonal allergic rhinitis and nonatopic migraineurs. The disability caused by allergic symptoms also did not influence the MIDAS scores of patients with allergic rhinitis. The frequency of headache days during the last three months was higher in the subset of patients without allergic rhinitis (median and interquartile range 12 [8–19.2] vs. 8 [4–14]; p = 0.03). Conclusions Our results suggest that current allergic rhinitis, allergic rhinoconjunctivitis, and seasonal allergic rhinitis are not related to headache disability in adults with episodic migraine.

Aim of this study is to evaluate if migraine, daily chronic headache and fibromyalgia in the same patient can be considered as an evolutive continuum of non organic chronic pain. Therefore, migraine, daily chronic headache and fibromyalgia should be considered the expression of chronic antinociceptive system alteration.

In the present study, 23 patients with migraine without aura were monitored during a migraine attack. Plasma levels of interleukin (IL)-4, IL-5, IL-10, and interferon-gamma were measured by enzyme-linked immunosorbent assay techniques. Interestingly, we observed low to undetectable IL-5 and IL-4 levels, whereas high IL-10 levels were seen in 52.2% of the patients. Interferon-gamma plasma levels were undetectable in all patients. After treatment with sumatriptan, 10 patients showed a subsequent decrease in IL-10 and an increase in both IL-4 and IL-5 plasma levels. Although these findings are derived from a limited number of patients, the apparent return to the IL-4 and IL-5 cytokine profile observed during the interictal period leads us to speculate that a preferential enhancement of TH2-type cytokine production may contribute to the pathogenesis of migraine.

This observational study was designed to examine the pattern of sumatriptan use in patients with cluster headache using more than the recommended daily dose of subcutaneously injected (s.c.) sumatriptan. Thirteen patients suffering from episodic cluster headache were asked to record the characteristics of their attacks and drug intake for 1 year. All reported a high daily frequency of attacks (more than 3 per day) and the related overuse of s.c. sumatriptan. The results show that the overall incidence of adverse events among patients receiving sumatriptan injections for the treatment of cluster headache is low. The extended administration of this drug in episodic cluster headache did not result in tolerance problems or tachyphylaxis. Only 4 patients experienced minor adverse events and recovered more slowly than the others. They suffered from migraine without aura and cluster headache, and showed a family history of migraine. Even though they must be viewed with caution, due to the observational nature of the study and the low number of patients included, these results suggest that the profile of sumatriptan may differ in cluster headache compared with migraine.

Thirty-two patients suffering from migraine without aura were assessed during in interictal period to evaluate the contribution of cytokines to the pathophysiology of migraine. To this end, plasma levels of IFN-gamma, IL-4, IL-5, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA) techniques. Plasma levels of both IFN-gamma and IL-10 were not increased in the patients and did not differ significantly from healthy controls. Of interest, we observed a strong increase of IL-5 levels in 84.3% as well as increased IL-4 levels in 37.5% of patients with migraine without aura. These results suggests a preferential enhancement of some Th2-type cytokines, and may support the growing arguments of an immunoallergic mechanism in the pathophysiology of migraine.

Our study examines the effectiveness of an educational approach to migraine patients. A course in migraine education was set up for 30 patients suffering from this disease; meetings were structured taking into consideration specific educational aims, with parameters evaluated before the course, at the end of the course and at a 3-month follow-up. The results, particularly the increase in the migraineurs' knowledge of their disease and the decrease in the use of symptomatic drugs, suggest the effectiveness of the course. Furthermore, our study suggests that there is a need to build educational processes into therapeutic protocols, as they enable patients to manage their chronic diseases more correctly.

The authors, in order to evaluate the important role of gastrointestinal dysfunction during the migraine attack, have studied 53 patients with migraine without aura during the asymptomatic stage between attacks. Patients were examined functionally with a pH meter test of the gastroesophageal tract over 24 hours and morphologically with esophagogastroduodenoscopy. The results of this study point out that in a high percentage of patients with migraine, both evaluations are normal. The authors suggest the possibility of detecting, even hypothetically, an alteration of the common neurotransmitter substrate in the origin of migraine attacks and accompanying symptoms.

The authors describe three patients with episodic cluster headache whose attacks were all treated with subcutaneous sumatriptan. The patients described had a high frequency of attacks (more than two per day); therefore, far higher dosage of the drug was taken than commonly used in cluster headache. The patients did not experience any particular side effects, neither during the treatment period nor on abrupt withdrawal of the drug. Moreover, neither tachyphylaxis nor addiction were observed. The authors point out both the efficacy of sumatriptan, confirmed in all the treated attacks, and its safety even at higher dosages than recommended.

This italian multicentre, double blind, parallel groups study compared the efficacy, safety and tolerability of oral sumatriptan, given as new film-coated tablet, with placebo in the acute treatment of migraine. 88 Patients received placebo and 162 patients received sumatriptan 100 mg (plus an optional dose 2 h later if the headache persisted plus a further optional dose for recurrence within 24 h). Sumatriptan was significantly more effective than placebo at releiving headache at 2 h (51% versus 31%, P = 0.003) and 4 h (71% versus 35%, P < 0.001). Fewer sumatriptan-treated patients required a second dose compared with placebo-treated patients (49% versus 74%, P < 0.001). Sumatriptan was more effective than placebo at relieving nausea, vomiting and photophobia/phonophobia. Few patients were evaluable for treatment of headache recurrence, and statistical analysis was not possible. More sumatriptan-treated patients than placebo-treated patients reported adverse events (29% versus 16%) but the difference was not statistically significant. More of these events were mild to moderate in severity, of short duration and resolved without treatment. Sumatriptan had no clinically significant effect on blood pressure, heart rate, electrocardiogram or laboratory test results. It is concluded that oral sumatriptan 100 mg, given as a film-coated, tablet, provides an effective and well-tolerated acute treatment for migraine.

Forty patients aged 65-80 with minor-medium signs of brain aging were treated for 6 months with daily 90 mg doses of nimodipine. Treatment was well tolerated in that the minor side effects reported by a few of the patients never required withdrawal of the drug. Treatment proved useful, as shown by a variety of mental tests, in 69.5% of cases. In 20% conditions remained unchanged and in 9.5% further deterioration was observed. The authors conclude that nimodipine may be considered a useful therapeutic resource for phenomena of brain aging.