First known case of human bertiellosis in a child in Paraná, Brazil / Primeiro caso conhecido de bertielose humana em uma criança no Paraná, Brasil

ABSTRACT Objective: To describe the first known case of human Bertiellosis in Paraná (Brazil). Case description: A 6-year-old male residing in the Brazilian state of Paraná was suffering from intermittent nonspecific abdominal pain and abdominal distension, associated with expulsion of live tapeworms in his feces for 7 months. He had a history of interaction with monkeys on an island. His first feces analysis was inconclusive, with an initial hypothesis of an atypical Taenia. However, after additional research, the parasitologist identified pregnant proglottids of Bertiella sp. The patient was initially treated with an unknown dosage of albendazole and nitazoxanide, as it was believed he had been infected with Taenia sp. Since the symptoms persisted, praziquantel 10 mg/kg was prescribed without further proglottids elimination. Comments: Human Bertiellosis is a rare zoonosis, with less than one hundred cases reported. However, it is a cause of chronic abdominal pain and should be kept as a differential diagnosis, especially in cases reporting recurrent tapeworm expulsion in feces and refractory treatment with albendazole.

RESUMO Objetivo: Descrever o primeiro caso conhecido de bertielose humana no Paraná, Brasil. Descrição do caso: Criança de seis anos do sexo masculino, residente no Paraná, Brasil, apresentava dor abdominal inespecífica intermitente e distensão abdominal, associadas à expulsão de helmintos vivos em suas fezes havia sete meses. Tinha um histórico de interação com macacos em uma ilha. Sua primeira análise de fezes foi inconclusiva, com hipótese inicial de uma Taenia atípica. No entanto, após pesquisas adicionais, o parasitologista identificou proglótides gravídicas de Bertiella sp. O paciente foi inicialmente tratado com uma dosagem desconhecida de albendazol e nitazoxanida, pois se acreditava que havia sido infectado por Taenia sp. Diante da persistência dos sintomas, foi prescrito praziquantel 10 mg/kg, sem mais eliminação de proglótides. Comentários: A bertielose humana é uma zoonose rara, com menos de cem casos relatados. No entanto, é uma causa de dor abdominal crônica e deve ser mantida como diagnóstico diferencial, principalmente nos casos que relatam expulsão recorrente de helmintos nas fezes e que são refratários ao tratamento com albendazol.

First known case of human bertiellosis in a child in Paraná, Brazil.

OBJECTIVE: To describe the first known case of human Bertiellosis in Paraná (Brazil). CASE DESCRIPTION: A 6-year-old male residing in the Brazilian state of Paraná was suffering from intermittent nonspecific abdominal pain and abdominal distension, associated with expulsion of live tapeworms in his feces for 7 months. He had a history of interaction with monkeys on an island. His first feces analysis was inconclusive, with an initial hypothesis of an atypical Taenia. However, after additional research, the parasitologist identified pregnant proglottids of Bertiella sp. The patient was initially treated with an unknown dosage of albendazole and nitazoxanide, as it was believed he had been infected with Taenia sp. Since the symptoms persisted, praziquantel 10 mg/kg was prescribed without further proglottids elimination. COMMENTS: Human Bertiellosis is a rare zoonosis, with less than one hundred cases reported. However, it is a cause of chronic abdominal pain and should be kept as a differential diagnosis, especially in cases reporting recurrent tapeworm expulsion in feces and refractory treatment with albendazole.

TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation.

TIGIT is an inhibitory receptor expressed on lymphocytes and can inhibit T cells by preventing CD226 co-stimulation through interactions in cis or through competition of shared ligands. Whether TIGIT directly delivers cell-intrinsic inhibitory signals in T cells remains unclear. Here we show, by analysing lymphocytes from matched human tumour and peripheral blood samples, that TIGIT and CD226 co-expression is rare on tumour-infiltrating lymphocytes. Using super-resolution microscopy and other techniques, we demonstrate that ligation with CD155 causes TIGIT to reorganise into dense nanoclusters, which coalesce with T cell receptor (TCR)-rich clusters at immune synapses. Functionally, this reduces cytokine secretion in a manner dependent on TIGIT's intracellular ITT-like signalling motif. Thus, we provide evidence that TIGIT directly inhibits lymphocyte activation, acting independently of CD226, requiring intracellular signalling that is proximal to the TCR. Within the subset of tumours where TIGIT-expressing cells do not commonly co-express CD226, this will likely be the dominant mechanism of action.

Antibody Afucosylation Augments CD16-Mediated Serial Killing and IFNγ Secretion by Human Natural Killer Cells.

One mechanism by which monoclonal antibodies (mAb) help treat cancer or autoimmune disease is through triggering antibody-dependent cellular cytotoxicity (ADCC) via CD16 on Natural Killer (NK) cells. Afucosylation is known to increase the affinity of mAbs for CD16 on NK cells and here, we set out to assess how mAb afucosylation affects the dynamics of NK cell interactions, receptor expression and effector functions. An IgG1 version of a clinically important anti-CD20 mAb was compared to its afucosylated counterpart (anti-CD20-AF). Opsonization of CD20-expressing target cells, 721.221 or Daudi, with anti-CD20-AF increased NK cell cytotoxicity and IFNγ secretion, compared to anti-CD20. The afucosylated mAb also caused a more rapid and greater loss of CD16 from NK cell surfaces. Loss of CD16 has recently been shown to be important for NK cell detachment and sequential engagement of multiple target cells. Here, live-cell time-lapse microscopy of individual cell-cell interactions in an aqueous environment and a three-dimensional matrix, revealed that anti-CD20-AF induced more rapid killing of opsonized target cells. In addition, NK cells detached more quickly from target cells opsonized with anti-CD20-AF compared to anti-CD20, which increased engagement of multiple targets and enabled a greater proportion of NK cells to perform serial killing. Inhibition of CD16 shedding with TAPI-0 led to reduced detachment and serial killing. Thus, disassembly of the immune synapse caused by loss of cell surface CD16 is a factor determining the efficiency of ADCC and antibody afucosylation alters the dynamics of intercellular interactions to boost serial killing.

Advances in Extraction Methods to Recover Added-Value Compounds from Seaweeds: Sustainability and Functionality.

Seaweeds are a renewable natural source of valuable macro and micronutrients that have attracted the attention of the scientists in the last years. Their medicinal properties were already recognized in the ancient traditional Chinese medicine, but only recently there has been a considerable increase in the study of these organisms in attempts to demonstrate their health benefits. The extraction process and conditions to be used for the obtention of value-added compounds from seaweeds depends mainly on the desired final product. Thermochemical conversion of seaweeds, using high temperatures and solvents (including water), to obtain high-value products with more potential applications continues to be an industrial practice, frequently with adverse impact on the environment and products' functionality. However more recently, alternative methods and approaches have been suggested, searching not only to improve the process performance, but also to be less harmful for the environment. A biorefinery approach display a valuable idea of solving economic and environmental drawbacks, enabling less residues production close to the much recommended zero waste system. The aim of this work is to report about the new developed methods of seaweeds extractions and the potential application of the components extracted.

Estudo epidemiológico da associação entre fatores de risco e excisões incompletas no câncer de pele / An epidemiological study of the association between risk factors and skin cancer incomplete excisions

Introdução: A crescente incidência de câncer de pele leva a um alto número de procedimentos cirúrgicos em todo o mundo. O principal objetivo do tratamento cirúrgico do câncer de pele é sua excisão completa, preservando a função e o melhor resultado estético. A ressecção inicial incompleta pode resultar em recorrências e danos graves. O objetivo é analisar os fatores de risco para margens positivas no seguimento de lesões cutâneas removidas cirurgicamente, por um ano, no departamento de cirurgia plástica do Hospital Royal Perth. Métodos: Foi analisado um levantamento de amostras histopatológicas de 947 pacientes operados. Todos os pacientes com excisão incompleta confirmada (EI) foram submetidos a uma segunda cirurgia ou até mesmo a uma terceira vez. Resultados: No total, 947 lesões foram encontradas, 6,6% das cirurgias tiveram margens comprometidas, com distribuição histopatológica de 75% de carcinoma basocelular (CBC), 21,4% de carcinoma de células escamosas (CCE) e 3,6% de outras lesões. A relação da presença de margens cirúrgicas comprometidas entre o CCE, quando comparada ao CBC, leva a um risco relativo de 2,8 e um valor p de 0,041, sugerindo que o primeiro é um fator de risco para a presença de margens cirúrgicas comprometidas. Para o estadiamento, a necessidade de uma segunda abordagem cirúrgica esteve presente em 61,29% dos pacientes, 20,9% estavam em observação, 3,2% estavam ausentes do serviço, 8% foram diretamente à quimioterapia ou radioterapia e 6,4% remarcaram a cirurgia. Conclusão: O conhecimento dos fatores de risco para margens positivas é necessário para que o cirurgião entenda o prognóstico e o acompanhamento de cada paciente.

Introduction: The increasing incidence of skin cancer leads to a high number of surgical procedures worldwide. The surgical treatment of skin cancer's main objective is its complete excision, preserving the function and the best aesthetic result. Incomplete initial resection can result in recurrences and major damage. The objective is to analyze the risk factors for positive margins in the follow-up of cutaneous lesions surgically removed, for one year, in the plastic surgery department of the Royal Perth Hospital. Methods: A survey of histopathological samples from 947 operated patients was analyzed. All patients with confirmed incomplete excision (IE) underwent a second surgery or even a third time. Results: In total, 947 lesions were found, 6.6% of surgeries had compromised margins, with a histopathological distribution of 75% of basal cell carcinoma, 21.4% of squamous cell carcinoma, and 3.6% of other lesions. The relation of the presence of compromised surgical margins between the SCC, compared to BCC, leads to a relative risk of 2.8 and a p-value of 0.041, which suggests that the SCC is a risk factor for the presence of compromised surgical margins. For staging, the need for a second surgical approach was present in 61.29% of the patients, 20.9% were under observation, 3.2% were absent from the service, 8% went directly to chemotherapy or radiotherapy, and 6.4% rescheduled the surgery. Conclusion: Knowledge of risk factors for positive margins is necessary for the surgeon to understand the prognosis and monitoring of each patient.

A análise estatística do risco relativo entre a percepção corporal e o interesse em realizar cirurgias plásticas / Statistical analysis of the correlation between body perception and desire to undergo plastic surgery

Introdução: A maior exposição nas mídias sociais gerou uma maior autoavaliação e a consequente busca pela aparência ideal. Dessa forma, a motivação de utilizar métodos cirúrgicos para melhora da aparência física cresce exponencialmente. Métodos: Foram distribuídos 3 questionários para 64 alunos: "Body Shape Questionnaire" (BSQ), "Escala de Investimento Corporal" (EIC) e "Questionário de interesse em cirurgias plásticas futuras" (QICPF). A partir da tabulação dos dados, foi realizada a análise estatística quantitativa por meio do teste qui-quadrado e risco relativo, para estudo objetivo e cruzado dos questionários. Resultados: O BSQ médio foi de 98,04, a relação de maior pontuação nesse questionário com QIRCP apresentou Risco Relativo (RR=2,41 e p=0,002). A média do EIC foi de 91 e, quando relacionado com QIRCP, não se apresentou estatisticamente relevante (RR=0,94 e p=0,83). Quanto à pergunta objetiva de satisfação corporal e o QIRCP, nota-se que a maior insatisfação corporal é fator de risco para querer realizar mais cirurgias plásticas (RR=1,94 e p=0,003) e as mulheres apresentam-se como o gênero de maior interesse (RR=3,01 e p=0,01). Conclusões: A análise estatística para a população estudada sugere que BSQ elevado, insatisfação corporal e mulheres apresentam maior interesse em realizar cirurgia plástica.

Introduction: Social media has generated an increase in selfevaluation and the search for the ideal appearance. Thus, the motivation to use surgical methods to improve physical appearance has grown exponentially. Methods: The Body Shape Questionnaire (BSQ), Body Investment Scale (BIS), and Questionnaire of Interest in Future Plastic Surgeries (QIFPS) were administered to 64 students. Once the data were collected, a quantitative statistical analysis using the chi-square test and relative risk (RR) was conducted. Results: The BSQ mean was 98.04, the relation of greater punctuation in this questionnaire with QIFPS presented an RR of 2.41; (p = 0.002). The mean BIS score was 91; compared to the QIFPS, it was not statistically relevant (RR = 0.94; p = 0.83). Regarding the objective question of body satisfaction and QIFPS, highest body dissatisfaction was a risk factor for desiring more plastic surgeries (RR = 1.94; p = 0.003), as was female sex (RR = 3.01; p = 0.01). Conclusions: Our findings suggest that a high BSQ score, high body dissatisfaction, and female sex are risk factors for a desire to undergo plastic surgery.

Shedding of CD16 disassembles the NK cell immune synapse and boosts serial engagement of target cells.

Natural Killer (NK) cells can engage multiple virally infected or tumor cells sequentially and deliver perforin for cytolytic killing of these targets. Using microscopy to visualize degranulation from individual NK cells, we found that repeated activation via the Fc receptor CD16 decreased the amount of perforin secreted. However, perforin secretion was restored upon subsequent activation via a different activating receptor, NKG2D. Repeated stimulation via NKG2D also decreased perforin secretion, but this was not rescued by stimulation via CD16. These different outcomes of sequential stimulation could be accounted for by shedding of CD16 being triggered by cellular activation. The use of pharmacological inhibitors and NK cells transfected to express a noncleavable form of CD16 revealed that CD16 shedding also increased NK cell motility and facilitated detachment of NK cells from target cells. Disassembly of the immune synapse caused by CD16 shedding aided NK cell survival and boosted serial engagement of target cells. Thus, counterintuitively, shedding of CD16 may positively impact immune responses.

Hearing, language, motor and social skills in the child development: a screening proposal / Habilidades auditivas, de linguagem, motoras e sociais no desenvolvimento infantil: uma proposta de triagem

ABSTRACT Purpose: to analyze the hearing, language, motor and social skills of children and propose a screening of child development. Methods: 129 preschool children of both sexes, aged between three and six years old, enrolled in educational institutions and 25 teachers of kindergarten from public and private institutions, with no history of hearing disorders, with type A tympanometric curves and the presence of acoustic reflexes participated. For the children, the neuropsychomotor test, Denver II, and the evaluation of sound localization and temporal ordination of three verbal and non-verbal sounds were applied. For the educators responsible for the children, the Scale of Auditory Behaviors (SAB), was used. Results: most participants with normal SAB presented hearing abilities or standard Denver II; while in the amended SAB group, most participants presented alterations in Denver II or in the auditory abilities tests. It was found, also, that part of the children with standard Denver II were pointed, by the educators, as misbehaving in SAB. Conclusion: the combination of the findings of the Denver II, hearing tests of sound localization and temporal ordination and the SAB Scale is useful in the characterization of child development and, thus, the use of these three instruments for screening in this age group is recommended.

RESUMO Objetivo: analisar as habilidades auditivas, de linguagem, motoras e sociais de crianças e propor uma triagem do desenvolvimento infantil. Métodos: participaram 129 pré-escolares, de ambos os sexos, com idades entre três e seis anos, matriculadas em instituições de educação infantil e 25 educadores do ensino infantil oriundos de instituições públicas e particulares. Todas as crianças com curvas timpanométricas tipo A e presença de reflexos acústicos. Nas crianças, aplicou-se o teste de desenvolvimento neuropsicomotor, Denver II, e a avaliação da localização sonora e da ordenação temporal de três sons verbais e não verbais. Com as educadoras, foi aplicado a Escala SAB. Resultados: verificou-se que a grande maioria dos participantes com SAB normal apresentaram habilidades auditivas ou Denver II normal; enquanto no grupo de SAB alterado, grande parte dos participantes apresentou alteração no Denver II ou nos testes de habilidades auditivas. Foi constatado, ainda, que parte das crianças com Denver II normal foram apontados, pelos educadores, como com comportamento inadequado no SAB. Conclusão: a combinação entre os achados do Denver II, de testes auditivos de localização sonora e ordenação temporal e a Escala SAB são úteis na caracterização do desenvolvimento infantil, assim, recomenda-se o uso dos três instrumentos como triagem.

Hope or hype in the treatment of schizophrenia - what's the role of the physician?

According to the experience of people with schizophrenia, their psychiatrists' attitude towards the outcome of their illness is lacking in hope, which directly affects mutual faith in treatment. Here we discuss the scientific basis of hope and show its instrumental role in optimising the best treatment strategies for schizophrenia. Declaration of interest R.A.B has received honoraria for educational input and non-financial support from Ache; honoraria for educational input from Lundbeck; grants, honoraria for educational input and non-financial support from Janssen; all outside the submitted work. G.E.M.G. has received honoraria for educational input and non-financial support from Janssen outside the submitted work. G.M. reports support from Janssen-Cilag, outside the submitted work, and is an employee at Janssen-Cilag. S.S. has received grants and honoraria for educational input from EnVivo Pharmaceuticals, Takeda, AbbVie and Janssen Pharmaceuticals, outside the submitted work.

Effects of acute physical exercise in the light phase of sleep in rats with temporal lobe epilepsy.

OBJECTIVE: Our aim was to investigate the influence of an acute exercise session on sleep pattern in rats with temporal lobe epilepsy (TLE). METHODS: Twenty male Wistar rats were randomly assigned to 4 groups: control (C); acute exercise (EX); epilepsy (E) and epilepsy acute exercise (EEX). Two sleep electrocorticography recordings were performed during the light phase [baseline and day 2 (after the acute physical exercise session)]. After baseline recording, the exercise groups (EX and EEX) were submitted to an exercise session on a motor-driven treadmill at 12m/min for 30min. Twelve hours later, the rats were submitted to the second sleep recording. RESULTS: At baseline, the E group showed a higher wakefulness and a lower Total sleep time, Slow Wave Sleep and REM sleep compared with the C group. After acute exercise, there was an increase in Total sleep time and Slow Wave Sleep and a decrease of wakefulness in EEX (+11.10%, +20.29% and -11.25%, respectively) and EX (+5.20%, +11.60% and -8.12%, respectively) groups. CONCLUSION: These findings suggest that acute physical exercise positively impacts the sleep pattern of rats with TLE, inducing a more consolidated sleep.

The effects of sleep deprivation on microRNA expression in rats submitted to pilocarpine-induced status epilepticus.

Epilepsy is a neurological disorder with significant prevalence and the individuals affected by this disease have a great probability of occurrence of a lethal phenomenon known as Sudden Unexpected Death in Epilepsy (SUDEP). SUDEP occurs mainly during the night and probably during sleep. The pathophysiological mechanisms involved in this lethal phenomenon are still obscure and new evidences that could corroborate in this area are warranted. Thus, the aim of the present study was to evaluate the effect of sleep deprivation in the expression of microRNA (miRNA) in the frontal cortex and heart tissues of adult male rats after 50days of saline (SAL) or pilocarpine-induced status epilepticus (PILO). Initially 389 miRNA expressions were evaluated between SAL and PILO groups by microarray. Subsequently, 3 differentially expressed miRNAs of each tissue were investigated after total sleep deprivation (TSD 6h) and paradoxical sleep deprivation (PSD 24h). Still, it was analyzed that the effects of sleep rebound with equivalent duration of PSD and TSD. There was a significant increase of miR-146a expression, an important inflammatory modulator in the frontal cortex of PILO rats when compared to SAL animals. Animals treated with pilocarpine were affected by TSD (through overexpression of miRNAs related to inflammatory process) and these changes were maintained even after a sleep window of 6h. In contrast, miRNAs associated with heart diseases were down-regulated in PSD rebound, suggesting a possible restoration of homeostasis in cardiovascular system of SAL and PILO groups.

Modafinil ameliorates cognitive deficits induced by maternal separation and sleep deprivation.

Animals exposed to an early adverse event may be more susceptible to a second source of stress later in life, and these stressors may have additive deleterious effects. Sleep deprivation is known to be a stressor, affecting multiple body functions such as the cognition. Modafinil enhances working memory and attention in healthy non-sleep deprived subjects and in animal models of sleep deprivation. The first aim of the present study was to investigate the effects of maternal separation (MS) combined with paradoxical sleep deprivation (PSD) in adulthood on recognition memory in rats. Second, we aimed to evaluate whether the administration of modafinil would be able to ameliorate memory deficits induced by MS and PSD. Wistar rat pups were initially distributed into MS and handling (H) groups, with their litters standardized in 4 females and 4 males. In adulthood, the male rats were submitted to PSD or control condition, being redistributed afterwards in modafinil- or vehicle-treatment immediately after the training session of object recognition task. PSD did not potentiate the cognitive deficit due to MS. However, modafinil was able to recover memory impairments associated to PSD and also to MS in the neonatal period. This study demonstrates for the first time that modafinil ameliorates cognitive deficits associated to MS and to PSD in adulthood, independent from MS in the neonatal period.

Association between leisure time, physical activity, and mood disorder levels in individuals with epilepsy.

The aim of this study was to investigate the association between physical activity levels (occupational, sports, and leisure time activities), depression, anxiety, and epilepsy. The behavioral outcomes of individuals with epilepsy (E) were also compared with healthy control subjects (C). The sample included 31 individuals with epilepsy (12 with idiopathic generalized epilepsy and 19 with partial epilepsy) and 31 control subjects. Self-rating questionnaires were used to assess mood (State-Trait Anxiety Inventory and Beck Depression Inventory), anxiety, and depression as well as habitual physical activity. Patients with epilepsy were more severely impaired compared to control subjects in both mood questionnaires and presented higher levels of depression (35%), state anxiety (18%), and trait anxiety (12.6%) when compared to the C group. Although physical activity level did not differ significantly between groups, linear regression analyses showed that the physical activity leisure level predicted 31% of depression levels and 26% of anxiety levels in the E group. These data suggest that low levels of physical activity may be considered a risk factor for the development of depression and anxiety and can play an important role in the quality of life of individuals with epilepsy.

Changes in gene expression in the frontal cortex of rats with pilocarpine-induced status epilepticus after sleep deprivation.

Sleep and epilepsy present a bidirectional interaction. Sleep complaints are common in epilepsy, and sleep deprivation may provoke seizures. However, the mechanisms underlying this relationship are unknown. Thus, this study investigated the effects of paradoxical sleep deprivation (PSD24h) and total sleep deprivation (TSD6h) in the expression of genes related to reactive oxygen species and nitric oxide production in the frontal cortex of a rodent model of temporal lobe epilepsy (PILO). The data show that PILO rats had increased NOX-2 expression and decreased SOD expression, independent of sleep. Higher NOX-2 expression was observed only in PILO rats subjected to the control condition and TSD6h. Also, eNOS and DDAH1 were increased in the PILO group submitted to TSD6h. Moreover, CAT expression in the frontal cortex of PILO rats submitted to PSD24h was reduced compared to that of PILO rats that were not sleep-deprived. The molecular changes found in the frontal cortex of PILO rats following sleep deprivation suggest a mechanism via oxidative stress.

Sleep and epilepsy: exploring an intriguing relationship with a translational approach.

The relationship between sleep and epilepsy has been well established. There is a high prevalence of sleep disturbances in epilepsy, which are associated with a decreased quality of life of individuals with epilepsy. In view of this fact, preclinical research is necessary to address many gaps in knowledge. For instance, it is well known that sleep deprivation can trigger seizures; however, this is a complex pathophysiological event. In this context, there are many valuable animal models of epilepsy that reproduce clinical symptoms and can be used. Investigations using animal models that simulate clinical epilepsy are imperative. Furthermore, preclinical studies that reveal mechanisms related to sleep-epilepsy interactions are very important. Results of such studies can, in turn, improve the understanding of epilepsy itself and can be useful in developing new antiepileptic drugs and preventive measures to control seizures. Preclinical research should be performed using a translational framework with experimental designs that can lead to advances in the quality of life of individuals with epilepsy. In view of the fact that more than 50 million of people are affected by epilepsy around the world, understanding the relationship between sleep and epilepsy is imperative.