Systematic review and meta-analysis of the visual mismatch negativity in schizophrenia.

Mismatch negativity (MMN) is an event-related potential component automatically elicited by events that violate predictions based on prior events. To elicit this component, researchers use stimulus repetition to induce predictions, and the MMN is obtained by subtracting the brain response to rare or unpredicted stimuli from that of frequent stimuli. Under the Predictive Processing framework, one increasingly popular interpretation of the mismatch response postulates that MMN represents a prediction error. In this context, the reduced MMN amplitude to auditory stimuli has been considered a potential biomarker of Schizophrenia, representing a reduced prediction error and the inability to update the mental model of the world based on the sensory signals. It is unclear, however, whether this amplitude reduction is specific for auditory events or if the visual MMN reveals a similar pattern in schizophrenia spectrum disorder. This review and meta-analysis aimed to summarise the available literature on the vMMN in schizophrenia. A systematic literature search resulted in 10 eligible studies that resulted in a combined effect size of g = -.63, CI [-.86, -.41], reflecting lower vMMN amplitudes in patients. These results are in line with the findings in the auditory domain. This component offers certain advantages, such as less susceptibility to overlap with components generated by attentional demands. Future studies should use vMMN to explore abnormalities in the Predictive Processing framework in different stages and groups of the SSD and increase the knowledge in the search for biomarkers in schizophrenia.

Case Report: Diffuse Polymicrogyria Associated With a Novel ADGRG1 Variant.

Pathogenic variants of the ADGRG1 gene are associated with bilateral frontoparietal polymicrogyria, defined radiologically by polymicrogyria with an anterior-posterior gradient, pontine and cerebellar hypoplasia and patchy white matter abnormalities. We report a novel homozygous ADGRG1 variant with atypical features. The patient presented at 8 months of age with motor delay, esotropia, hypotonia with hyporeflexia and subsequently developed refractory epilepsy. At the last assessment, aged 12 years, head control, sitting and language were not acquired. Magnetic resonance imaging revealed diffuse polymicrogyria with relative sparing of the anterior temporal lobes, without an anterior-posterior gradient, diffuse hypomyelination and pontine and cerebellar hypoplasia. A panel targeting brain morphogenesis defects yielded an unreported homozygous ADGRG1 nonsense variant (dbSNP rs746634404), present in the heterozygous state in both parents. We report a novel ADGRG1 variant associated with diffuse polymicrogyria without an identifiable anterior-posterior gradient, diffuse hypomyelination and a severe motor and cognitive phenotype. Our case highlights the phenotypic diversity of ADGRG1 pathogenic variants and the clinico-anatomical overlap between recognized polymicrogyria syndromes.

Acute Axonal Motor Neuropathy With Completely Reversible Conduction Failure-Is It Really Axonal?

ABSTRACT: We present the case of a 24-year-old man with a 3-day history of limb weakness and flaccid tetraparesis, hyporreflexia, and gait difficulties (Hughes grade 3) in the examination. Electromyography at presentation revealed severe amplitude reduction in distal compound muscle action potentials of several nerves without features of demyelination, fulfilling electrodiagnostic criteria for acute axonal motor neuropathy. The patient was treated with immunoglobulin and recovered completely 21 days after symptom onset. Electromyography at this timepoint showed normalization of compound muscle action potentials without increased temporal dispersion. The electroclinical recovery profile in this patient is consistent with reversible conduction failure in distal nerve segments in detriment of axonal degeneration. Thus, it is an "axonal motor neuropathy" where axonopathy is unlikely, giving strength to the concept of "nodopathies/paranodopathies."

Etiology and Clinical Impact of Interictal Periodic Discharges on the Routine Outpatient Scalp EEG.

PURPOSE: Periodic discharges (PDs) are common in acute structural or metabolic brain lesions, but their occurrence during follow-up of epileptic patients in an outpatient setting is rare. Aim of this article was to study whether PDs on the routine outpatient scalp EEG of patients with epilepsy, as compared with nonperiodic epileptiform discharges, are associated with drug refractoriness and the decompensation of epilepsy and particular etiologies. METHODS: A retrospective case-control study. EEG reports were screened for PDs and their variants. The inclusion criteria were as follows: a diagnosis of epilepsy, epileptogenic lesion on imaging, or a normal 3-T MRI. Inpatient EEGs or EEGs performed in patients with acute cerebral lesions were excluded. Age- and sex-matched controls presenting with other epileptiform EEG abnormalities were selected, and similar selection criteria were applied. RESULTS: Forty-one patients with PDs and 82 controls were selected. There were no significant differences between the cases and controls in the rates of epilepsy decompensation at the time of EEG collection or drug refractoriness. Stroke, hippocampal sclerosis, and malformations of cortical development were the most frequent etiologies, without significant differences between the groups. CONCLUSIONS: By performing a case-control study, the authors have shown that PDs are not a marker of epilepsy decompensation and drug refractoriness and that the finding of PDs is not suggestive of particular epilepsy etiologies, when compared with other epileptiform abnormalities.

Isolated parkinsonism is an atypical presentation of GRN and C9orf72 gene mutations.

INTRODUCTION: A phenotype of isolated parkinsonism mimicking Idiopathic Parkinson's Disease (IPD) is a rare clinical presentation of GRN and C9orf72 mutations, the major genetic causes of frontotemporal dementia (FTD). It still remains controversial if this association is fortuitous or not, and which clinical clues could reliably suggest a genetic FTD etiology in IPD patients. This study aims to describe the clinical characteristics of FTD mutation carriers presenting with IPD phenotype, provide neuropathological evidence of the mutation's causality, and specifically address their "red flags" according to current IPD criteria. METHODS: Seven GRN and C9orf72 carriers with isolated parkinsonism at onset, and three patients from the literature were included in this study. To allow better delineation of their phenotype, the presence of supportive, exclusion and "red flag" features from MDS criteria were analyzed for each case. RESULTS: Amongst the ten patients (5 GRN, 5 C9orf72), seven fulfilled probable IPD criteria during all the disease course, while behavioral/language or motoneuron dysfunctions occurred later in three. Disease duration was longer and dopa-responsiveness was more sustained in C9orf72 than in GRN carriers. Subtle motor features, cognitive/behavioral changes, family history of dementia/ALS were suggestive clues for a genetic diagnosis. Importantly, neuropathological examination in one patient revealed typical TDP-43-inclusions without alpha-synucleinopathy, thus demonstrating the causal link between FTD mutations, TDP-43-pathology and PD phenotype. CONCLUSION: We showed that, altogether, family history of early-onset dementia/ALS, the presence of cognitive/behavioral dysfunction and subtle motor characteristics are atypical features frequently present in the parkinsonian presentations of GRN and C9orf72 mutations.

Recombinant Inga Laurina Trypsin Inhibitor (ILTI) Production in Komagataella Phaffii Confirms Its Potential Anti-Biofilm Effect and Reveals an Anti-Tumoral Activity.

Protease inhibitors have a broad biotechnological application ranging from medical drugs to anti-microbial agents. The Inga laurina trypsin inhibitor (ILTI) previously showed a great in vitro inhibitory effect under the adherence of Staphylococcus species, being a strong candidate for use as an anti-biofilm agent. Nevertheless, this is found in small quantities in its sources, which impairs its utilization at an industrial scale. Within this context, heterologous production using recombinant microorganisms is one of the best options to scale up the recombinant protein production. Thus, this work aimed at utilizing Komagataella phaffii to produce recombinant ILTI. For this, the vector pPIC9K+ILTI was constructed and inserted into the genome of the yeast K. phaffii, strain GS115. The protein expression was highest after 48 h using methanol 1%. A matrix-assisted laser desorption ionization⁻time-of-flight (MALDI⁻TOF) analysis was performed to confirm the production of the recombinant ILTI and its activity was investigated trough inhibitory assays using the synthetic substrate Nα-Benzoyl-D,L-arginine p-nitroanilide hydrochloride (BAPNA). Finally, recombinant ILTI (rILTI) was used in assays, showing that there was no significant difference between native and recombinant ILTI in its inhibitory activity in biofilm formation. Anti-tumor assay against Ehrlich ascites tumor (EAT) cells showed that rILTI has a potential anti-tumoral effect, showing the same effect as Melittin when incubated for 48 h in concentrations above 25 µg/mL. All together the results suggests broad applications for rILTI.

Traction of impacted canines in a skeletal Class III malocclusion: A challenging orthodontic treatment.

This case report describes the successful traction of 2 severely impacted canines. The patient, a 7-year-old girl, had good general health, nasal breathing, crossbite of the lateral incisors and canines, and a Class I molar relationship. The panoramic radiograph showed that the permanent canines were positioned above the roots of the lateral incisors, with the right canine in an accentuated inclination. The cephalometric analysis showed a skeletal Class III malocclusion with a predominance of horizontal growth. The Haas appliance associated with maxillary protraction was used during the first stage of treatment for 14 months. The second stage included the extraction of the deciduous molars, distal movement of the permanent molars to create space, and traction of the canines, and was associated with complete orthodontic treatment. The patient showed good esthetic and functional results at the end of treatment, verified by the stability over a period of 8 years after retention.

Production of a modified peptide clavanin in Pichia pastoris: cloning, expression, purification and in vitro activities.

Antimicrobial peptides are one of the most promising peptide-based drugs due to their enormous potential as novel biopharmaceuticals in both human and animal industries. In order to develop strategies to over produce such molecules, heterologous production of a modified version of clavanin A, here named clavanin MO (clavMO), was successfully achieved in the methylothopic yeast Pichia pastoris. ClavMO was fused to thioredoxin as a carrier protein and the construction was tested using two promoters, PAOX1 and PGAP, based on either induced or constitutive expression systems, respectively. After growth in 5 L Bioreactor, clavMO-thio was recovered and purified through size exclusion chromatography. Our findings show that both constitutive and inducible expression systems produce active clavMO fused to thioredoxin against both Gram-negative Klebsiella pneumoniae and Gram-positive Staphylococcus aureus microorganisms.

Female breast cancer mortality in Brazil and its regions.

OBJECTIVE: to analyze female breast cancer mortality trends in Brazil and its regions. METHODS: female breast cancer mortality in Brazil and its regions was analyzed using mortality data from the Ministry of Health's Mortality Information System and the National Cancer Institute between 1991 and 2010. The variables analyzed were. proportional mortality from female breast cancer in relation to total deaths in women, mortality rates of the five primary locations of the neoplasms most common in women, and mortality rates for female breast cancer: Linear regression models were estimated to analyze mortality trends: RESULTS: a growth in proportional mortality due to female breast cancer in Brazil and its regions was observed: In relation to the mortality rates for the five primary types of cancer, breast cancer persisted in first place in Brazil and its regions, except the North region, where cervical cancer was the most frequent: Rising female breast cancer mortality rates were observed for Brazil (p = 0.017), Northeastern (p < 0.001), North (p < 0.001) and the Mid-West (p = 0.001), regions, and declining rates for the Southeast region (p = 0.047), and stable rates for the South region. CONCLUSION: the results emphasize the importance of the disease in terms of public health in the country, reinforcing the need for early detection and appropriate treatment.

Female breast cancer mortality in Brazil and its regions / Câncer de mama feminino: análise da mortalidade no Brasil e regiões

Objective: to analyze female breast cancer mortality trends in Brazil and its regions. Methods: female breast cancer mortality in Brazil and its regions was analyzed using mortality data from the Ministry of Health's Mortality Information System and the National Cancer Institute between 1991 and 2010. The variables analyzed were. proportional mortality from female breast cancer in relation to total deaths in women, mortality rates of the five primary locations of the neoplasms most common in women, and mortality rates for female breast cancer: Linear regression models were estimated to analyze mortality trends: Results: a growth in proportional mortality due to female breast cancer in Brazil and its regions was observed: In relation to the mortality rates for the five primary types of cancer, breast cancer persisted in first place in Brazil and its regions, except the North region, where cervical cancer was the most frequent: Rising female breast cancer mortality rates were observed for Brazil (p = 0.017), Northeastern (p < 0.001), North (p < 0.001) and the Mid-West (p = 0.001), regions, and declining rates for the Southeast region (p = 0.047), and stable rates for the South region. Conclusion: the results emphasize the importance of the disease in terms of public health in the country, reinforcing the need for early detection and appropriate treatment. .

Objetivo: analisar a evolução da mortalidade por câncer de mama feminino nas regiões do Brasil. Métodos: foi analisada a mortalidade por câncer de mama feminino nas regiões do país, com dados do Sistema de Informações sobre Mortalidade do Ministério da Saúde e do Instituto Nacional do Câncer, entre 1991 e 2010. As variáveis analisadas foram: mortalidade proporcional por câncer de mama feminino em relação ao total de óbitos em mulheres; taxas de mortalidade das cinco localizações primárias das neoplasias mais frequentes em mulheres; e taxas de mortalidade por câncer de mama feminino. Modelos de regressão linear foram estimados para analisar a tendência de mortalidade. Resultados: foi observado o crescimento da mortalidade proporcional por câncer de mama feminino para as regiões brasileiras. Com relação às taxas de mortalidade das cinco localizações primárias de câncer mais frequentes, o câncer de mama é o que persiste em primeiro lugar nas regiões e no Brasil, com exceção da região Norte, onde o câncer de colo do útero foi o mais frequente. Observou-se tendência significativa de aumento das taxas de mortalidade por câncer de mama no Brasil (p = 0,017) e nas regiões Nordeste (p < 0,001), Norte (p < 0,001) e Centro-Oeste (p = 0,001), de diminuição na região Sudeste (p = 0,047) e estacionária na região Sul. Conclusão: os resultados encontrados enfatizam a importância da doença em termos de saúde pública no país, reforçando a necessidade da detecção precoce e do tratamento adequado. .