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Luisa Terroni,1 Edson Amaro Jr,2 Dan V Iosifescu,3 Patricia Mattos,4 Fabio I Yamamoto,5 Gisela Tinone,5 Adriana B Conforto,5 Matildes FM Sobreiro,1 Valeri D Guajardo,1 Mara Cristina S De Lucia,7 Ayrton C Moreira,6 Milberto Scaff,5 Claudia C Leite,2 Renerio Fraguas1 1Consultation-Liaison Psychiatry Group, Department and Institute of Psychiatry, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil; 2Department of Radiology, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil; 3Mood and Anxiety Disorders Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil; 5Department of Neurology, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil; 6Department of Medicine, University of São Paulo, School of Medicine, Ribeirão Preto, Brazil; 7Division of Psychology, Central Institute, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil Background: Anhedonia constitutes a coherent construct, with neural correlates and negative clinical impact, independent of depression. However, little is known about the neural correlates of anhedonia in stroke patients. In this study, we investigated the association of post-stroke anhedonia with salivary cortisol levels and stroke location and volume.Patients and methods: A psychiatrist administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition to identify anhedonia in 36 inpatients, without previous depression, consecutively admitted in a neurology clinic in the first month after a first-ever ischemic stroke. Salivary cortisol levels were assessed in the morning, evening, and after a dexamethasone suppression test. We used magnetic resonance imaging and a semi-automated brain morphometry method to assess stroke location, and the MRIcro program according to the Brodmann Map to calculate the lesion volume.Results: Patients with anhedonia had significantly larger diurnal variation (P-value =0.017) and higher morning levels of salivary cortisol (1,671.9±604.0 ng/dL versus 1,103.9±821.9 ng/dL; P-value =0.022), and greater stroke lesions in the parahippocampal gyrus (Brodmann area 36) compared to those without anhedonia (10.14 voxels; standard deviation ±17.72 versus 0.86 voxels; standard deviation ±4.64; P-value =0.027). The volume of lesion in the parahippocampal gyrus (Brodmann area 36) was associated with diurnal variation of salivary cortisol levels (rho=0.845; P-value =0.034) only in anhedonic patients.Conclusion: Our findings suggest that anhedonia in stroke patients is associated with the volume of stroke lesion in the parahippocampal gyrus and with dysfunction of the hypothalamic–pituitary–adrenal axis. Keywords: anhedonia, stroke, glucocorticoids, depression, hippocampus, parahippocampal

Malformations of cortical development (MCD) are structural anomalies that disrupt the normal process of cortical development. Patients with these anomalies frequently present with seizures, developmental delay, neurologic deficits, and cognitive impairment, resulting in a wide spectrum of neurologic outcomes. The severity and type of malformation, in addition to the genetic pathways of brain development involved, contribute to the observed variability. While neuroimaging plays a central role in identifying congenital anomalies in vivo, the precise definition and classification of cortical developmental defects have undergone significant transformations in recent years due to advances in molecular and genetic knowledge. The authors provide a concise overview of embryologic brain development, recently standardized nomenclature, and the categorization system for abnormalities in cortical development, offering valuable insights into the interpretation of their neuroradiologic patterns. © RSNA, 2024 Supplemental material is available for this article. The slide presentation from the RSNA Annual Meeting is available for this article.

Introduction: This bibliometric review analyzed the research trends and main characteristics of articles related to Electronic Apex Locators (EALs)., Methods: The search was conducted in November 2023 on the Web of Science Core Collection. Narrative and systematic reviews, observational and intervention studies, laboratory, and clinical studies were included. Two researchers selected the articles and extracted the number of citations, year of publication, journal, study design, theme, country, continent, institutions, author, and keywords. Collaborative networks were generated using the VOSviewer software. The relationship between data were determined by Spearman's correlation., Results: The search resulted in 374 articles, of which 294 were included. Most cited article had 175 citations. The most prevalent journal was the Journal of Endodontics (n = 84). The predominant study design was the laboratory-based (n = 223). The predominant theme was the EALs accuracy (n = 175). Piasecki L was the author with the highest number of articles (n = 11). Only 8.16% of the studies were conducted in deciduous teeth. The country with the most studies was Brazil (n = 46). Asia (n = 107) was the continent with the highest number of publications. There was a weak positive correlation between the number of citations and impact factor (rho = .294), and a strong negative correlation between citations and year of publication (rho = -.710)., Conclusions: The majority of articles were laboratory-based studies conducted on permanent teeth, focusing on the accuracy of EALs. Future studies should prioritize research on deciduous teeth, systematic reviews, and, notably, clinical trials., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS., Methods: We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS., Results: CMI prevalence was 11.8% in DS, 4.7% in controls, and 17.5% in sporadic AD. In DS, CMI increased in prevalence with age and the AD clinical continuum, was clustered in the parietal lobes, and was associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions., Discussion: In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype., Highlights: This is the first study to assess cortical microinfarcts (assessed with 3T magnetic resonance imaging) in adults with Down syndrome (DS). We studied the prevalence of cortical microinfarcts in DS and its relationship with age, the Alzheimer's disease (AD) clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition. The prevalence of cortical microinfarcts was 11.8% in DS and increased with age and along the AD clinical continuum. Cortical microinfarcts were clustered in the parietal lobes, and were associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The absence of a natural animal model is one of the main challenges in Alzheimer's disease research. Despite the challenges of using nonhuman primates in studies, these animals can bridge mouse models and humans, as nonhuman primates are phylogenetically closer to humans and can spontaneously develop AD-type pathology. The capuchin monkey, a New World primate, has recently attracted attention due to its skill in creating and using instruments. We analyzed one capuchin brain using structural 7 T MRI and performed a neuropathological evaluation of three animals. Alzheimer-type pathology was found in the two of the capuchins. Widespread β-amyloid pathology was observed, mainly in focal deposits with variable morphology and a high density of mature plaques. Notably, plaque-associated dystrophic neurites associated with disruption of axonal transport and early cytoskeletal alteration were frequently found. Unlike in other species of New World monkeys, cerebral arterial angiopathy was not the predominant form of β-amyloid pathology. Additionally, abnormal aggregates of hyperphosphorylated tau, resembling neurofibrillary pathology, were observed in the temporal and frontal cortex. Astrocyte hypertrophy surrounding plaques was found, suggesting a neuroinflammatory response. These findings indicate that aged capuchin monkeys can spontaneously develop Alzheimer-type pathology, indicating that they may be an advantageous animal model for research in Alzheimer's disease., (© 2024. The Author(s).)

Objective: Describe a safe surgery learning experience based on interactive escape room activities to engage and train nursing and physician teams., Design: This paper is based on the authors' participatory and observational experiences creating the Escape Room activity., Setting: Jundiai Regional Hospital, Surgical Department., Participants: Nurses, nurses assistant/technician and physicians and medical residents who work in the surgical center., Results: Results identified were promising, which broadens the perspective for further studies using the Escape Room activity in the hospital environment through structured research that can assess its implications for teaching and learning., Conclusion: We see opportunities for using the escape room activity as a teaching tool to implement other learning objectives., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Professional soccer athletes are exposed to repetitive head impacts and are at risk of developing chronic traumatic encephalopathy., Objective: To evaluate regional brain glucose metabolism (rBGM) and gray matter (GM) volume in retired soccer players (RSPs)., Methods: Male RSPs and age and sex-matched controls prospectively enrolled between 2017 and 2019 underwent neurological and neuropsychological evaluations, brain MRI and [18F]FDG-PET in a 3.0-Tesla PET/MRI scanner. Visual analysis was performed by a blinded neuroradiologist and a blinded nuclear physician. Regional brain glucose metabolism and GM volume were assessed using SPM8 software. Groups were compared using appropriate statistical tests available at SPM8 and R., Results: Nineteen RSPs (median [IQR]: 62 [50-64.5] years old) and 20 controls (60 [48-73] years old) were included. Retired soccer players performed worse on mini-mental state examination, digit span, clock drawing, phonemic and semantic verbal fluency tests, and had reduced rBGM in the left temporal pole (pFDR = 0.008) and the anterior left middle temporal gyrus (pFDR = 0.043). Semantic verbal fluency correlated with rBGM in the right hippocampus, left temporal pole, and posterior left middle temporal gyrus (p ≤ 0.042). Gray matter volume reduction was observed in similar anatomic regions but was less extensive and did not survive correction for multiple comparisons (pFDR ≥ 0.085). Individual [18F]FDG-PET visual analysis revealed seven RSPs with overt hypometabolism in the medial and lateral temporal lobes, frontal lobes, and temporoparietal regions. Retired soccer players had a higher prevalence of septum pellucidum abnormalities on MRI., Conclusion: Retired soccer players had reduced rBGM and GM volume in the temporal lobes and septum pellucidum abnormalities, findings possibly related to repetitive head impacts., Competing Interests: Dr. JF has received compensation for consultancies to Novartis, AC Immune, Biogen, and Esteve. The other authors have no conflict of interest to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)

Zika virus (ZIKV) diagnostics are crucial for proper antenatal and postnatal care and also for surveillance and serosurvey studies. Since the viremia during ZIKV infection is fleeting, serological testing is highly valuable to inform diagnosis. However, current serology tests using whole virus antigens frequently suffer from cross reactivity issues, delays, and technical complexity, especially in low and middle income countries (LMICs) and endemic countries. Here, we describe an indirect ELISA to detect specific IgG antibodies using the ZIKV envelope domain III (EDIII) protein expressed in Drosophila S2 cells as an immunogen. Using a total of 367 clinical samples, we showed that the EDIII-ELISA was able to detect IgG antibodies against ZIKV with high sensitivity of 100.0% and specificity of 94.7% when compared to plaque reduction neutralization tests (PRNTs) as the gold standard and using 0.208 as the cut-off OD value. These results show the usefulness of the recombinant envelope domain III as an alternative to standard whole virus proteins for ZIKV diagnostics as it improves the sensitivity and specificity of IgG ELISA assay when used as an immunogen. This method should, therefore, be extended to serological diagnostic techniques for other members of the flavivirus genus and for use in IgM diagnostic testing.

Background: The coronavirus 2019 (COVID-19) pandemic changed the way people live. As a result, workload and mental health problems increased, especially in healthcare workers., Objective: To verify the prevalence of common mental disorders (CMD) and its association with sociodemographic and work variables in healthcare workers of a Family Health Support Center in the Primary Health Care context (NASF-AB) in Brazil during the COVID-19 pandemic., Methods: This cross-sectional study was conducted with 68 healthcare workers, both sex (55 female/13 male), from the Primary Health Care context in Brazil, particularly NASF-AB of Salvador Bahia. NASF-AB is part of a policy to consolidate Primary Health Care in Brazil. NASF-AB of Salvador has twelve multidisciplinary teams distributed in twelve health districts. The data collection was performed from May to August 2021. The self-reporting questionnaire - 20 (SRQ-20), that assessed the prevalence of CMD, and a sociodemographic questionnaire assessed sociodemographic and work variables via Google forms., Results: The prevalence of CMD was 39.71%. On SRQ-20, 70, 59% of participants felt nervous; 54, 41% felt tired all the time and 51, 47% felt tired easily. CMD was also significantly associated with females (p < 0.001)., Conclusion: The prevalence of CMD was high (39, 71%), with females (n = 27/55) being more susceptible to CMD than males (n = 0/13). Feel nervous, tired all the time and easily tired were the most frequent symptoms reported by the participants, indicating depressive/anxious mood, and reduced vital energy. Our findings highlight the need for specific measures to improve health and quality of life of healthcare workers.

The hippocampus is one of the most sophisticated structures in the brain, owing to its complex anatomy, intriguing functions, relationship with other structures, and relevant associated symptoms. Despite being a structure analyzed for centuries, its anatomy and physiology in the human body are still being extensively studied, as well as associated pathologic conditions and potential biomarkers. It can be affected by a broad group of diseases that can be classified as congenital, degenerative, infectious or inflammatory, neoplastic, vascular, or toxic-metabolic disease. The authors present the anatomy and close structures, function, and development of the hippocampus, as well as an original algorithm for imaging diagnosis. The algorithm includes pathologic conditions that typically affect the hippocampus and groups them into nodular (space occupying) and nonnodular pathologic conditions, serving as a guide to narrow the differential diagnosis. MRI is the imaging modality of choice for evaluation of the hippocampus, and CT and nuclear medicine also improve the analysis. The MRI differential diagnosis depends on anatomic recognition and careful characterization of associated imaging findings such as volumetric changes, diffusion restriction, cystic appearance, hyperintensity at T1-weighted imaging, enhancement, or calcification, which play a central role in diagnosis along with clinical findings. Some pathologic conditions arising from surrounding structures such as the amygdala are also important to recognize. Pathologic conditions of the hippocampus can be a challenge to diagnose because they usually manifest as similar clinical syndromes, so the imaging findings play a potential role in guiding the final diagnosis. Online supplemental material is available for this article. © RSNA, 2022.

Nanoparticles such as zinc oxide nanoparticles (ZnO-NP) that are incorporated in consumer and industrial products have caused concern about their potential ecotoxicological impact when released into the environment. Bivalve mollusks are susceptible targets for nanoparticle toxicity since nanomaterials can enter the cells by endocytosis mechanisms. The aim of this study was to evaluate the influence of ZnO-NP on the redox metabolism in Limnoperna fortunei and the DNA damage after exposure to ZnO-NP. Adult bivalves were incubated with 1-, 10-, and 50-μg mL -1 ZnO-NP for 2, 4, and 24 h. Ionic Zn release, enzymatic and non-enzymatic antioxidant activity, oxidative damage, and DNA damage were evaluated. Oxidative damage to proteins and lipids were observed after 4-h exposure and returned to baseline levels after 24 h. Superoxide dismutase levels decreased after 4-h exposure and increased after 24 h. No significant alteration was observed in the catalase activity or even DNA double-strand cleavage. The dissociation of ZnO may occur after 24 h, releasing ionic zinc (Zn 2+ ) by hydrolysis, which was confirmed by the increase in the ionic Zn concentration following 24-h exposure. In conclusion, ZnO-NP were able to induce oxidative stress in exposed golden mussels. The golden mussel can modulate its own antioxidant defenses in response to oxidative stress and seems to be able to hydrolyze the nanoparticles and consequently, release Zn 2+ into the cellular compartment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Benign prostatic hyperplasia (BPH) is a noncancerous growth of the transitional zone of the prostate, which surrounds the prostatic urethra. Consequently, it can cause lower urinary tract symptoms (LUTS) and bladder outlet obstruction symptoms that may substantially reduce a patient's quality of life. Several treatments are available for BPH, including medications such as α-blockers and 5α-reductase inhibitors and surgical options including transurethral resection of the prostate and prostatectomy. Recently, prostatic artery embolization (PAE) has emerged as a minimally invasive treatment option for selected men with BPH and moderate to severe LUTS. Adequate pre- and postprocedural evaluations with clinical examinations and questionnaires, laboratory tests, and urodynamic and imaging examinations (particularly US, MRI, and CT) are of key importance to achieve successful treatment. Considering that the use of PAE has been increasing in tertiary hospital facilities, radiologists and interventional radiologists should be aware of the main technical concepts of PAE and the key features to address in imaging reports in pre- and postprocedural settings. An invited commentary by Lopera is available online. Online supplemental material is available for this article. © RSNA, 2021.

The diagnosis and treatment of bipolar depression (BDep) poses complex clinical challenges for psychiatry. Proton magnetic resonance spectroscopy ( 1 H-MRS) is a useful imaging tool for investigating in vivo levels of brain neuro-metabolites, critical to understanding the process of mood dysregulation in Bipolar Disorder. Few studies have evaluated longitudinal clinical outcomes in BDep associated with 1 H-MRS metabolic changes. This study aimed to longitudinally assess brain 1 H-MRS metabolites in the anterior cingulate cortex (ACC) correlated with improvement in depression (from BDep to euthymia) after lithium treatment in BDep patients versus matched healthy controls (HC). Twenty-eight medication-free BDep patients and 28 HC, matched for age and gender, were included in this study. All subjects were submitted to a 3-Tesla brain 1 H-MRS scan in the ACC using a single-voxel (8cm 3 ) PRESS sequence at baseline. At follow-up (6 weeks), 14 BDep patients repeated the exam in euthymia. Patients with current BDep had higher baseline Myo-inositol/Cr (mI/Cr) and Choline/Cr (Cho/Cr) compared to HC. After six weeks, mI/Cr or Cho/Cr levels in subjects that achieved euthymia no longer differed to levels in HC, while high Cho/Cr levels persisted in non-responders . Elevated ACC mI/Cr and Cho/Cr in BDep might indicate increased abnormal membrane phospholipid metabolism and phosphatidylinositol (PI) cycle activity. Return of mI/Cr and Cho/Cr to normal levels after lithium-induced euthymia suggests a critical regulatory effect of lithium targeting the PI cycle involved in mood regulation., Competing Interests: Declaration of Competing Interest None of the authors report biomedical financial interests or potential conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

The construction of forest roads in Brazilian Amazon is costly and has a significant environmental impact. Several practices and principles must be observed to comply with legislation, to preserve the remaining forest, and to ensure sustainable exploitation. Road planning is complex in this context, based on the number of aspects and variables that must be considered. This research aimed to evaluate computational methods' effectiveness in planning forest roads, optimizing resources to reduce damage to the remaining forest, compared to traditional planning methods. The study area was a native forest under a sustainable forest management regime located in municipalities of Terra Santa and Oriximiná, in Pará, in Brazilian Amazon. Data obtained from area made it possible formulate six instances of different sizes. A binary integer linear programming model was used, solved using CPLEX software, and Dijkstra, Bellman-Ford, Dial, and D'Esopo-Pape shortest path algorithm, implemented in C programming language. During processing of instances, the time taken to obtain the solution increased according to size of instance, however, time difference was not significant. Among the evaluated algorithms, the D'Esopo-Pape algorithm showed the best performance. The evaluated methods were effective in obtaining an optimal solution for proposed forest road planning. The solutions obtained using computational methods more effectively considered the restrictions associated with sustainable forest management, in contrast to those derived from the traditional planning by forestry company., (Published by Elsevier Ltd.)

Objective : The goal is to evaluate longitudinally with diffusion tensor imaging (DTI) the integrity of cerebral white matter in patients with moderate and severe DAI and to correlate the DTI findings with cognitive deficits. Methods : Patients with DAI (n = 20) were scanned at three timepoints (2, 6 and 12 months) after trauma. A healthy control group (n = 20) was evaluated once with the same high-field MRI scanner. The corpus callosum (CC) and the bilateral superior longitudinal fascicles (SLFs) were assessed by deterministic tractography with ExploreDTI. A neuropschychological evaluation was also performed. Results : The CC and both SLFs demonstrated various microstructural abnormalities in between-groups comparisons. All DTI parameters demonstrated changes across time in the body of the CC, while FA (fractional anisotropy) increases were seen on both SLFs. In the splenium of the CC, progressive changes in the mean diffusivity (MD) and axial diffusivity (AD) were also observed. There was an improvement in attention and memory along time. Remarkably, DTI parameters demonstrated several correlations with the cognitive domains. Conclusions : Our findings suggest that microstructural changes in the white matter are dynamic and may be detectable by DTI throughout the first year after trauma. Likewise, patients also demonstrated improvement in some cognitive skills.

Objectives: Although a large number of studies have shown brain volumetric differences between men and women, only a few investigations have analyzed brain tissue volumes in representative samples of the general elderly population. We investigated differences in gray matter (GM) volumes, white matter (WM) volumes, and intracranial volumes (ICVs) between the sexes in individuals older than 66 years using structural magnetic resonance imaging (MRI)., Methods: Using FreeSurfer version 5.3, we obtained the ICVs and GM and WM volumes from the MRI datasets of 84 men and 92 women. To correct for interindividual variations in ICV, GM and WM volumes were adjusted with a method using the residuals of a least-square-derived linear regression between raw volumes and ICVs. We then performed an analysis of covariance comparing men and women, including age and years of schooling as confounding factors., Results: Women had a lower socioeconomic status overall and fewer years of schooling than men. The comparison of unadjusted brain volumes showed larger GM and WM volumes in men. After the ICV correction, the adjusted volumes of GM and WM were larger in women., Conclusion: After the ICV correction and taking into account differences in socioeconomic status and years of schooling, our results confirm previous findings of proportionally larger GM in women, as well as larger WM volumes. These results in an elderly population indicate that brain volumetric differences between sexes persist throughout the aging process. Additional studies combining MRI and other biomarkers to identify the hormonal and molecular bases influencing such differences are warranted.

The Response Assessment in Neuro-Oncology criteria were developed as an objective tool for radiologic assessment of treatment response in high-grade gliomas. Imaging plays a critical role in the management of the patient with glioma, from initial diagnosis to posttreatment follow-up, which can be particularly challenging for radiologists. Interpreting findings after surgery, radiation, and chemotherapy requires profound knowledge about the tumor biology, as well as the peculiar changes expected to ensue as a consequence of each treatment technique. In this article, we discuss the imaging findings associated with tumor progression, tumor response, pseudoprogression, and pseudoresponse according to the Response Assessment in Neuro-Oncology criteria for high-grade and lower-grade gliomas. We describe relevant practical issues when evaluating patients with glioma, such as the need for imaging in the first 48 hours, the radiation therapy planning and isodose curves, the significance of T2/FLAIR hyperintense lesions, the impact of the timing for the evaluation after radiation therapy, and the definition of progressive disease on the histologic specimen. We also illustrate the correlation among the findings on conventional MR imaging with advanced techniques, such as perfusion, diffusion-weighted imaging, spectroscopy, and amino acid PET. Because many of the new lesions represent a mixture of tumor cells and tissue with radiation injury, the radiologist aims to identify the predominant component of the lesion and categorize the findings according to Response Assessment in Neuro-Oncology criteria so that the patient can receive the best treatment., (© 2020 by American Journal of Neuroradiology.)

Background: Coordinated patterns of gray matter morphology can be represented as networks, and network disruptions may explain cognitive dysfunction related to multiple sclerosis (MS)., Objective: To investigate whether single-subject gray matter network properties are related to impaired cognition in MS., Methods: We studied 148 MS patients (99 female) and 33 healthy controls (HC, 21 female). Seven network parameters were computed and compared within MS between cognitively normal and impaired subjects, and associated with performance on neuropsychological tests in six cognitive domains with regression models. Analyses were controlled for age, gender, whole-brain gray matter volumes, and education level., Results: Compared to MS subjects with normal cognition, MS subjects with cognitive impairment showed a more random network organization as indicated by lower lambda values (all p < 0.05). Worse average cognition and executive function were associated with lower lambda values. Impaired information processing speed, working memory, and attention were associated with lower clustering values., Conclusion: Our findings indicate that MS subjects with a more randomly organized gray matter network show worse cognitive functioning, suggesting that single-subject gray matter graphs may capture neurological dysfunction due to MS.

Introduction: Portugal presents the highest incidence of stage 5 chronic kidney disease in Europe. It is speculated that a high consumption of non-steroidal anti-inflammatory drugs (NSAIDS) may contribute to this high incidence. Our aim was to characterize the prescription of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus in Portugal., Material and Methods: We analyzed the national prescription database in triennium 2015 - 2017. In patients with diabetes mellitus, we evaluated the prescription of non-steroidal anti-inflammatory drugs according to age, gender and region of the patient and specialty of the prescribing physician. We evaluated the prescription of non-steroidal anti-inflammatory drugs in all patients with diabetes mellitus, in patients with presumed renal impairment, and in those with concomitant prescription of angiotensin converting enzyme inhibitors or angiotensin receptor antagonists., Results: We analyzed 23 320 620 prescriptions, corresponding to 610 157 adults, including 104 306 patients with diabetes mellitus. The most prescribed non-steroidal anti-inflammatory drugs were ibuprofen (20.1%), metamizole (14.7%), and diclofenac (11.4%). The prescription of non-steroidal anti-inflammatory drugs was higher in females, in patients aged 51 - 70 years and in the Alentejo region. Non-steroidal anti-inflammatory drugs were prescribed to 70.6% of patients with diabetes mellitus, from which 10.6% were prescribed ≥ 10 packages during the three years. Among patients with diabetes mellitus on angiotensin converting enzyme inhibitors/angiotensin receptor antagonists and with presumed reduction in kidney function, 69.3% were prescribed non-steroidal anti-inflammatory drugs and 11.5% were prescribed ≥ 10 packages during the three years., Discussion: The level of prescribing of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus is high. The concern of reducing non-steroidal anti-inflammatory drugs prescription to patients already on angiotensin converting enzyme inhibitors/angiotensin receptor antagonists and/or decreased renal function does not seem to exist., Conclusion: In Portugal, the level of prescribing of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus should be reduced, particularly in the subgroups identified with higher prescription and with higher risk of progression to stage 5 chronic kidney disease.

Background and Objective: Diffuse axonal injury (DAI) induces a long-term process of brain atrophy and cognitive deficits. The goal of this study was to determine whether there are correlations between brain volume loss, microhaemorrhage load (MHL) and neuropsychological performance during the first year after DAI., Methods: Twenty-four patients with moderate or severe DAI were evaluated at 2, 6 and 12 months post-injury. MHL was evaluated at 3 months, and brain volumetry was evaluated at 3, 6 and 12 months. The trail making test (TMT) was used to evaluate executive function (EF), and the Hopkins verbal learning test (HVLT) was used to evaluate episodic verbal memory (EVM) at 6 and 12 months., Results: There were significant white matter volume (WMV), subcortical grey matter volume and total brain volume (TBV) reductions during the study period (p < 0.05). MHL was correlated only with WMV reduction. EF and EVM were not correlated with MHL but were, in part, correlated with WMV and TBV reductions., Conclusions: Our findings suggest that MHL may be a predictor of WMV reduction but cannot predict EF or EVM in DAI. Brain atrophy progresses over time, but patients showed better EF and EVM in some of the tests, which could be due to neuroplasticity.

Parkinson's disease (PD) is a neurodegenerative disorder that affects motor skills and cognition. As brain structure and function are compromised, functional magnetic resonance imaging (fMRI) can be a helpful tool to further investigate how intrinsic connectivity is impaired on the disease. The precuneus and medial prefrontal cortex (mPFC) are hub regions involved on the default mode network (DMN), a system that is active during rest and related to cognitive processes. We hypothesized that PD patients would present a decrease in functional connectivity among these two regions and the rest of the brain. Our goal was to identify regions in which functional connectivity to precuneus and mPFC was altered in PD. This study was based on resting-state fMRI data from 37 healthy subjects and 55 PD patients. Precuneus and mPFC were selected as seed regions in a whole brain functional connectivity mapping. As expected, we found abnormal connectivity from precuneus to motor system regions in PD patients, pointing toward a decreased connectivity in the disease. No significant group effects were found for the mPFC. Our findings suggest that internetwork connectivity from DMN to motor system is impaired in PD.

Background: Machine learning techniques such as support vector machine (SVM) have been applied recently in order to accurately classify individuals with neuropsychiatric disorders such as Alzheimer's disease (AD) based on neuroimaging data. However, the multivariate nature of the SVM approach often precludes the identification of the brain regions that contribute most to classification accuracy. Multiple kernel learning (MKL) is a sparse machine learning method that allows the identification of the most relevant sources for the classification. By parcelating the brain into regions of interest (ROI) it is possible to use each ROI as a source to MKL (ROI-MKL)., Methods: We applied MKL to multimodal neuroimaging data in order to: 1) compare the diagnostic performance of ROI-MKL and whole-brain SVM in discriminating patients with AD from demographically matched healthy controls and 2) identify the most relevant brain regions to the classification. We used two atlases (AAL and Brodmann's) to parcelate the brain into ROIs and applied ROI-MKL to structural (T1) MRI, 18 F-FDG-PET and regional cerebral blood flow SPECT (rCBF-SPECT) data acquired from the same subjects (20 patients with early AD and 18 controls). In ROI-MKL, each ROI received a weight (ROI-weight) that indicated the region's relevance to the classification. For each ROI, we also calculated whether there was a predominance of voxels indicating decreased or increased regional activity (for 18 F-FDG-PET and rCBF-SPECT) or volume (for T1-MRI) in AD patients., Results: Compared to whole-brain SVM, the ROI-MKL approach resulted in better accuracies (with either atlas) for classification using 18 F-FDG-PET (92.5% accuracy for ROI-MKL versus 84% for whole-brain), but not when using rCBF-SPECT or T1-MRI. Although several cortical and subcortical regions contributed to discrimination, high ROI-weights and predominance of hypometabolism and atrophy were identified specially in medial parietal and temporo-limbic cortical regions. Also, the weight of discrimination due to a pattern of increased voxel-weight values in AD individuals was surprisingly high (ranging from approximately 20% to 40% depending on the imaging modality), located mainly in primary sensorimotor and visual cortices and subcortical nuclei., Conclusion: The MKL-ROI approach highlights the high discriminative weight of a subset of brain regions of known relevance to AD, the selection of which contributes to increased classification accuracy when applied to 18 F-FDG-PET data. Moreover, the MKL-ROI approach demonstrates that brain regions typically spared in mild stages of AD also contribute substantially in the individual discrimination of AD patients from controls.

Objectives: To detect by diffusion tensor imaging (DTI) the extent of microstructural integrity changes of the corpus callosum (CC) in patients with hippocampal sclerosis (HS) and to evaluate possible association with clinical characteristics., Methods: Fourty-two patients with temporal lobe epilepsy (TLE) and HS and 30 control subjects were studied with DTI. We grouped patients according to lesion side (left or right) HS. Mean diffusivity (MD), fractional anisotropy (FA), radial (RD) and axial diffusivity (AD) were extracted from five segments in CC midsagittal section obtained by automatic segmentation. CC DTI findings were compared between groups. We also evaluated association of DTI changes and clinical characteristics., Results: HS patients displayed decreased FA and increased MD and RD in the anterior, mid-posterior and posterior CC segments, compared to controls. No differences were observed in AD. Patients reporting febrile seizure as the initial precipitating event presented more intense diffusion changes. No differences were seen comparing left and right HS. Age at epilepsy onset, disease duration and seizure frequency were not associated with DTI findings., Conclusions: This is one of the largest series of TLE-HS patients evaluating CC white matter fiber integrity by DTI, which allowed us to study how some clinical characteristics, such as seizure frequency, disease duration and lesion side, are related to CC integrity. Occurrence of febrile seizure was the only factor that had significant impact on tract integrity. Diffusion changes were not restricted to the posterior part of the CC; we observed the same changes for the anterior part of the CC. Diffusion changes were characterized by an increase in RD, while the AD remained intact for all regions of the CC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To conduct the first support vector machine (SVM)-based study comparing the diagnostic accuracy of T1-weighted magnetic resonance imaging (T1-MRI), F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and regional cerebral blood flow single-photon emission computed tomography (rCBF-SPECT) in Alzheimer's disease (AD)., Method: Brain T1-MRI, FDG-PET and rCBF-SPECT scans were acquired from a sample of mild AD patients (n=20) and healthy elderly controls (n=18). SVM-based diagnostic accuracy indices were calculated using whole-brain information and leave-one-out cross-validation., Results: The accuracy obtained using PET and SPECT data were similar. PET accuracy was 68∼71% and area under curve (AUC) 0.77∼0.81; SPECT accuracy was 68∼74% and AUC 0.75∼0.79, and both had better performance than analysis with T1-MRI data (accuracy of 58%, AUC 0.67). The addition of PET or SPECT to MRI produced higher accuracy indices (68∼74%; AUC: 0.74∼0.82) than T1-MRI alone, but these were not clearly superior to the isolated neurofunctional modalities., Conclusion: In line with previous evidence, FDG-PET and rCBF-SPECT more accurately identified patients with AD than T1-MRI, and the addition of either PET or SPECT to T1-MRI data yielded increased accuracy. The comparable SPECT and PET performances, directly demonstrated for the first time in the present study, support the view that rCBF-SPECT still has a role to play in AD diagnosis.

Certain subgroups of Escherichia coli have congenital or acquired virulence properties that allow them to cause a wide spectrum of disease. The aim of this study was to investigate the occurrence of diarrheagenic E. coli strains in ready-to-eat (RTE) foods produced in institutional, commercial and hotel restaurants in Salvador, Brazil. The presence of virulent isolates and antimicrobial resistance were evaluated. Four hundred forty-six samples were collected and grouped into cereals and vegetables, meat-based preparations, cooked salads, raw salads, garnishes, soups and sauces, desserts and juices. E. coli were detected using the most probable number method, the presence of virulence factors in isolates was determined by polymerase chain reaction (PCR) assays, and antibiotic resistance was analyzed using the disc diffusion method. In total, 15 isolates (3.1%) of E. coli were recovered; raw salads had the highest detection rate, 1.4%, followed by cooked salads, 0.8%; meat-based preparations, 0.4%; and cereals and vegetables, 0.4%. PCR assays showed that none of the isolates had the virulence genes cnf1, cnf2, eae , sta, lt1, stx1, stx2 or cdtB . The isolates showed resistance to nine antibiotics of the 15 tested, and the highest levels of resistance were found for sulfamethoxazole/trimethoprim, tetracycline, ampicillin, and chloramphenicol (13.3% of isolates for each antibiotic). One isolate from cooked salad had plasmid-mediated multidrug resistance to tetracycline, trimethoprim/sulfamethoxazole, ampicillin and chloramphenicol. These results suggest that RTE foods, especially raw salads, can be reservoirs of E. coli and facilitate the spread of antibiotic resistance genes to the gastrointestinal microbiota of humans.

Objective:: Using magnetic resonance imaging, we aimed to assess the presence of silent brain vascular lesions in a sample of apparently healthy elderly individuals who were recruited from an economically disadvantaged urban region (São Paulo, Brazil). We also wished to investigate whether the findings were associated with worse cognitive performance., Methods:: A sample of 250 elderly subjects (66-75 years) without dementia or neuropsychiatric disorders were recruited from predefined census sectors of an economically disadvantaged area of Sao Paulo and received structural magnetic resonance imaging scans and cognitive testing. A high proportion of individuals had very low levels of education (4 years or less, n=185; 21 with no formal education)., Results:: The prevalence of at least one silent vascular-related cortical or subcortical lesion was 22.8% (95% confidence interval, 17.7-28.5), and the basal ganglia was the most frequently affected site (63.14% of cases). The subgroup with brain infarcts presented significantly lower levels of education than the subgroup with no brain lesions as well as significantly worse current performance in cognitive test domains, including memory and attention (p<0.002)., Conclusions:: Silent brain infarcts were present at a substantially high frequency in our elderly sample from an economically disadvantaged urban region and were significantly more prevalent in subjects with lower levels of education. Covert cerebrovascular disease significantly contributes to cognitive deficits, and in the absence of magnetic resonance imaging data, this cognitive impairment may be considered simply related to ageing. Emphatic attention should be paid to potentially deleterious effects of vascular brain lesions in poorly educated elderly individuals from economically disadvantaged environments.

Objectives: Our goal was to estimate the diagnostic accuracy of substantia nigra fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample similar to the clinical setting, including patients with essential tremor (ET) and healthy controls (HC). We also performed a systematic review and meta-analysis to estimate mean change in SN-FA induced by PD and its diagnostic accuracy., Methods: Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC. To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI results of this sample were pooled into a meta-analysis that included 1,432 subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic accuracy measures., Results: In our sample, we did not observe a significant effect of disease on SN-FA and it was uninformative for diagnosis. The results of the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI: 58-70), respectively. There was high heterogeneity between studies (I 2  = 91.9 %)., Conclusions: SN-FA cannot be used as an isolated measure to diagnose PD., Key Points: • SN-FA appears insufficiently sensitive and specific to diagnose PD. • Radiologists must be careful when translating mean group results to clinical practice. • Imaging protocol and analysis standardization is necessary for developing reproducible quantitative biomarkers.

Objective: Mitochondrial dysfunction and energy metabolism impairment are key components in the pathophysiology of bipolar disorder (BD) and may involve a shift from aerobic to anaerobic metabolism. Measurement of brain lactate in vivo using proton magnetic resonance spectroscopy (H-MRS) represents an important tool to evaluate mitochondrial and metabolic dysfunction during mood episodes, as well as to monitor treatment response. To date, very few studies have quantified brain lactate in BD. In addition, no study has longitudinally evaluated lactate using H-MRS during depressive episodes or its association with mood stabilizer therapy. This study aimed to evaluate cingulate cortex (CC) lactate using 3-T H-MRS during acute depressive episodes in BD and the possible effects induced by lithium monotherapy., Methods: Twenty medication-free outpatients with short length of BD (80% drug-naive) in a current major depressive episode were matched with control subjects. Patients were treated for 6 weeks with lithium monotherapy at therapeutic doses in an open-label trial (blood level, 0.48 ± 0.19 mmol/L). Cingulate cortex lactate was measured before (week 0) and after lithium therapy (week 6) using H-MRS. Antidepressant efficacy was assessed with the 21-item Hamilton Depression Rating Scale as the primary outcome., Results: Subjects with BD depression showed a significantly higher CC lactate in comparison to control subjects. Furthermore, a significant decrease in CC lactate was observed after 6 weeks of lithium treatment compared with baseline (P = 0.002). CC Lactate levels was associated with family history of mood disorders and plasma lithium levels., Conclusions: This is the first report of increased CC lactate in patients with bipolar depression and lower levels after lithium monotherapy for 6 weeks. These findings indicate a shift to anaerobic metabolism and a role for lactate as a state marker during mood episodes. Energy and redox dysfunction may represent key targets for lithium's therapeutic actions., Competing Interests: DECLARATION OF INTEREST A patent for the use of ketamine in depression has been awarded that lists Dr. Zarate among the inventors; he has assigned his rights on the patent to the US government, but will share a percentage of any royalties that may be received by the government. All other authors declare no potential conflict of interest.

Purpose: Hepatic resection is the only potentially curative treatment for patients with colorectal liver metastasis (CRLM). Many multidisciplinary approaches, including the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure, have been proposed to increase the resectability rate in these patients. ALPPS is the most recently described staged liver resection technique, representing an advantageous strategy to induce a rapid and marked increase in the future liver remnant (FLR) volume. The aim of this article is to describe the radiological evaluation of this procedure and its variation., Methods: This retrospective study included 9 patients with CRLM who underwent the ALPPS procedure. Abdominal imaging studies were reviewed, with an emphasis on a rational radiological approach. The number of liver metastases, the FLR volume (pre- and postportal vein ligation), anatomical variations, potential pitfalls related to disease progression, and postoperative complications were evaluated., Results: The types of hepatic resection included 4 classical ALPPS cases, 3 right ALPPS variations, and 2 left ALPPS variations. The mean FLR volume calculated in the initial evaluation was 453 mL (213-790 mL). Following the first surgery, the mean FLR volume increased to 634 mL (410-957 mL), which indicated a mean volume increase of 181.1 mL (95% CI 149.7-212.5 mL; p < 0.001) and a mean absolute volume increase of 48% (19%-88%)., Conclusion: The ALPPS procedure is an emerging form of two-stage hepatectomy. In this context, radiologists should provide crucial preoperative and perioperative information that may change surgical planning and contribute to an improvement in the oncologic outcome.

Objective: to assess the structure and results obtained by the "Chronic Renal Patients Care Program" in a Brazilian city., Method: epidemiological, cross-sectional study conducted in 14 PHC units and a secondary center from 2010 to 2013. The Donabedian Model was the methodological framework used. A total of 14 physicians, 13 supervisors, and 11 community health agents from primary healthcare were interviewed for the assessment of structure and process and 1,534 medical files from primary healthcare and 282 from secondary care were consulted to assess outcomes., Results: most units lacked sufficient offices for physicians and nurses to provide consultations, had incomplete staffing, and most professionals had not received proper qualification to provide care for chronic renal disease. Physicians from PHC units classified as capable more frequently referred patients to the secondary care service in the early stages of chronic renal disease (stage 3B) when compared to physicians of units considered not capable (58% vs. 36%) (p=0.049). Capable PHC units also more frequently presented stabilized glomerular filtration rates (51%) when compared to partially capable units (36%) and not capable units (44%) (p=0.046)., Conclusion: patients cared for by primary healthcare units that scored higher in structure and process criteria presented better clinical outcomes., Objective: to identify the coping strategies of family members of patients with mental disorders and relate them to family member sociodemographic variables and to the patient's clinical variables., Method: this was a descriptive study conducted at a psychiatric hospital in the interior of the state of São Paulo, with 40 family members of hospitalized patients over the age of 18, and who followed the patient before and during hospitalization. We used tools to characterize the subjects and the Folkman and Lazarus Inventory of Coping Strategies., Results: the coping strategies most often used by family members were social support and problem solving. Mothers and fathers used more functional strategies (self-control p=0.037, positive reappraisal p=0.037, and social support p=0,021). We found no significant differences between the strategies and other variables examined., Conclusion: despite the suffering resulting from the illness of a dear one, family members make more use of functional strategies, allowing them to cope with adversities in a more well-adjusted way., Objetivo: avaliar estrutura, processo e resultado do "Programa de Atenção a Doentes Renais Crônicos" em um município brasileiro., Método: estudo epidemiológico, transversal, realizado em 14 unidades de atenção primária e um centro de atenção secundária, no período de 2010-2013. Utilizou-se o referencial metodológico de Donabedian. Para avaliação de estrutura e processo, foram entrevistados 14 médicos, 13 supervisores e 11 agentes comunitários de saúde da atenção primária. Para avaliação de resultado, foram utilizados 1.534 prontuários de saúde na atenção primária e 282 na atenção secundária., Resultados: na maioria das unidades faltam consultórios para atendimento médico e de enfermagem, as equipes estavam incompletas e a maioria dos profissionais não participou de capacitação para atenção à doença renal crônica. Médicos das unidades primárias, classificadas como capacitadas, encaminharam usuários à atenção secundária em estágios mais precoces da doença renal crônica (estágio 3B) quando comparados aos médicos das unidades não capacitadas (58% vs 36%) (p=0,049). As unidades de atenção primária, classificadas como capacitadas, apresentaram melhores taxas de estabilização da filtração glomerular (51%) quando comparadas às unidades parcialmente capacitadas (36%) e não capacitadas (44%) (p=0,046)., Conclusão: usuários atendidos nas unidades de atenção primária com pontuação mais elevada em critérios de estrutura e processo apresentaram melhores resultados clínicos., Objetivo: evaluar la estructura, el proceso y los resultados del "Programa de Atención a Enfermos Renales Crónicos" en un municipio brasileño., Método: estudio epidemiológico, transversal, realizado en 14 unidades de atención primaria y en un centro de atención secundario, en el período de 2010 a 2013. Se utilizó el referencial metodológico de Donabedian. Para evaluación de estructura y proceso; fueron entrevistados 14 médicos, 13 supervisores y 11 agentes comunitarios de salud de la atención primaria. Para evaluación del resultado, fueron utilizadas 1.534 fichas médicas en la atención primaria y 282 en la atención secundaria., Resultados: en la mayoría de las unidades faltaban consultorios para la atención médica y de enfermería, los equipos estaban incompletos y la mayoría de los profesionales no participó de capacitaciones sobre la atención a la enfermedad renal crónica. Los médicos de las unidades primarias, clasificados como capacitados, encaminaron usuarios para la atención secundaria en etapas más precoces de la enfermedad renal crónica (etapa 3B) cuando comparados a los médicos de las unidades no capacitadas (58% vs 36%) (p=0,049). Las unidades de atención primaria, clasificadas como capacitadas, presentaron mejores tasas de estabilización de la filtración glomerular (51%) cuando comparadas a las unidades parcialmente capacitadas (36%) y no capacitadas (44%) (p=0,046)., Conclusión: los usuarios atendidos en las unidades de atención primaria, con puntuación más elevada en criterios de estructura y proceso, presentaron mejores resultados clínicos.

TiO2 nanoparticles (TiO2-NP) have been incorporated into a large range of materials for different applications in the last decades and are very likely to appear in wastewater and effluents, eventually reaching the aquatic environment. Therefore, the assessment of the biological impact of TiO2-NP on aquatic ecosystem is of a major concern. The mussels represent a target group for TiO2-NP toxicity, as they are filter feeders and are capable of bioaccumulating toxic compounds. Furthermore, the exotic organism Limnoperna fortunei, golden mussel, is a freshwater bivalve that has been used in biomonitoring environmental conditions. In this work, the TiO2-NP's ability to interact with haemocytes of golden mussel was assessed by transmission electron microscopy. The enzymatic and non-enzymatic antioxidant defenses were evaluated by superoxide dismutase (Sod) and catalase (Cat) activities and protein sulfhydryl content, which were measured after the golden mussel was exposed to TiO2-NP (1, 5, 10 and 50μgmL(-1)). Results demonstrate that TiO2-NP was internalized by cells, causing alterations in haemocytes membrane. Antioxidant activity of Sod and Cat decreased after 2h TiO2-NP exposure. After 4h exposure, the enzymatic antioxidant activity was restored. Notably, the protein sulfhydryl content decreased after 2h to all the TiO2-NP concentrations and no alterations were observed after 4h of TiO2-NP exposure. These results demonstrate the potential of golden mussel as sentinel organism to TiO2-NP exposure., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity., Methods: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes., Results: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regions were directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region., Conclusion: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions.

Objective: The objective of this study was to evaluate brain lithium levels using (7) Li magnetic resonance spectroscopy after 6 weeks of lithium therapy in bipolar depression to test the hypothesis that brain and plasma lithium are correlated. It was also tested whether responders and remitters have different pharmacokinetics, blood and brain lithium levels (ratio) compared with those presenting suboptimal antidepressant improvement., Method: Twenty-three patients with bipolar disorder (I and II) during depressive episodes were included and followed up for 6 weeks at the University of Sao Paulo using flexible dose of lithium (450-900 mg/day). Sixteen patients were drug-naïve. At endpoint, patients underwent a (7) Li-MRS scan and brain lithium concentrations were calculated., Results: A significant association between central and peripheral lithium levels was found only in remitters (r = 0.7, P = 0.004) but not in non-remitters (r = -0.12, P = 0.76). Also, brain lithium (but not plasma) was inversely correlated with age (r = -0.46, P = 0.025). Plasma lithium did not correlate with any clinical outcome, lithium dosage or adverse effects., Conclusion: These findings suggest that non-remitters may not transport lithium properly to the brain, which may underlie treatment resistance to lithium in BD. Future studies with (7) Li-MRS integrated with the evaluation of blood-brain barrier transport mechanisms and longitudinal clinical outcomes in BD and aging are warranted., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A giant cell tumor (GCT) is an intermediate grade, locally aggressive neoplasia. Despite advances in surgical and clinical treatments, cases located on the spine and pelvic bones remain a significant challenge. Failure of clinical treatment with denosumab and patient refusal of surgical procedures (hemipelvectomy) led to the use of cryoablation. We report the use of percutaneous CT-guided cryoablation as an alternative treatment, shown to be a minimally invasive, safe, and effective option for a GCT with extensive involvement of the pelvic bones and allowed structural and functional preservation of the involved bones.

The anterior cingulate cortex (ACC) is a key area in mood regulation. To date, no longitudinal study has specifically evaluated lithium׳s effects on ACC metabolites using (1)H-MRS, as well as its association with clinical improvement in bipolar depression. This (1)H-MRS (TE=35ms) study evaluated 24 drug-free BD patients during depressive episodes and after lithium treatment at therapeutic levels. Brain metabolite levels (N-acetyl aspartate (NAA), creatine (tCr), choline, myo-inositol, and glutamate levels) were measured in the ACC at baseline (week 0) and after lithium monotherapy (week 6). The present investigation showed that ACC glutamate (Glu/tCr) and glutamate+glutamine (Glx/tCr) significantly increased after six weeks of lithium therapy. Regarding the association with clinical improvement, remitters showed an increase in myoinositol levels (mI/tCr) after lithium treatment compared to non-remitters. The present findings reinforce a role for ACC glutamate-glutamine cycling and myoinositol pathway as key targets for lithium׳s therapeutic effects in BD., (Published by Elsevier B.V.)

Molecular methodologies were used to identify 28 Achromobacter spp. from patients with cystic fibrosis (CF). Multilocus sequence typing (MLST) identified 17 Achromobacter xylosoxidans isolates (all bla(OXA-114) positive), nine Achromobacter ruhlandii isolates (all bla(OXA-114) positive), one Achromobacter dolens isolate, and one Achromobacter insuavis isolate. All less common species were misidentified as A. xylosoxidans by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Chronic colonization by clonally related A. ruhlandii isolates was demonstrated.

Bipolar disorder (BD) is highly heritable. First-degree relatives of BD patient have an increased risk to develop the disease. We investigated abnormalities in gray matter (GM) volumes in healthy first-degree relatives of BD patients to identify possible brain structural endophenotypes for the disorder. 3D T1-weighted magnetic resonance images were obtained from 25 DSM-IV BD type I patients, 23 unaffected relatives, and 27 healthy controls (HC). A voxel-based morphometry protocol was used to compare differences in GM volumes between groups. BD patients presented reduced GM volumes bilaterally in the thalamus compared with HC. Relatives presented no global or regional GM differences compared with HC. Our negative results do not support the role of GM volume abnormalities as endophenotypes for BD. Thalamic volume abnormalities may be associated the pathophysiology of the disease., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To assess the integrity of the arcuate fasciculus (AF) with diffusion tensor imaging (DTI) and tractography in patients with congenital polymicrogyria (PMG) and language disorders., Methods: Twelve patients with PMG and 12 matched controls were prospectively evaluated with DTI (32 gradient encoding directions, b-value=1000 s/mm(2)) at 3.0T. The AF was virtually dissected with a deterministic streamline approach. DTI metrics included FA (fractional anisotropy), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). A subset of patients (n=4) was evaluated to assess cognitive performance and language skills., Results: Qualitative evaluation revealed several abnormalities in tracts size and architecture in nearly all PMG patients. Remarkably, in 3 patients with bilateral PMG, the AF was not delineated on both hemispheres. In comparison to controls, patients exhibited significant decrease of FA (p=0.003) in addition to increase of RD (p=0.03) in the right AF, whereas there was significant increase of MD in the left AF (p=0.04). All 4 patients with language evaluation had suboptimal performance on lexical fluency and prosodic linguistic., Conclusions: DTI and tractography suggest that the AF is severely disrupted in patients with PMG, providing an anatomical in vivo substrate for the language disorders commonly associated with these cortical malformations., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce., Objective: To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers., Methods: Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated., Results: The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93., Conclusion: rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls., Competing Interests: Disclosure: The authors report no conflits of interest.

Background: Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up., Objective: To evaluate the development of CPHD in a group of childhood-onset IGHD followed at a single tertiary center over a long period of time., Patients and Methods: We retrospectively analyzed data from 83 patients initially diagnosed as IGHD with a mean follow-up of 15.2 years. The Kaplan-Meier method and Cox regression analysis was used to estimate the temporal progression and to identify risk factors to development of CPHD over time., Results: From 83 patients initially with IGHD, 37 (45%) developed CPHD after a median time of follow up of 5.4 years (range from 1.2 to 21 years). LH and FSH deficiencies were the most common pituitary hormone (38%) deficiencies developed followed by TSH (31%), ACTH (12%) and ADH deficiency (5%). ADH deficiency (3.1 ± 1 years from GHD diagnosis) presented earlier and ACTH deficiency (9.3 ± 3.5 years) presented later during follow up compared to LH/FSH (8.3 ± 4 years) and TSH (7.5 ± 5.6 years) deficiencies. In a Cox regression model, pituitary stalk abnormalities was the strongest risk factor for the development of CPHD (hazard ratio of 3.28; p = 0.002)., Conclusion: Our study indicated a high frequency of development of CPHD in patients initially diagnosed as IGHD at childhood. Half of our patients with IGHD developed the second hormone deficiency after 5 years of diagnosis, reinforcing the need for lifelong monitoring of pituitary function in these patients.

Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS) or resistance (TR) to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis.

Introduction: Neuroimaging studies demonstrate that not only the lesions of malformations of cortical development (MCD) but also the normal-appearing parenchyma (NAP) present metabolic impairments, as revealed with (1)H-MRS. We have previously detected biochemical disturbances in MCD lesions with phosphorus-31 magnetic resonance spectroscopy (31P-MRS). Our hypothesis is that pH abnormalities extend beyond the visible lesions., Methods: Three-dimensional 31P-MRS at 3.0 T was performed in 37 patients with epilepsy and MCD, and in 31 matched-control subjects. The patients were assigned into three main MCD subgroups: cortical dysplasia (n=10); heterotopia (n=14); schizencephaly/polymicrogyria (n=13). Voxels (12.5 cm3) were selected in five homologous regions containing NAP: right putamen; left putamen; frontoparietal parasagittal cortex; right centrum semiovale; and left centrum semiovale. Robust methods of quantification were applied, and the intracellular pH was calculated with the chemical shifts of inorganic phosphate (Pi) relative to phosphocreatine (PCr)., Results: In comparison to controls and considering a Bonferroni adjusted p-value <0.01, MCD patients presented significant reduction in intracellular pH in the frontoparietal parasagittal cortex (6.985±0.022), right centrum semiovale (7.004±0.029), and left centrum semiovale (6.995±0.030), compared to controls (mean values±standard deviations of 7.087±0.048, 7.096±0.042, 7.088±0.045, respectively). Dunnet and Dunn tests demonstrated that the differences in pH values remained statistically significant in all MCD subgroups. No significant differences were found for the putamina., Conclusion: The present study demonstrates widespread acidosis in the NAP, and reinforces the idea that MCD visible lesions are only the tip of the iceberg., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that can characterize white matter (WM) architecture and microstructure. DTI has demonstrated extensive WM changes in patients with several epileptic syndromes, but few studies have focused on patients with malformations of cortical development (MCD). Our aim was to investigate the quantitative diffusion properties of the corpus callosum (CC), a major commissural bundle critical in inter-hemispheric connectivity, in a large group of patients with MCD., Methods: Thirty-two MCD patients and 32 age and sex-matched control subjects were evaluated with DTI at 3.0 T. We analyzed the three major subdivisions of the CC (genu, body, and splenium) with deterministic tractography to yield fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (λ||) and perpendicular diffusivity (λ⊥). We further assessed the CC with region of interest (ROI)-based analyses and evaluated different subgroups of MCD (polymicrogyria/schizencephaly, heterotopia, and cortical dysplasia). Partial correlations between diffusion changes and clinical parameters (epilepsy duration and age at disease onset) were also queried., Results: There were significant reductions of FA, accompanied by increases in MD and λ⊥ in all segments of the CC in the patients group with both analytical methods. The absolute differences in FA were greater on ROI-analyses. There were no significant differences between the MCD subgroups, and no correlations between clinical parameters of epilepsy and FA., Conclusions: Our study indicates DTI abnormalities consistent with microstructural changes in the corpus callosum of MCD patients. The findings support the idea that patients with epilepsy secondary to cortical malformations present widespread WM changes that extend beyond the macroscopic MRI-visible lesions., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: Knowledge about the nature and impact of symptoms faced by patients with systemic sclerosis (SSc) is needed to identify targets for research and treatment. The aim of this study was to assess and compare the frequency and impact on everyday activities of SSc symptoms among patients from five European countries., Methods: European patients with SSc were invited through announcements by patient associations to complete an online survey. The survey included items assessing the frequency of 40 SSc symptoms and the impact on daily activities, if present. Chi-square tests were utilised to assess the differences in frequency and impact of symptoms across countries., Results: In total, 537 patients were included from France (n=111), the Netherlands (n=229), Spain (n=61), Switzerland (n=50), and the United Kingdom (n=86). Symptoms experienced by ≥ 70% of patients in all countries were fatigue, Raynaud's phenomenon, joint pain, and muscle pain. Twenty symptoms were experienced by ≥ 50% of patients in all countries. Thirty symptoms had an impact on daily activities in ≥ 50% of patients who reported that the symptom was present in all countries. There were significant differences among countries in the prevalence of 17 out of 40 symptoms. Furthermore, in 24 out of 40 symptoms significant differences in the proportion of patients reporting impact of a specific symptom on everyday activities were observed., Conclusions: European patients with SSc experience a broad range of symptoms that have an impact on everyday activities. International research initiatives should target common SSc symptoms cooperatively. Further research is needed to better understand the differences in SSc symptoms among countries.