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Introduction: Developed by the Global Vascular Guidelines committee, the Global Limb Anatomic Staging System (GLASS) is an angiographic scoring system used for quantifying infrainguinal disease extent and predicting treatment success with endovascular techniques (EVT). Currently, no other risk prediction model is available for patients with chronic limb threatening ischemia (CLTI) undergoing EVT. GLASS' validation and adoption outside academic institutions for research are limited. Thus, this longitudinal multicenter prospective study aims to examine GLASS' validity and reliability in predicting major acute limb events and overall survival (OS) in patients with CLTI undergoing EVT., Methods and Analysis: This prospective, international, multicenter, observational study will include patients with CLTI undergoing EVT (PROMOTE-GLASS) (ClinicalTrials.gov; ID: NCT06186544) identified through routine clinical referrals and emergency visits to vascular units in participating centers. Only patients who are referred for EVT will be recruited. The primary outcomes are immediate technical success, immediate technical failure, and 1-year limb base patency. The secondary outcomes are major adverse limb events, major lower limb amputation, and OS in patients presenting with CLTI who undergo EVT up to 1 year after the procedure. Clinical and imaging data will be analyzed at the end of follow-up to validate risk prediction. This protocol outlines our approach for identifying cases, GLASS score calculation, outcome measures assessment, and a statistical analysis plan., Anticipated Implications: PROMOTE-GLASS holds significant implications and can potentially revolutionize clinical decision-making by assisting clinicians in identifying patients who are likely to benefit from EVT. Ultimately, reduce the need for more invasive procedures and improve patient outcomes. Furthermore, PROMOTE-GLASS can provide useful information, including patient selection, for future randomized controlled trials (RCTs) investigating EVT for CLTI. PROMOTE-GLASS anticipated implications on the vascular community are rooted in its potential to improve patient care, inform future research, and address limitations in existing literature regarding CLTI treatment outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Tailings dams' breaks are environmental disasters with direct and intense degradation of soil. This study analyzed the impacts of B1 tailings dam rupture occurred in the Ribeirão Ferro-Carvão watershed (Brumadinho, Brazil) in January 25, 2019. Soil organic carbon (SOC) approached environmental degradation. The analysis encompassed wetlands (high-SOC pools) located in the so-called Zones of Decreasing Destructive Capacity (DCZ5 to DCZ1) defined along the Ferro-Carvão's stream bed and banks after the disaster. Remote sensed water indices were extracted from Landsat 8 and Sentinel-2 satellite images spanning the 2017-2021 period and used to distinguish the wetlands from other land covers. The annual SOC was extracted from the MapBiomas repository inside and outside the DCZs in the same period, and assessed in the field in 2023. Before the dam collapse, the DCZs maintained stable levels of SOC, while afterwards they decreased substantially reaching minimum values in 2023. The reductions were abrupt: for example, in the DCZ3 the decrease was from 51.28 ton/ha in 2017 to 4.19 ton/ha in 2023. Besides, the SOC increased from DCZs located near to DCZs located farther from the dam site, a result attributed to differences in the percentages of clay and silt in the tailings, which also increased in the same direction. The Ferro-Carvão stream watershed as whole also experienced a slight reduction in the average SOC levels after the dam collapse, from nearly 43 ton/ha in 2017 to 38 ton/ha in 2021. This result was attributed to land use changes related with the management of tailings, namely opening of accesses to remove them from the stream valley, creation of spaces for temporary deposits, among others. Overall, the study highlighted the footprints of tailings dams' accidents on SOC, which affect not only the areas impacted with the mudflow but systemically the surrounding watersheds. This is noteworthy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze cognitive performance and brain activation during a working memory task in patients with migraine during various phases of the migraine cycle and compare to healthy participants., Background: Cognitive difficulties reported during migraine attacks remain poorly understood, despite evidence that the lateral frontoparietal network undergoes reversible disturbances and decreased activation during attacks. Recent findings in resting state functional magnetic resonance imaging suggest that brain areas involved in this network interact with subcortical regions during spontaneous migraine attacks., Methods: In this prospective, within-subject study, 10 patients with diagnosed menstrual-related episodic migraine without aura underwent 3T functional magnetic resonance imaging assessments while performing a working memory task across four phases of the natural migraine cycle: peri-ictal (preictal, ictal, postictal) phases and interictally (between attacks). Migraine prophylaxis was an exclusion criterion. Fourteen healthy controls were assessed during the corresponding phases of their menstrual cycles., Results: The protocol was completed by 24 female participants aged 21 to 47 years: 10 with migraine (four sessions each) and 14 healthy controls (two sessions each) yielding a total of 68 analyzed datasets. Patients and controls showed similar performance on the working memory task and displayed increased brain activity in regions linked to this function, namely the middle frontal gyrus, inferior parietal lobe, and anterior cingulate cortex, during all phases of the migraine/menstrual cycle. Patients with migraine (N = 10) exhibited a significant decrease in hypothalamic activity (p = 0.007) as measured by the percent signal change (PSC) during the postictal phase compared to perimenstrual controls (N = 14), with -2 (16) and 31 (35) PSC, respectively. Comparing across the migraine cycle, the change in hypothalamic activity relative to controls in the postictal phase -0.33 (0.2) ΔPSC was significantly different from the ones in the interictal (0.006 [0.5] ΔPSC; p = 0.002) and preictal (-0.08 [0.4] ΔPSC; p = 0.034) phases., Conclusion: During a working memory task, cognition-related brain activation was present across all phases of the migraine cycle similarly to healthy control participants. Patients with migraine, however, displayed lower neural activity at the subcortical level in the postictal phase. Nonetheless, the sample size is a limitation for the generalization of our results. More research is needed to fully understand how the brain copes with cognitive demands during spontaneous migraine attacks., (© 2024 American Headache Society.)

The collapse of B1 dam at the Córrego do Feijão mine of Vale, S.A., located in the Ferro-Carvão stream watershed (Brazil), released 11.7 Mm 3 of tailings rich in iron and manganese, and 2.8 Mm 3 entered the Paraopeba River 10 km downstream. Seeking to predict the evolution of environmental deterioration in the river since the dam break on January 25, 2019, the present study generated exploratory and normative scenarios based on predictive statistical models, and proposed mitigating measures and subsides to ongoing monitoring plans. The scenarios segmented the Paraopeba into three sectors: "anomalous" for distances ≤63.3 km from the B1 dam site, "transition" (63.3-155.3 km), and "natural" (meaning unimpacted by the mine tailings in 2019; >155.3 km). The exploratory scenarios predicted a spread of the tailings until reaching the "natural" sector in the rainy season of 2021, and their containment behind the weir of Igarapé thermoelectric plant located in the "anomalous" sector, in the dry season. Besides, they predicted the deterioration of water quality and changes to the vigor of riparian forests (NDVI index) along the Paraopeba River, in the rainy season, and a restriction of these impacts to the "anomalous" sector in the dry season. The normative scenarios indicated exceedances of chlorophyll-a in the period January 2019-January 2022, but not exclusively caused by the rupture of B1 dam as they also occurred in areas not affected by the accident. Conversely, the manganese exceedances clearly flagged the dam failure, and persist. The most effective mitigating measure is likely the dredging of the tailings in the "anomalous" sector, but currently it represents solely 4.6 % of what has entered the river. Monitoring is paramount to update the scenarios until the system enters a route towards rewilding, and must include water and sediments, the vigor of riparian vegetation, and the dredging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Oxidation of PUFAs in LDLs trapped in the arterial intima plays a critical role in atherosclerosis. Though there have been many studies on the atherogenicity of oxidized derivatives of PUFA-esters of cholesterol, the effects of cholesteryl hemiesters (ChEs), the oxidation end products of these esters, have not been studied. Through lipidomics analyses, we identified and quantified two ChE types in the plasma of CVD patients and identified four ChE types in human endarterectomy specimens. Cholesteryl hemiazelate (ChA), the ChE of azelaic acid (n-nonane-1,9-dioic acid), was the most prevalent ChE identified in both cases. Importantly, human monocytes, monocyte-derived macrophages, and neutrophils exhibit inflammatory features when exposed to subtoxic concentrations of ChA in vitro. ChA increases the secretion of proinflammatory cytokines such as interleukin-1β and interleukin-6 and modulates the surface-marker profile of monocytes and monocyte-derived macrophage. In vivo, when zebrafish larvae were fed with a ChA-enriched diet, they exhibited neutrophil and macrophage accumulation in the vasculature in a caspase 1- and cathepsin B-dependent manner. ChA also triggered lipid accumulation at the bifurcation sites of the vasculature of the zebrafish larvae and negatively impacted their life expectancy. We conclude that ChA behaves as an endogenous damage-associated molecular pattern with inflammatory and proatherogenic properties., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to compare outcomes of single or multistage approach during fenestrated-branched endovascular aortic repair (FB-EVAR) of extensive thoracoabdominal aortic aneurysms (TAAAs)., Methods: We reviewed the clinical data of consecutive patients treated by FB-EVAR for extent I to III TAAAs in 24 centers (2006-2021). All patients received a single brand manufactured patient-specific or off-the-shelf fenestrated-branched stent grafts. Staging strategies included proximal thoracic aortic repair, minimally invasive segmental artery coil embolization, temporary aneurysm sac perfusion and combinations of these techniques. Endpoints were analyzed for elective repair in patients who had a single- or multistage approach before and after propensity score adjustment for baseline differences, including the composite 30-day/in-hospital mortality and/or permanent paraplegia, major adverse event, patient survival, and freedom from aortic-related mortality., Results: A total of 1947 patients (65% male; mean age, 71 ± 8 years) underwent FB-EVAR of 155 extent I (10%), 729 extent II (46%), and 713 extent III TAAAs (44%). A single-stage approach was used in 939 patients (48%) and a multistage approach in 1008 patients (52%). A multistage approach was more frequently used in patients undergoing elective compared with non-elective repair (55% vs 35%; P < .001). Staging strategies were proximal thoracic aortic repair in 743 patients (74%), temporary aneurysm sac perfusion in 128 (13%), minimally invasive segmental artery coil embolization in 10 (1%), and combinations in 127 (12%). Among patients undergoing elective repair (n = 1597), the composite endpoint of 30-day/in-hospital mortality and/or permanent paraplegia rate occurred in 14% of single-stage and 6% of multistage approach patients (P < .001). After adjustment with a propensity score, multistage approach was associated with lower rates of 30-day/in-hospital mortality and/or permanent paraplegia (odds ratio, 0.466; 95% confidence interval, 0.271-0.801; P = .006) and higher patient survival at 1 year (86.9±1.3% vs 79.6±1.7%) and 3 years (72.7±2.1% vs 64.2±2.3%; adjusted hazard ratio, 0.714; 95% confidence interval, 0.528-0.966; P = .029), compared with a single stage approach., Conclusions: Staging elective FB-EVAR of extent I to III TAAAs was associated with decreased risk of mortality and/or permanent paraplegia at 30 days or within hospital stay, and with higher patient survival at 1 and 3 years., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Onychomycosis is the most common disease affecting the nail unit and accounts for at least 50% of all nail diseases. In addition, Candida albicans is responsible for approximately 70% of onychomycoses caused by yeasts. This study investigated the antifungal effect of (R) and (S)-citronellal enantiomers, as well as its predictive mechanism of action on C. albicans from voriconazole-resistant onychomycoses. For this purpose, in vitro broth microdilution and molecular docking techniques were applied in a predictive and complementary manner to the mechanisms of action. The main results of this study indicate that C. albicans was resistant to voriconazole and sensitive to the enantiomers (R) and (S)-citronellal at a dose of 256 and 32 µg/mL respectively. In addition, there was an increase in the minimum inhibitory concentration (MIC) of the enantiomers in the presence of sorbitol and ergosterol, indicating that these molecules possibly affect the integrity of the cell wall and cell membrane of C. albicans. Molecular docking with key biosynthesis proteins and maintenance of the fungal cell wall and plasma membrane demonstrated the possibility of (R) and (S)-citronellal interacting with two important enzymes: 1,3-β-glucan synthase and lanosterol 14α-demethylase. Therefore, the findings of this study indicate that the (R) and (S)-citronellal enantiomers are fungicidal on C. albicans from onychomycoses and probably these substances cause damage to the cell wall and cell membrane of these micro-organisms possibly by interacting with enzymes in the biosynthesis of these fungal structures.

Eighteen interviews were used in this research to inductively conceptualize the factors that influence digital transformation (DT) in Kibs companies that provide multidisciplinary Knowledge Intensive Business Services. Two main groups were identified: factors of DT and use in the new digital environment. Using the findings obtained, a comparison was made with the existing literature and the most relevant aspects of DT as a disruptive phenomenon which can generate intra-organizational competitive advantage are exposed., Objective: To identify the factors of innovation-oriented organizational management, generated by the collaboration of the professional grouping of Kibs companies through the systematization of knowledge, which serve to conceptually delimit the DT phenomenon. Ultimately, it is expected to establish recommendations for this type of companies based on providing services with high knowledge value that strive to digitally transform their businesses., Originality: the paper contributes to advancing the conceptual understanding of DT through the study of Kibs companies, which remain understudied. Likewise, there is no known study that analyzes the factors that give rise to DT in a professional grouping of small Kibs companies. It is clear that this union of small companies generates a strong internal capacity for knowledge absorption, through daily interactions with clients and public administrations, which favors the process of implementing certain technological and strategic components that are beneficial for the development of professional activity and increases the propensity to innovate., Methodology: qualitative content was analysed using a grounded theory methodology including interviews with experts and the managers of the Kibs companies in the professional sector to obtain a solid basis that can be used to identify the most relevant factors of DT., Findings/results: as DT is a multidimensional phenomenon of individual companies, this study presents a conceptual framework for the term with the strategic requirements of the market, organizations, public institutions and technological infrastructures of the professional sector. By considering the disruptive factors of digital development in this macroenvironment, conclusions can be made about the basic principles and effects of DT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marino-Romero, Palos-Sanchez, Velicia-Martin and Rodrigues.)

The present study aimed to investigate the rupture of B1 tailings dam of Córrego do Feijão mine, which drastically affected the region of Brumadinho (Minas Gerais, Brazil). The contamination of water resources reached 155.3 km from the dam site. In the river channel, high concentrations of Mn, Al, As and Fe were detected and correlated to the spillage of the tailings in the river. The presence of the tailings also affected the chlorophyll-a content in the water, as well as the reflectance of riparian forests. With the increase of metal(oid) concentrations above permitted levels, water management authorities suspended the use of Paraopeba River as resource in the impacted areas, namely the drinking water supply to the Metropolitan region of Belo Horizonte. This study aimed to evaluate possible links between tailings distribution, river water quality, and environmental degradation, which worked as latent variables in partial least squares regression models. The latent variables were represented by numerous physical and chemical parameters of water and sediment, measured four times in 22 locations during the rainy season of 2019, in addition to stream flow and to NDVI evaluated in satellite images processed daily. The modeling results suggested a relationship between river flow turbulence and increased arsenic release from sand fractions, as well as desorption of Mn from metal oxides, both representing causes of water quality reduction. They also revealed increasing iron concentrations affecting the forest NDVI (greening), which was interpreted as environmental degradation. The increase of chlorophyll-a concentrations (related with turbidity decreases), as well as the increase of river flows (responsible for dilution effects), seemed to work out as attenuators of degradation. Although applied to a specific site, our modeling approach can be transposed to equivalent dam failures and climate contexts, helping water resource management authorities to decide upon appropriate recovery solutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (IDDFBA) is a recently described autosomal dominant entity caused by pathogenic variants, mostly de novo, in the FBXO11 gene. It presents in the first years of life with highly variable clinical manifestations. The main features of IDDFBA include borderline-to-severe intellectual disability, behavioral problems, hypotonia, facial dysmorphisms, minor skeletal abnormalities, and recurrent infections. Although eye problems, such as refractive errors, eye misalignment and minor visual changes, have been described in about 48% of patients, a major ocular defect, namely, bilateral optic nerve hypoplasia, has been reported in the literature only once. We report an 8-year-old boy with a novel de novo pathogenic variant in FBXO11 gene (NM&#95;001190274.1: c.1166dup, p.Cys390Metfs∗3) and a complex ophthalmological phenotype, consisting of right microphthalmia, very shallow anterior chamber, and persistent pupillary membrane, right dense nuclear cataract, bilateral optic nerve hypoplasia, and bilateral horizontal manifest nystagmus., (Copyright © 2022 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

This study investigated the collapse of B1 mine-tailings dam that occurred in 25 January 2019 and severely affected the Brumadinho region (Minas Gerais state, Brazil) socially, economically and environmentally. As regards water resources, the event impacted the Paraopeba River in the first 155.3 km counted from the dam site, meaning nearly half the main water course downstream of B1. In the impacted sector, high concentrations of tailings-related Al, Fe, Mn, P in river sediment-tailings mixtures and water were detected, as well as changes to the reflectance of riparian forests. In the river water, the metal concentrations raised significantly above safe levels. For caution, the water management authorities declared immediate suspension of Paraopeba River as drinking water source to the Metropolitan Region of Belo Horizonte (6 million people), irrespective of representing nearly 30% of all supply. In this study, the main purpose was to assess potential links between tailings distribution, river water composition and reflectance of forest vegetation, which worked out as latent variables in regression models. The latent variables were represented by numerous physical and chemical parameters, measured 4 times in 22 sites during the dry period of 2019. The modeling results suggested the release of aluminum and phosphorus from sand fractions in the mine tailings as major cause of water contamination. The NDVI changes were interpreted as environmental deterioration. Changes in redox potential may have raised manganese concentrations in surface water further affecting the forest NDVI. Distance from the B1 dam and dissolved calcium appear to attenuate deterioration. Overall, the regressions allowed robust prognoses of environmental deterioration in the Paraopeba River under low flow conditions. More importantly, they can be transposed to similar dam ruptures helping environmental authorities to decide upon measures that can bring the affected rivers to pre-rupture conditions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Technological advances in both genome sequencing and prenatal imaging are increasing our ability to accurately recognize and diagnose Mendelian conditions prenatally. Phenotype-driven early genetic diagnosis of fetal genetic disease can help to strategize treatment options and clinical preventive measures during the perinatal period, to plan in utero therapies, and to inform parental decision-making. Fetal phenotypes of genetic diseases are often unique and at present are not well understood; more comprehensive knowledge about prenatal phenotypes and computational resources have an enormous potential to improve diagnostics and translational research. The Human Phenotype Ontology (HPO) has been widely used to support diagnostics and translational research in human genetics. To better support prenatal usage, the HPO consortium conducted a series of workshops with a group of domain experts in a variety of medical specialties, diagnostic techniques, as well as diseases and phenotypes related to prenatal medicine, including perinatal pathology, musculoskeletal anomalies, neurology, medical genetics, hydrops fetalis, craniofacial malformations, cardiology, neonatal-perinatal medicine, fetal medicine, placental pathology, prenatal imaging, and bioinformatics. We expanded the representation of prenatal phenotypes in HPO by adding 95 new phenotype terms under the Abnormality of prenatal development or birth (HP:0001197) grouping term, and revised definitions, synonyms, and disease annotations for most of the 152 terms that existed before the beginning of this effort. The expansion of prenatal phenotypes in HPO will support phenotype-driven prenatal exome and genome sequencing for precision genetic diagnostics of rare diseases to support prenatal care., (© 2022 The Authors. American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.)

Background: Acridine compounds have been described as promising anticancer agents. Previous studies showed that (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a spiro-acridine compound, has antitumor activity on Ehrlich tumor and low toxicity. Herein, we investigated its antitumor effect against human cells in vitro., Methods: MTT assay was used to assess cytotoxicity of AMTAC-06 (3.125-200 µM) against tumor and non-tumor cells, and the half-maximal inhibitory concentration (IC 50 ) and the selectivity index (SI) were calculated. The effects on the cell cycle (propidium iodide-PI-staining), apoptosis (Annexin V-FITC/PI double staining by flow cytometry), and production of reactive oxygen species, ROS (DCFH assay) were also evaluated. Statistical analysis was achieved using ANOVA followed by Tukey's post-test., Results: AMTAC-06 showed higher cytotoxicity against colorectal carcinoma HCT-116 cells (IC 50 : 12.62 µM). The SI showed that AMTAC-06 was more selective for HCT-116 cells (HaCaT SI: 1.41; PBMC SI: 0.62) than doxorubicin (HaCaT SI: 0.10; PBMC SI: 0.01). AMTAC-06 (15 and 30 µM) induced an increase in the sub-G1 peak (p < 0.000001) and cell cycle arrest in S phase (p = 0.003547). Moreover, treatment with this compound (15 and 30 µM) resulted in increased early (p < 0.000001) and late apoptotic cells (p < 0.000001). In addition, there was a reduction on ROS production (p < 0.000001)., Conclusions: AMTAC-06 presents anticancer activity against HCT-116 cells by regulating the cell cycle, inducing apoptosis and an antioxidant action., (© 2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

The relationship between migraine and vision is complex. Besides migraine aura status and persistent visual aura without infarction, recognized by International Headaches Classification 3, cases of persistent monocular alterations have been described in migraineurs. To discuss the role of migraine as a risk factor for persistent monocular visual loss. We present five new cases of persistent monocular visual loss in migraineurs, discuss the differential diagnosis and possible relationship with migraine. Five young healthy patients are reported (three women) with a history of migraine (four with visual aura), that developed persistent monocular visual defects, four during an episode of migraine with aura. All patients were submitted to an extensive investigation. In three patients the scotoma was identified on automated perimetry; one of these patients had retinal hemorrhagic lesions, with fluorescein angiography revealing an isolated retinal vasculitis. In two patients fundoscopy revealed transient cotton wools spots. Except for the patient with retinal vasculitis, etiologic investigation was not conclusive. Monocular visual loss can occur in the setting of multiple pathologies that affect the eye and related structures. Although diseases requiring emergent intervention should always be excluded, we propose migraine should be considered as a contributing factor for unexplained monocular persistent scotoma.Monocular visual loss can occur in the setting of multiple pathologies that affect the eye and related structures. Although diseases requiring emergent intervention should always be excluded, we propose migraine should be considered as a contributing factor for unexplained monocular persistent scotoma., (© 2021. Belgian Neurological Society.)

The inadequate management of soils and the absence of conservation practices favor the degradation of pastures and can trigger adverse environmental alterations and damage under the terms of Brazilian Federal Law no. 6.938/1981. Based on this premise, this study aimed to estimate soil losses caused by water erosion in pasture areas using the brightness index (BI) from the annual series of Landsat 8 images in different geological formations. A specifically prepared Google Earth Engine (GEE) script automatically extracted the BI from the images. The study occurred in the Environmental Protection Area (EPA) of Uberaba River basin (Minas Gerais, Brazil). To accomplish the goal, 180 digital 500-wide random buffers were selected from 3 geologic types (60 points per type), and then analyzed for zonal statistics of USLE (Universal Soil Loss Equation) soil loss and BI in a Geographic Information System. The regression models BI versus USLE soil loss allowed estimating BI soil losses over the pastures of EPA. The model fittings were remarkable. The validation of soil loss maps in the EPA occurred in pasture phytophysiognomies through the probing of penetration resistance in 37 randomly selected locations. The results were satisfactory, mostly those based on the BI. The BI losses increased for greater resistances. Amplified losses also occurred in regions exposed to environmental land use conflicts (actual uses that deviate from land capability or natural use). Overall, the BI approach proved efficient to accurately track soil losses and pasture degradation over large areas, with the advantage of standing on a single parameter easily accessed through remote sensed data. From an environmental standpoint, this is an important result, because the accurate diagnosis and prognosis of degraded pastures is paramount to implement mitigation measures following the "polluter pays principle", even more in Brazil where the areas occupied by degraded pastures are enormous., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background/aim: Studies with acridine compounds have reported anticancer effects. Herein, we evaluated the toxicity and antitumor effect of the (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a promising anticancer spiro-acridine compound., Materials and Methods: The toxicity of AMTAC-06 was evaluated on zebrafish and mice. Antitumor activity was assessed in Ehrlich ascites carcinoma model. Effects on angiogenesis, cytokine levels and cell cycle were also investigated., Results: AMTAC-06 did not induce toxicity on zebrafish and mice (LD 50 approximately 5000 mg/kg, intraperitoneally). No genotoxicity was observed on micronucleus assay. AMTAC-06 significantly reduced the total viable Ehrlich tumor cells and increased sub-G 1 peak, suggesting apoptosis was triggered. Moreover, the compound significantly decreased the density of peritumoral microvessels, indicating an anti-angiogenic action, possibly dependent on the cytokine modulation (TNF-α, IL-1β and IFN-γ). No significant toxicological effects were recorded for AMTAC-06 on tumor transplanted animals., Conclusion: AMTAC-06 has low toxicity and a significant antitumor activity., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

De novo absence status is clinically characterized by a confusional syndrome and neurophysiologically by the presence of periodic spike/polyspike-and-wave discharges on EEG. The treatment should be started promptly, and fast recovery is usually seen. However, cognitive symptoms can be very difficult to detect, and no consensus exists on how cognitive improvement can be clinically monitored. We report a patient with absence status epilepticus, whose therapeutic response was monitored neurophysiologically with EEG and clinically with a cognitive test; the Montreal Cognitive Assessment (MoCA). Based on this case report, we describe the use of the MoCA for monitoring cognitive function in a patient with absence status epilepticus. MoCA was evaluated on three occasions, with a total score ranging from 9, before treatment, to 23, when an EEG with no epileptiform discharges was obtained. We suggest that MoCA may be a useful tool to monitor cognitive improvement in absence status epilepticus.

Nine new spiroacridine derivatives were synthetized by introducing cyano-N-acylhydrazone group between the acridine and phenyl-substituted rings followed by spontaneous cyclization. The new compounds were assayed for their DNA binding properties, human topoisomerase IIα inhibition and bovine serum albumin (BSA) interaction. Besides, docking analysis were performed in order to better understanding the biomolecule-compounds interactions. All compounds interacted with BSA which was demonstrated by the fluorescence suppression constant of 10 4  M -1 . Compounds with chloro and NO 2 substituents at that para-position on phenyl ring demonstrated the best results for BSA interaction. DNA binding constant determined by UV-vis data demonstrated high values for AMTAC-11 and AMTAC-14, 1.1 × 10 8  M -1 and 4.8 × 10 6  M -1 , respectively, and all others presented constant values of 10 5  M -1 . AMTAC-06 with chloro at para-position on phenyl ring presented a topoisomerase II inhibition of 84.34% in comparison to the positive controls used. Docking studies indicated that AMTAC-06 is able to intercalate the DNA base pairs at topoisomerase IIα active site, preventing DNA connection after break, in a process known as poisoning. Topoisomerase enzyme inhibition result was correlated to BSA interaction profile, since AMTAC-06 showed the best results in both analysis. The findings obtained here proved that methoxy or chloro substitution on phenyl ring at para-position is fundamental for in vitro activity of new spiroacridine derivatives, and indicates that AMTAC-06 is a promising entity and should serve as a lead compound in the development of new DNA and protein binders, as well as human topoisomerase II inhibitors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Monitoring of immunosuppressive drugs, such as calcineurin and mTOR inhibitors, is essential to avoid undesirable kidney transplant outcomes. Polymorphisms in pharmacokinetics-related genes have been associated with variability in blood levels of immunosuppressive drugs and adverse effects, but influence of pharmacodynamics-related genes remains to be elucidated. The influence of polymorphisms in genes of the mTOR and calcineurin signaling pathways on long-term clinical outcomes was investigated in Brazilian kidney transplant recipients within the 1-year post-transplant. Two-hundred and sixty-nine kidney transplant recipients were enrolled at a kidney transplant center in São Paulo city, Brazil, and treated with tacrolimus plus everolimus or mycophenolate sodium (clinical trial NCT01354301). Clinical and laboratory data, including renal function parameters and drug blood levels were recorded. Genomic DNA was extracted from blood samples. Polymorphisms in MTOR rs1057079 (c.4731G>A), rs1135172 (c.1437T>C), and rs1064261 (c.2997C>T); PPP3CA rs3730251 (c.249G>A); FKBP1A rs6033557 (n.259+24936T>C); FKBP2 rs2159370 (c.-2110G>T); and FOXP3 rs3761548 (c.-23+2882A>C) and rs2232365 (c.-22-902A>G) were analyzed by real-time PCR. Frequencies of gene polymorphisms did not differ among the treatment groups. Analysis of primary outcomes showed that patients carrying MTOR c.1437CC and FOXP3 c.-23+2882CC genotypes had higher serum creatinine than non-carriers ( p < 0.05) at 1-year post-transplant. MTOR c.4731G allele (AG+GG genotype) was associated with increased risk for acute rejection (OR = 3.53, 95% CI = 1.09-11.48, p = 0.037). Moreover, 1-year cumulative incidence of rejection was higher in MTOR c.4731G allele carriers compared to AA genotype carriers ( p = 0.027). Individually, analysis of secondary outcomes revealed that FKBP2 c.-2110GG genotype carriers had higher risk of leukopenia, FKBP1A n.259+24936C allele carriers had increased risk of constipation, and FOXP3 c.-22-902A or c.-23+2882A allele had higher risk of gastrointestinal disorders ( p < 0.05). However, these results were not maintained in the multivariable analysis after p -value adjustment. In conclusion, variants in genes of mTOR and calcineurin pathways are associated with long-term impaired renal function, increased risk of acute rejection, and, individually, with adverse events in Brazilian kidney transplant recipients.

Biomechanical analysis of pelvic floor dysfunction requires knowledge of certain biomechanical parameters, such as muscle fiber direction, in order to adequately model function. Magnetic resonance (MR) diffusion tensor imaging (DTI) provides an estimate of overall muscle fiber directionality based on the mathematical description of water diffusivity. This work aimed at evaluating the concurrence between pubovisceralis muscle fiber representations obtained from DTI, and the maximum principal stress lines obtained through the finite element method. Seven datasets from axial T2-weighted images were used to build numerical models, and muscle fiber orientation estimated from the DT images. The in-plane projections of the first eigenvector of both vector fields describing muscle fiber orientation were extracted and compared. The directional consistency was evaluated by calculating the angle between the normalized vectors for the entire muscle and also for the right and left insertions, middle portions, and anorectal area. The values varied between 28° ± 6 (right middle portion) and 34° ± 9 (anorectal area), and were higher than the angular precision of the DT estimates, evaluated using wild bootstrapping analysis. Angular dispersion ranged from 17° ± 4 (left middle portion) to 23° ± 5 (anorectal area). Further studies are needed to examine acceptability of these differences when integrating the vectors estimated from DTI in the numerical analysis.

Background: The study was a collaboration between Lifting The Burden (LTB) and the European Headache Federation (EHF). Its aim was to evaluate the implementation of quality indicators for headache care Europe-wide in specialist headache centres (level-3 according to the EHF/LTB standard)., Methods: Employing previously-developed instruments in 14 such centres, we made enquiries, in each, of health-care providers (doctors, nurses, psychologists, physiotherapists) and 50 patients, and analysed the medical records of 50 other patients. Enquiries were in 9 domains: diagnostic accuracy, individualized management, referral pathways, patient's education and reassurance, convenience and comfort, patient's satisfaction, equity and efficiency of the headache care, outcome assessment and safety., Results: Our study showed that highly experienced headache centres treated their patients in general very well. The centres were content with their work and their patients were content with their treatment. Including disability and quality-of-life evaluations in clinical assessments, and protocols regarding safety, proved problematic: better standards for these are needed. Some centres had problems with follow-up: many specialised centres operated in one-touch systems, without possibility of controlling long-term management or the success of treatments dependent on this., Conclusions: This first Europe-wide quality study showed that the quality indicators were workable in specialist care. They demonstrated common trends, producing evidence of what is majority practice. They also uncovered deficits that might be remedied in order to improve quality. They offer the means of setting benchmarks against which service quality may be judged. The next step is to take the evaluation process into non-specialist care (EHF/LTB levels 1 and 2).

Background: Cancer is a critical disease that affects millions of people and families around the world. In 2012 about 14.1 million new cases of cancer occurred globally. Because of many reasons like the severity of some cases, the side effects of some treatments and death of other patients, cancer patients tend to be affected by serious emotional disorders, like depression, for instance. Thus, monitoring the mood of the patients is an important part of their treatment. Many cancer patients are users of online social networks and many of them take part in cancer virtual communities where they exchange messages commenting about their treatment or giving support to other patients in the community. Most of these communities are of public access and thus are useful sources of information about the mood of patients. Based on that, Sentiment Analysis methods can be useful to automatically detect positive or negative mood of cancer patients by analyzing their messages in these online communities., Objective: The objective of this work is to present a Sentiment Analysis tool, named SentiHealth-Cancer (SHC-pt), that improves the detection of emotional state of patients in Brazilian online cancer communities, by inspecting their posts written in Portuguese language. The SHC-pt is a sentiment analysis tool which is tailored specifically to detect positive, negative or neutral messages of patients in online communities of cancer patients. We conducted a comparative study of the proposed method with a set of general-purpose sentiment analysis tools adapted to this context., Methods: Different collections of posts were obtained from two cancer communities in Facebook. Additionally, the posts were analyzed by sentiment analysis tools that support the Portuguese language (Semantria and SentiStrength) and by the tool SHC-pt, developed based on the method proposed in this paper called SentiHealth. Moreover, as a second alternative to analyze the texts in Portuguese, the collected texts were automatically translated into English, and submitted to sentiment analysis tools that do not support the Portuguese language (AlchemyAPI and Textalytics) and also to Semantria and SentiStrength, using the English option of these tools. Six experiments were conducted with some variations and different origins of the collected posts. The results were measured using the following metrics: precision, recall, F1-measure and accuracy, Results: The proposed tool SHC-pt reached the best averages for accuracy and F1-measure (harmonic mean between recall and precision) in the three sentiment classes addressed (positive, negative and neutral) in all experimental settings. Moreover, the worst accuracy value (58%) achieved by SHC-pt in any experiment is 11.53% better than the greatest accuracy (52%) presented by other addressed tools. Finally, the worst average F1 (48.46%) reached by SHC-pt in any experiment is 4.14% better than the greatest average F1 (46.53%) achieved by other addressed tools. Thus, even when we compare the SHC-pt results in complex scenario versus others in easier scenario the SHC-pt is better., Conclusions: This paper presents two contributions. First, it proposes the method SentiHealth to detect the mood of cancer patients that are also users of communities of patients in online social networks. Second, it presents an instantiated tool from the method, called SentiHealth-Cancer (SHC-pt), dedicated to automatically analyze posts in communities of cancer patients, based on SentiHealth. This context-tailored tool outperformed other general-purpose sentiment analysis tools at least in the cancer context. This suggests that the SentiHealth method could be instantiated as other disease-based tools during future works, for instance SentiHealth-HIV, SentiHealth-Stroke and SentiHealth-Sclerosis., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Purpose: The aim of this work was to perform a qualitative and quantitative comparison of the performance of two fat suppression techniques on breast diffusion-weighted imaging (DWI)., Materials and Methods: Fifty-one women underwent clinical breast magnetic resonance imaging, including DWI with short TI inversion recovery (STIR) and spectral attenuated inversion recovery (SPAIR). Four were excluded from the analysis due to image artefacts. Rating of fat suppression uniformity and lesion visibility were performed. Agreement between the two sequences was evaluated. Additionally, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values for normal gland, benign and malignant lesions were compared. Receiver operating characteristic analysis was also performed., Results: From the 52 lesions found, 47 were detected by both sequences. DWI-STIR evidenced more homogeneous fat suppression (p = 0.03). Although these lesions were seen with both techniques, DWI-SPAIR evidenced higher score for lesion visibility in nine of them. SNR and CNR were comparable, except for SNR in benign lesions (p < 0.01), which was higher for DWI-SPAIR. Mean ADC values for lesions were similar. ADC for normal fibroglandular tissue was higher when using DWI-STIR (p = 0.006). Sensitivity, specificity, accuracy and area under the curve values were alike: 84.0 % for both; 77.3, 71.4 %; 80.9, 78.3 %; 82.5, 81.3 % for DWI-SPAIR and DWI-STIR, respectively., Conclusion: DWI-STIR showed superior fat suppression homogeneity. No differences were found for SNR and CNR, except for SNR in benign lesions. ADCs for lesions were comparable. Findings in this study are consistent with previous studies at 1.5 T, meaning that both fat suppression techniques are appropriate for breast DWI at 3.0 T.

Diffusion kurtosis imaging (DKI) is a diffusion-weighted technique which overcomes limitations of the commonly used diffusion tensor imaging approach. This technique models non-Gaussian behaviour of water diffusion by the diffusion kurtosis tensor (KT), which can be used to provide indices of tissue heterogeneity and a better characterisation of the spatial architecture of tissue microstructure. In this study, the geometry of the KT is elucidated using synthetic data generated from multi-compartmental models, where diffusion heterogeneity between intra- and extra-cellular media is taken into account, as well as the sensitivity of the results to each model parameter and to synthetic noise. Furthermore, based on the assumption that the maxima of the KT are distributed perpendicularly to the direction of well-aligned fibres, a novel algorithm for estimating fibre direction directly from the KT is proposed and compared to the fibre directions extracted from DKI-based orientation distribution function (ODF) estimates previously proposed in the literature. Synthetic data results showed that, for fibres crossing at high intersection angles, direction estimates extracted directly from the KT have smaller errors than the DKI-based ODF estimation approaches (DKI-ODF). Nevertheless, the proposed method showed smaller angular resolution and lower stability to changes of the simulation parameters. On real data, tractography performed on these KT fibre estimates suggests a higher sensitivity than the DKI-based ODF in resolving lateral corpus callosum fibres reaching the pre-central cortex when diffusion acquisition is performed with five b-values. Using faster acquisition schemes, KT-based tractography did not show improved performance over the DKI-ODF procedures. Nevertheless, it is shown that direct KT fibre estimates are more adequate for computing a generalised version of radial kurtosis maps., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Automatic recognition of words from letter strings is a critical processing step in reading that is lateralized to the left-hemisphere middle fusiform gyrus in the so-called Visual Word Form Area (VWFA). Surgical lesions in this location can lead to irreversible alexia. Very early left hemispheric lesions can lead to transfer of the VWFA to the nondominant hemisphere, but it is currently unknown if this capability is preserved in epilepsies developing after reading acquisition. In this study, we aimed to determine the lateralization of the VWFA in late-onset left inferior occipital lobe epilepsies and also the effect of surgical disconnection from the adjacent secondary visual areas. Two patients with focal epilepsies with onset near the VWFA underwent to surgery for epilepsy, with sparing of this area. Neuropsychology evaluations were performed before and after surgery, as well as quantitative evaluation of the speed of word reading. Comparison of the surgical localization of the lesion, with the BOLD activation associated with the contrast of words-strings, was performed, as well as a study of the associated main white fiber pathways using diffusion-weighted imaging. Neither of the patients developed alexia after surgery (similar word reading speed before and after surgery) despite the fact that the inferior occipital surgical lesions reached the neighborhood (less than 1cm) of the VWFA. Surgeries partly disconnected the VWFA from left secondary visual areas, suggesting that pathways connecting to the posterior visual ventral stream were severely affected but did not induce alexia. The anterior and superior limits of the resection suggest that the critical connection between the VWFA and the Wernicke's Angular Gyrus cortex was not affected, which is supported by the detection of this tract with probabilistic tractography. Left occipital lobe epilepsies developing after reading acquisition did not produce atypical localizations of the VWFA, even with foci in the close neighborhood. Surgery for occipital lobe epilepsy should take this into consideration, as well as the fact that disconnection from the left secondary visual areas may not produce alexia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: In Brazil, demographic, socioeconomic and epidemiological changes over time have led to a transition in nutritional standards, resulting in a gradual reduction of malnutrition and an increased prevalence of overweight and obese individuals, similar to the situation in developed countries in previous decades. This study assessed the body mass index (BMI) and the prevalence of an overweight status and obesity, adjusted for various factors, in a population in northeastern Brazil including all age groups., Methods: This is a cross-sectional population-based epidemiological study using single sampling procedure composed of levels. Given the heterogeneity of the variable "income" and the relationship between income, prevalence of diseases and nutrition, a stratified sampling on blocks in the first level was used. In this, city districts were classified by income into 10 strata, according to information obtained from IBGE. A systematic sampling was applied on randomly selected blocks in order to choose the residences that would be part of the sample (second level), including 1165 participants from all age groups., Results and Discussion: The prevalence of an overweight status or obesity was adjusted for demographic, socioeconomic and lifestyle variables. When the Chi-square test was applied, a relationship was observed between the prevalence of an overweight status or obesity and the age group, gender, educational level and income of the participants. Regarding lifestyle parameters, only smoking was associated with the prevalence of an overweight status or obesity, in both adults and in the total sample. The results for the following groups were significant (p < 0.05): the age group from 20 to 59 years, when the individual presented an educational level greater than or equal to high school; and the age group ≥ 60 years, when the individual was female. It is noteworthy that educational level and being female were significant in adjusting for the total population as major factors influencing an increased BMI, followed by the variables physical activity and family income., Conclusions: The adjusted results justify the adoption of intervention and prevention policies to combat these clinical conditions for the study population as a whole, particularly directed toward adults with higher education level as well as elderly females.

Background: Nitric oxide (NO) has been largely associated with cardiovascular protection through improvement of endothelial function. Recently, new evidence about modulation of NO release by microRNAs (miRs) has been reported, which could be involved with statin-dependent pleiotropic effects, including anti-inflammatory properties related to vascular endothelium function., Objective: To evaluate the effects of cholesterol-lowering drugs including the inhibitors of cholesterol synthesis, atorvastatin and simvastatin, and the inhibitor of cholesterol absorption ezetimibe on NO release, NOS3 mRNA expression and miRs potentially involved in NO bioavailability., Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to atorvastatin, simvastatin or ezetimibe (0 to 5.0 μM). Cells were submitted to total RNA extraction and relative quantification of NOS3 mRNA and miRs -221, -222 and -1303 by qPCR. NO release was measured in supernatants by ozone-chemiluminescence., Results: Both statins increased NO levels and NOS3 mRNA expression but no influence was observed for ezetimibe treatment. Atorvastatin, simvastatin and ezetimibe down-regulated the expression of miR-221, whereas miR-222 was reduced only after the atorvastatin treatment. The magnitude of the reduction of miR-221 and miR-222 after treatment with statins correlated with the increment in NOS3 mRNA levels. No influence was observed on the miR-1303 expression after treatments., Conclusion: NO release in endothelial cells is increased by statins but not by the inhibitor of cholesterol absorption, ezetimibe. Our results provide new evidence about the participation of regulatory miRs 221/222 on NO release induction mediated by statins. Although ezetimibe did not modulate NO levels, the down-regulation of miR-221 could involve potential effects on endothelial function.

Purpose: We aimed to compare two different methods of region of interest (ROI) demarcation and determine interobserver variability on apparent diffusion coefficient (ADC) in breast lesions., Methods: Thirty-two patients with 39 lesions were evaluated with a 3.0 Tesla scanner using a diffusion-weighted sequence with several b-values. Two observers independently performed the ADC measurements using: 1) a small fixed area of 10 mm2 ROI within the area with highest restriction; 2) a large ROI so as to include the whole lesion. Differences were assessed using the Wilcoxon-rank test. Bland-Altman method and Spearman coefficient were applied for interobserver variability and correlation analysis., Results: ADC values measured using the two ROI demarcation methods were significantly different for both observers (P = 0.026; P = 0.033). There was no interobserver variability in ADC values using either method (large ROI, P = 0.21; small ROI, P = 0.64). ADC values of malignant lesions were significantly different between the two methods (P < 0.001). Variability in ADC was ≤0.008×10-3 mm2/s for both methods. When using the same method, ADC values were significantly correlated between the observers (small ROI: r=0.990, P < 0.001; large ROI: r=0.985, P < 0.001)., Conclusion: The choice of ROI demarcation method influences ADC measurements. Small ROIs show less overlap in ADC values and higher ADC reproducibility, suggesting that this method may improve lesion discrimination. Interobserver variability was low for both methods.

Background: Evaluating quality of health care is increasingly recognized as an important contributor to the advancement of health-care delivery. We recently developed a set of quality indicators for headache care, intended to be applicable across countries, cultures and settings so that deficiencies in headache care worldwide might be recognized and rectified. These indicators themselves require evaluation and proof of fitness for purpose. This pilot study begins this process., Methods: We tested the quality indicators in the tertiary headache centres of the University of Duisburg-Essen in Essen, Germany, and the Hospital da Luz in Lisbon, Portugal. Using seven previously-developed enquiry instruments, we interrogated health-care providers (HCPs), including doctors, nurses, psychologists and physiotherapists, as well as consecutive patients and their medical records., Results: The questionnaires were easily understood by both HCPs and patients and were not unduly time-consuming. The results from the two headache centres were comparable despite their differences in structure, staffing and language. These findings met the purpose of the study. Diagnoses were made according to ICHD criteria and critically evaluated during follow-up. However, diagnostic diaries and instruments assessing burden and response to treatment were not always in place or routinely utilised. Triage systems adjusted waiting times to urgency of need. Treatment plans included pathways to other specialities. Patients felt welcomed, reassured and educated, and were mostly satisfied. Discussion points arose over inclusion of psychological therapies in treatment plans; over recording of outcomes; over indicators of efficiency and equitability (protocols to limit wastage of resources, systems to measure input costs and means of ensuring equal access to the services); and over protocols for reporting serious adverse events., Conclusion: This pilot study to assess feasibility of the methods and acceptability of the instruments of headache service quality evaluation was successful. The project is ready to be taken into its next stages.

The aim of this study was to analyze the association between waist-to-height ratio (WHtR) and C-reactive protein (CRP) in the elderly (considering their most prevalent morbidities and lifestyles), to investigate the relationship between this anthropometric index and the presence of the most prevalent morbidities (isolated or combined), and to identify which morbidities (analyzed individually) would have greater associations with WHtR. This cross-sectional population-based epidemiological study of a stratified sampling comprised 170 elderly individuals between 60 and 90 years of age (both genders). Home visits were used to administer questionnaires and to perform anthropometric measurements and blood collection. The mean patient age was younger than 70 years, with women comprising the majority (69.41%) and with 90% of the patients presenting with inadequate WHtR. Hypertension was the most prevalent morbidity in this cohort (58.52%), and when analyzed in combination, hypertension plus obesity were the most frequently diagnosed morbidities (17.65%). Obesity, which was among the most prevalent comorbidities, was the only comorbidity combined with WHtR (p = 0.0019). Individuals with no morbidities had lower mean WHtR values compared with individuals with at least one morbidity (p = 0.0075). In the multiple linear regression model, it was identified that when individuals had one or more of the most prevalent comorbidities, the mean WHtR increased by 0.0415 (p = 0.0065). A correlation between WHtR and CRP (p = 0.0379) was also verified. Based on the relationships observed between WHtR (isolated or in combination, data unpublished) and CRP among the elderly, WHtR may represent a screening tool because it is a simple and effective anthropometric index.

Objectives: To evaluate diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) in the differentiation and characterisation of breast lesions., Methods: Thirty-six women underwent breast magnetic resonance imaging (MRI) including a DWI sequence with multiple b-values (50-3,000 s/mm(2)). Mean values for apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis (MK) were calculated by lesion type and histological subtype. Differences and correlation between parameters were determined., Results: Forty-four lesions were found. There were significant differences between benign and malignant lesions for all parameters (ADC, p = 0.017; MD, p = 0.028; MK, p = 0.017). ADC and MD were higher for benign (1.96 ± 0.41 × 10(-3) and 2.17 ± 0.42 × 10(-3) mm(2)/s, respectively) than for malignant lesions (1.33 ± 0.18 × 10(-3) and 1.52 ± 0.50 × 10(-3) mm(2)/s). MK was higher for malignant (0.61 ± 0.27) than benign lesions (0.37 ± 0.18). We found differences between invasive ductal carcinoma (IDC) and fibroadenoma (FA) for all parameters (ADC, MD and MK): p = 0.016, 0.022 and 0.016, respectively. FA and fibrocystic change (FC) showed differences only in MK (p = 0.016)., Conclusions: Diffusion in breast lesions follows a non-Gaussian distribution. MK enables differentiation and characterisation of breast lesions, providing new insights into microstructural complexity. To confirm these results, further investigation in a broader sample should be performed.

Background: Low calcium:phosphorus ratios (Ca:P ratio) in habitual diet have been observed worldwide, and it has been shown to be harmful to the bone health of the population. However, no study associating this ratio with obesity was found. Thus, considering that the intake of calcium and phosphorus will generate a ratio between them, which may be associated with obesity, this research seeks at evaluating the relation between obesity and the Ca:P ratio in the habitual diet of adults., Methods: Cross-sectional population-based epidemiological study with stratified and systematic sampling. The sample was composed of 506 adults, aged between 18 and 60 years, of both genders. Information on socioeconomic and demographic conditions was obtained through questionnaires completed during home visits, where anthropometric and dietary evaluations were also conducted., Results: In the habitual diet consumed by the study subjects, a Ca:P ratio above the median of 0.57 reduced the risk of central obesity based on waist-to-height ratio (WHtR) (OR: 0.61; 95% CI: 0.41 - 0.92). Habitual dietary intake of calcium (OR: 0.65; 95% CI: 0.43 - 0.97) and dairy products (OR: 0.56; 95% CI: 0.37 - 0.84) above the median value (485.4 mg and 0.9 servings, respectively) was found to be a protective factor related to central obesity based on WHtR., Conclusions: Values above the median for the Ca:P ratio found in the habitual diet were negatively associated with central obesity based on WHtR. In addition, calcium and dairy consumption were negatively associated with central obesity based on WHtR. Therefore, higher Ca:P ratios contributed to a lower prevalence of central obesity.

The aim of this study was to evaluate the relationships between fasting glucose levels, hs-CRP, BMI and serum retinol and diet in elderly people. For this study, a cross-sectional, epidemiological, population-based format was adopted. One hundred and sixty-three individuals between 60 and 90 years of age participated; the participants were from different socioeconomic and health backgrounds, except for the individuals diagnosed with diabetes. Most subjects had serum concentrations in the reference ranges for all variables. There was not a significant relationship between fasting glucose and serum retinol or diet. There was a significant correlation between hs-CRP and BMI (r=0.22, p=0.0082) and hs-CRP and total calorie intake (p=0.0091), which reinforces the notion that an increased intake of calories results in being overweight and/or obese. Considering the importance of vitamin A in various physiological processes, more studies on these relationships are necessary to establish a recommendation of vitamin A for the treatment and prevention of changes in fasting glucose and obesity in the elderly population., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Mangrove forests encompass a group of trees species that inhabit the intertidal zones, where soil is characterized by the high salinity and low availability of oxygen. The phyllosphere of these trees represent the habitat provided on the aboveground parts of plants, supporting in a global scale, a large and complex microbial community. The structure of phyllosphere communities reflects immigration, survival and growth of microbial colonizers, which is influenced by numerous environmental factors in addition to leaf physical and chemical properties. Here, a combination of culture-base methods with PCR-DGGE was applied to test whether local or plant specific factors shape the bacterial community of the phyllosphere from three plant species (Avicenia shaueriana, Laguncularia racemosa and Rhizophora mangle), found in two mangroves. The number of bacteria in the phyllosphere of these plants varied between 3.62 x 10(4) in A. schaeriana and 6.26 x 10(3) in R. mangle. The results obtained by PCR-DGGE and isolation approaches were congruent and demonstrated that each plant species harbor specific bacterial communities in their leaves surfaces. Moreover, the ordination of environmental factors (mangrove and plant species), by redundancy analysis (RDA), also indicated that the selection exerted by plant species is higher than mangrove location on bacterial communities at phyllosphere.

Objectives: To evaluate the efficacy of soy isoflavones extract (SIE) in the treatment of depressive symptoms in women with climacteric syndrome., Methods: Placebo-controlled double-blind randomized study with 84 climacteric outpatients attended in the Lauro Wanderley University Hospital in Joao Pessoa (PB), Brazil. In the assessment of the depressive symptoms, the Brazilian version of the Center of Epidemiologic Studies of Depression (CES-D) scale was used, on the pre-treatment visits (VT1), 8th (VT2) and 16th (VT3) weeks after treatment. The experimental group (EG) received the daily dose of 120mg SIE and the control group (CG), placebo. The primary efficacy measure was the comparison of the percent reductions in the CES-D scores from VT1 to VT3 between EG and CG (t-test, p<0.05). The security analysis consisted of laboratory and clinical evaluation of adverse events., Results: The CES-D scores in the EG reduced from 12.5 (+/-4.2) in VT1 to 9.9 (+/-3.6) in VT2 (VT20.05). In the outcome of the 16-week treatment (VT1-VT3), reduction of the CES-D scores did not reach statistical significance between groups. There were no clinically relevant adverse events attributable to the treatment., Conclusions: The treatment with soy isoflavones did not produce significant reduction on the depressive symptoms of a predominantly affective nature evaluated in this study. The symptomatic reduction initially observed was apparently a nonspecific response to treatment, corroborating evidences from the literature on the placebo phenomenon in treatment of the climacteric syndrome.

Familial hemiplegic migraine is a rare autosomal dominant subtype of migraine with aura. Three genes have been identified, all involved in ion transport. There is considerable clinical variation associated with FHM mutations. Genotype-phenotype correlation studies are needed, but are challenging mainly because the number of carriers of individual mutations is low. One exception is the recurrent T666M mutation in the FHM1 CACNA1A gene that was identified in almost one-third of FHM families and showed variable associated clinical features and severity, both within and among FHM families. Similar studies in the FHM2 ATP1A2 gene have not been performed because of the low number of carriers with individual mutations. Here we report on the recurrence of ATP1A2 mutations M731T and T376M that affect sodium-potassium pump functioning in two Portuguese FHM families. Considerably increasing the number of mutation carriers with these mutations indicated a clear genotype-phenotype correlation: both mutations are associated with pure FHM. In addition, we show that recurrent mutations for ATP1A2 are more frequent than previously thought, which has implications for genotype-phenotype correlations and genetic testing.

Unlabelled: Pain aggravation by movement and avoidance of movement (kinesiophobia) is often reported by patients during migraine attacks. Yet its specific contribution to migraine diagnosis is undetermined. To characterize the frequency and severity of kinesiophobia during migraine and its role in the diagnosis of primary headaches, we questioned 150 patients (126 women and 24 men, average age 38.5 yrs) with migraine (n = 111) or tension-type headache (TTH) (n = 39) about aggravation of pain by bending forward, brisk head movements (jolt), and avoidance of movement during the attacks. The degree of pain worsening by each stimulus was measured through a visual analog scale and compared to worsening produced by other sensory stimuli such as light, sound, and smell. The discrimination power of kinesiophobia between migraine and TTH was calculated, using the International Classification of Headache Disorders criteria as gold standard. Sensitivity/specificity of studied symptoms was high in differentiating the 2 headache types: bending forward: 98%/85.7%; jolt: 96.3%/81.6%; and immobility during the attacks: 100%/70%. The degree of kinesiophobia was identical to photo- and phonophobia in migraine patients. We conclude that kinesiophobia discriminates between migraine and TTH. Bending forward and jolt may be useful additional questions to ask patients for the differentiation of headache attacks., Perspective: This article evaluates the specific role of movement (movement-induced pain aggravation and avoidance of movement) in primary headaches. Kinesophobia is an easy symptom to screen, explained by migraine pathophysiology, and proved to be a sensitive and specific measure to identify migraine attacks when compared to tension-type headache.

Primary lateral sclerosis (PLS) is a very rare disease characterized by pure upper motor neuron findings. Although a number of previous reports have evaluated this condition, no study has addressed the respiratory function in PLS. Six patients meeting previously proposed diagnostic criteria for PLS were submitted to a number of respiratory tests: forced vital capacity, maximal pressures, phrenic nerve responses, needle electromyography of the respiratory muscles, percutaneous nocturnal oximetry (PNO) and polysomnography (two patients). Our results show that the diaphragm is not affected in this condition, but some respiratory function tests (RFT) and PNO had abnormal values. Voluntary muscular activation to perform RFT may be limited in these patients. PNO and polysomnography suggest that respiratory central drive dysfunction can occur when upper motor neurons are severely affected, in PLS. However, we did not verify progression on follow-up.

Unlabelled: Strokes are one of the most common causes of mortality and long term severe disability. Risk factors for stroke include: age, gender, diabetes mellitus (DM), hypertension, and many others., Objective: To evaluate obesity and hypertension in patients affected by acute ischemic stroke., Method: We compared the anthropometric variables between type II diabetic patients and non-diabetic patients. We evaluated a total of 60 patients, divided into two groups: 34 non-diabetic patients and a group of 26 type II diabetic subjects., Results: The predominance of obesity, as well as hypertension, was very high among the studied groups, presenting no differences among the waist-hip ratio (WHR) values of the study group compared to the ones of the control group., Conclusion: The predominance of obesity was very high among the studied groups and there was prevalence the android type obesity. There was no significative difference in the anthropometric evaluation by the measurement of WHR and the waist in the groups.

Neuromuscular diseases are a known risk factor for immobilization-induced osteoporosis. The aim of the study was to analyse bone mineral density (BMD) in patients with familial amyloid polyneuropathy (FAP) type I (Val30 Met) and to compare them with a population of patients with other neuromuscular disorders. We studied 24, ambulatory, neuromuscular patients, all men and premenopausal women. We included 12 FAP patients (GI) and 12 patients with other disorders (GII). Clinical data included age, sex, height, weight, alcohol intake, smoking, calcium intake, physical activity and history of fractures. Serum and urinary calcium, osteocalcin, bone alkaline phosphatase, parathyroid hormone, thyroid stimulating hormone and urinary N-telopeptide cross-linked type 1 collagen were determined in all patients. Bone mineral density of lumbar spine, hip and wrist were determined by dual energy X-ray absorptiometry scan. No statistical differences were found in clinical or analytic data between the two groups, except for body mass index and calciuria, which were lower in GI. In GI, 54.5% were osteoporotic, against 23.1% in GII (P = 0.04). Bone mineral density was lower in GI when compared with GII, and tended to decrease with disease duration. Decreased BMI and the early autonomic involvement in GI probably explain the results. The prevention and early treatment of osteoporosis, in FAP patients should be considered a priority.

Background: Some patients with otherwise typical cluster headache (CH) have persistent attacks free of cranial autonomic symptoms (CAS). The factors responsible for this atypical presentation are not known., Objectives: To identify factors associated to the absence of CAS in patients with CH., Methods: A prospective series of 157 patients with the diagnosis of CH was analyzed, comparing 148 typical CH patients with 9 CH patients without CAS., Results: Patients without CAS reported significantly less intense attacks (P = .003) when compared to those with CAS. There was also a tendency (not reaching statistical significance) for a higher frequency of females and chronic CH among those without CAS. Otherwise, there were no differences between the two groups (in age, duration of illness, follow-up time, attack duration or frequency, nor side or site of pain). A logistic regression analysis showed that only pain intensity could explain the difference between the two groups, since the other explanatory variables were also associated with different intensity of attacks., Conclusions: These results support the hypothesis that CH without cranial autonomic symptoms represents a milder form of CH.

The objective is to identify the pathogenesis of each autonomic manifestation in cluster headache (CH). Through a deductive statistics method (factor analysis) we analysed the type of autonomic symptoms reported by 157 CH patients. Three principal components were identified in the analysis: parasympathetic activation (lacrimation, conjunctival injection and rhinorrhoea), sympathetic defect (miosis and ptosis) and parasympathetic mediated effect (nasal congestion, eyelid oedema and forehead sweating). This work suggests that there are three different mechanisms underlying autonomic manifestations in CH.