Brain damage serum biomarkers induced by COVID-19 in patients from northeast Brazil.

Neurological symptoms have been often reported in COVID-19 disease. In the present study, we evaluated brain damage associated with the increase of serum levels of neurological biomarkers S100B and neuron-specific enolase (NSE) induced by SARS-CoV-2 infection, in a population from Northeastern Brazil. Thirty-six healthy control (G1) individuals and 141 patients with confirmed COVID-19 were enrolled in this study. Positive-COVID-19 patients were divided into two groups according to the severity of illness by the National Institute of Health (NIH) criteria, 76 patients with mild symptoms for COVID-19 and (G2) and 65 with acute respiratory conditions requiring supplemental oxygenation via intensive care unit (ICU) admission (G3). A follow-up study was conducted with 23 patients from G2 14 (D14) and 21 (D21) days after the onset of symptoms. Serum levels of NSE and S100B were measured using the enzyme-linked immunoassay method (ELISA). Results revealed a significant positive association between G3 patients and S100B serum expression (p = 0.0403). The serum levels of NSE were also significantly enhanced in the G3 group compared to the control (p < 0.0001) and G2 group (p < 0.0001). In addition, clinical features such as symptoms and oxygenation status were not correlated with NSE or S100B serum expression. The follow-up study demonstrated a decrease over time (21 days) in NSE serum expression (p < 0.0001). These results suggest that brain damage is followed by acute virus exposure, with no long-term effects. Future work examining COVID-19 recovery will shed light on chronic neurological damage of SARS-CoV-2 infection.

Synthesis of novel thiazolidinic-phthalimide derivatives evaluated as new multi-target antiepileptic agents.

Epilepsy is a disease that affects millions of people around the globe and has a multifactorial cause. Inflammation is a process that can be involved in the development of seizures. Thus, the present study proposed the design and synthesis of new candidates for antiepileptic drugs that would also control the inflammatory process. Nine new derivatives of the substituted thiazophthalimide hybrid core were obtained with satisfactory purity ≥99% and yields between 27% and 87%. All compounds showed cell viability values greater than 90% in the culture of PBMC cells from healthy volunteers and, therefore, were not considered cytotoxic. These compounds modulated proinflammatory cytokines IFN-y and IL-17A and can mitigate inflammation. Acute toxicity studies of compound 7i in an animal model indicated that the compound has low toxicity and an LD50 greater than 2 g/kg in healthy adult rats. The same compound did not show positive results for anticonvulsant activity through the PTZ test. However, 7i demonstrates the interaction with the target GABA-A receptor in silico, indicating a possible activity as an agonist of that receptor. Thus, further studies are needed to investigate the anticonvulsant activity, in particular, using models in which the inflammatory process triggers epileptic seizures.

Impaired Th1 Response Is Associated With Therapeutic Failure in Patients With Cutaneous Leishmaniasis Caused by Leishmania braziliensis.

BACKGROUND: Leishmania skin test (LST) evaluates the delayed type hypersensitivity to Leishmania antigens (LA) and has been used for diagnosis of cutaneous leishmaniasis (CL). In CL patients LST is usually positive but a small percentage have negative LST. The aim of this study was to determine the clinical and immunologic features and response to antimony therapy in LST-negative CL patients. METHODS: We compare the clinical presentation, response to therapy, and immune response of CL patients with negative vs positive LST. RESULTS: The clinical presentation was similar in both groups but LST-negative patients had a lower cure rate. In the lesions, LST-negative patients displayed less inflammation and necrosis, and higher frequency of CD8+ T cells. Mononuclear cells from LST-negative patients had a poor T helper 1 cell (Th1) response but levels of interleukin-1ß (IL-1ß), IL-6, IL-17, granzyme B, and metalloproteinase-9 (MMP-9) were similar to the LST-positive group upon stimulation with LA. Leishmania internalization and killing by macrophages were similar in both groups. Cure of disease was associated with restoration of Th1 response. CONCLUSIONS: In LST-negative patients, impaired Th1 response is associated with therapeutic failure. Increased frequency of CD8+ T cells and high production of inflammatory cytokines, granzyme B, and MMP-9 contributes to immunopathology.

Association of KLOTHO polymorphisms with clinical complications of sickle cell anemia.

The clinical and phenotypic heterogeneity of patients with sickle cell anemia (SCA) is influenced by environmental and genetic factors. Several genetic modifiers, such as the KLOTHO (KL) gene, have been associated with SCA clinical outcomes. The KL gene and its encoded proteins are implicated in important biological pathways, which affect the disease's pathophysiology, such as expression of adhesion molecules VCAM-1 and ICAM-1, oxidative stress, and nitric oxide biology. Here, we evaluated the clinical relevance of two polymorphisms found on the KL gene (rs685417 and rs211239) in 588 unrelated patients with SCA. Genotyping analyses were performed using the TaqMan system. The KL rs211239 was associated with increased number of vaso-occlusive crisis (VOCs) per year (P = 0.001), while KL rs685417 was associated with increased frequency of stroke (P = 0.034), priapism (P = 0.011), number of complications (P = 0.019), and with a lower incidence of priapism (P = 0.036). Additionally, the associations with VOCs, stroke, and priapism remained consistent in multivariate analyses (P < 0.05). Our data highlight the clinical importance of KL in SCA.

Galectin-3 is modulated in pancreatic cancer cells under hypoxia and nutrient deprivation.

Pancreatic ductal adenocarcinoma is one of the most aggressive tumors with a microenvironment marked by hypoxia and starvation. Galectin-3 has been evaluated in solid tumors and seems to present both pro/anti-tumor effects. So, this study aims to characterize the expression of Galectin-3 from pancreatic tumor cells and analyze its influence for cell survive and motility in mimetic microenvironment. For this, cell cycle and cell death were accessed through flow cytometry. Characterization of inside and outside Galectin-3 was performed through Real-Time Quantitative Reverse Transcription PCR (qRT-PCR), immunofluorescence, Western blot, and ELISA. Consequences of Galectin-3 extracellular inhibition were investigated using cell death and scratch assays. PANC-1 showed increased Galectin-3 mRNA expression when cultivated in hypoxia for 24 and 48 h. After 24 h in simultaneously hypoxic/deprived incubation, PANC-1 shows increased Galectin-3 protein and secreted levels. For Mia PaCa-2, cultivation in deprivation was determinant for the increasing in Galectin-3 mRNA expression. When cultivated in simultaneously hypoxic/deprived condition, Mia PaCa-2 also presented increasing for the Galectin-3 secreted levels. Treatment of PANC-1 cells with lactose increased the death rate when cells were incubated simultaneously hypoxic/deprived condition. Therefore, it is possible to conclude that the microenvironmental conditions modulate the Galectin-3 expression on the transcriptional and translational levels for pancreatic cancer cells.

Newborn screening for lysosomal disorders in Brazil: A pilot study using customized fluorimetric assays.

Lysosomal storage disorders (LSDs) are a group of genetic disorders characterized by deficiency of specific lysosomal enzymes. In general, patients are clinically normal at birth, and progressively develop severe signs and symptoms. Diagnosis is usually made several years after onset of manifestations, preventing patients to have the benefits of the early treatment. Newborn screening programs are being considered for LSDs to allow early diagnosis and treatment. The present study evaluated the feasibility of a customized screening approach based on modified fluorometric assays with reduced amounts of reagents, substrates and samples for: mucopolysaccharidosis (MPS) type I (MPS I), MPS VI, Fabry, Gaucher, and Pompe diseases. We also evaluated the advantages of including blood chitotriosidase and urinary glycosaminoglycans in the protocol. By the measurement of the specific disease-associated enzymes (plus blood chitotriosidase and urinary glycosaminoglycans) we analyzed 834 de-identified DBS of unselected newborns. No positive case was detected, and the false-positive rates were low. Taking into consideration the limitations of this methodology, we believe that, after defining proper cutoffs, it could be a viable alternative to provide NBS for LSDs by laboratories that may not be able to afford the commercial methods available.

Oxidative and nitrative stress and pro-inflammatory cytokines in Mucopolysaccharidosis type II patients: effect of long-term enzyme replacement therapy and relation with glycosaminoglycan accumulation.

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease caused by a deficient activity of iduronate-2-sulfatase, leading to abnormal accumulation of glycosaminoglycans (GAG). The main treatment for MPS II is enzyme replacement therapy (ERT). Previous studies described potential benefits of six months of ERT against oxidative stress in patients. Thus, the aim of this study was to investigate oxidative, nitrative and inflammatory biomarkers in MPS II patients submitted to long term ERT. It were analyzed urine and blood samples from patients on ERT (mean time: 5.2years) and healthy controls. Patients presented increased levels of lipid peroxidation, assessed by urinary 15-F2t-isoprostane and plasmatic thiobarbituric acid-reactive substances. Concerning to protein damage, urinary di-tyrosine (di-Tyr) was increased in patients; however, sulfhydryl and carbonyl groups in plasma were not altered. It were also verified increased levels of urinary nitrate+nitrite and plasmatic nitric oxide (NO) in MPS II patients. Pro-inflammatory cytokines IL-1ß and TNF-α were increased in treated patients. GAG levels were correlated to di-Tyr and nitrate+nitrite. Furthermore, IL-1ß was positively correlated with TNF-α and NO. Contrastingly, we did not observed alterations in erythrocyte superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, in reduced glutathione content and in the plasmatic antioxidant capacity. Although some parameters were still altered in MPS II patients, these results may suggest a protective role of long-term ERT against oxidative stress, especially upon oxidative damage to protein and enzymatic and non-enzymatic defenses. Moreover, the redox imbalance observed in treated patients seems to be GAG- and pro-inflammatory cytokine-related.

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction.

Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1ß translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

IL2RA genetic variants reduce IL-2-dependent responses and aggravate human cutaneous leishmaniasis.

The outcome of Leishmania infections varies substantially, depending on the host and the parasite strain; infection may be asymptomatic or cause mild or severe skin ulcers (cutaneous leishmaniasis [CL]), limited or disseminated lesions, or lethal visceral disease. We previously reported an association between IL-2R mutations and susceptibility to visceral leishmaniasis in children infected with Leishmania donovani. In the present study, we evaluated the possible role of IL-2 signaling in human CL. We first showed that the transcripts of several genes of the IL-2 pathway were abundant in skin lesions caused by Leishmania braziliensis. We then carried out a genetic analysis, focusing on major genes of the IL-2 pathway. We used a family-based approach and found that polymorphisms of several genes appeared to be associated with CL in a Brazilian population. Moreover, two polymorphisms of the IL2RA gene were significantly and independently associated with CL. We confirmed this result in a second Brazilian sample (also exposed to L. braziliensis) and in Iranians infected with Leishmania tropica: IL2RA rs10905669 T (Pcombined = 6 × 10(-7)) and IL2RA rs706778 T (Pcombined = 2 × 10(-9)) were associated with greater susceptibility to lesion development. These alleles were also correlated with a poor IFN-γ response and poor FOXP3(+) regulatory T cell activation. Thus, IL-2 plays a crucial role in protection against the cutaneous ulcers caused by Leishmania, and the IL-2 pathway is a potential target for strategies aiming to control Leishmania-related diseases.

Elevation of glycosaminoglycans in the amniotic fluid of a fetus with mucopolysaccharidosis VII.

OBJECTIVE: The aim of this study was to quantify glycosaminoglycans (GAGs) in amniotic fluid (AF) from an MPS VII fetus compared with age-matched fetuses obtained from normal pregnancies. METHOD: Disaccharides were measured by liquid chromatography tandem mass spectrometry, compared to age-matched controls. Enzyme assay was performed in AF supernatant or cultured amniocytes. GUSB was analyzed by next generation sequencing using Ion Torrent Personal Genome Machine with a customized panel. RESULTS: No activity of ß-glucuronidase was detected in fetal cells. The pregnancy was spontaneously terminated in the third trimester. Genetic studies identified a homozygous mutation of p.N379D (c.1135A > G) in the GUSB gene. Liquid chromatography tandem mass spectrometry showed that chondroitin sulfate, dermatan sulfate, heparan sulfate, and keratan sulfate levels were markedly increased in the MPS VII AF, compared to those in age-matched control AF (dermatan sulfate, heparan sulfate, and chondroitin-6-sulfate more than 10 × than age-matched controls; chondroitin-4-sulfate and keratan sulfate more than 3 times higher). CONCLUSION: This is the first report of specific GAG analysis in AF from an MPS VII fetus, indicating that GAG elevation in AF occurs by 21 weeks of gestation and could be an additional tool for prenatal diagnosis of MPS VII and potentially other MPS types. © 2017 John Wiley & Sons, Ltd.

Quantification and Analysis of Leaflet Flutter on Biological Prosthetic Cardiac Valves.

The use of porcine or bovine pericardium biological cardiac valves has as its main disadvantage a relatively short lifespan, with failures due to calcification and fatigue. Increasing these valves' durability constitutes a great challenge. An understudied phenomenon is the effect of flutter, an oscillation of the leaflets that can cause regurgitation and accelerate calcification and fatigue. As a starting point to study how to reduce or prevent these oscillations, a method was developed to quantify the flutter frequencies occurring at the point of the valve's full opening. On a test bench that simulates the heart flow, the cusp behaviors of eight biological valves were filmed with a high speed camera at 2000 frames per second at different flow rates and motion capture software obtained the frequencies and amplitudes of the vibrations of each leaflet. Oscillations in the range of 200 Hz with average amplitudes of 0.4 mm were found; larger nominal diameter valves obtained lower values, and bovine pericardial valves had superior performance compared to porcine valves. A dimensionless analysis was performed to find a relationship between the geometric and mechanical properties of the valves with the critical speed of the onset of fluttering. This relationship inspired a method to predict whether flutter will occur in the bioprosthesis. This method is a new tool for the consideration of maximizing the life of prosthetic valves.

Oxidative stress and inflammation in mucopolysaccharidosis type IVA patients treated with enzyme replacement therapy.

Mucopolysaccharidosis type IVA (MPS IVA) is an inborn error of glycosaminoglycan (GAG) catabolism due to the deficient activity of N-acetylgalactosamine-6-sulfate sulfatase that leads to accumulation of the keratan sulfate and chondroitin 6-sulfate in body fluids and in lysosomes. The pathophysiology of this lysosomal storage disorder is not completely understood. The aim of this study was to investigate oxidative stress parameters, pro-inflammatory cytokine and GAG levels in MPS IVA patients. We analyzed urine and blood samples from patients under ERT (n=17) and healthy age-matched controls (n=10-15). Patients presented a reduction of antioxidant defense levels, assessed by a decrease in glutathione content and by an increase in superoxide dismutase activity in erythrocytes. Concerning lipid and protein damage, it was verified increased urine isoprostanes and di-tyrosine levels and decreased plasma sulfhydryl groups in MPS IVA patients compared to controls. MPS IVA patients showed higher DNA damage than control group and this damage had an oxidative origin in both pyrimidine and purine bases. Interleukin 6 was increased in patients and presented an inverse correlation with GSH levels, showing a possible link between inflammation and oxidative stress in MPS IVA disease. The data presented suggest that pro-inflammatory and pro-oxidant states occur in MPS IVA patients even under ERT. Taking these results into account, supplementation of antioxidants in combination with ERT can be a tentative therapeutic approach with the purpose of improving the patient's quality of life. To the best of our knowledge, this is the first study relating MPS IVA patients with oxidative stress.

Low-dose fractionated radiotherapy and concomitant chemotherapy for recurrent or progressive glioblastoma: final report of a pilot study.

BACKGROUND: Evaluated in this study were the feasibility and the efficacy of concurrent low dose fractionated radiotherapy (LD-FRT) and chemotherapy as palliative treatment for recurrent/progressive glioblastoma multiforme (GBM). PATIENTS AND METHODS: Eligible patients had recurrent or progressive GBM, Karnofsky performance status ≥ 70, prior surgery, and standard radiochemotherapy treatment. Recurrence/progression disease during temozolomide (TMZ) received cisplatin (CDDP; 30 mg/m(2) on days 1, 8, 15), fotemustine (FTM; 40 mg/m(2) on days 2, 9, 16), and concurrent LD-FRT (0.3 Gy twice daily); recurrence/progression after 4 months from the end of adjuvant TMZ were treated by TMZ (150/200 mg/m(2) on days 1-5) concomitant with LD-FRT (0.4 Gy twice daily). Primary endpoints were safety and toxicity. RESULTS: A total of 32 patients were enrolled. Hematologic toxicity G1-2 was observed in 18.7 % of patients and G3-4 in 9.4 %. One patient (3.1 %) had complete response, 3 (9.4 %) had partial response, 8 (25 %) had stable disease for at least 8 weeks, while 20 patients (62.5 %) experienced progressive disease. The clinical benefit was 37.5 %. Median progression-free survival (PFS) and overall survival (OS) were 5 and 8 months, respectively. Survival rate at 12 months was of 27.8 %. CONCLUSION: LD-FRT and chemotherapy for recurrent/progressive GBM have a good toxicity profile and clinical outcomes, even though further investigation of this novel palliative treatment approach is warranted.

Anatomical variants of the basal vein of Rosenthal: prevalence in idiopathic subarachnoid hemorrhage.

BACKGROUND: Spontaneous, non traumatic subarachnoid hemorrhage (SAH) is a significant clinical problem that occurs most commonly as a result of aneurysm rupture. In approximately 15 % of cases, nor aneurysm or other vascular malformation can be identified by cerebral angiography as origin of the hemorrhage, and these are commonly defined as idiopathic SAH (ISAH). Because of the negative angiography, limited extension of the bleeding with prevalent prepontine pattern and the benign prognosis, the venous causes has been preferred rather than the arterial ones. In the literature recent studies have suggested a possible contribution by primitive variants of Basal vein of Rosenthal (BVR) in its the pathogenesis of ISAH, commonly grouped according Watanabe classification (type A, B and C). In this paper we evaluated the prevalence of anatomical variants of BVR in ISAH. METHODS: Venous drainage at angiography was retrospectively analyzed in 40 patients with ISAH and in 40 with unruptured aneurysms as controls. RESULTS AND CONCLUSIONS: Previous studies displayed a significant prevalence of BVR type C variants in ISAH. Conversely in our study we recognized variant B as prevalent, in which the BVR bifurcates to drain anteriorly into the uncal vein and posteriorly into the Galenic system. Similarly to variant C (in which the BVR drains via perimesencephalic "bridging" veins into cavernous, sphenoparietal, petrosal sinus or directly into transverse sinus) also variant B might be subjected to those stress mechanisms and intrinsic system 'fragility' and for reasons yet to determine, sets off a consequent hemorrhage with clinical and radiological features typical of ISAH.

Vitreous-lens interface changes after cataract surgery using active fluidics and active sentry with high and low infusion pressure settings.

PURPOSE: To determine whether the infusion pressure used during phacoemulsification may have a detrimental effect on the anterior hyaloid membrane barrier (AHMB) in a pressure fluctuation-free environment using diagnostic spectral-domain optical coherence tomography (SD-OCT) postoperatively. SETTING: Tandil Eye Clinic, Tandil, Buenos Aires, Argentina, and Centro Oftalmológico Dr. Charles, CABA, Buenos Aires, Argentina. DESIGN: Prospective, randomized, multicenter, experimental, and double-masked study. METHODS: Phacoemulsification with intraocular lens implantation was performed in all patients with the Centurion Vision System equipment with active fluidics and active sentry. Patients were randomly assigned to configuration 1 or 2. Configuration 1 had intraocular pressure (IOP) 30 mm Hg and configuration 2 IOP 80 mm Hg. Inclusion criteria were axial length >22 mm and <25 mm, age older than 50 and younger than 70 years, and complete adhesion of AHMB. RESULTS: 80 eyes of 80 patients were included. Berger space was identified in 17 cases (42.5%) of group 2 and 3 cases (7.5%) of group 1 postoperatively using SD-OCT. A statistically significant relationship was established using Fisher exact test ( P = .0003). Postoperatively, we observed posterior vitreous detachment changes in only 1 patient (1.25%) during the 3 months of follow-up ( P = .5). According to the Wong-Baker FACES Scale, the patient's subjective perception was better for the low infusion pressure group ( P = .0001, Fisher exact test). CONCLUSIONS: Phacoemulsification with high infusion pressure can change the vitreous-lens interface. Positive Berger space after phacoemulsification is a biomarker of this change and can occur in eyes without risk factors. Incidence is directly related to the infusion pressure used.

Angioarchitectural features of brain arteriovenous malformations associated with seizures: a single center retrospective series.

BACKGROUND AND PURPOSE: Epileptic seizures account for 24-40% of all clinical onsets in patients with brain arteriovenous malformations (AVMs). METHODS: We retrospectively reviewed the angioarchitectural features of AVMs associated with seizures in 168 patients admitted to our Department from 1997 to 2012. Patients were dichotomized according to demographic characteristics, type of treatment, bleeding occurrence, and morphological and topographic features. Clinical status at admission and discharge was also recorded. The association of each one of these variables with seizures occurrence was statistically tested. Continuous variables and outcome were compared with Student's t-test, whereas categorical ones were compared using Fisher's exact test. The independent contribution of some seizures predictors was assessed with a logistic regression model. Associations were considered significant for P < 0.05. RESULTS: About 29% patients showed seizures and 47% bleeding. No significant difference in age and sex was observed between patients with and without seizures. AVMs > 4 cm (P = 0.001) and those fed by dilated arterial feeders (P = 0.02) were associated with increased risk of seizures. A higher risk of seizures occurrence was also observed in cortical AVMs compared with deeper ones (75.5% vs. 55.4%; P = 0.01), and in AVMs fed by middle and posterior cerebral arteries branches compared with the other vessels (81.6% vs. 45.3%; P < 0.001 and 48.9% vs. 23.5%; P = 0.002, respectively). No lobar predisposition was observed. A nidus > 4 cm also appeared as an independent risk factor of seizures occurrence (OR 2.82; 95% CI, 1.26-6.31; P = 0.009) at logistic regression analysis. CONCLUSIONS: AVM morphology, especially nidus dimension, appeared to more significantly influence seizures occurrence than their topography.

Transcriptional profile characterization for the identification of peripheral blood biomarkers in patients with cerebral aneurysms.

We tried to identify molecular markers in peripheral blood to predict high risk of aneurysm rupture. Extraction of the total population of peripheral blood mononuclear cell (PBMC) from total blood volume, total RNA extraction from PBMC and Agilent One Color Gene-expression Oligo-Microarray were performed on peripheral venous blood samples from 45 patients with ruptured, unruptured cerebral aneurysms and control group (15). Mean foreground/ background signal intensities and A (log2(R*G)/2) values were calculated for each spot. Genes with absolute fold change (FC) greater than or equal to plus or minus 1.5 and p-value less than 0.05 were considered differentially expressed in the 3 groups (Student T-test). Genes coding for MMPs were strongly underexpressed in ruptured aneurysms group, suggesting a possible role in aneurysms development more than their rupture. Genes coding for adhesine proteins of the extracellular matrix (ICAM1) and cytoskeleton (WIPF1,TUBA4A) were underexpressed in ruptured aneurysms. Genes coding proteins involved in the regulation of apoptotic processes may be important in aneurysm development and rupture, resulting into an increased rate of remodeling processes in the arterial wall. Fas coding gene, SUMO1, ZFAT, BCL2, CCR5 genes were all over-represented in unruptured aneurysms. The coexisting over-representation of pro-apoptotic genes and the underexpression of cytoskeleton and extracellular matrix genes confirms that aneurysms development and evolution are part of a degenerative process of the arterial wall not involved in aneurysms rupture. MMPs may be involved in repairing chronic damages to the arterial walls and preventing SAH. Unexpectedly, Heat Shock Proteins (HSP90AA1, HSPA1A, HSPB1), G and RAS proteins, generally activated by stress situations were under-represented in aneurysmal walls. Further PCR and Western Blotting studies are needed to confirm such findings and to identify diagnostic and prognostic markers in order to define screening protocols for intracranial aneurysms.

Three-dimensional rotational angiography for craniotomy planning and postintervention evaluation of intracranial aneurysms.

PURPOSE: The authors evaluated the usefulness of three-dimensional rotational angiography (3DRA) in surgical planning and postoperative evaluation of cerebral aneurysms. MATERIALS AND METHODS: A total of 111 consecutive aneurysms in 100 patients (32 emergency referrals due to haemorrhage) were evaluated with 3DRA over a period of 3 years. The rotational study was always performed with a single injection of 20 cc of contrast agent in the afferent vessel after diagnostic cerebral angiography in the two orthogonal projections. Three-dimensional reconstructions were obtained for the pre- and postoperative assessment. RESULTS: Three-dimensional RA provides a virtual view of the surgical field with the same orientation required for the surgical approach and, compared with surgical findings, reliably defined location, orientation, morphology and relationship with parent vessels of the aneurysm in all cases. Postoperatively, it allowed better assessment of any residual lesion and of the relationship between surgical clips and parent vessels, compared with standard 2D angiography. CONCLUSIONS: 3DRA is a reliable method for preliminary assessment of cerebral aneurysms undergoing surgery. It provides multiple projections with a preview of the surgical field and study of lesion characteristics, which can help achieve faster and safer surgery. Compared with 2D angiography, the 3D model, with its multiple views, allows better assessment of postoperative outcomes. The method also significantly reduces the number of angiographic projections and therefore radiation and contrast-medium dose to the patient.

Nanoimmunosensor for the electrochemical detection of oncostatin M receptor and monoclonal autoantibodies in systemic sclerosis.

Systemic sclerosis (SSc) is a chronic, autoimmune disease that primarily affects connective tissue. SSc can be classified into limited cutaneous (lSSc) and diffuse cutaneous (dSSc). Oncostatin M receptor (sOSMR) is an important inflammatory biomarker expressed in the serum of patients with autoimmune diseases. A nanoengineered immunosensor surface was developed. The biosensor was composed of a conductive layer of polypyrrole, electrodeposited gold nanoparticles, and sOSMR protein for anti-human OSMR monoclonal antibody biorecognition. The electrochemical response evaluated by cyclic voltammetry and electrochemical impedance spectroscopy indicated the detection of the target analyte present in clinical samples from lSSc and dSSc patients. The voltammetric anodic shift for lSSc specimens was 82.7% ± 0.9-93.6% ± 3.2, and dSSc specimens was 118.7 ± 2.6 to 379.6 ± 2.6, revealing a differential diagnostic character for SSc subtypes. The sensor platform was adapted for identifying sOSMR, using anti-OSMR antibodies as bioreceptors. With a linear response range estimated from 0.005 to 500 pg mL-1 and a limit of detection of 0.42 pg mL-1, the sensing strategy demonstrated high sensitivity in identifying the human OSMR protein in clinical samples. The proposed biosensor is a promising and innovative tool for SSc-related biomarker research.

New patterns of the tree beta diversity and its determinants in the largest savanna and wetland biomes of South America.

Clear and data-driven bioregionalizations can provide a framework to test hypotheses and base biodiversity conservation. Here we used occurrence and abundance data in combination with objective analytical methods to propose two bioregionalization schemes for tree species of the Cerrado and the Pantanal in South America. We also evaluated the contribution of three sets of determinants of the occurrence- and abundance-based subregions. We compiled data on tree species composition from 894 local assemblages based on species occurrences, and from 658 local assemblages based on species abundances. We used an unconstrained community-level modelling approach and clustering techniques to identify and map tree subregions for the occurrence and the abundance data sets, separately. Hierarchical clustering analyses were conducted to investigate floristic affinities between the subregions and to map broader floristic regions. We used multinomial logistic regression models, deviance partitioning, and rank-sum tests to assess the main subregion correlates. We identified 18 occurrence- and four abundance-based subregions in the Cerrado-Pantanal. The hierarchical classifications grouped the occurrence-based subregions into nine floristic zones and abundance-based subregions into two broad floristic zones. Variation in subregions were explained mainly by environmental factors and spatial structure in both occurrence and abundance data sets. The occurrence- and abundance-based subregions are complementary approaches to disentangle macroecological patterns and to plan conservation efforts in the Cerrado and the Pantanal. Our findings based on occurrence data revealed more complex and interdigitated boundaries between subregions of tree species than previously reported. The environment, historical stability, and human effects act in a synergetic way on the distribution of the subregions. Finally, the relevance of contemporary environmental factors to the subregion patterns we found alert us to the profound impact global warming may have on the spatial organization of the Cerrado-Pantanal tree flora.