Correlation between maxillofacial radiographic features and systemic severity as sickle cell disease severity predictor

This study was conducted to investigate the relationship among radiographic features observed on panoramic radiographs of sickle cell disease patients and analyze their relationship with history of systemic severity of the disease. Panoramic radiographs of 71 subjects with sickle cell disease were evaluated for the presence of the following radiographic bony alterations: radiopaque areas, increased spacing of bony trabeculae, horizontal arrangement of bony trabeculae and corticalization of mandibular canal. History of clinical systemic severity was assessed through direct questioning about the frequency of vaso-occlusive crisis, history of stroke, clinical jaundice, femur head necrosis, and leg ulceration. Chi-square or Fisher's exact test were applied in order to analyze possible associations between radiographic features and history of complications, with < 0.05 significance level. Increased spacing of bony trabeculae was statistically associated with absence of corticalization of mandibular canal ( < 0.01) and horizontal arrangement of bony trabeculae ( = 0.04). Statistically significant associations were demonstrated between history of clinical jaundice and presence of increased spacing of bony trabeculae ( = 0.02) and between history of stroke and presence of horizontal arrangement of bony trabeculae ( = 0.04). Based on the results of the current study, maxillofacial radiographic features may be associated with clinical parameters of systemic complications in sickle cell disease patients. The relationship between radiographic features and history of complications associated with clinical severity of sickle cell disease has not been demonstrated in the literature. Acknowledgment of such possible association may help establish prognosis and influence clinical treatment of systemic and oral complications.

Thoughts on the diversity of convergent evolution of bioluminescence on earth

The widespread independent evolution of analogous bioluminescent systems is one of the most impressive and diverse examples of convergent evolution on earth. There are roughly 30 extant bioluminescent systems that have evolved independently on Earth, with each system likely having unique enzymes responsible for catalysing the bioluminescent reaction. Bioluminescence is a chemical reaction involving a luciferin molecule and a luciferase or photoprotein that results in the emission of light. Some independent systems utilize the same luciferin, such as the use of tetrapyrrolic compounds by krill and dinoflagellates, and the wide use of coelenterazine by marine organisms, while the enzymes involved are unique. One common thread among all the different bioluminescent systems is the requirement of molecular oxygen. Bioluminescence is found in most forms of life, especially marine organisms. Bioluminescence in known to benefit the organism by: attraction, repulsion, communication, camouflage, and illumination. The marine ecosystem is significantly affected by bioluminescence, the only light found in the pelagic zone and below is from bioluminescent organisms. Transgenic bioluminescent organisms have revolutionized molecular research, medicine and the biotechnology industry. The use of bioluminescence in studying molecular pathways and disease allows for non-invasive and real-time analysis. Bioluminescence-based assays have been developed for several analytes by coupling luminescence to many enzyme-catalysed reactions. Received 17 February 2012, accepted 27 March 2012, first published online 2 May 2012

Motor Neuron Disease and Acquired Axonal Neuropathy Association in HIV Infection: Case Report and Update

Background: A possible viral etiology has been documented in the genesis of motor neuron disorders and acquired peripheral neuropathies, mainly due to the vulnerability of peripheral nerves and the anterior horn to certain viruses. In recent years, several reports show association of HIV infection with Amyotrophic Lateral Sclerosis Syndrome, Motor Neuron Diseases and peripheral neuropathies. Objective: To report a case of an association between Motor Neuron Disease and Acquired Axonal neuropathy in HIV infection, and describe the findings of neurological examination, cerebrospinal fluid, neuroimaging and electrophysiology. Methods: The patient underwent neurological examination. General medical examinations were performed, including, specific neuromuscular tests, analysis of cerebrospinal fluid, muscle biopsy and imaging studies. Results and Discussion: The initial clinical presentation of our case was marked by cramps and fasciculations with posterior distal paresis and atrophy in the left arm. We found electromyography tracings with deficits in the anterior horn of the spinal cord and peripheral nerves. Dysphagia and release of primitive reflexes were also identified. At the same time, the patient was informed to be HIV positive with high viral load. He received antiretroviral therapy, with load control but with no clinical remission. Conclusion: Motor Neuron disorders and peripheral neuropathy may occur in association with HIV infection. However, a causal relationship remains uncertain. It is noteworthy that the antiretroviral regimen may be implicated in some cases.

Diversity of the KIR gene cluster in an urban Brazilian population

The activity of natural killer cells depends on the balance between activating and inhibitory signals coming from their receptors. Among these are the killer cell immunoglobulin-like receptors (KIR) that recognize specific HLA class I allotypes. Here we characterized KIR genetic diversity and their HLA ligands in the population of Curitiba, Parana State (n = 164), and compared it with other worldwide populations. The distribution of 2DL4 alleles was also analyzed. The Curitiba population did not differ significantly from European and Euro-descendant populations, but as an admixed population showed higher genetic diversity. We found 27 KIR profiles, many of them uncommon in European populations, in agreement with the elevated historically recent gene flow in the study population. The frequencies of KIR genes and their respective HLA ligands were distributed independently and none of the analyzed individuals lacked functional KIR-HLA ligand combinations. KIR gene frequencies of 33 worldwide populations were consistent with geographic and ethnic distribution, in agreement with demography being the major factor shaping the observed gene content diversity of the KIR locus.

Lipid Peroxidation Is Associated with the Severity of Periodontal Disease and Local Inflammatory Markers in Patients with Type 2 Diabetes

Context: Periodontitis is the most common lytic disease of bone and is recognized as a common complication of diabetes. Lipid peroxidation (LPO) is increased in diabetes and may be related to modulation of the inflammatory response. LPO levels in patients with diabetes and periodontal disease have not been evaluated. Objective: The aim of this study was to evaluate the levels of LPO and its correlation with periodontal status and inflammatory cytokines in type 2 diabetic and nondiabetic patients. Design and Setting: This is a cross-sectional study involving Brazilian patients recruited at the State University of Sao Paulo. Patients: The sample comprised 120 patients divided into four groups based upon diabetic and dyslipidemic status: poorly controlled diabetics with dyslipidemia, well-controlled diabetics with dyslipidemia, normoglycemic individuals with dyslipidemia, and healthy individuals. Main Outcome Measures: Blood analyses were carried out for fasting plasma glucose, glycated hemoglobin, and lipid profile. Periodontal examinations were performed, and gingival crevicular fluid was collected. LPO levels were evaluated by measuring oxidized low-density lipoprotein (ELISA) and malondialdehyde (HPLC). Cytokines were evaluated by the multiplex bead technique. Results: LPO evaluated by malondialdehyde in plasma and gingival crevicular fluid was significantly increased in diabetes groups. Significant correlations between LPO markers and periodontal parameters indicate a direct relationship between these levels and the severity of inflammation and secretion of inflammatory cytokines, particularly in diabetic patients. Conclusion: These findings suggest an important association for LPO with the severity of the local inflammatory response to bacteria and the susceptibility to periodontal disease in diabetic patients. (J Clin Endocrinol Metab 97: E1353-E1362, 2012)

Dentomaxillofacial manifestations of Gaucher's disease: preliminary clinical and radiographic findings

Objectives: A wide variety of manifestations is presented in patients with Gaucher's disease (GD), including bone, haematology and visceral disturbances. This study was conducted to ascertain the main maxillofacial abnormalities by means of clinical survey, panoramic and cone beam CT (CBCT); to compare the patient's group with an age-sex matched control group; and to correlate clinical and radiological data. Methods: Ten patients previously diagnosed with GD were submitted to clinical and radiological surveys (CBCT and panoramic radiographs). The examination consisted of anamnesis, extra- and intraoral examinations and analyses of each patient's records. Imaging data were collected from the point of view of 3 observers, and the results compared with a healthy group (20 individuals) by means of statistical analysis (Fisher's exact test). Results: Gaucher patients had significantly more manifestations than otherwise healthy carriers. The most prevalent findings were enlarged marrow spaces, generalized osteopenia and effacement of jaw structures (mandibular canal, lamina dura and mental foramen). Here we describe a case in which thickening of the maxillary sinus mucosa was observed on CBCT rather than opacification of the sinus as seen on panoramic radiographs. Pathological fractures, root resorption and delay on tooth eruption were not observed. Conclusions: A poor relationship could be observed between clinical and radiological data. Patients showed important bone manifestations, which require careful diagnostic and surgical planning whenever necessary. Although panoramic radiographs have shown significant differences, CBCT is more effective in pointing out differences between patients and a control group, thus showing it as an important tool for evaluation of Gaucher patients. Dentomaxillofacial Radiology (2012) 41, 541-547. doi: 10.1259/dmfr/143023353

Pilot Studies for Development of an HIV Subtype Panel for Surveillance of Global Diversity

The continued global spread and evolution of HIV diversity pose significant challenges to diagnostics and vaccine strategies. NIAID partnered with the FDA, WRAIR, academia, and industry to form a Viral Panel Working Group to design and prepare a panel of well-characterized current and diverse HIV isolates. Plasma samples that had screened positive for HIV infection and had evidence of recently acquired infection were donated by blood centers in North and South America, Europe, and Africa. A total of 80 plasma samples were tested by quantitative nucleic acid tests, p24 antigen, EIA, and Western blot to assign a Fiebig stage indicative of approximate time from initial infection. Evaluation of viral load using FDA-cleared assays showed excellent concordance when subtype B virus was tested, but lower correlations for subtype C. Plasma samples were cocultivated with phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from normal donors to generate 30 viral isolates (50-80% success rate for samples with viral load >10,000 copies/ml), which were then expanded to 10(7)-10(9) virus copies per ml. Analysis of env sequences showed that sequences derived from cultured PBMCs were not distinguishable from those obtained from the original plasma. The pilot collection includes 30 isolates representing subtypes B, C, B/F, CRF04_cpx, and CRF02_AG. These studies will serve as a basis for the development of a comprehensive panel of highly characterized viral isolates that reflects the current dynamic and complex HIV epidemic, and will be made available through the External Quality Assurance Program Oversight Laboratory (EQAPOL).

Higher incidence of death in multi-vessel coronary artery disease patients associated with polymorphisms in chromosome 9p21

Background: We investigated whether 9p21 polymorphisms are associated with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function. Methods: The participants of the MASS II were genotyped for 9p21 polymorphisms (rs10757274, rs2383206, rs10757278 and rs1333049). Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, death from cardiac causes and myocardial infarction using a Cox proportional hazards survival model. Results: We observed significant differences between patients within each polymorphism genotype group for baseline characteristics. The frequency of diabetes was lower in patients carrying GG genotype for rs10757274, rs2383206 and rs10757278 (29.4%, 32.8%, 32.0%) compared to patients carrying AA or AG genotypes (49.1% and 39.2%, p = 0.01; 52.4% and 40.1%, p = 0.01; 47.8% and 37.9%, p = 0.04; respectively). Significant differences in genotype frequencies between double and triple vessel disease patients were observed for the rs10757274, rs10757278 and rs1333049. Finally, there was a higher incidence of overall mortality in patients with the GG genotype for rs2383206 compared to patients with AA and AG genotypes (19.5%, 11.9%, 11.0%, respectively; p = 0.04). Moreover, the rs2383206 was still significantly associated with a 1.75-fold increased risk of overall mortality (p = 0.02) even after adjustment of a Cox multivariate model for age, previous myocardial infarction, diabetes, smoking and type of coronary anatomy. Conclusions: Our data are in accordance to previous evidence that chromosome 9p21 genetic variation may constitute a genetic modulator in the cardiovascular system in different scenarios. In patients with established CAD, we observed an association between the rs2383206 and higher incidence of overall mortality and death from cardiac causes in patients with multi-vessel CAD.

Prevalence of celiac disease among blood donors in Sao Paulo - the most populated city in Brazil

OBJECTIVE: Celiac disease is a permanent enteropathy caused by the ingestion of gluten, which leads to an immune-mediated inflammation of the small intestine mucosa. The prevalence of celiac disease varies among different nations and ethnic backgrounds, and its diversity is determined by genetic and environmental factors. Sao Paulo city is one of the largest cities in the world, with a vast population and an important history of internal migratory flow from other Brazilian regions, as well as immigration from other, primarily European, countries, resulting in significant miscegenation. The aim of the present study was to estimate the prevalence of adults with undiagnosed celiac disease among blood donors of Sao Paulo by collecting information on the ancestry of the population studied. METHODS: The prevalence of celiac disease was assessed by screening for positive IgA transglutaminase and IgA endomysium antibodies in 4,000 donors (volunteers) in the Fundacao Pro-Sangue Blood Center of Sao Paulo, Sao Paulo, Brazil. The antibody-positive subjects were asked to undergo a small bowel biopsy. RESULTS: Of the 4,000 subjects, twenty-four had positive tests, although both antibody tests were not always concordant. For example, ten subjects were positive for IgA tissue transglutaminase only. In twenty-one positive patients, duodenal biopsies were performed, and the diagnosis of celiac disease was confirmed in fourteen patients (Marsh criteria modified by Oberhuber). In this group, 67% claimed to have European ancestry, mainly from Italy, Portugal and Spain. CONCLUSION: The prevalence of celiac disease is at least 1: 286 among supposedly healthy blood bank volunteers in Sao Paulo, Brazil.

Subthalamic deep brain stimulation modulates small fiber-dependent sensory thresholds in Parkinson's disease

The effects of deep brain stimulation of the subthalamic nucleus on nonmotor symptoms of Parkinson's disease (PD) rarely have been investigated. Among these, sensory disturbances, including chronic pain (CP), are frequent in these patients. The aim of this study was to evaluate the changes induced by deep brain stimulation in the perception of sensory stimuli, either noxious or innocuous, mediated by small or large nerve fibers. Sensory detection and pain thresholds were assessed in 25 PD patients all in the off-medication condition with the stimulator turned on or off (on- and off-stimulation conditions, respectively). The relationship between the changes induced by surgery on quantitative sensory testing, spontaneous CP, and motor abilities were studied. Quantitative sensory test results obtained in PD patients were compared with those of age-matched healthy subjects. Chronic pain was present in 72% of patients before vs 36% after surgery (P = .019). Compared with healthy subjects, PD patients had an increased sensitivity to innocuous thermal stimuli and mechanical pain, but a reduced sensitivity to innocuous mechanical stimuli. In addition, they had an increased pain rating when painful thermal stimuli were applied, particularly in the off-stimulation condition. In the on-stimulation condition, there was an increased sensitivity to innocuous thermal stimuli but a reduced sensitivity to mechanical or thermal pain. Pain provoked by thermal stimuli was reduced when the stimulator was turned on. Motor improvement positively correlated with changes in warm detection and heat pain thresholds. Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with PD and specifically modulates small fiber-mediated sensations. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.

Mosquitoes in degraded and preserved areas of the Atlantic Forest and potential for vector-borne disease risk in the municipality of Sao Paulo, Brazil

In order to assess the epidemiological potential of the Culicidae species in remaining areas of the Brazilian Atlantic Forest, specimens of this family were collected in wild and anthropic environments. A total of 9,403 adult mosquitoes was collected from May, 2009 to June, 2010. The most prevalent among species collected in the wild environment were Anopheles (Kerteszia) cruzii, the Melanoconion section of Culex (Melanoconion), and Aedes serratus, while the most common in the anthropic site were Coquillettidia chrysonotum/albifera, Culex (Culex) Coronator group, and An. (Ker.) cruzii. Mosquito richness was similar between environments, although the abundance of individuals from different species varied. When comparing diversity patterns between environments, anthropic sites exhibited higher richness and evenness, suggesting that environmental stress increased the number of favorable niches for culicids, promoting diversity. Increased abundance of opportunistic species in the anthropic environment enhances contact with culicids that transmit vector-borne diseases.

Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney disease: SSTR5 polymorphism and PKD1 mutation

A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0-5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48-255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Pathologic, cytogenetic, molecular and in silico analysis was undertaken. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.142C > A (p.L48M, rs4988483) in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subjected to extensive morphological, ultrastructural, cytogenetic and molecular studies. The physical proximity of the PKD1 and SSTR5 genes on chromosome 16 suggests a causal relationship between ADPKD and somatotroph adenoma.

Analysis of Hepatitis C Virus Intrahost Diversity across the Coding Region by Ultradeep Pyrosequencing

Hepatitis C virus (HCV) is the leading cause of liver disease worldwide. In this study, we analyzed four treatment-naive patients infected with subtype 1a and performed Roche/454 pyrosequencing across the coding region. We report the presence of low-level drug resistance mutations that would most likely have been missed using conventional sequencing methods. The approach described here is broadly applicable to studies of viral diversity and could help to improve the efficacy of direct-acting antiviral agents (DAA) in the treatment of HCV-infected patients.

Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations

Abstract Background N-acetyltransferase type 2 (Nat2) is a phase II drug- metabolizing enzyme that plays a key role in the bioactivation of aromatic and heterocyclic amines. Its relevance in drug metabolism and disease susceptibility remains a central theme for pharmacogenetic research, mainly because of its genetic variability among human populations. In fact, the evolutionary and ethnic-specific SNPs on the NAT2 gene remain a focus for the potential discoveries in personalized drug therapy and genetic markers of diseases. Despite the wide characterization of NAT2 SNPs frequency in established ethnic groups, little data are available for highly admixed populations. In this context, five common NAT2 SNPs (G191A, C481T, G590A, A803G and G857A) were investigated in a highly admixed population comprised of Afro-Brazilians, Whites, and Amerindians in northeastern Brazil. Thus, we sought to determine whether the distribution of NAT2 polymorphism is different among these three ethnic groups. Results Overall, there were no statistically significant differences in the distribution of NAT2 polymorphism when Afro-Brazilian and White groups were compared. Even the allele frequency of 191A, relatively common in African descendents, was not different between the Afro-Brazilian and White groups. However, allele and genotype frequencies of G590A were significantly higher in the Amerindian group than either in the Afro-Brazilian or White groups. Interestingly, a haplotype block between G590A and A803G was verified exclusively among Amerindians. Conclusions Our results indicate that ethnic admixture might contribute to a particular pattern of genetic diversity in the NAT2 gene and also offer new insights for the investigation of possible new NAT2 gene-environment effects in admixed populations.

Genetic diversity of Leishmania amazonensis strains isolated in northeastern Brazil as revealed by DNA sequencing, PCR-based analyses and molecular karyotyping

Abstract Background Leishmania (Leishmania) amazonensis infection in man results in a clinical spectrum of disease manifestations ranging from cutaneous to mucosal or visceral involvement. In the present study, we have investigated the genetic variability of 18 L. amazonensis strains isolated in northeastern Brazil from patients with different clinical manifestations of leishmaniasis. Parasite DNA was analyzed by sequencing of the ITS flanking the 5.8 S subunit of the ribosomal RNA genes, by RAPD and SSR-PCR and by PFGE followed by hybridization with gene-specific probes. Results ITS sequencing and PCR-based methods revealed genetic heterogeneity among the L. amazonensis isolates examined and molecular karyotyping also showed variation in the chromosome size of different isolates. Unrooted genetic trees separated strains into different groups. Conclusion These results indicate that L. amazonensis strains isolated from leishmaniasis patients from northeastern Brazil are genetically diverse, however, no correlation between genetic polymorphism and phenotype were found.