El Nino and arboviral disease prediction

Recent El Nino events have stimulated interest in the development of modeling techniques to forecast extremes of climate and related health events. Previous studies have documented associations between specific climate variables (particularly temperature and rainfall) and outbreaks of arboviral disease. In some countries, such diseases are sensitive to Fl Nino. Here we describe a climate-based model for the prediction of Ross River virus epidemics in Australia. From a literature search and data on case notifications, we determined in which years there were epidemics of Ross River virus in southern Australia between 1928 and 1998. Predictor variables were monthly Southern Oscillation index values for the year of an epidemic or lagged by 1 year. We found that in southeastern states, epidemic years were well predicted by monthly Southern Oscillation index values in January and September in the previous year. The model forecasts that there is a high probability of epidemic Ross River virus in the southern states of Australia in 1999. We conclude that epidemics of arboviral disease can, at least in principle, be predicted on the basis of climate relationships.

A protocol for the fluorometric quantification of mGFP5-ER and sGFP(S65T) in transgenic plants

The Green Fluorescent Protein (GFP) from Aequorea victor-in has begun to be used as a reporter protein in plants. It is particularly useful as GFP fluorescence can be detected in a non-destructive manner, whereas detection of enzyme-based reporters often requires destruction of the plant tissue. The use of GFP as a reporter enables transgenic plant tissues to be screened in vivo at any growth stage. Quantification of GFP in transgenic plant extracts will increase the utility of GFP as a reporter protein. We report herein the quantification of a mGFP5-ER Variant in tobacco leaf extracts by UV excitation and a sGFP(S65T) variant in sugarcane leaf and callus extracts by blue light excitation using the BioRad VersaFluor(TM) Fluorometer System or the Labsystems Fluoroskan Ascent FL equipped with a narrow band emission filter (510 +/- 5 nm). The GFP concentration in transgenic plant extracts was determined from a GFP-standard series prepared in untransformed plant extract with concentrations ranging from 0.1 to 4 mu g/ml of purified rGFP. Levels of sgfp(S65T) expression, driven by the maize ubiquitin promoter, in sugarcane calli and leaves ranged up to 0.525 mu g and 2.11 mu g sGFP(S65T) per mg of extractable protein respectively. In tobacco leaves the expression of mgfPS-ER, driven by the cauliflower mosaic virus (CaMV) 35S promoter, ranged up to 7.05 mu g mGFP5-ER per mg extractable protein.

Recombinant human growth hormone, but not insulin-like growth factor-I, enhances central fat loss in postmenopausal women undergoing a diet and exercise program

We examined the effect of recombinant human growth hormone (rhGH) and/or recombinant human insulin-like growth factor-I (rhIGF-I) on regional fat loss in postmenopausal women undergoing a weight loss regimen of diet plus exercise. Twenty-seven women aged 59-79 years, 20-40% above ideal body weight, completed a 12-week program consisting of resistance training 2 days/week and walking 3 days/week, while consuming a diet that was 500 kcal/day less than that required for weight maintenance, Participants were randomly assigned in a double-blind fashion to receive rhGH (0.025 mg/kg BW/day: n=7), rhIGF-I (0.015 mg/kg BW/day: n=7), rhGH + rhIGF-I (n = 6), or placebo (PL: n = 7). Regional and whole body fat mass were determined by dual X-ray absorptiometry. Body fat distribution was assessed by the ratios of trunk fat-to-limb fat (TrF/LimbF) and trunk fat-to-total fat (TrF/TotF), Limb and trunk fat decreased in all groups (p < 0.01). For both ratios of fat distribution, the rhGH treated group experienced an enhanced loss of truncal compared to peripheral fat (p less than or equal to 0.01), with no significant change for those administered rhIGF-I or FL. There was no association between change in fat distribution and indices of cardiovascular disease risk as determined by serum lipid/lipoprotein levels and maximal aerobic capacity. These results suggest that administration of rhGH facilitates a decrease in central compared to peripheral fat in older women undertaking a weight loss program that combines exercise and moderate caloric restriction, although no beneficial effects are conferred to lipid/lipoprotein profiles, Further, the effect of rhGH is not enhanced by combining rhCH with rhIGF-I administration. In addition, rhIGF-I does not augment the loss of trunk fat when administered alone.

X-linked myoclonic epilepsy with spasticity and intellectual disability - Mutation in the homeobox gene ARX

Objective: To describe a new syndrome of X-linked myoclonic epilepsy with generalized spasticity and intellectual disability (XMESID) and identify the gene defect underlying this disorder. Methods: The authors studied a family in which six boys over two generations had intractable seizures using a validated seizure questionnaire, clinical examination, and EEG studies. Previous records and investigations were obtained. Information on seizure disorders was obtained on 271 members of the extended family. Molecular genetic analysis included linkage studies and mutational analysis using a positional candidate gene approach. Results: All six affected boys had myoclonic seizures and TCS; two had infantile spasms, but only one had hypsarrhythmia. EEG studies show diffuse background slowing with slow generalized spike wave activity. All affected boys had moderate to profound intellectual disability. Hyperreflexia was observed in obligate carrier women. A late-onset progressive spastic ataxia in the matriarch raises the possibility of late clinical manifestations in obligate carriers. The disorder was mapped to Xp11.2-22.2 with a maximum lod score of 1.8. As recently reported, a missense mutation (1058C>T/P353L) was identified within the homeodomain of the novel human Aristaless related homeobox gene (ARX). Conclusions: XMESID is a rare X-linked recessive myoclonic epilepsy with spasticity and intellectual disability in boys. Hyperreflexia is found in carrier women. XMESID is associated with a missense mutation in ARX. This disorder is allelic with X-linked infantile spasms (ISSX; MIM 308350) where polyalanine tract expansions are the commonly observed molecular defect. Mutations of ARX are associated with a wide range of phenotypes; functional studies in the future may lend insights to the neurobiology of myoclonic seizures and infantile spasms.

Na,K-ATPase activity and epithelial interfaces in gills of the freshwater shrimp Macrobrachium amazonicum (Decapoda, Palaemonidae)

Diadromous freshwater shrimps are exposed to brackish water both as an obligatory part of their larval life cycle and during adult reproductive migration; their well-developed osmoregulatory ability is crucial to survival in such habitats. This study examines gill microsomal Na,K-ATPase (K-phosphatase activity) kinetics and protein profiles in the freshwater shrimp Macrobrachium amazonicum when in fresh water and after 10-days of acclimation to brackish water (21 parts per thousand salinity), as well as potential routes of Na(+) uptake across the gill epithelium in fresh water. On acclimation, K-phosphatase activity decreases 2.5-fold, Na,K-ATPase alpha-subunit expression declines, total protein expression pattern is markedly altered, and enzyme activity becomes redistributed into different density membrane fractions, possibly reflecting altered vesicle trafficking between the plasma membrane and intracellular compartments. Ultrastructural analysis reveals an intimately coupled pillar cell-septal cell architecture and shows that the cell membrane interfaces between the external medium and the hemolymph are greatly augmented by apical pillar cell evaginations and septal cell inviginations, respectively. These findings ire discussed regarding the putative movement of Na(+) across the pillar cell interfaces and into the hemolymph via the septal cells, powered by the Na,K-ATPase located in their invaginations. (C) 2008 Elsevier Inc. All rights reserved.

Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development

A dendritic cell (DC) imbalance with a marked deficiency in CD4(-)8(+) DC occurs in non-obese diabetic (NOD) mice, a model of human autoimmune diabetes mellitus. Using a NOD congenic mouse strain, we find that this CD4(-)8(+) DC deficiency is associated with a gene segment on chromosome 4, which also encompasses non-MHC diabetes susceptibility loci. Treatment of NOD mice with fms-like tyrosine kinase 3 ligand (FL) enhances the level of CD4(-)8(+) DC, temporarily reversing the DC subtype imbalance. At the same time, fms-like tryosine kinase 3 ligand treatment blocks early stages of the diabetogenic process and with appropriately timed administration can completely prevent diabetes development. This points to a possible clinical use of FL to prevent autoimmune disease.

Tooth loss in Brazilian middle-aged adults: multilevel effects

Objective. To examine the link between tooth loss and multilevel factors in a national sample of middle-aged adults in Brazil. Material and methods. Analyses were based on the 2003 cross-sectional national epidemiological survey of the oral health of the Brazilian population, which covered 13 431 individuals (age 35-44 years). Multistage cluster sampling was used. The dependent variable was tooth loss and the independent variables were classified according to the individual or contextual level. A multilevel negative binomial regression model was adopted. Results. The average tooth loss was 14 (standard deviation 9.5) teeth. Half of the individuals had lost 12 teeth. The contextual variables showed independent effects on tooth loss. It was found that having 9 years or more of schooling was associated with protection against tooth loss (means ratio range 0.68-0.76). Not having visited the dentist and not having visited in the last >= 3 years accounted for increases of 33.5% and 21.3%, respectively, in the risk of tooth loss (P < 0.05). The increase in tooth extraction ratio showed a strong contextual effect on increased risk of tooth loss, besides changing the effect of protective variables. Conclusions. Tooth loss in middle-aged adults has important associations with social determinants of health. This study points to the importance of the social context as the main cause of oral health injuries suffered by most middle-aged Brazilian adults.

Prevalence of Epilepsy in Children From a Brazilian Area of High Deprivation

This study assessed the prevalence rate of epilepsy and its causes in children and adolescents in one area of high deprivation in Sao Paulo, Sao Paulo, in Southeast Brazil. Between July 2005 and June 2006, 4947 families from a population of 22,013 inhabitants (including 10,405 children and adolescents between the ages of 0 and 16 years) living in the shantytown of Paraisopolis, were interviewed. In the first phase, a validated questionnaire was administered, to identify the occurrence of seizures. In the second phase, clinical history, neurologic examination, electroencephalography, and structural neuroimaging were performed. The diagnosis of epilepsy, including etiology, seizure types, and epileptic syndrome classification, was according to criteria of the International League Against Epilepsy. The screening phase identified 353 presumptive cases. In the second phase, 101 of these cases (33.8%) received the diagnosis of epilepsy. Crude prevalence of epilepsy was 9.7/1000 and prevalence of active epilepsy was 8.7/1000. Partial seizures were the most frequent seizure type (62/101). Symptomatic focal epilepsy was the most common form, and hypoxic-ischemic encephalopathy the most common etiology, reflecting the socioeconomic conditions of this specific population. Adequate public policies regarding perinatal assistance could help reduce the prevalence of epilepsy. (C) 2010 by Elsevier Inc. All rights reserved.

Analysis of the PTPN11 gene in idiopathic short stature children and Noonan syndrome patients

Background Mutations in the PTPN11 gene are the main cause of Noonan syndrome (NS). The presence of some NS features is a frequent finding in children with idiopathic short stature (ISS). These children can represent the milder end of the NS clinical spectrum and PTPN11 is a good candidate for involvement in the pathogenesis of ISS. Objective To evaluate the presence of mutations in PTPN11 in ISS children who presented NS-related signs and in well-characterized NS patients. Patients and methods We studied 50 ISS children who presented at least two NS-associated signs but did not fulfil the criteria for NS diagnosis. Forty-nine NS patients diagnosed by the criteria of van der Burgt et al. were used to assess the adequacy of these criteria to select patients for PTPN11 mutation screening. The coding region of PTPN11 was amplified by polymerase chain reaction (PCR), followed by direct sequencing. Results No mutations or polymorphisms were found in the coding region of the PTPN11 gene in ISS children. Nineteen of the 49 NS patients (39%) presented mutations in PTPN11. No single characteristic enabled us to distinguish between NS patients with or without PTPN11 mutations. Conclusion Considering that no mutations were found in the present cohort with NS-related signs, it is unlikely that mutations would be found in unselected ISS children. The van der Burgt et al. criteria are adequate in attaining NS diagnosis and selecting patients for molecular studies. Mutations in the PTPN11 gene are commonly involved in the pathogenesis of NS but are not a common cause of ISS.

Surgical removal of small petroclival meningiomas

Treatment of large petroclival meningiomas causing brain stem compression is surgical removal followed by radiotherapy or radiosurgery if the lesion was partially resected. The management of small petroclival meningiomas is, however, controversial. Clinical observation, radiosurgery and surgical removal are the options of treatment. The natural history of these tumours is not well known. Published series of patients treated with radiosurgery are not comparable with surgical series because the latter also includes large size tumours. In this paper we present a series of 18 patients with small petroclival meningiomas (diameter <= 2.8cm) treated with radical surgical removal. Total resection (Simpson`s Grade 1) [43] was possible with minimal morbidity and no mortality. Background. We present a series of small petroclival meningiomas (SPM) treated by radical surgical removal and compare the outcome with other management modalities proposed for these lesions. Methods. Eighteen patients with SPM were surgically treated at our department of neurological surgery. The tumours were classified as small when they had a diameter < 3.0cm. Headaches (n = 12), diplopia (n = 8), facial hypoaesthesia (n = 3) and tinnitus (n = 6) were the most frequent symptoms at presentation. The approaches used were retrosigmoid (n = 14), fronto-orbito-zygomatic (n = 3) and presigmoid (n = 1). The post-operative follow-up ranged from 1 to 110 months (mean 41.8 months). Findings. Radical tumour resection (Simpson`s Grades 1 and 2) was achieved in all patients. There was no major morbidity or mortality related to the surgical procedure. Transient abducent nerve palsy was the only post-operative complication. The pre-operative cranial nerves deficits improved after surgery. Only one patient had persistent diplopia postoperatively. Conclusion. Radical surgical removal of SPM is possible with minimal morbidity and may cure the patient. The effectiveness and outcome of surgery for small petroclival meningiomas should be compared with series treated by radiosurgery.

The phylogeography of African Brazilians

Background/Aims: Approximately four million Africans were taken as slaves to Brazil, where they interbred extensively with Amerindians and Europeans. We have previously shown that while most White Brazilians carry Y chromosomes of European origin, they display high proportions of African and Amerindian mtDNA lineages, because of sex-biased genetic admixture. Methods: We studied the Y chromosome and mtDNA haplogroup structure of 120 Black males from Sao Paulo, Brazil. Results: Only 48% of the Y chromosomes, but 85% of the mtDNA haplogroups were characteristic of sub-Saharan Africa, confirming our previous observation of sexually biased mating. We mined literature data for mtDNA and Y chromosome haplogroup frequencies for African native populations from regions involved in Atlantic Slave Trade. Principal Components Analysis and Bayesian analysis of population structure revealed no genetic differentiation of Y chromosome marker frequencies between the African regions. However, mtDNA examination unraveled considerable genetic structure, with three clusters at Central-West Africa, West Africa and Southeast Africa. A hypothesis is proposed to explain this structure. Conclusion: Using these mtDNA data we could obtain for the first time an estimate of the relative ancestral contribution of Central-West (0.445), West (0.431) and Southeast Africa (0.123) to African Brazilians from Sao Paulo. These estimates are consistent with historical information. Copyright (c) 2008 S. Karger AG, Basel.

Comparison of Humanized IgG and FvFc Anti-CD3 Monoclonal Antibodies Expressed in CHO Cells

Two humanized monoclonal antibody constructs bearing the same variable regions of an anti-CD3 monoclonal antibody, whole IgG and FvFc, were expressed in CHO cells. Random and site-specific integration were used resulting in similar expression levels. The transfectants were selected with appropriate selection agent, and the surviving cells were plated in semi-solid medium for capture with FITC-conjugated anti-human IG antibody and picked with the robotic ClonePix FL. Conditioned media from selected clones were purified by affinity chromatography and characterized by SDS-PAGE, Western-blot, SEC-HPLC, and isoelectric focusing. Binding to the target present in healthy human mononuclear cells was assessed by flow cytometry, as well as by competition between the two constructs and the original murine monoclonal antibody. The humanized constructs were not able to dislodge the murine antibody while the murine anti-CD3 antibody could dislodge around 20% of the FvFc or IgG humanized versions. Further in vitro and in vivo pre-clinical analyses will be carried out to verify the ability of the humanized versions to demonstrate the immunoregulatory profile required for a humanized anti-CD3 monoclonal antibody.

Structural and electron self-exchange rate variations in isomeric (hexaamine)cobalt(III/II) complexes

The syntheses and characterisation of the new macrocyclic hexaamine trans-(5(S),7(S),12(R),14(R)-tetramethyl)-1,4,8,11-tetraazacyclotetradecane-6,13-diamine (L-6) and its Co-III complex are reported. The X-ray crystal structural analyses of [CoL6]Cl-2(ClO4) [monoclinic, space group C2/c, a = 16.468(3) Angstrom, b = 9.7156(7) Angstrom, c = 15.070(3) Angstrom, beta = 119.431(8)degrees, Z = 4] and the closely related cis-diamino-substituted macrocyclic complex [CoL2](ClO4)(3) . 2H(2)O (L-2 = cis-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane-6,13-diamine) [orthorhombic, space group Pna2(1), a = 16.8220(8) Angstrom, b = 10.416(2) Angstrom, c = 14.219(3) Angstrom, Z = 4] reveal significant variations in the observed Co-N bond lengths and coordination geometries, which may be attributed to the trans or cis disposition of the pendent primary amines. The Co-III/II self-exchange electron transfer rate constants for these and other closely related hexaamines have been determined, and variations of some 2 orders of magnitude are found between pairs of trans and cis isomeric Co-III complexes.

Correlation between CD34(+) and exercise capacity, functional class, quality of life and norepinephrine in heart failure patients

Background: A previous study associated CD34(+) levels with NYHA functional class in heart failure patients. The aim of this study was to correlate CD34(+) levels to exercise capacity, functional class, quality of life and norepinephrine in heart failure patients. Methods: Twenty three sedentary patients (52 +/- 7 years, 78% male) answered the Minnesota Living with Heart Failure Questionnaire and rested for 20 minutes before an investigator collect a blood sample. After this, patients performed a cardiopulmonary exercise test to determine the heart rate at anaerobic and ventilatory threshold and oxygen consumption at peak effort, at anaerobic and ventilatory threshold. One other blood sample was collected during the peak effort to investigate the norepinephrine and CD34(+) levels. Results: Rest percentage of CD34(+) did not show correlation with: left ventricle ejection fraction (r = 0.03, p = 0.888), peakVO(2) (r = 0.32, p = 0.13), VO(2) at anaerobic threshold (VO(2)AT) (r = 0.03, p = 0.86), VO(2) at ventilatory threshold (VO(2)VT) (r = 0.36, p = 0.08), NYHA functional class (r = -0.2, p = 0.35), quality of life (Minnesota) (r = -0.17, p = 0.42). CD34(+) did not show correlation, either, with: peak VO(2) (r = 0.38, p = 0.06), VO(2)AT (r = 0.09, p = 0.65), VO(2)VT (r = 0.43, p = 0.4), NYHA functional class (r = -0.13, p = 0.54), quality of life (r = 0.00, p = 0.99). Conclusions: CD34(+) levels did not correlate with exercise capacity, functional class, quality of life and norepinephrine. Percentage of CD34(+) levels did not increase during the cardiopulmonary exercise test in heart failure patients. (Cardiol J 2009; 16, 5: 426-431)