A mathematical model for malaria involving differential susceptibility, exposedness and infectivity of human host

The main purpose of this article is to formulate a deterministic mathematical model for the transmission of malaria that considers two host types in the human population. The first type is called "non-immune" comprising all humans who have never acquired immunity against malaria and the second type is called "semi-immune". Non-immune are divided into susceptible, exposed and infectious and semi-immune are divided into susceptible, exposed, infectious and immune. We obtain an explicit formula for the reproductive number, R(0) which is a function of the weight of the transmission semi-immune-mosquito-semi-immune, R(0a), and the weight of the transmission non-immune-mosquito-non-immune, R(0e). Then, we study the existence of endemic equilibria by using bifurcation analysis. We give a simple criterion when R(0) crosses one for forward and backward bifurcation. We explore the possibility of a control for malaria through a specific sub-group such as non-immune or semi-immune or mosquitoes.     

Severe malaria in Burkina Faso: urban and rural environment

The age distribution and the clinical patterns of severe malaria (SM) were compared in patients from urban areas characterized by relatively low transmission, and from rural areas where the mean inoculation rates are at least twenty fold higher. The mean age of the urban and rural patients was 4.8 +/- 3.0 and 2.2 +/- 1.9 respectively (p < 0.000). The prevalence of coma was higher in the urban subsample (53.6 vs 28.9%, p < 0.000) while that of severe anemia (hemoglobin < 5 g/dl) was higher in rural patients (47.4 vs 14.8%, p < 0.000). Our data, in line with previous results obtained comparing rural areas characterized by different inoculation rates, show that the epidemiological context influences the clinical presentation of SM.     

DHPLC-based method for DNA methylation analysis of differential methylated regions from imprinted genes

The bisulfite genomic sequencing method is one of the most widely used techniques for methylation analysis in heterogeneous unbiased PCR, amplifying for both methylated and unmethylated alleles simultaneously. However, it requires labor-intensive and time-consuming cloning and sequencing steps. In the current study, we used a denaturing high-performance liquid chromatography (DHPLC) procedure in a complementary way with the bisulfite genomic sequencing to analyze the methylation of differentially methylated regions (DMRs) of imprinted genes. We showed reliable and reproducible results in distinguishing overall methylation profiles of DMRs regions of human SNRPN, H19, MEST/PEG1, LIT1, IGF2, TSSC5, WT1 antisense, and mouse H19, Mest/Peg1, Igf2R imprinted genes. These DHPLC profiles were in accordance with bisulfite genomic sequencing data and may serve as a type of "fingerprint," revealing the overall methylation status of DMRs associated with sample heterogeneity. We conclude that DHPLC analysis could be used to increase the throughput efficiency of methylation pattern analysis of imprinted genes after the bisulfite conversion of genomic DNA and unbiased PCR amplification.     

A pathophysiological study of abdominal organs following intraperitoneal injections of chloral hydrate in rats: comparison between two anaesthesia protocols

Chloral hydrate (CH) is used as an anaesthetic agent in laboratory rats. Side effects occurring with high concentrations have mainly occurred in abdominal organs. The objective of the present study was to minimize these side effects following intraperitoneal administration of CH using lower concentrations. Animals were evaluated using different procedures including a general necropsy, intraperitoneal white cell counts, histology and duodenal peristalsis and acetylcholine-induced contractions. Results clearly show that lower concentrations of CH while keeping the same anaesthetic dose (400 mg/kg) will minimize the irritancy of CH on abdominal organs while providing the same level of anaesthesia.     

Complex segregation analysis provides compelling evidence for a major gene underlying obsessive-compulsive disorder and for heterogeneity by sex

Evidence from twin and family studies supports a genetic etiology for obsessive-compulsive disorder (OCD). The purpose of this study was to test whether a major gene is implicated in a proportion of families with OCD. Complex segregation analyses of 153 families (80 case and 73 control), ascertained in the Johns Hopkins OCD Family Study, provided strong evidence for a major gene. A Mendelian-dominant model, with significant sex effects and with residual familial effects, best explained the observed data. Stratification of the sample by the sex of probands provided further evidence of heterogeneity with respect to familial aggregation. Segregation analyses of 86 families with a female proband and of the 67 families with a male proband suggested that a Mendelian-dominant model with familial residual effects was the most parsimonious model explaining the inheritance of OCD in both subgroups.     

Determination of the gene structure of human oligophrenin-1 and identification of three novel polymorphisms by screening of DNA from 164 patients with non-specific X-linked mental retardation

We have recently shown that mutations in oligophrenin-1 (OPHN1) are responsible for non-specific X-linked mental retardation (MRX). The structure of the gene encoding the OPHN1 protein was determined by isolation of genomic DNA clones from the human cosmid library. Genomic fragments containing exons were sequenced, and the sequences of the exons and flanking introns were defined. Knowledge of the genomic structure of the OPHN1 gene, which spans at least 500 kb and consists of 25 exons, will facilitate the search for additional mutations in OPHN1. OPHN1 was screened for mutations in 164 subjects with non-specific mental retardation. Three nucleotide substitutions were identified, one of which was a silent mutation in the codon threonine 301 at position 903 (G-->C). The other substitutions were located in exon 2, a G-->A substitution at position 133 (A45T), and in exon 10, a C-->T substitution at position 902 (T301M), but these are common polymorphisms rather than disease-causing mutations.     

2,6,9-Trisubstituted purine derivatives as protein A mimetics for the treatment of autoimmune diseases

A series of 9-substituted and 2,9-disubstituted 6-(3-aminophenylamino) purines were synthesized and evaluated for their ability to mimic protein A binding to human IgG antibody. The structure–activity relationship (SAR) demonstrates that the 6-(3-aminoanilinyl) purine component was essential for activity. Purine 14 demonstrated significant activity, compared to protein A. These compounds may prove useful for the treatment of autoimmune diseases.     

Vaccine-related mumps infections in Thailand and the identification of a novel mutation in the mumps fusion protein

An outbreak of nine cases of mumps was reported from a total of 97 vaccinated nursing students at two medical colleges in Thailand in 2010, 16–26 days after administration of MMR vaccine containing the L-Zagreb mumps strain. Symptoms ranged in severity from fever and parotid swelling to orchitis. Clinical samples were obtained from seven patients and three were suitable for further study.Sequencing confirmed that the SH gene of the mumps virus in the unpassaged clinical specimens was identical to the L-Zagreb SH gene in the vaccine. Further analysis of the viral genome identified nucleotide position 5170 as a novel mutation which corresponds to an amino acid change in the fusion protein.This study provides another virologically confirmed example of mumps resulting from the L-Zagreb vaccine strain.