Developmental and reproductive patterns of Triatoma brasiliensis infected with Trypanosoma cruzi under laboratory conditions

The aim of this work was to study the interaction between Trypanosoma cruzi-1 and Triatoma brasiliensis. A group of 1st instar nymphs was initially fed on T. cruzi-infected mice and a control group was fed on uninfected mice. From the second feeding onwards, both groups were otherwise fed on non-infected mice. The resulting adults were grouped in pairs: infected male/uninfected female, uninfected male/infected female, infected male and female and uninfected male/uninfected female. The infection affected only the 1st instar nymphs, which took significantly more time to reach the 2nd instar than uninfected nymphs. The differences in the molting time between the infected and uninfected nymphs from the 2nd to the 5th instars were not statistically significant. Both groups presented similar rates of nymphal mortality and reproductive performance was not significantly affected by infection in any of the treatments.

The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis

BACKGROUND The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. METHODOLOGY AND RESULTS We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. CONCLUSIONS Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

Developmental changes in lateralized inhibition of symmetric movements in children with and without Developmental Coordination Disorder.

The present study investigates developmental changes in selective inhibition of symmetric movements with a lateralized switching task from bimanual to unimanual tapping in typically developing (TD) children and with Developmental Coordination Disorder (DCD) from 7 to 10 years old. Twelve right-handed TD children and twelve gender-matched children with DCD and probable DCD produce a motor switching task in which they have (1) to synchronize with the beat of an auditory metronome to produce bimanual symmetrical tapping and (2) to selectively inhibit their left finger's tapping while continuing their right finger's tapping and conversely. We assess (1) the development of the capacity to inhibit the stopping finger (number of supplementary taps after the stopping instruction) and (2) the development of the capacity to maintain the continuing finger (changes in the mean tempo and its variability for the continuing finger's tapping) and (3) the evolution of performance through trials. Results indicate that (1) TD children present an age-related increase in the capacity to inhibit and to maintain the left finger's tapping, (2) DCD exhibits persistent difficulties to inhibit the left finger's tapping, and (3) both groups improve their capacity to inhibit the left finger's movements through trials. In conclusion, the lateralized switching task provides a simple and fine tool to reveal differences in selective inhibition of symmetric movements in TD children and children with DCD. More theoretically, the specific improvement in selective inhibition of the left finger suggests a progressive development of inter-hemispheric communication during typical development that is absent or delayed in children with DCD.

Responsiveness of the Multiple Sclerosis International Quality of Life questionnaire to disability change: a longitudinal study.

BACKGROUND Responsiveness, defined as the ability to detect a meaningful change, is a core psychometric property of an instrument measuring quality of life (QoL) rarely reported in multiple sclerosis (MS) studies. OBJECTIVE To assess the responsiveness of the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire to change in disability over 24 months, defined by change in the Expanded Disability Status Scale (EDSS) score. METHODS Patients with MS were enrolled into a multicenter, longitudinal observational study. QoL was assessed using both the MusiQoL and the 36-Item Short-Form (SF-36) instruments at baseline and every 6 months thereafter up to month 24; neurological assessments, including EDSS score, were performed at each evaluation. RESULTS The 24-month EDSS was available for 524 patients. In the 107 worsened patients, two specific dimensions of MusiQoL, the sentimental and sexual life and the relationships with health care system dimensions, and 'physical' scores of SF-36 showed responsiveness. CONCLUSIONS Whereas specific dimensions of MusiQoL identified EDSS changes, the MusiQoL index did not detect disability changes in worsened MS patients in a 24-month observational study. Future responsiveness validation studies should include longer follow-up and more representative samples.

Conservation and developmental expression of ubiquitin isopeptidases in Schistosoma mansoni

Several genes related to the ubiquitin (Ub)-proteasome pathway, including those coding for proteasome subunits and conjugation enzymes, are differentially expressed during the Schistosoma mansoni life cycle. Although deubiquitinating enzymes have been reported to be negative regulators of protein ubiquitination and shown to play an important role in Ub-dependent processes, little is known about their role in S. mansoni . In this study, we analysed the Ub carboxyl-terminal hydrolase (UCHs) proteins found in the database of the parasite’s genome. An in silicoana- lysis (GeneDB and MEROPS) identified three different UCH family members in the genome, Sm UCH-L3, Sm UCH-L5 and SmBAP-1 and a phylogenetic analysis confirmed the evolutionary conservation of the proteins. We performed quantitative reverse transcription-polymerase chain reaction and observed a differential expression profile for all of the investigated transcripts between the cercariae and adult worm stages. These results were corroborated by low rates of Z-Arg-Leu-Arg-Gly-Gly-AMC hydrolysis in a crude extract obtained from cercariae in parallel with high Ub conjugate levels in the same extracts. We suggest that the accumulation of ubiquitinated proteins in the cercaria and early schistosomulum stages is related to a decrease in 26S proteasome activity. Taken together, our data suggest that UCH family members contribute to regulating the activity of the Ub-proteasome system during the life cycle of this parasite.

The adolescent with a chronic condition. Part I: developmental issues.

The prevalence of chronic conditions among adolescents is difficult to assess due to the lack of quality data focusing specifically on this age group, as well as the diversity in methodology and definitions used. However, surveys carried out by self administered questionnaires among in-school adolescent populations indicate that around 10% of adolescents suffer from such a condition. The aim of this paper is to analyse the reciprocal effects of chronic conditions and adolescent development by reviewing the effect of chronic disease on growth and puberty and on psychosocial development, and the effect of developmental issues on the course and management of chronic disease.

Cross-coding from the Swiss Disability Insurance listing to the ICIDH.

It has been suggested that converting, via a process of cross-coding, the listing used by the Swiss Disability Insurance (SDI) for their statistics into codes of the International Classification of Impairments, Disabilities, and Handicaps (ICIDH) would improve the quality and international comparability of disability statistics for Switzerland. Using two different methods we tested the feasibility of this cross-coding on a consecutive sample of 204 insured persons, examined at one of the medical observation centres of the SDI. Cross-coding is impossible, for all practical purposes, in a proportion varying between 30% and 100%, depending on the method of cross-coding, the level of disablement and the required quality of the resulting codes. Failure is due to lack of validity of the SDI codes: diseases are poorly described, consequences of diseases (disability and handicap, including loss of earning capacity), insufficiently described or not at all. Assessment of disability and handicap would provide necessary information for the SDI. It is concluded that the SDI should promote the use of the ICIDH in Switzerland, especially among medical practitioners whose assessment of work capacity is the key element in the decision to award benefits or propose rehabilitation.

Developmental effects of basic fibroblast growth factor and platelet-derived growth factor on glial cells in a three-dimensional cell culture system.

In order to study peptide growth factor action in a three-dimensional cellular environment, aggregating cell cultures prepared from 15-day fetal rat telencephalon were grown in a chemically defined medium and treated during an early developmental stage with either bovine fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF homodimers AA and BB). A single dose (5-50 ng/ml) of either growth factor given to the cultures on day 3 greatly enhanced the developmental increase of the two glia-specific enzyme activities, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and glutamine synthetase (GS), whereas it had relatively little effect on total protein and DNA content. Distinct patterns of dose-dependency were found for CNP and GS stimulation. At low concentrations of bFGF (0.5-5 ng/ml) and at all PDGF concentrations applied, the oligodendroglial marker enzyme CNP was the most affected. A relatively small but significant mitogenic effect was observed after treatment with PDGF, particularly at higher concentrations or after repetitive stimulation. The two PDGF homodimers AA and BB were similar in their biological effects and potency. The present results show that under histotypic conditions both growth factors, bFGF and PDGF, promote the maturation rather than the proliferation of immature oligodendrocytes and astrocytes.

TBC1D7 mutations are associated with intellectual disability, macrocrania, patellar dislocation, and celiac disease.

TBC1D7 forms a complex with TSC1 and TSC2 that inhibits mTORC1 signaling and limits cell growth. Mutations in TBC1D7 were reported in a family with intellectual disability (ID) and macrocrania. Using exome sequencing, we identified two sisters homozygote for the novel c.17_20delAGAG, p.R7TfsX21 TBC1D7 truncating mutation. In addition to the already described macrocephaly and mild ID, they share osteoarticular defects, patella dislocation, behavioral abnormalities, psychosis, learning difficulties, celiac disease, prognathism, myopia, and astigmatism. Consistent with a loss-of-function of TBC1D7, the patient's cell lines show an increase in the phosphorylation of 4EBP1, a direct downstream target of mTORC1 and a delay in the initiation of the autophagy process. This second family allows enlarging the phenotypic spectrum associated with TBC1D7 mutations and defining a TBC1D7 syndrome. Our work reinforces the involvement of TBC1D7 in the regulation of mTORC1 pathways and suggests an altered control of autophagy as possible cause of this disease.

Validation transculturelle de l'Oswestry disability index en français [Cross-cultural validation of the Oswestry disability index in French]

AIM: The aim of this study was to interpret and validate a French version of the Oswestry disability index (ODI), using a cross-cultural validation method. The validity and reliability of the questionnaire was assessed in order to ensure the psychometric characteristics. METHOD: The cross-cultural validation was carried out according to Beaton's methodology. The study was conducted with 41 patients suffering from low back pain. The correlation between the ODI and the Roland-Morris disability questionnaire (RMDQ), the medical outcome survey short form-36 (MOS SF-36) and a pain visual analogical scale (VAS) was assessed. RESULTS: The validity of the Oswestry questionnaire was studied using the Cronbach Alpha coefficient calculation: 0.87 (n=36). The significant correlation between the ODI and RMDQ was 0.8 (P<0.001, n=41) and 0.71 (P<0.001, n=36) for the pain VAS. The correlation between the ODI and certain subscales (physical functioning 0.7 (P<0.001, n=41), physical role 0.49 et bodily pain 0.73 (P<0.001, n=41)) of the MOS SF-36 were equally significant. The reproducibility of the ODI was calculated using the Wilcoxon matched pairs test: there was no significant difference for eight out of ten sections or for the final score. CONCLUSION: This French translation of the ODI should be considered as valid and reliable. It should be used for any future clinical studies carried out using French language patients. Complimentary studies must be completed in order to assess its sensitivity to change in the event of any modifications in the patients functional capacity.

Developmental, metabolic and immunological costs of flea infestation in the common vole

Parasites use resources from their hosts, which can indirectly affect a number of host functions because of trade-offs in resource allocation. In order to get a comprehensive view of the costs imposed by blood sucking parasites to their hosts, it is important to monitor multiple components of the development and physiology of parasitized hosts over long time periods. The effect of infestation by fleas on body mass, body length growth, haematocrit, resistance to oxidative stress, resting metabolic rate and humoral immune response were experimentally evaluated. During a 3-month period, male common voles, Microtus arvalis, were either parasitized by rat fleas (Nosopsyllus fasciatus), which are naturally occurring generalist ectoparasites of voles, or reared without fleas. Then voles were challenged twice by injecting Keyhole Limpet Haemocyanin (KLH) to assess whether the presence of fleas affects the ability of voles to produce antibodies against a novel antigen. During the immune challenge we measured the evolution of body mass, haematocrit, resistance to oxidative stress and antibody production. Flea infestation negatively influenced the growth of voles. Moreover, parasitized voles had reduced haematocrit, higher resting metabolic rate and lower production of antibodies against the KLH. Resistance to oxidative stress was not influenced by the presence of fleas. During the immune challenge with KLH, body mass decreased in both groups, while the resistance to oxidative stress remained stable. In contrast, the haematocrit decreased only in parasitized voles. Our experiment shows that infestation by a haematophageous parasite negatively affects multiple traits like growth, energy consumption and immune response. Fleas may severely reduce the survival probability and reproductive success of their host in natural conditions.