Tumor necrosis factor receptor II gene polymorphism and severity of rheumatoid arthritis

OBJECTIVE: The gene encoding tumor necrosis factor receptor type II (TNFRII) is a strong candidate in the pathogenesis of rheumatoid arthritis (RA). An association between a single-nucleotide polymorphism (196M/R) in exon 6 of the TNFRII gene and familial RA was recently reported. The present study was undertaken to test the hypothesis that there is an association between this polymorphism and the severity of RA. METHODS: One hundred two white patients with early RA were included in this prospective study. The French version of the Health Assessment Questionnaire (F-HAQ) and a radiographic damage score (modified Sharp/van der Heijde method) were used to quantify the functional and structural severity of RA at baseline and after 4 years of followup. TNFRII 196M/R polymorphism genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Among the 102 patients with RA, 63 (61.8%) were homozygous for the 196M allele, 36 (35.3%) were heterozygous for alleles 196M and 196R, and 3 (2.9%) were homozygous for the 196R allele. At baseline, the median radiographic and F-HAQ scores did not differ between RA patients who carried the 196R allele and those who did not. After 4 years of followup, the F-HAQ score was higher in RA patients carrying the 196R allele (median 1 [interquartile range (IQR) 0.125, 1.375]) than in noncarriers (0.375 [IQR 0, 1]) (P = 0.02), while the median radiographic score did not differ between RA patients who carried the 196R allele and those who did not. CONCLUSION: The results of the present study support the hypothesis that there is an association between the TNFRII 196 M/R gene polymorphism and the functional severity of early RA.     

A framework for the comparison of mobile patient monitoring systems

A mobile patient monitoring system makes use of mobile computing and wireless communication technologies for continuous or periodic measurement and analysis of biosignals of a mobile patient. In a number of trials these systems have demonstrated their user-friendliness, convenience and effectiveness for both patients and healthcare professionals. In this paper we propose a generic architecture, associated terminology and a classificatory framework for comparing mobile patient monitoring systems. We then apply this comparison framework to classify six mobile patient monitoring systems selected according to the following criteria: use of diverse mobile communication techniques, evidence of practical trials and availability of sufficient published scientific information. We also show how to use this framework to determine feature sets of prospective real-time mobile patient monitoring systems using the example of epilepsy monitoring. This paper is aimed at both healthcare professionals and computer professionals. For healthcare professionals, this paper provides a general understanding of technical aspects of the mobile patient monitoring systems and highlights a number of issues implied by the use of these systems. The proposed framework for comparing mobile patient monitoring systems can be used by healthcare professionals to determine feature sets of prospective mobile patient monitoring systems to address particular healthcare related needs. Computer professionals are expected to benefit by gaining an understanding of the latest developments in the important emerging application area of mobile patient monitoring systems.     

Progressive polyepiphyseal dysplasia with arthropathy: a distinct disorder from idiopathic juvenile arthritis and pseudorheumatoid dysplasia?

Juvenile idiopathic arthritis is an inflammatory disease with various onset-forms which can sometimes be difficult to distinguish from genetic inflammatory/rheumatoid-like osteoarthropathies. In this report, we describe two boys with severe chronic arthralgia, stiffness and swelling of joints, motor weakness and joints contractures evolving despite immunosuppressive treatments and for whom all biological and molecular exams failed to identify a prompt diagnosis. Some findings also overlap with pseudorheumatoid dysplasia but WISP3 gene molecular analysis failed to identify any mutation for both patients. Therefore, we propose that these boys show a clinical entity distinct from the actually known genetic inflammatory/rheumatoid-like osteoarthropathies.     

IMPAD1 mutations in two Catel-Manzke like patients

Catel-Manzke syndrome is characterized by hyperphalangism with bilateral deviation of the index fingers and micrognathia with or without cleft palate. Some atypical patients present with additional malformations. No molecular basis is yet available. Most patients have an unremarkable family history but autosomal recessive inheritance has been recently suggested in a consanguineous family with recurrence in sibs. Catel-Manzke syndrome has overlapping features with Desbuquois dysplasia type 1 due to CANT1 (calcium-activated nucleotidase 1) mutations and also with "chondrodysplasia with joint dislocations, gPAPP type" due to IMPAD1 (Inositol Monophosphatase Domain containing 1) mutations recently reported in four patients, all characterized by short stature, joint dislocations, brachydactyly and cleft palate. The aim of our study was to screen CANT1 and IMPAD1 in Catel-Manzke patients. Three patients were diagnosed as classical Catel-Manzke syndrome and two as Catel-Manzke like patients, based on the presence of additional features. We identified two homozygous loss-of-function IMPAD1 mutations in the two Catel-Manzke like patients (p.Arg187X and p.Ser108ArgfsX48). The phenotype was characterized by severe growth retardation with short and abnormal extremities, cleft palate with micrognathia and knee hyperlaxity. Radiographs of hands and feet revealed numerous accessory bones with abnormally shaped phalanges and carpal synostosis. Based on this report, we concluded that IMPAD1 should be screened for patients with Catel-Manzke and additional features. ? 2012 Wiley Periodicals, Inc.     

Goats Primed with Mycobacterium bovis BCG and Boosted with a Recombinant Adenovirus Expressing Ag85A Show Enhanced Protection against Tuberculosis

This is the first efficacy study using the experimental goat model, a natural host of tuberculosis (TB), to evaluate the efficacy of heterologous Mycobacterium bovis bacillus Calmette-Guérin (BCG) prime followed by boosting with a replication-deficient adenovirus expressing the antigen Ag85A (AdAg85A). Three experimental groups of 11 goat kids each were used: BCG vaccinated, BCG vaccinated and AdAg85A boosted, and nonvaccinated. Twenty-two goat kids were vaccinated with ～5 × 10(5) CFU of BCG (week 0), and 11 of them were boosted at week 8 with 10(9) PFU of AdAg85A. At week 14, all goats were challenged by the endobronchial route with ～1.5 × 10(3) CFU of Mycobacterium caprae. The animals were euthanized at week 28. Cellular and humoral immunity induced by vaccination and M. caprae infection was measured throughout the study. After challenge BCG-AdAg85A-vaccinated animals exhibited reduced pathology compared to BCG-vaccinated animals in lungs and in pulmonary lymph nodes. There were significant reductions in bacterial load in both groups of vaccinated goats, but the reduction was more pronounced in prime-boosted animals. Antigen-specific gamma interferon (IFN-γ) and humoral responses were identified as prognostic biomarkers of vaccination outcome depending on their correlation with pathological and bacteriological results. As far as we know, this is the first report using multidetector computed tomography (MDCT) to measure vaccine efficacy against pulmonary TB in an animal model. The use in vaccine trials of animals that are natural hosts of TB may improve research into human TB vaccines.     

BBS proteins interact genetically with the IFT pathway to influence SHH-related phenotypes

There are numerous genes for which loss-of-function mutations do not produce apparent phenotypes even though statistically significant quantitative changes to biological pathways are observed. To evaluate the biological meaning of small effects is challenging. Bardet-Biedl syndrome (BBS) is a heterogeneous autosomal recessive disorder characterized by obesity, retinopathy, polydactyly, renal malformations, learning disabilities and hypogenitalism, as well as secondary phenotypes including diabetes and hypertension. BBS knockout mice recapitulate most human phenotypes including obesity, retinal degeneration and male infertility. However, BBS knockout mice do not develop polydacyly. Here we showed that the loss of BBS genes in mice result in accumulation of Smoothened and Patched 1 in cilia and have a decreased Shh response. Knockout of Bbs7 combined with a hypomorphic Ift88 allele (orpk as a model for Shh dysfuction) results in embryonic lethality with e12.5 embryos having exencephaly, pericardial edema, cleft palate and abnormal limb development, phenotypes not observed in Bbs7(-/-) mice. Our results indicate that BBS genes modulate Shh pathway activity and interact genetically with the intraflagellar transport (IFT) pathway to play a role in mammalian development. This study illustrates an effective approach to appreciate the biological significance of a small effect.     

Phylogenetic Distribution of CTX-M- and Non-Extended-Spectrum-β-Lactamase-Producing Escherichia coli Isolates: Group B2 Isolates, Except Clone ST131, Rarely Produce CTX-M Enzymes

Escherichia coli is the species most frequently associated with clinical infections by extended-spectrum-β-lactamase (ESBL)-producing isolates, with the CTX-M ESBL enzymes being predominant and found in genetically diverse E. coli isolates. The main objective of this study was to compare, on the basis of a case-control design, the phylogenetic diversity of 152 CTX-M-producing and 152 non-ESBL-producing clinical E. coli isolates. Multilocus sequence typing revealed that even though CTX-M enzymes were largely disseminated across the diversity of E. coli isolates, phylogenetic group B2 showed a particularly heterogeneous situation. First, clone ST131 of group B2 was strongly associated with CTX-M production (55 [79%] of 70 isolates), with CTX-M-15 being predominant. Second, the remaining members of group B2 were significantly less frequently associated with CTX-M production (9 [12%] of 75) than E. coli phylogenetic groups A, B1, and D (88 [55%] of 159). CTX-M-producing ST131 E. coli isolates were significantly more frequent in patients hospitalized in geriatric wards or long-term care facilities. Besides, the non-ESBL ST131 isolates significantly more frequently showed resistance to penicillins than the non-ESBL, non-ST131 isolates did. In conclusion, the present study emphasizes the particular antimicrobial resistance and epidemiologic characteristics of clone ST131 within group B2, which could result from the higher antibiotic exposure of this clone, as it is the predominant clone of group B2 carried in the human gut.     

Transplantation of an alginate-matrigel matrix containing isolated ovarian cells: first step in developing a biodegradable scaffold to transplant isolated preantral follicles and ovarian cells

For women diagnosed with leukemia, transplantation of cryopreserved ovarian tissue after disease remission is not advisable. Therefore, to restore fertility in these patients, we aim to develop a biodegradable artificial ovary that offers an environment where isolated follicles and ovarian cells (OCs) can survive and grow. Four NMRI mice were ovariectomized and their ovaries used to isolate OCs. Groups of 50,000 OCs were embedded in an alginate-matrigel matrix for further fixation (fresh controls), one week of in vitro culture (IVC) or heterotopic autografting. OC proliferation (Ki67), apoptosis (TUNEL), scaffold degradation, vessel formation (CD34) and inflammation (CD45) were analyzed. Ki67-positive OCs were found in 2.3%, 9.0% and 15.5% cells of cases in fresh, IVC and grafted beads respectively, while cells were TUNEL-positive in 0%, 1.5% and 6.9% of cases. After IVC or grafting, the beads degraded, losing their original round aspect, and infiltrating blood capillaries could be observed in the grafted beads. CD34-positive cells and 22% CD45-positive cells were found around and inside the matrix. In conclusion, our results demonstrate that an alginate-based matrix is a promising proposition to graft isolated OCs. After transplantation, this matrix was able to degrade, allowed vascularization and elicited a low inflammatory response.