Widening the scope of PPR diagnostic: Adaptation and development to target atypical host species and field situations

Background Peste-des-petits ruminants (PPR) is a highly contagious and devastat-ing viral disease affecting sheep, goats, and a large number of spe-cies within the order Artiodactyla. Robust commercial serological and virological diagnostic kits are available to detect PPR infection, but they were mainly developed for domestic small ruminants (goat and sheep) and for high quality, invasive samples sometimes hard to obtain in the field. New tools are needed to detect PPR infection in atypical hosts (e.g. camels, wildlife) and in complex field situations. Here we present adaptation of existing methods and new diagnostic tools to resolve some of these issues. In some regions, farmers are reluctant to have their animals handled and tested for PPR infection. As well, in the case of wildlife survey, animal capture is very costly and demands complicated logistics. Detection of PPR virus in non- invasive samples (feces) can be extremely useful in such cases. Methods and results We adapted methods of RNA extraction, RT-PCR, RT-QPCR and anti-gen capture ELISA to detect PPR viral particles or genetic material from fecal samples. The methods were validated with samples col-lected during an infection experiment. Our protocol was then used with fecal samples obtained in the field in Tanzania in 2015, and compared to results obtained from ocular swab samples taken from the same animals. Another issue is that existing LFD tests used in the field do not allow for direct confirmation by PCR. Here we present a new rapid penside test, produced and distributed by IDvet (France), which can be performed without any lab equipment. Lastly, we also tackled the issue of PPR antibody detection from camelid sera, usually suboptimal because of their particular antibody structure. Results Our results show that virus particles can be detected in fecal sam-ples from 4 days post infection (dpi) until at least 14 dpi. Sensitivity of RT-QPCR from fecal samples was similar to RT-QPCR and lateral flow device (LFD) on ocular swab samples. The penside test was as sensi-tive as the antigen capture ELISA test. Once dried, positive strips can be stored and used later on for confirmation by RT-QPCR or RT-PCR. A simple modification of the protocol of a commercially available competitive ELISA for PPR antibody detection (IDvet) increased the sensitivity of the test on camelid serum. Conclusion These tools will be extremely useful to unravel important questions that still remain about PPR epidemiology, notably the role of atypical host in PPR transmission dynamics

A multicentre epidemiological study on sunbed use and cutaneous melanoma in Europe

A large European case-control study investigated the association between sunbed use and cutaneous melanoma in an adult population aged between 18 and 49 years. Between 1999 and 2001 sun and sunbed exposure was recorded in 597 newly diagnosed melanoma cases and 622 controls in Belgium, France, The Netherlands, Sweden and the UK. Fifty three precent of cases and 57% of controls ever used sunbeds. The overall adjusted odds ratio (OR) associated with ever sunbed use was 0.90 (95% CI: 0.71-1.14). There was a South-to-North gradient with high prevalence of sunbed exposure in Northern Europe and lower prevalence in the South (prevalence of use in France 20%, OR: 1.19 (0.68-2.07) compared to Sweden, prevalence 83%, relative risk 0.62 (0.26-1.46)). Dose and lag-time between first exposure to sunbeds and time of study were not associated with melanoma risk, neither were sunbathing and sunburns (adjusted OR for mean number of weeks spent in sunny climates >14 years: 1.12 (0.88-1.43); adjusted OR for any sunburn >14 years: 1.16 (0.9-1.45)). Host factors such as numbers of naevi and skin type were the strongest risk indicators for melanoma. Public health campaigns have improved knowledge regarding risk of UV-radiation for skin cancers and this may have led to recall and selection biases in both cases and controls in this study. Sunbed exposure has become increasingly prevalent over the last 20 years, especially in Northern Europe but the full impact of this exposure on skin cancers may not become apparent for many years

Variant Histone H2A.Z Is Globally Localized to the Promoters of Inactive Yeast Genes and Regulates Nucleosome Positioning

H2A.Z is an evolutionary conserved histone variant involved in transcriptional regulation, antisilencing, silencing, and genome stability. The mechanism(s) by which H2A.Z regulates these various biological functions remains poorly defined, in part due to the lack of knowledge regarding its physical location along chromosomes and the bearing it has in regulating chromatin structure. Here we mapped H2A.Z across the yeast genome at an approximately 300-bp resolution, using chromatin immunoprecipitation combined with tiling microarrays. We have identified 4,862 small regions—typically one or two nucleosomes wide—decorated with H2A.Z. Those “Z loci” are predominantly found within specific nucleosomes in the promoter of inactive genes all across the genome. Furthermore, we have shown that H2A.Z can regulate nucleosome positioning at the GAL1 promoter. Within HZAD domains, the regions where H2A.Z shows an antisilencing function, H2A.Z is localized in a wider pattern, suggesting that the variant histone regulates a silencing and transcriptional activation via different mechanisms. Our data suggest that the incorporation of H2A.Z into specific promoter-bound nucleosomes configures chromatin structure to poise genes for transcriptional activation. The relevance of these findings to higher eukaryotes is discussed

Analysis of short tandem repeats linked to polyglutamine diseases from whole-genome sequencing reveals intermediate alleles of HTT associated with an early disease onset in C9orf72 carriers

Carriers of the GGGGCC pathogenic expansion in C9orf72 can develop symptoms of frontotemporal dementia and/or amyotrophic lateral sclerosis, with variable and unpredictable ages at onset. Previous studies aiming to decipher the genetic bases of the clinical variability in this rare disease included bi-allelic polymorphisms, excluding short tandem repeats. Whole-genome sequencing data of 195 C9orf72 patients were used to consider all short tandem repeats linked to polyglutamine disorders as potential genetic modifiers given the existing links between C9orf72 and polyglutamine diseases. Intermediate alleles of HTT encoding huntingtin were associated with an earlier age at onset among C9orf72 carriers in the discovery cohort (n = 195, P = 0.0003) and in a European replication cohort (n = 145, P = 0.006). In the merged cohort (n = 340), the average difference of age at disease onset was 9.42 ± 2.14 years (P = 1.3 × 10e-5) between carriers and non-carriers of HTT-intermediate alleles. Neuropathology of one C9orf72 case heterozygous for HTT-intermediate allele showed typical TDP-43 inclusions related to the C9orf72 pathogenic expansion and was negative for polyglutamine inclusion. No somatic expansion of HTT was detected in blood of all C9orf72exp/HTT-intermediate carriers. If this study reinforces potential biological links between huntingtin and C9orf72 that remain to be explored, the results also illustrate the interest of considering short tandem repeats from whole-genome data in association studies which paves the way to more exhaustive approaches to explore the trait heritability due to short-tandem-repeats still hidden in the genome

iFR/FFR/IVUS Discordance and Clinical Implications: Results From the Prospective Left Main Physiology Registry

peer reviewedOBJECTIVES: This study aimed to assess discordance between results of instantaneous wave-free ratio (iFR), fractional flow reserve (FFR), and intravascular ultrasound (IVUS) in intermediate left main coronary (LM) lesions, and its impact on clinical decision making and outcome. METHODS: We enrolled 250 patients with a 40%-80% LM stenosis in a prospective, multicenter registry. These patients underwent both iFR and FFR measurements. Of these, 86 underwent IVUS and assessment of the minimal lumen area (MLA), with a 6 mm 2 cutoff for significance. RESULTS: Isolated LM disease was recognized in 95 patients (38.0%), while 155 patients (62.0%) had both LM disease and downstream disease. In 53.2% of iFR+ and 56.7% of FFR+ LM lesions, the measurement was positive in only one daughter vessel. iFR/FFR discordance occurred in 25.0% of patients with isolated LM disease and 36.2% of patients with concomitant downstream disease (P=.049). In patients with isolated LM disease, discordance was significantly more common in the left anterior descending artery and younger age was an independent predictor of iFR-/FFR+ discordance. iFR/MLA and FFR/MLA discordance occurred in 37.0% and 29.4%, respectively. Within 1 year of follow-up, major cardiac adverse events (MACE) occurred in 8.5% and 9.7% (P=.763) of patients whose LM lesion was deferred or revascularized, respectively. Discordance was not an independent predictor of MACE. CONCLUSIONS: Current methods of estimating LM lesion significance often yield discrepant findings, complicating therapeutic decision-making

Traitement de la sclérose en plaques par la mitoxantrone (une étude rétrospective de 44 cas)

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

Ex-Yougoslavie : Retour de Tuzla

Bataille Claire, Vigan Marie-Annick, Gérard Isabelle. Ex-Yougoslavie : Retour de Tuzla. In: Cahiers du féminisme, n°74, 1995. Dossier : Menaces sur le droit à l’avortement (automne 1995) pp. 36-41

Algérie : La vie malgré tout

Akrouf Sanhadja, Bataille Claire, Vigan Marie-Annick. Algérie : La vie malgré tout. In: Cahiers du féminisme, n°77, 1996. Du Nord au Sud, le libéralisme contre les femmes (été 1996) pp. 31-32