Cet article traite de diverses manières de « donner la mort » pratiquées pendant la rébellion muléliste en République démocratique du Congo (1963-1968), ainsi que de la politique qui les ...sous-tendait, comme se souviennent certains survivants. S’appuyant sur des entretiens oraux approfondis, aussi bien que sur des documents d’archives de la rébellion et sur un corpus théorique de psychanalyse et de phénoménologie, cet article soutient que la rébellion et l’État congolais avaient une manière particulière d’infliger la douleur et la souffrance aux corps de leurs ennemis. Cette façon d’administrer la douleur et la souffrance était un produit hybride. Elle s’appuyait sur la triple logique de la cruauté, de l’excès et du sadisme, et avait d’énormes conséquences tant pour les morts que pour les vivants.
A feeding trial was conducted to determine the effect of dietary administration of Pediococcus acidilactici MA18/5M and short chain fructooligosaccharides (scFOS) on Atlantic salmon (Salmo salar L.) ...intestinal health. Salmon (initial average weight 250 g) were allocated into triplicate sea pens and were fed either a control diet (commercial diet: 45% protein, 20% lipid) or a synbiotic treatment diet (control diet + P. acidilactici at 3.5 g kg−1 and 7 g kg−1 scFOS) for 63 days. At the end of this period, fish were sampled for intestinal microbiology, intestinal histology and the expression of selected immune-related genes (IL1β, TNFα, IL8, TLR3 and MX-1) in the intestine.
Compared to the control fish, the total bacterial levels were significantly lower in the anterior mucosa, posterior mucosa and posterior digesta of the synbiotic fed fish. qPCR revealed good recovery (log 6 bacteria g−1) of the probiotic in the intestinal digesta of the synbiotic fed fish and PCR-DGGE revealed that the number of OTUs, as well as the microbial community diversity and richness were significantly higher in the anterior digesta of the synbiotic fed fish than the control. Compared to the control fed fish, the mucosal fold (villi) length and the infiltration of epithelial leucocytes were significantly higher in the anterior and posterior intestine, respectively, in the synbiotic group. Real-time PCR demonstrated that all of the genes investigated were significantly up-regulated in the anterior and posterior intestine of the synbiotic fed salmon, compared to the control group. At the systemic level, serum lysozyme activity was significantly higher in the synbiotic fed fish and growth performance, feed utilisation and biometric measurements (condition factor, gutted weight and gut loss) were not affected.
Together these results suggest that the synbiotic modulation of the gut microbiota has a protective action on the intestinal mucosal cells, improving morphology and stimulating the innate immune response without negatively affecting growth performance or feed utilization of farmed Atlantic salmon.
•Dietary synbiotic application modulates the gut microbiota of Atlantic salmon.•Dietary synbiotic application modulates the Atlantic salmon intestinal immune response.•Modulation of the intestinal microbiota and immune status did not have adverse affects on Atlantic salmon growth performance.
Genetic alterations that activate the mitogen-activated protein kinase (MAP kinase) pathway occur commonly in cancer. For example, the majority of melanomas harbor mutations in the BRAF oncogene, ...which are predicted to confer enhanced sensitivity to pharmacologic MAP kinase inhibition (e.g., RAF or MEK inhibitors). We investigated the clinical relevance of MEK dependency in melanoma by massively parallel sequencing of resistant clones generated from a MEK1 random mutagenesis screen in vitro, as well as tumors obtained from relapsed patients following treatment with AZD6244, an allosteric MEK inhibitor. Most mutations conferring resistance to MEK inhibition in vitro populated the allosteric drug binding pocket or α-helix C and showed robust (almost equal to100-fold) resistance to allosteric MEK inhibition. Other mutations affected MEK1 codons located within or abutting the N-terminal negative regulatory helix (helix A), which also undergo gain-of-function germline mutations in cardio-facio-cutaneous (CFC) syndrome. One such mutation, MEK1(P124L), was identified in a resistant metastatic focus that emerged in a melanoma patient treated with AZD6244. Both MEK1(P124L) and MEK1(Q56P), which disrupts helix A, conferred cross-resistance to PLX4720, a selective B-RAF inhibitor. However, exposing BRAF-mutant melanoma cells to AZD6244 and PLX4720 in combination prevented emergence of resistant clones. These results affirm the importance of MEK dependency in BRAF-mutant melanoma and suggest novel mechanisms of resistance to MEK and B-RAF inhibitors that may have important clinical implications.
STUDY QUESTION
Based on the best available evidence in the literature, what is the optimal management of routine psychosocial care at infertility and medically assisted reproduction (MAR) clinics?
...SUMMARY ANSWER
Using the structured methodology of the Manual for the European Society of Human Reproduction and Embryology (ESHRE) Guideline Development, 120 recommendations were formulated that answered the 12 key questions on optimal management of routine psychosocial care by all fertility staff.
WHAT IS ALREADY KNOWN
The 2002 ESHRE Guidelines for counselling in infertility has been a reference point for best psychosocial care in infertility for years, but this guideline needed updating and did not focus on routine psychosocial care that can be delivered by all fertility staff.
STUDY, DESIGN, SIZE, DURATION
This guideline was produced by a group of experts in the field according to the 12-step process described in the ESHRE Manual for Guideline Development. After scoping the guideline and listing a set of 12 key questions in PICO (Patient, Intervention, Comparison and Outcome) format, thorough systematic searches of the literature were conducted; evidence from papers published until April 2014 was collected, evaluated for quality and analysed. A summary of evidence was written in a reply to each of the key questions and used as the basis for recommendations, which were defined by consensus within the guideline development group (GDG). Patient and additional clinical input was collected during the scoping and the review phase of the guideline development.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The guideline group, comprising psychologists, two medical doctors, a midwife, a patient representative and a methodological expert, met three times to discuss evidence and reach consensus on the recommendations.
MAIN RESULTS AND THE ROLE OF CHANCE: THE GUIDELINE PROVIDES
120 recommendations that aim at guiding fertility clinic staff in providing optimal evidence-based routine psychosocial care to patients dealing with infertility and MAR. The guideline is written in two sections. The first section describes patients' preferences regarding the psychosocial care they would like to receive at clinics and how this care is associated with their well-being. The second section of the guideline provides information about the psychosocial needs patients experience across their treatment pathway (before, during and after treatment) and how fertility clinic staff can detect and address these. Needs refer to conditions assumed necessary for patients to have a healthy experience of the fertility treatment. Needs can be behavioural (lifestyle, exercise, nutrition and compliance), relational (relationship with partner if there is one, family friends and larger network, and work), emotional (well-being, e.g. anxiety, depression and quality of life) and cognitive (treatment concerns and knowledge).
LIMITATIONS, REASONS FOR CAUTION
We identified many areas in care for which robust evidence was lacking. Gaps in evidence were addressed by formulating good practice points, based on the expert opinion of the GDG, but it is critical for such recommendations to be empirically validated.
WIDER IMPLICATIONS OF THE FINDINGS
The evidence presented in this guideline shows that providing routine psychosocial care is associated with or has potential to reduce stress and concerns about medical procedures and improve lifestyle outcomes, fertility-related knowledge, patient well-being and compliance with treatment. As only 45 (36.0%) of the 125 recommendations were based on high-quality evidence, the guideline group formulated recommendations to guide future research with the aim of increasing the body of evidence.
STUDY FUNDING/COMPETING INTEREST(S)
The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with literature searches, and with the implementation of the guideline. The GDG members did not receive payment. S.G., E.D., C.d.K., M.E., U.V.d.B., C.L.-J. and N.V. report no conflicts of interest. J.B. reports grants from Merck & Co, consulting fees from Merck Serono S.A. and Speaker's fees from Merck Serono S.A. P.T. reports consulting fees from the German government and being the Chair of the German Society for Fertility Counselling. C.V. reports consulting fees from Merck Serono S.A. C.M.V. reports being adviser in projects for Merck Serono S.A. and Ferring S.A. on patient educational material. T.W. reports speaker's fees from Repromed, DGPM, Breitbach, DAAG, fiore, LPTW, MSD, salary/position funding at TAB-beim-Bundestag, BZgA, and being the Vice-chair of the German Society for Fertility Counselling.
TRIAL REGISTRATION NUMBER
NA.
Aim
To assess the effects of dietary Saccharomyces cerevisiae β‐(1,3)(1,6)‐d‐glucan supplementation (MacroGard®) on mirror carp (Cyprinus carpio L.) intestinal microbiota and ultrastructure of the ...enterocyte apical brush border.
Methods and Results
Carp were fed either a control diet or diets supplemented with 0·1, 1 or 2% w/w MacroGard®. Culture‐dependent microbiology revealed that aerobic heterotrophic bacterial levels were unaffected by dietary MacroGard® after 2 and 4 weeks. No effects were observed on the allochthonous lactic acid bacteria (LAB) populations at either time point; however, reduced autochthonous LAB populations were observed at week 4. PCR‐DGGE confirmed these findings through a reduction in the abundance of autochthonous Lactococcus sp. and Vagococcus sp. in MacroGard®‐fed fish compared with the control‐fed fish. Overall, sequence analysis detected microbiota belonging to the phyla Proteobacteria, Firmicutes, Fusobacteria and unidentified uncultured bacteria. DGGE analyses also revealed that dietary MacroGard® reduced the number of observed taxonomical units (OTUs) and the species richness of the allochthonous microbiota after 2 weeks, but not after 4 weeks. In contrast, dietary MacroGard® reduced the number of OTUs, the species richness and diversity of the autochthonous microbiota after 2 weeks, and those parameters remained reduced after 4 weeks. Transmission electron microscopy revealed that intestinal microvilli length and density were significantly increased after 4 weeks in fish fed diets supplemented with 1% MacroGard®.
Conclusions
This study indicates that dietary MacroGard® supplementation modulates intestinal microbial communities of mirror carp and influences the morphology of the apical brush border.
Significance and Impact of the Study
To the authors' knowledge, this is the first study to investigate the effects of β‐(1,3)(1,6)‐d‐glucans on fish gut microbial communities, using culture‐independent methods, and the ultrastructure of the apical brush border of the enterocytes in fish. This prebiotic‐type effect may help to explain the mechanisms in which β‐glucans provide benefits when fed to fish.
Schistosomiasis remains a public health concern across sub-Saharan Africa; current control programmes rely on accurate mapping and high mass drug administration (MDA) coverage to attempt disease ...elimination. Inter-species hybridisation can occur between certain species, changing epidemiological dynamics within endemic regions, which has the potential to confound control interventions. The impact of hybridisation on disease dynamics is well illustrated in areas of Cameroon where urogenital schistosomiasis, primarily due to Schistosoma haematobium and hybrid infections, now predominate over intestinal schistosomiasis caused by Schistosoma guineensis. Genetic markers have shown the ability to identify hybrids, however the underlying genomic architecture of divergence and introgression between these species has yet to be established. In this study, restriction site associated DNA sequencing (RADseq) was used on archived adult worms initially identified as; Schistosoma bovis (n = 4), S. haematobium (n = 9), S. guineensis (n = 3) and S. guineensis x S. haematobium hybrids (n = 4) from Mali, Senegal, Niger, São Tomé and Cameroon. Genome-wide evidence supports the existence of S. guineensis and S. haematobium hybrid populations across Cameroon. The hybridisation of S. guineensis x S. haematobium has not been demonstrated on the island of São Tomé, where all samples showed no introgression with S. haematobium. Additionally, all S. haematobium isolates from Nigeria, Mali and Cameroon indicated signatures of genomic introgression from S. bovis. Adaptive loci across the S. haematobium group showed that voltage-gated calcium ion channels (Cav) could play a key role in the ability to increase the survivability of species, particularly in host systems. Where admixture has occurred between S. guineensis and S. haematobium, the excess introgressive influx of tegumental (outer helminth body) and antigenic genes from S. haematobium has increased the adaptive response in hybrids, leading to increased hybrid population fitness and viability.
Mesenteric infection by the parasitic blood fluke Schistosoma bovis is a common veterinary problem in Africa and the Middle East and occasionally in the Mediterranean Region. The species also has the ...ability to form interspecific hybrids with the human parasite S. haematobium with natural hybridisation observed in West Africa, presenting possible zoonotic transmission. Additionally, this exchange of alleles between species may dramatically influence disease dynamics and parasite evolution. We have generated a 374 Mb assembly of the S. bovis genome using Illumina and PacBio-based technologies. Despite infecting different hosts and organs, the genome sequences of S. bovis and S. haematobium appeared strikingly similar with 97% sequence identity. The two species share 98% of protein-coding genes, with an average sequence identity of 97.3% at the amino acid level. Genome comparison identified large continuous parts of the genome (up to several 100 kb) showing almost 100% sequence identity between S. bovis and S. haematobium. It is unlikely that this is a result of genome conservation and provides further evidence of natural interspecific hybridization between S. bovis and S. haematobium. Our results suggest that foreign DNA obtained by interspecific hybridization was maintained in the population through multiple meiosis cycles and that hybrids were sexually reproductive, producing viable offspring. The S. bovis genome assembly forms a highly valuable resource for studying schistosome evolution and exploring genetic regions that are associated with species-specific phenotypic traits.
. Chao C, Klein NP, Velicer CM, Sy LS, Slezak JM, Takhar H, Ackerson B, Cheetham TC, Hansen J, Deosaransingh K, Emery M, Liaw K‐L, Jacobsen SJ (Kaiser Permanente Southern California, Pasadena, CA; ...Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, CA; Merck Research Laboratories, Upper Gwynedd, PA; South Bay Medical Center, Kaiser Permanente Southern California, Los Angeles, CA; and Kaiser Permanente Southern California, Downey, CA, USA). Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med 2012; 271: 193–203.
Objective. An observational safety study of the quadrivalent human papillomavirus vaccine (HPV4) in women was conducted. This report presents findings from autoimmune surveillance.
Design. Subjects were followed for 180 days after each HPV4 dose for new diagnoses of 16 prespecified autoimmune conditions.
Setting. Two managed care organizations in California.
Subjects. Number of 189 629 women who received ≥1 dose of HPV4 between 08/2006 and 03/2008.
Outcome. Potential new‐onset autoimmune condition cases amongst HPV4 recipients were identified by electronic medical records. Medical records of those with ≥12‐month health plan membership prior to vaccination were reviewed by clinicians to confirm the diagnosis and determine the date of disease onset. The incidence of each autoimmune condition was estimated for unvaccinated women at one study site using multiple imputations and compared with that observed in vaccinated women. Incidence rate ratios (IRR) were calculated. Findings were reviewed by an independent Safety Review Committee (SRC).
Results. Overall, 1014 potential new‐onset cases were electronically identified; 719 were eligible for case review; 31–40% were confirmed as new onset. Of these, no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition. None of the estimated IRR was significantly elevated except Hashimoto’s disease IRR = 1.29, 95% confidence interval: 1.08–1.56. Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions. The SRC and the investigators identified no autoimmune safety concerns in this study.
Conclusions. No autoimmune safety signal was found in women vaccinated with HPV4.
Background Schistosomiasis is a parasitic disease that is transmitted by skin contact with waterborne schistosome cercariae. Mass drug administration with praziquantel is an effective control method, ...but it cannot prevent reinfection if contact with cercariae infested water continues. Providing safe water for contact activities such as laundry and bathing can help to reduce transmission. In this study we examine the direct effect of UV light on Schistosoma mansoni cercariae using ultraviolet light-emitting diodes (UV LEDs) and a low-pressure (LP) mercury arc discharge lamp. Methodology S. mansoni cercariae were exposed to UV light at four peak wavelengths: 255 nm, 265 nm, 285 nm (UV LEDs), and 253.7 nm (LP lamp) using bench scale collimated beam apparatus. The UV fluence ranged from 0-300 mJ/cm.sup.2 at each wavelength. Cercariae were studied under a stereo-microscope at 0, 60, and 180 minutes post-exposure and the viability of cercariae was determined by assessing their motility and morphology. Conclusion Very high UV fluences were required to kill S. mansoni cercariae, when compared to most other waterborne pathogens. At 265 nm a fluence of 247 mJ/cm.sup.2 (95% confidence interval (CI): 234-261 mJ/cm.sup.2) was required to achieve a 1-log.sub.10 reduction at 0 minutes post-exposure. Cercariae were visibly damaged at lower fluences, and the log reduction increased with time post-exposure at all wavelengths. Fluences of 127 mJ/cm.sup.2 (95% CI: 111-146 mJ/cm.sup.2) and 99 mJ/cm.sup.2 (95% CI: 85-113 mJ/cm.sup.2) were required to achieve a 1-log.sub.10 reduction at 60 and 180 minutes post-exposure at 265 nm. At 0 minutes post-exposure 285 nm was slightly less effective, but there was no statistical difference between 265 nm and 285 nm after 60 minutes. The least effective wavelengths were 255 nm and 253.7 nm. Due to the high fluences required, UV disinfection is unlikely to be an energy- or cost-efficient water treatment method against schistosome cercariae when compared to other methods such as chlorination, unless it can be demonstrated that UV-damaged cercariae are non-infective using alternative assay methods or there are improvements in UV LED technology.
The recovery and analysis of genetic material obtained from thermally altered human bones and teeth are increasingly important to forensic investigations, especially in cases where soft-tissue ...identification is no longer possible. Although little is known about how these fire-related processes affect DNA degradation over time, next-generation sequencing technology in combination with traditional osteobiographical applications may provide us clues to these questions. In this study, we compare whole mitochondrial genome data generated using two different DNA extraction methods from 27 thermally altered samples obtained from fire victims (Maricopa County, Arizona) . DNA extracts were converted to double-stranded DNA libraries and enriched for whole mitochondrial DNA (mtDNA) using synthetic biotinylated RNA baits, then sequenced on an Illumina MiSeq. We processed the mitochondrial data using an in-house computational pipeline (MitoPipe1.0) composed of ancient DNA and modern genomics applications, then compared the resulting information across the two extraction types and five burn categories. Our analysis shows that DNA fragmentation increases with temperature, but that the acute insult from fire combined with the lack of water is insufficient to produce 5′ and 3′ terminal deamination characteristic of ancient DNA. Our data also suggest an acute and significant point of DNA degradation between 350 °C and 550 °C, and that the likelihood of generating high quality mtDNA haplogroup calls decreases significantly at temperatures > 550 °C. This research is part of a concerted effort to understand how fire affects our ability to generate genetic profiles suitable for forensic identification purposes.
•Comparative next-generation sequencing analysis of burned human remains using two different extraction methods.•Whole-mitochondrial genomes captured over two rounds of enrichment.•Significant decrease in DNA yields between burn category III and IV.•High quality mtDNA haplogroups reconstructed across all five burn categories.
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