This is a prospective study conducted in December 2012 among 128 at the Nianankoro Fomba Hospital in Segou in order to assess their knowledge and practices on Blood Exposure Accidents (BEA). The ...average age of caregivers was 35.4 ± 9 years (range: 22-59 years). The nurses were predominant with 37.5%. The definition of BEA was mastered by 43.8%. The main transmissible infectious agents (HIV, HBVand HCV) were ignored by 76.6%. Questioning revealed that during the treatment, 78.9% wore gloves and 36.0% recapped needles after use. The concept of washing and disinfection after BEA was known by 68.8%. The disinfectant applied was correct for 21.9% of the cases, the time of application for 69.5%. Consulting a referring physician after BEA was mandatory for 32% of them. The time limit of 48 hours delay for the declaration of BEA was experienced by 51.3%. Among staff interviewed 82 caregivers (64.1%) experienced at least one BEA. Students and nursing students were most at risk. Needle pricks were the most frequent (73.2%). BEA is a major problem in the Segou Nianankoro Fomba Hospital. Compliance with standard precautions is not of common practice. Post-exposure care is not widely known. The experienced cases show poor management of BEA in the structure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
Résumé
Il s’agit d’une étude rétrospective sur une cohorte de 811 patients adultes mis sous antirétroviraux entre janvier 2004 et décembre 2011 à l’hôpital Nianankoro Fomba de Ségou au Mali, afin de ...décrire leur profil épidémio-clinique et évolutif au 48
e
mois de suivi. L’âgemoyen des patients était de 35,2 ± 9,4 ans. Le sex-ratio H/F était de 0,6. 58,3 % des patients venaient du milieu rural. Le VIH1 concernait 95,8 % des cas. La fièvre prolongée, l’amaigrissement et la diarrhée chronique étaient les principauxmotifs de dépistage. Lamajorité des patients (64,5 %) était au stade III de l’OMS. La moyenne de lymphocytes CD4 était de 144 ± 135,8/mm
3
au dépistage. L’évolution clinique et immunologique était favorable sous antirétroviraux. Le taux de survie à 48 mois de suivi était de 78 % 64,1 %–81,3 %. Les patients suivis dans la structure sont en majorité des ruraux, de sexe féminin et d’âge jeune. Ils sont dépistés au stade avancé de l’infection à VIH. Le traitement antirétroviral a permis le renforcement du système immunitaire et l’amélioration des paramètres cliniques avec un taux de survie à 78 %.
Islet grafts can contribute to their own destruction via the elaboration of proinflammatory genes, many of which are transcriptionally regulated by nuclear factor κ-light-chain-enhancer of activated ...B-cells (NF-κB). Thus, NF-κB constitutes an enticing gene therapy candidate to improve the success of islet transplantation. To test this hypothesis in vivo, we blocked NF-κB in BALB/c (H2d) to C57/BL6 (H2b) mouse islet allografts by genetically engineering islets to express the NF-κB superrepressor, IκBα. Here we show by microarray and RTqPCR that islets exhibit an intrinsic early immediate proinflammatory response, with the most highly upregulated proinflammatory genes comprising the chemokines Cxcl1, Cxcl2, Cxcl10, and Ccl2; the cytokines Tnf-α and Il-6; and the adhesion molecule Icam1. Overexpression of IκBα inhibited the expression of these genes by 50–95% in islets and MIN6 β-cells in vitro, by inhibiting NF-κB-dependent gene transcription. Histological and RTqPCR analysis at postoperative day (POD) 10 revealed that IκBα-transduced islet allografts exhibited improved islet architecture and strong insulin-labeling with decreased Ccl2 and Il-6 mRNA levels compared to the GFP-transduced control grafts. Despite these protective effects, NF-κB-blocked islet allografts were promptly rejected in our MHC-mismatched mouse model. However, IκBα-expressing grafts did harbor localized “pockets” of Foxp3+ mononuclear cells not evident in the control grafts. This result suggested that the effect of the NF-κB blockade might synergize with regulatory T-cell-sparing rapamycin. Indeed, combining intragraft IκBα expression with low-dose rapamycin increased the mean survival time of islet allografts from 20 to 81 days, with 20% of the grafts surviving for greater than 100 days. In conclusion, rapamycin unmasks the protective potential of intragraft NF-κB blockade, which can, in some cases, permit permanent allograft survival without continuous systemic immunosuppression.
Resisting and tolerating microbes are alternative strategies to survive infection, but little is known about the evolutionary mechanisms controlling this balance. Here genomic analyses of ...anatomically modern humans, extinct Denisovan hominins and mice revealed a TNFAIP3 allelic series with alterations in the encoded immune response inhibitor A20. Each TNFAIP3 allele encoded substitutions at non-catalytic residues of the ubiquitin protease OTU domain that diminished IκB kinase-dependent phosphorylation and activation of A20. Two TNFAIP3 alleles encoding A20 proteins with partial phosphorylation deficits seemed to be beneficial by increasing immunity without causing spontaneous inflammatory disease: A20 T108A;I207L, originating in Denisovans and introgressed in modern humans throughout Oceania, and A20 I325N, from an N-ethyl-N-nitrosourea (ENU)-mutagenized mouse strain. By contrast, a rare human TNFAIP3 allele encoding an A20 protein with 95% loss of phosphorylation, C243Y, caused spontaneous inflammatory disease in humans and mice. Analysis of the partial-phosphorylation A20 I325N allele in mice revealed diminished tolerance of bacterial lipopolysaccharide and poxvirus inoculation as tradeoffs for enhanced immunity.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The nuclear factor κB (NF-κB) pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic β cell dysfunction in the metabolic syndrome. Whereas ...canonical NF-κB signaling is well studied, there is little information on the divergent noncanonical NF-κB pathway in the context of pancreatic islet dysfunction. Here, we demonstrate that pharmacological activation of the noncanonical NF-κB-inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. We identify NIK as a critical negative regulator of β cell function, as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of noncanonical NF-κB components p100 to p52, and accumulation of RelB. TNF and receptor activator of NF-κB ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive β cell-intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the noncanonical NF-κB transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to β cell failure. These studies reveal that NIK contributes a central mechanism for β cell failure in diet-induced obesity.
Rapporter les aspects épidémiologiques, diagnostiques, thérapeutiques du prolapsus urétral.
Il s’agissait d’une étude transversale descriptive sur une période de 8 ans (Janvier 2006 à Décembre 2013). ...Elle a été réalisée sur 12 patientes âgées de moins de 16 ans et prise en charge pour prolapsus urétral dans le service de chirurgie pédiatrique de l’hôpital Aristide Le Dantec. Nous avons étudié les variables suivantes: la fréquence, l’âge, les facteurs favorisants, les signes cliniques et para cliniques, le traitement et l’évolution.
Notre incidence annuelle était de 1,5 cas. L’âge moyen de nos patientes était de 4,02 ans. L’hémorragie génitale (11 cas) était le principal motif de consultation suivi de la dysurie (8 cas). L’examen physique retrouvait une tuméfaction circulaire sous clitoridienne et centrée par un orifice cathétérisable chez toutes nos patientes. L’examen cytobactériologique des urines réalisé chez 10 patientes avait permis d’isoler un germe dans 2 cas. Une exérèse chirurgicale de la muqueuse prolabée a été réalisée chez toutes nos patientes et était associée à une suture muco-muqueuse dans 7 cas. L’évolution était toujours favorable.
Le prolapsus urétral est une pathologie rare. Son diagnostic est clinique. L’exérèse chirurgicale constitue le traitement radical du prolapsus urétral et donne de bons résultats.
To report on the epidemiological, diagnostic, and therapeutic aspects of urethral prolapse.
The current study is a descriptive cross-sectional study over a period of 8 years (January 2006-December 2013). It was conducted on 12 patients aged under 16 and managed for urethral prolapse in the pediatric surgery department of the hospital Aristide Le Dantec. We studied the following variables: frequency, age, predisposing factors, clinical signs and investigations, treatment and evolution.
Our annual incidence was 1.5 cases. The average age for our patients was 4.02 years. Genital hemorrhage (11 cases) was the main reason for consultation followed by dysuria (8 cases). Physical examination revealed a circular swelling below the clitoris with a cathétérisable opening in its center in all our patients. Urine analysis and culture performed in 10 patients revealed a germ in 2 cases. Surgical resection of the prolapsed mucosa was performed in all of our patients and was associated with a muco-cutaneous suture in 7 cases. The outcome was always favorable.
Urethral prolapse is a rare disease. Its diagnosis is clinical. Surgical excision is the radical treatment of urethral prolapse and is associated with a favorable outome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This is a retrospective study on a cohort of 811 adult patients placed on ART between January 2004 and December 2011 at the hospital Nianankoro Fomba Segou in Mali, to describe their epidemiological, ...clinical and developmental profile for 48 months. The average age of patients was 35.2±9.4 years. The sex-ratio was 0.6. Approximately 58.3% of the patients were from rural areas. HIV1 represented 95.8%. Prolonged fever, weight loss and chronic diarrhea were the main reasons for testing. The majority of patients (64.5%) had stage III WHO. The mean CD4 cell count was 144±135.8/mm³ at screening. The evolution was favorable under immunological antiretroviral therapy. The survival rate at 48 months follow-up was 78% 64.1%-81.3%. Patients followed in the structure are predominantly rural, female and young aged. They are diagnosed with advanced HIV infection. Antiretroviral therapy has led to the strengthening of the immune system and improved the clinical outcomes with a survival rate of 78%.
In this study, a critical and novel role for TNF receptor (TNFR) associated factor 2 (TRAF2) is elucidated for peripheral CD8+ T‐cell and NKT‐cell homeostasis. Mice deficient in TRAF2 only in their T ...cells (TRAF2TKO) show ∼40% reduction in effector memory and ∼50% reduction in naïve CD8+ T‐cell subsets. IL‐15‐dependent populations were reduced further, as TRAF2TKO mice displayed a marked ∼70% reduction in central memory CD8+CD44hiCD122+ T cells and ∼80% decrease in NKT cells. TRAF2TKO CD8+CD44hi T cells exhibited impaired dose‐dependent proliferation to exogenous IL‐15. In contrast, TRAF2TKO CD8+ T cells proliferated normally to anti‐CD3 and TRAF2TKO CD8+CD44hi T cells exhibited normal proliferation to exogenous IL‐2. TRAF2TKO CD8+ T cells expressed normal levels of IL‐15‐associated receptors and possessed functional IL‐15‐mediated STAT5 phosphorylation, however TRAF2 deletion caused increased AKT activation. Loss of CD8+CD44hiCD122+ and NKT cells was mechanistically linked to an inability to respond to IL‐15. The reduced CD8+CD44hiCD122+ T‐cell and NKT‐cell populations in TRAF2TKO mice were rescued in the presence of high dose IL‐15 by IL‐15/IL‐15Rα complex administration. These studies demonstrate a critical role for TRAF2 in the maintenance of peripheral CD8+ CD44hiCD122+ T‐cell and NKT‐cell homeostasis by modulating sensitivity to T‐cell intrinsic growth factors such as IL‐15.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aims/hypothesis
Administration of anti-CD40 ligand (CD40L) antibodies has been reported to allow long-term islet allograft survival in non-human primates without the need for exogenous ...immunosuppression. However, the use of anti-CD40L antibodies was associated with thromboembolic complications. Targeting downstream intracellular components shared between CD40 and other TNF family co-stimulatory molecules could bypass these complications. TNF receptor associated factor 2 (TRAF2) integrates multiple TNF receptor family signalling pathways that are critical for T cell activation and may be a central node of alloimmune responses.
Methods
T cell-specific
Traf2
-deficient mice (
Traf2
TKO) were generated to define the role of TRAF2 in CD4
+
T cell effector responses that mediate islet allograft rejection in vivo. In vitro allograft responses were tested using mixed lymphocyte reactions and analysis of IFN-γ and granzyme B effector molecule expression. T cell function was assessed using anti-CD3/CD28-mediated proliferation and T cell polarisation studies.
Results
Traf2
TKO mice exhibited permanent survival of full MHC-mismatched pancreatic islet allografts without exogenous immunosuppression.
Traf2
TKO CD4
+
T cells exhibited reduced proliferation, activation and acquisition of effector function following T cell receptor stimulation; however, both
Traf2
TKO CD4
+
and CD8
+
T cells exhibited impaired alloantigen-mediated proliferation and acquisition of effector function. In polarisation studies,
Traf2
TKO CD4
+
T cells preferentially converted to a T helper (Th)2 phenotype, but exhibited impaired Th17 differentiation. Without TRAF2, thymocytes exhibited dysregulated TNF-mediated induction of c-Jun N-terminal kinase (JNK) and canonical NFκB pathways. Critically, targeting TRAF2 in T cells did not impair the acute phase of CD8-dependent viral immunity. These data highlight a specific requirement for a TRAF2–NFκB and TRAF2–JNK signalling cascade in T cell activation and effector function in rejecting islet allografts.
Conclusion/interpretation
Targeting TRAF2 may be useful as a therapeutic approach for immunosuppression-free islet allograft survival that avoids the thromboembolic complications associated with the use of anti-CD40L antibodies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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