Long-term microglia depletion impairs synapse elimination and auditory brainstem function.

Specialized sound localization circuit development requires synapse strengthening, refinement, and pruning. Many of these functions are carried out by microglia, immune cells that aid in regulating neurogenesis, synaptogenesis, apoptosis, and synaptic removal. We previously showed that postnatal treatment with BLZ945 (BLZ), an inhibitor of colony stimulating factor 1 receptor (CSF1R), eliminates microglia in the brainstem and disables calyceal pruning and maturation of astrocytes in the medial nucleus of the trapezoid body (MNTB). BLZ treatment results in elevated hearing thresholds and delayed signal propagation as measured by auditory brainstem responses (ABR). However, when microglia repopulate the brain following the cessation of BLZ, most of the deficits are repaired. It is unknown whether this recovery is achievable without the return of microglia. Here, we induced sustained microglial elimination with a two-drug approach using BLZ and PLX5622 (PLX). We found that BLZ/PLX treated mice had impaired calyceal pruning, diminished astrocytic GFAP in the lateral, low frequency, region of MNTB, and elevated glycine transporter 2 (GLYT2) levels. BLZ/PLX treated mice had elevated hearing thresholds, diminished peak amplitudes, and altered latencies and inter-peak latencies. These findings suggest that microglia are required to repopulate the brain in order to rectify deficits from their ablation.

Cell-Tak coating interferes with DNA-based normalization of metabolic flux data.

Metabolic flux investigations of cells and tissue samples are a rapidly advancing tool in diverse research areas. Reliable methods of data normalization are crucial for an adequate interpretation of results and to avoid a misinterpretation of experiments and incorrect conclusions. The most common methods for metabolic flux data normalization are to cell number, DNA and protein. Data normalization may be affected by a variety of factors, such as density, healthy state, adherence efficiency, or proportional seeding of cells. The mussel-derived adhesive Cell-Tak is often used to immobilize poorly adherent cells. Here we demonstrate that this coating strongly affects the fluorescent detection of DNA leading to an incorrect and highly variable normalization of metabolic flux data. Protein assays are much less affected and cell counting can virtually completely remove the effect of the coating. Cell-Tak coating also affects cell shape in a cell line-specific manner and may change cellular metabolism. Based on these observations we recommend cell counting as a gold standard normalization method for Seahorse metabolic flux measurements with protein content as a reasonable alternative.

Synapse Maturation and Developmental Impairment in the Medial Nucleus of the Trapezoid Body.

Sound localization requires rapid interpretation of signal speed, intensity, and frequency. Precise neurotransmission of auditory signals relies on specialized auditory brainstem synapses including the calyx of Held, the large encapsulating input to principal neurons in the medial nucleus of the trapezoid body (MNTB). During development, synapses in the MNTB are established, eliminated, and strengthened, thereby forming an excitatory/inhibitory (E/I) synapse profile. However, in neurodevelopmental disorders such as autism spectrum disorder (ASD), E/I neurotransmission is altered, and auditory phenotypes emerge anatomically, molecularly, and functionally. Here we review factors required for normal synapse development in this auditory brainstem pathway and discuss how it is affected by mutations in ASD-linked genes.

Edaravone attenuates disease severity of experimental auto-immune encephalomyelitis and increases gene expression of Nrf2 and HO-1.

The aim of this study was to evaluate therapeutic potential of edaravone in the murine model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE) and to expand the knowledge of its mechanism of action. Edaravone (6 mg/kg/day) was administered intraperitoneally from the onset of clinical symptoms until the end of the experiment (28 days). Disease progression was assessed daily using severity scores. At the peak of the disease, histological analyses, markers of oxidative stress (OS) and parameters of mitochondrial function in the brains and spinal cords (SC) of mice were determined. Gene expression of inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha was determined at the end of the experiment. Edaravone treatment ameliorated EAE severity and attenuated inflammation in the SC of the EAE mice, as verified by histological analysis. Moreover, edaravone treatment decreased OS, increased the gene expression of the Nrf2 and HO-1, increased the activity of the mitochondrial complex II/III, reduced the activity of the mitochondrial complex IV and preserved ATP production in the SC of the EAE mice. In conclusion, findings in this study provide additional evidence of edaravone potential for the treatment of multiple sclerosis and expand our knowledge of the mechanism of action of edaravone in the EAE model.

CX3CR1 mutation alters synaptic and astrocytic protein expression, topographic gradients, and response latencies in the auditory brainstem.

The precise and specialized circuitry in the auditory brainstem develops through adaptations of cellular and molecular signaling. We previously showed that elimination of microglia during development impairs synaptic pruning that leads to maturation of the calyx of Held, a large encapsulating synapse that terminates on neurons of the medial nucleus of the trapezoid body (MNTB). Microglia depletion also led to a decrease in glial fibrillary acidic protein (GFAP), a marker for mature astrocytes. Here, we investigated the role of signaling through the fractalkine receptor (CX3CR1), which is expressed by microglia and mediates communication with neurons. CX3CR1-/- and wild-type mice were studied before and after hearing onset and at 9 weeks of age. Levels of GFAP were significantly increased in the MNTB in mutants at 9 weeks. Pruning was unaffected at the calyx of Held, but we found an increase in expression of glycinergic synaptic marker in mutant mice at P14, suggesting an effect on maturation of inhibitory inputs. We observed disrupted tonotopic gradients of neuron and calyx size in MNTB in mutant mice. Auditory brainstem recording (ABR) revealed that CX3CR1-/- mice had normal thresholds and amplitudes but decreased latencies and interpeak latencies, particularly for the highest frequencies. These results demonstrate that disruption of fractalkine signaling has a significant effect on auditory brainstem development. Our findings highlight the importance of neuron-microglia-astrocyte communication in pruning of inhibitory synapses and establishment of tonotopic gradients early in postnatal development.

Auditory Brainstem Deficits from Early Treatment with a CSF1R Inhibitor Largely Recover with Microglial Repopulation.

Signaling between neurons and glia is necessary for the formation of functional neural circuits. A role for microglia in the maturation of connections in the medial nucleus of the trapezoid body (MNTB) was previously demonstrated by postnatal microglial elimination using a colony stimulating factor 1 receptor (CSF1R). Defective pruning of calyces of Held and significant reduction of the mature astrocyte marker glial fibrillary acidic protein (GFAP) were observed after hearing onset. Here, we investigated the time course required for microglia to populate the mouse MNTB after cessation of CSF1R inhibitor treatment. We then examined whether defects seen after microglial depletion were rectified by microglial repopulation. We found that microglia returned to control levels at four weeks of age (18 d postcessation of treatment). Calyceal innervation of MNTB neurons was comparable to control levels at four weeks and GFAP expression recovered by seven weeks. We further investigated the effects of microglia elimination and repopulation on auditory function using auditory brainstem recordings (ABRs). Temporary microglial depletion significantly elevated auditory thresholds in response to 4. 8, and 12 kHz at four weeks. Treatment significantly affected latencies, interpeak latencies, and amplitudes of all the ABR peaks in response to many of the frequencies tested. These effects largely recovered by seven weeks. These findings highlight the functions of microglia in the formation of auditory neural circuits early in development. Further, the results suggest that microglia retain their developmental functions beyond the period of circuit refinement.

Psychometric Properties of the Psychological Well-being at Work Scale in Gabonese Public Administration.

The objective of this article is to corroborate the original Dagenais-Desmarais & Savoie psychological well-being measurement instrument in the civil service in Gabon. This instrument is composed of five factors relating to lived experiences of psychological well-being in the workplace. To adapt it to the civil service in Gabon, 310 civil servants from various ministries completed a measurement tool. This was also done for nomological purposes and to assess job demands, job control, social support, and job satisfaction. Following exploratory and confirmatory factor analyses, it appears that the dimensional structure of psychological well-being in the workplace (PWBW) is identical to the initial structure developed by Dagenais-Desmarais and Savoie. Moreover, the metric properties on the PWBW scale of the present research are satisfactory. The analyses confirm all the predictions of the nomological network, reinforcing the validity of the adaptation of the scale developed by Dagenais-Desmarais and Savoie to the world of public service work in Gabon.

[Epidemiology and prognosis of eclampsia in Bougouni]. / Epidemiologie et pronostic de l'eclampsie a Bougouni.

OBJECTIVES: The objectives were to describe the epidemiological and prognostic aspects of eclampsia in the Bougouni reference health center. METHODS: This was a transversal prospective, descriptive study from January 1 to December 31, 2015 in the gynecology-obstetrics department of Bougouni reference health center. Were included, all pregnant or postpartum women diagnosed with eclampsia during the study period. RESULTS: The frequency of eclampsia was 2.54%. They were adolescent girls in 50% of cases, primigest in 62.5% of cases, unschooled in 67.5% of cases, having not performed any antenatal care in 70% of cases. Eclampsia occurred in antepartum in 37.5% of cases, in 5% in perpartum and in 57.5% in postpartum. Therapeutically, nicardipine with 72.5% and nifedipine with 22.5% were the antihypertensive drugs used. As for anticonvulsants, magnesium sulfate (MgSO4) was used in 92.5% and diazepam in 7.5%. The maternal-fetal prognosis was marked by 2.5% of maternal death, 27% of prematurity and 27.5% of fetal death in utero. CONCLUSION: Eclampsia is a dreadful pathology with serious maternal and fetal complications.

OBJECTIFS: Les objectifs étaient de décrire les aspects épidémiologique et pronostique de l'éclampsie dans le centre de santé de référence de Bougouni. MÉTHODES: Il s'agissait d'une étude transversale prospective, descriptivedu 1er janvier au 31 décembre 2015 dans le service de gynécologie-obstétrique du centre de santé de référence de Bougouni. Ont été incluses, toutes les femmes enceintes ou les accouchées chez qui le diagnostic de crise d'éclampsie a été retenu pendant la période d'étude. RÉSULTATS: La fréquence de l'éclampsie a été de 2,54%. Il s'agissait d'adolescentes dans 50% des cas, primigestes dans 62,5% des cas, non scolarisées dans 67,5% des cas,n'ayant effectuées aucune consultation prénatale dans70% des cas. L'éclampsie est survenue en antépartumdans 37,5% des cas, dans 5% en perpartum et dans 57,5% en postpartum. Sur le plan thérapeutique, la nicardipine avec 72,5% et la nifédipine avec 22,5% ont été les antihypertenseurs utilisés. Quant aux anticonvulsivants, le sulfate de magnésium (MgSO4) a été utilisé dans 92,5% et le diazépam dans 7,5%. Le pronostic materno-fœtal a été marqué par 2,5% de décès maternel, 27% de prématurité et 27,5% de mort fœtale in-utéro. : L'éclampsie est une pathologie redoutable aux complications maternelles et fœtales graves.

[Spontaneous triple pregnancy on bicicatricial uterus in the referral health center of commune II of Bamako, Mali]. / Grossesse triple spontanee sur uterus bicicatriciel au centre de sante de reference de la commune II de Bamako, Mali.

The trimellar pregnancy on bicicatricial uterus is a rare situation. It can be associated with many maternal-fetal complications. Given these risks, some teams opt for an embryonic reduction. We report a case of spontaneous trimellar pregnancy on bicicatricial uterus. This was a 38 year-old patient, third pregnancy, second birth, 2 alive with a history of 2 caesareans. The evolution of the pregnancy was marked by a urinary tract infection at 34 weeks of gestation. The caesarean section performed at 36 weeks of gestation allowed the birth of 3 newborns, 2 of which were females in 2000 and 1900 grams, and one male weighing 2400 grams. The postpartum was marked by a rapidly resolved eclampsia crisis.

La survenue d'une grossesse triméllaire sur un utérus bicicatriciel est une situation rare. Elle peut être associée à de nombreuses complications materno-fœtales. Compte tenu de ces risques, certaines équipes optent pour une réduction embryonnaire. Nous rapportons un cas de grossesse triméllaire spontanée sur utérus bicicatriciel. Il s'agissait d'une patiente de 38 ans 3è geste, 2è pare avec 2 enfants vivants, ayant un antécédent de 2 césariennes. L'évolution de la grossesse a été marquée par une infection urinaire à 34 SA. La césarienne pratiquée à 36 SA a permit la naissance de 3 nouveaunés dont 2 de sexes féminins de 2000 et 1900g et un de sexe masculin pesant 2400g. Les suites de couches ont été marquées par une crise d'éclampsie rapidement résolue.

[Materno-Fetal Prognosis Of Anemia In Bougouni]. / Pronostic Materno-Fœtal De L'Anemie A Bougouni.

GOAL: The goal was to assess the maternal-fetal prognosis of anemia in pregnant women in the Bougouni reference health center. METHODS: We carried out a prospective descriptive and analytical cross-sectional study from January 1 to December 31, 2013 at the Bougouni reference health center. It covered all pregnant women with a hemoglobin level below 11g/dl regardless of the outcome of the pregnancy. RESULTS: The prevalence of anemia in pregnant women was 33.2%. They were women married to peasants in 88.6% of cases, unschooled in 93.2% of cases, having not done antenal care in 56.8% of cases. Malaria was the most common etiology in 75% of cases. Anemia was severe in 61.4% of cases. The maternal-fetal prognosis was dominated by 3.3% of maternal death, 12.5% of abortion, 7.6% of prematurity and 6.8% of fetal death in utero. CONCLUSION: Anemia in pregnant women is the source of many maternal-fetal complications.

BUT: Le but était d'évaluer le pronostic materno-fœtal de l'anémie chez la femme enceinte dans le centre de santé de référence de Bougouni. MÉTHODES: Nous avons réalisé une étude transversale prospective descriptive et analytique du 1er janvier au 31 décembre 2013 au centre de santé de référence de Bougouni. Elle a porté sur toutes les femmes enceintes ayant un taux d'hémoglobine inférieur à 11g/dl quelle que soit l'issue de la grossesse. RÉSULTATS: La prévalence de l'anémie chez les femmes enceintes a été de 33,2%. Il s'agissait de femmes mariées à des paysans dans 88,6% des cas, analphabètes dans 93,2% des cas, n'ayant pas fait de consultations prénatales dans 56,8% des cas. Le paludisme a été l'étiologie la plus fréquente dans 75% des cas. L'anémie était sévère dans 61,4% des cas. Le pronostic materno-fœtal a été dominé par 3,3% de décès maternel, 12,5% d'avortement, 7,6% de prématurité et 6,8% de mort fœtale in utéro. CONCLUSION: L'anémie chez la femme enceinte est pourvoyeuse de nombreuses complications materno-fœtales.

[Pregnancy And Delivery In The Large Multiparous In The Reference Health Center Of Commune II Of Bamako, Mali]. / Grossesse Et Accouchement Chez La Grande Multipare Au Centre De Sante De Reference De La Commune II De Bamako, Mali.

AIM: The aim was to compare the maternal-fetal prognosis of pregnancies in large multiparous with that of other parities. MATERIALS AND METHODS: We conducted a case-control study from March 1st, 2014 to February 1st, 2015. It concerned all parturients admitted in our service during the study period. We have chosen 1 case for 2 witnesses. All the large multiparous were included as cases and as witnesses the primiparous, the pauciparous and the multiparous who gave birth just before and after the case. The statistical test was the Chi2 with a significance level at 5%. RESULTS: The frequency of pregnancy in the large multiparous was 4.93%. They were housewives in 84% of cases, unschooled in 74.7% of cases. The maternal-fetal outcome was dominated by uterine rupture in 0.6% of cases, immediate postpartum hemorrhage in 9.8% of cases, vicious presentations in 5.5% of cases and cord prolapse in 6.8% of cases. CONCLUSION: Large multiparity is common in our practice. It is a high-risk pregnancy because of its many maternal-fetal complications.

BUT: Le but était de comparer le pronostic materno-fœtal des grossesses chez les grandes multipares à celui des autres parités. MATÉRIELS ET MÉTHODES: Nous avons réalisé une étude cas-témoins du 1er mars 2014 au 1er février 2015. Elle a concerné toutes les parturientes admises dans le service pendant la période d'étude. Nous avons choisi 1 cas pour 2 témoins. Ont été incluses comme cas toutes les grandes multipares et comme témoins les primipares, les paucipares et les multipares ayant accouchées juste avant et juste après le cas. Le test statistique utilisé a été le Chi2 avec un seuil de significativité fixé à 5%. RÉSULTATS: La fréquence de la grossesse chez la grande multipare était de 4,93%. Il s'agissait de femmes au foyer dans 84% des cas, non scolarisées dans 74,7% des cas. Le pronostic materno-fœtal a été dominé par la rupture utérine dans 0,6% des cas, l'hémorragie de la délivrance dans 9,8% des cas, les présentations vicieuses dans 5,5% des cas et la procidence du cordon dans 6,8% des cas. CONCLUSION: La grande multiparité est fréquente dans notre pratique. C'est une grossesse à haut risque à cause de ses nombreuses complications materno-fœtales.

[Infections associated with the care in the department of gynecology - obstetrics of the University Hospital Center Gabriel Touré]. / Les infections associees aux soins dans le departement de gynecologie ­ obstetrique du Centre Hospitalier Universitaire Gabriel Toure de bamako, mali.

OBJECTIF: the purpose of this work was to study the infections associated with the care in the department of gynecology - obstetrics of the University Hospital Center Gabriel Touré (CHU G. Touré). PATIENTS AND METHODS: This was an epidemiological, descriptive, and analytical study carried out in the gynecology-obstetrics department of G. Touré University Hospital, from April 11, 2016 to August 29, 2016 (4 monthset 18 days), with a prospective collection of data that focused on the characteristics clinical and laboratory-based care-associated infections in patients during their hospitalization. Included in the study were all hospitalized patients (operated or not) in the gynecology obstetrics department, who agreed to participate in the study. The criteria used to diagnose the infection associated with care were those of the CDC Atlanta and making a thick drop in our context. Operative wound monitoring was performed until the 30th postoperative day. RESULTS: We recorded 200 patients, including 138 operated and 62 nonoperated patients, of which 30 patients developed a care-associated infection at a rate of 15%. The mean age of the patients who presented an infection was 32.52 years ± 13.36 years against 29.36 years ± 10.28 years for the patients who did not present the infection. Seven point five percent of the evacuees had an infection associated with care. The most common types of infections were surgical site infection with 56.60% followed by malaria with 23.30% and urinary tract infection with 20.00%. Escherichia coli and Acinetobacter baumaniiwere the most recovered germs. Isolated organisms were 100% resistant to Amoxicillin, 88.88% were resistant to Ciprofloxacin and 77.77% were resistant to Amoxicillin + Clavulanic acid. The average duration of hospitalization for patients who developed the infection was 14.70 days with extremes of 5 and 46 days. The mortality rate was 1.50%. The average cost of management of patients who developed the infection was 119837 FCFA; the extremes were 17750 and 825750 FCFA and the standard deviation of 174998 CFA francs. CONCLUSION: the infections associated with the care remain frequent in our service and dominated by the infections of the operating site. The isolated organisms were all 100% resistant to Amoxicillin in 88.88% Ciprofloxacin.

LE BUT: de ce travail était d'étudier les infections associées aux soins dans le département de gynécologie ­obstétrique du Centre Hospitalier Universitaire Gabriel Touré (CHU G. Touré). PATIENTES ET MÉTHODES: Il s'agissait d'une étude épidémiologique, descriptive, analytique réalisée dans le département de gynécologie ­obstétrique du CHU G. Touré, allant du 11 Avril 2016 au 29 Août 2016 (4 mois et 18 jours) à collecte prospective des données qui a porté sur les caractéristiques cliniques et biologiques des infections associées aux soins chez les patientes au cours de leur hospitalisation. Etaient incluses dans l'étude toutes les patientes hospitalisées (opérées ou non) dans le service de gynécologie obstétrique, et qui ont accepté de participer à l'étude.Les critères utilisés pour le diagnostic de l'infection associée aux soins étaient ceux du CDC d'Atlanta et la réalisation d'une goutte épaisse dans notre contexte. Une surveillance des plaies opératoires a été faite jusqu'au 30ème jour post-opératoire. RÉSULTATS: Nous avons enregistrés 200 patientes dont 138 opérées et 62 non opérées parmi lesquelles 30 patientes ont développé une infection associée aux soins soit un taux de 15%. L'âge moyen des patientes ayant présenté une infection a été 32,52 ans ±13,36 ans contre 29.36 ans ±10,28 ans pour les patientes n'ayant pas présenté l'infection. Sept virgule cinq pourcent des patientes évacuées ont présenté une infection associée aux soins. Les types d'infections les plus retrouvés étaient l'infection du site opératoire avec 56,60% suivie du paludisme avec 23,30% et l'infection urinaire avec 20,00%. L'Escherichia coli et l'Acinetobacterbaumanii ont été les germes les plus retrouvés. Les germes isolés étaient dans 100% des cas résistants à l'Amoxicilline, dans 88,88% des cas résistants à la Ciprofloxacine et dans 77.77% des cas résistants à l'Amoxicilline +Acide clavulanique. La durée moyenne d'hospitalisation des patientes ayant développé l'infection a été 14,70 jours avec des extrêmes de 5 et 46 jours.Le taux de mortalité a été de 1,50%. Le coût moyen de prise en charge des patientes ayant développé l'infection a été 119837 FCFA ; les extrêmes ont été 17750 et 825750 FCFA et l'écart type de 174998 francs CFA. CONCLUSION: les infections associées aux soins restent fréquentes dans notre service et dominées par les infections du site opératoire. Les germes isolés étaient tous résistants dans 100% cas à l'Amoxicilline dans 88,88% cas à la Ciprofloxacine.

[Surgery wound infection at surgery "A" department of the University Hospital Point G]. / Infection du site operatoire dans le service de chirurgie « A ¼ du CHU du Point G.

AIM: To determine the frequency of the surgery wound infection, its favoring factors, causative germs and its antibiotic treatment of choice in the surgery "A" department of the University Hospital Point G. METHOD: In a retrospective descriptive study over a 6-month period in the surgery "A" department of the University Hospital Point G, we enrolled all patients who underwent surgery necessitating at least 48 hours of hospital admission during our study period and in conformity with the Atlanta CDC criteria. Surgery patients with less than 48 hours postoperative hospital stay and those admitted to the hospital without surgery were not included.After the surgery, the nature and location of the infection have been clarified. In this work, ethical considerations have been respected and there is no conflict of interest. RESULTS: Two hundred and sixty-five (n=265) patient files were collected including 24 cases of surgery wound infection (a hospital frequency of 9%. The average age was 41.41 years (y.o) old with extremes of 7 y.o and 102 y.o. The sex ratio was 0.9 in favor of women. The commonly studied pathologies were digestive surgery in 52.8%, gynecological surgery in 24.5%, etc… Patients were seen in regular outpatient surgery visits in 75.8% and surgical emergencies in 24.2%. Of the patients urgently admitted, 26.5% presented an ISO; for those received in ordinary consultation it was 3.48%. Fifteen (15) cases were classified ASA III and two (2) ASA II. Based on the Altemeier classification, surgery was clean in 66.8% of our patients, contaminated clean in 12.4%, contaminated in 12.1%, and dirty in 8.7% (including half resulting in surgery wound infection). In total, 79% of patients whose surgeries lasted more than two (2) hours presented a surgery wound infection. Postoperative infection of patients was superficial in 58.3% and deep in 33.3%. In 8.3% of cases, it was a space infection. At the cytobacteriological examination of the pus from the operative site, Escherichia coli (E. coli) was the most common germ with 58.3%. E. coli was sensitive to amoxicillin-clavulanic acid in 57.14%. Surgically, a re-intervention was performed in 20.8% of cases, a secondary suture in 12.5%, and a single dressing in 66.7%. The average postoperative stay was 6.5 days with extremes of 2 days and 69 days. In 3 months postoperatively we recorded 4 cases of death. CONCLUSION: The surgery wound infection constitutes a major complication in a surgical environment starting with surgical act itself.Particular emphasis should be placed on prevention, which will reduce the risks of ISO occurrence.

BUT: déterminer la fréquence des infections du site opératoire (ISO), les facteurs favorisants la survenue des ISO, les germes responsables et les antibiotiques actifssur les infections du site opératoire dans le service chirurgie « A ¼ du CHU du Point G. MÉTHODE: Il s'agissait d'une étude rétrospective et descriptive sur une période de 6 mois réalisée dans le service chirurgie « A ¼ du CHU du Point G. Ont été inclus tous les patients ayant subi une intervention chirurgicale pendant cette période et hospitalisés au moins 48 heures après, et qui ont répondu aux critères du CDC d'Atlanta. N'ont pas été inclus, les patients opérés dont le séjour post opératoire a été inférieur à 48 heures, les patients hospitalisés dans le service mais non opérés, et ceux opérés dans le service et non hospitalisés. En postopératoire la nature et le siège de l'infection ont été précisées. Dans ce travail les considérations éthiques ont été respectées et il n'y a pas de conflit d'intérêt. RÉSULTATS: deux cent soixante-cinq dossiers de patients ont été colligés dont 24 cas d'ISO soit 9% des cas. L'âge moyen a été de 41,41 ans avec des extrêmes de 7ans et 102 ans. Le sex ratio a été de 0,2 en faveur des femmes. Les principales pathologies étudiées ont été la chirurgie digestive dans 52,8%, la chirurgie gynécologique dans 24,5%. La majorité des patients ont été reçus en consultation ordinaire dans 75,8% des cas, et en urgences dans 24,2 %. Parmi les patients reçus en urgence 26,5% ont présenté une ISO ; pour ceux reçus en consultation ordinaire elle a été de 3,48%.Parmi les patients infectés 15 étaient classés ASA III et 2 ASA II. Selon la classification Altemeier, la chirurgie propre a occupé 66,8% des patients, la chirurgie propre contaminée 12,4%, la chirurgie contaminée 12,1%, et la chirurgie sale 8,7%. Parmi les patients opérés de chirurgie sales 50% ont présenté une ISO.L'ISO était présente chez 79% des patients ayant effectué plus de 2 heures d'intervention.En postopératoire l'infection était superficielle chez 58,3% des patients, et profonde chez 33,3% des patients. Dans 8,3% des cas, il s'agissait d'une infection d'espace. A l'examen cytobactériologique du pus Escherichia coli (E coli) avec 58,3% a été le germe le plus fréquent sur le site opératoire. E coli était sensible à l'association amoxicilline - acide clavulanique dans 57,14%. Sur le plan chirurgical une réintervention a été réalisée dans 20,8% des cas, une suture secondaire dans 12,5%, et un pansement seul dans 66,7%. La durée moyenne de séjour post opératoire était de 6,5 jours avec des extrêmes de 2 jours et 69 jours. En 3 mois postopératoire nous avons enregistré 4 cas de décès. CONCLUSION: L'ISO constitue une complication majeure en milieu chirurgical compromettant l'acte chirurgical. Un accent particulier doit être mis sur la prévention qui diminuerai les risques de survenue de l'ISO.

New insights in the mechanisms of impaired redox signaling and its interplay with inflammation and immunity in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination and axonal damage and resulting in a range of physical, mental or even psychiatric symptoms. Key role of oxidative stress (OS) in the pathogenesis of MS has been suggested, as indicated by the biochemical analysis of cerebrospinal fluid and blood samples, tissue homogenates, and animal models of multiple sclerosis. OS causes demyelination and neurodegeneration directly, by oxidation of lipids, proteins and DNA but also indirectly, by inducing a dysregulation of the immunity and favoring the state of pro-inflammatory response. In this review, we discuss the interrelated mechanisms of the impaired redox signaling, of which the most important are inflammation-induced production of free radicals by activated immune cells and growth factors, release of iron from myelin sheath during demyelination and mitochondrial dysfunction and consequent energy failure and impaired oxidative phosphorylation. Review also provides an overview of the interplay between inflammation, immunity and OS in MS. Finally, this review also points out new potential targets in MS regarding attenuation of OS and inflammatory response in MS.

Microglia Regulate Pruning of Specialized Synapses in the Auditory Brainstem.

The assembly of uniquely organized sound localization circuits in the brainstem requires precise developmental mechanisms. Glial cells have been shown to shape synaptic connections in the retinogeniculate system during development, but their contributions to specialized auditory synapses have not been identified. Here we investigated the role of microglia in auditory brainstem circuit assembly, focusing on the formation and pruning of the calyx of Held in the medial nucleus of the trapezoid body (MNTB). Microglia were pharmacologically depleted in mice early in development using subcutaneous injections of an inhibitor of colony stimulating factor 1 receptor, which is essential for microglia survival. Brainstems were examined prior to and just after hearing onset, at postnatal days (P) 8 and P13, respectively. We found that at P13 there were significantly more polyinnervated MNTB neurons when microglia were depleted, consistent with a defect in pruning. Expression of glial fibrillary acidic protein (GFAP), a mature astrocyte marker that normally appears in the MNTB late in development, was significantly decreased in microglia-depleted mice at P13, suggesting a delay in astrocyte maturation. Our results demonstrate that monoinnervation of MNTB neurons by the calyx of Held is significantly disrupted or delayed in the absence of microglia. This finding may reflect a direct role for microglia in synaptic pruning. A secondary role for microglia may be in the maturation of astrocytes in MNTB. These findings highlight the significant function of glia in pruning during calyx of Held development.

[Pregnancy and delivery for women aged 40 years and over at the reference health center of commune II of Bamako district, Mali]. / Grossesses et accouchements chez les femmes de 40 ans et plus au centre de sante de reference de la commune II du district de Bamako, Mali.

GOAL: The aim of this study was to compare the maternal-fetal prognosis of pregnancies at 40 years of age and above with that of pregnancies obtained before 40 years of age in the obstetric gynecology department of the reference health center of commune II of Bamako district. MATERIALS AND METHODS: This was a prospective cohort study that was conducted at the maternity ward of Reference Health Center of Commune II of Bamako district from 1st January to 31 December 2012. Were included in our study as patients exposed, all the pregnant women of 40 years and over and as unexposed patients, pregnant women aged 20-39 who gave birth in our service. Teenage pregnancies were not included in this study. The statistical tests used were Pearson's Khi2 and Fisher's test with a significance level of 5%. RESULTS: The frequency of pregnancy among women aged 40 and over was 1.68%. These were large multiparas unschooled patients in 60% of cases, with hypertension in 6.7% of cases. Pregnancy in her patients was associated with a high rate of caesarean section in 16.7% of cases, term overrun in 6.7% of cases, seat presentation in 6.7% of cases, macrosomia in 6.7% of cases and fetal malformation in 1.7% of cases. CONCLUSION: Slight account of its many maternal-fetal complications, pregnancies in women 40 years and older deserve special attention.

BUT: Le but de cette étude était de comparer le pronostic materno-foetal des grossesses chez les patientes de 40 ans et plus à celui des grossesses conçues avant 40 ans dans le service de gynécologie obstétrique du centre de santé de référence de la commune II de Bamako. MATÉRIELS ET MÉTHODES: Il s'agissait d'une étude prospective de Cohorte qui s'est déroulée à la maternité du Centre de Santé de Référence de la Commune II du 1er janvier au 31décembre 2012. Ont été incluses dans notre étude comme patientes exposées toutes les gestantes de 40 ans et plus et comme patientes non exposées les gestantes de 20-39 ans ayant accouchées dans notre service. N'ont pas été retenues dans cette étude, les grossesses chez les adolescentes. Les tests statistiques utilisés ont été le Khi2 de Pearson et le test de Fisher avec un seuil de significativité à 5%. RÉSULTATS: La fréquence de la grossesse chez les femmes de 40 ans et plus était de 1,68%. Il s'agissait de grandes multipares non scolarisées dans 60% des cas, présentant une HTA dans 6,7% des cas. La grossesse chez ces patientes a été associée à un taux élevé de césarienne dans 16,7% des cas, de dépassement de terme dans 6,7% des cas, de présentation du siège dans 6,7% des cas, de macrosomie dans 6,7% des cas et de malformation foetale dans 1,7% des cas. CONCLUSION: Compte ténu de ses nombreuses complications materno-foetales, les grossesses chez les femmes de 40 ans et plus méritent une attention particulière.

[Neoadjuvant chemotherapy in locally advanced cervical cancer in patients receiving a concomitant chemoradiotherapy in a low income country]. / Chimiotherapie neo adjudante dans les cancers localement avances du col uterin chez des patientes recevant une radiochimiotherapie concomitante dans pays aux ressources limitees.

PURPOSE: Delays to access to radiotherapy are long in our context. The purpose of this study was to analyze the effect of neoadjuvant chemotherapy to concomitant chemoradiotherapy in locally advanced cervical cancers. PATIENTS AND METHODS: We conducted a retrospective study from April 2014 to April 2016 at the radiotherapy center of "Hopital du Mali" in Bamako, Mali. Patients were allocated according to age, histological type, tumor size and the 2002 classification of the FIGO. Experimental protocol was the administration of a neoadjuvante chemotherapy with association of Paclitaxel 175mg/m2 + Carboplatine AUC 5 every 3 weeks and radiothérapy cure with avec linac 6 MV at 70 Gy due to 5 sessions of 2 Gy per week associated with a concomitant chemotherapy with cisplatin at 40 mg/m2/week. The clinical response was assessed at the end of neoadjuvant chemotherapy and of concomitant chemoradiotherapy. RESULTS: Thirty patients were included in the study. The mean age was 53.63 ± 8.9 years. The mean size of the tumor was 5.17 cm (2 to 7 cm). According to the 2002 classification of the FIGO stages IIB were 33% (n = 10); IIIB were 57% (n = 17) and IVA were 10% (n = 3). Clinical evaluation at the end of neoadjuvant chemotherapy found: complete response 17 % (n = 5), partial response 10% (n = 3) and stable disease 73 % (n = 22). Evaluation at the end of the concomitant chemoradiotherapy had found the complete response in 90% (n = 27) and stable disease in 10% (n = 3). CONCLUSION: Neoadjuvant chemotherapy to concomitant chemoradiotherapy in locally advanced cervical cancer allows stabilization of the tumor and improves local control. Due to long delays to access to radiotherapy treatment in our context; neoadjuvant chemotherapy is an alternative to stabilize the disease and prevent distant metastasis from locally advanced cervical cancers.

OBJECTIF: Les délais d'attente pour accéder à la radiothérapie sont longs dans note contexte. L'objet de cette étude était d'analyser le résultat de la chimiothérapie néo adjuvante à la radiothérapie dans les cancers localement avancés du col utérin. PATIENTS ET MÉTHODES: Nous avons réalisé une étude rétrospective allant d'avril 2014 à avril 2016 au centre de radiothérapie de l'hôpital du Mali. Les patients ont été regroupés selon l'âge, le type histologique, la taille de la tumeur, la classification de la FIGO 2002. Le schéma thérapeutique était une chimiothérapie néo adjuvante associant Paclitaxel 175 mg/m2 et Carboplatine AUC 5 toutes les 3 semaines suivie d'une radiothérapie avec linac 6 MV à la dose de 70 Gy en raison de 5 séances de 2 Gy par semaine faite concomitamment à une chimiothérapie avec du cisplatine à la dose de 40 mg/m2/semaine. La réponse clinique était évaluée à la fin de la chimiothérapie néoadjuvante et de la radiochimiothérapie concomitante. RÉSULTATS: Trente patientes ont été incluses dans l'étude. L'âge moyen était de 53.63 ± 8.9 ans. La taille moyenne de la tumeur était de 5,17 cm (2 à 7 cm). Selon la classification FIGO 2002, 10 (33%) étaient en stade IIB distal, 17 (57%) étaient en stade IIIB et 3 (10%) en stade IVA. L'évaluation clinique à la fin de la chimiothérapie néo adjuvante avait retrouvé 17 % de réponses complètes (n=5), 10% de réponses partielles (n=3) 73 % d'évolutions stables (n=22). L'évaluation à la fin de la radiochimiothérapie concomitante avait trouvé une réponse complète chez 27 patientes (90%) et une maladie stable chez 3 (10%). CONCLUSION: La chimiothérapie néo adjuvante à la chimioradiothérapie concomitante dans les cancers localement avancés du col utérin permet la stabilisation de la tumeur et améliore le control local. En raison des délais d'attente longs pour accéder à la radiothérapie, la chimiothérapie néo adjuvante est une alternative pour stabiliser la maladie et réduire le risque de métastases à distance des cancers du col utérin localement avancés.

Chimiothérapie neo adjudante dans les cancers localement avances du col utérin chez des patientes recevant une radio chimiothérapie concomitante dans pays aux ressources limitées

Les délais d'attente pour accéder à la radiothérapie sont longs dans note contexte. L'objet de cette étude était d'analyser le résultat de la chimiothérapie néo adjuvante à la radiothérapie dans les cancers localement avancés du col utérin. Patients et méthodes: Nous avons réalisé une étude rétrospective allant d'avril 2014 à avril 2016 au centre de radiothérapie de l'hôpital du Mali. Les patients ont été regroupés selon l'âge, le type histologique, la taille de la tumeur, la classification de la FIGO 2002. Le schéma thérapeutique était une chimiothérapie néo adjuvante associant Paclitaxel 175 mg/m2 et Carboplatine AUC 5 toutes les 3 semaines suivie d'une radiothérapie avec linac 6 MV à la dose de 70 Gy en raison de 5 séances de 2 Gy par semaine faite concomitamment à une chimiothérapie avec du cisplatine à la dose de 40 mg/m2/semaine. La réponse clinique était évaluée à la fin de la chimiothérapie néoadjuvante et de la radiochimiothérapie concomitante. Résultats : Trente patientes ont été incluses dans l'étude. L'âge moyen était de 53.63 ± 8.9 ans. La taille moyenne de la tumeur était de 5,17 cm (2 à 7 cm). Selon la classification FIGO 2002, 10 (33%) étaient en stade IIB distal, 17 (57%) étaient en stade IIIB et 3 (10%) en stade IVA. L'évaluation clinique à la fin de la chimiothérapie néo adjuvante avait retrouvé 17 % de réponses complètes (n=5), 10% de réponses partielles (n=3) 73 % d'évolutions stables (n=22). L'évaluation à la fin de laradiochimiothérapie concomitante avait trouvé une réponse complète chez 27 patientes (90%) et une maladie stable chez 3 (10%). Conclusion - La chimiothérapie néo adjuvante à la chimioradiothérapie concomitante dans les cancers localement avancés du col utérin permet la stabilisation de la tumeur et améliore le control local. En raison des délais d'attente longs pour accéder à la radiothérapie, la chimiothérapie néo adjuvante est une alternative pour stabiliser la maladie et réduire le risque de métastases à distance des cancers du col utérin localement avancés

Simultaneous downregulation of miR-21 and miR-155 through oleuropein for breast cancer prevention and therapy.

Breast cancer (BC) is the leading cause of cancer mortality in women worldwide. It recently was proven that miRNAs play a critical role in BC development. The use of natural agents for control of cancer by modulating miRNAs is promising. Oleuropein is a natural polyphenolic agent with anti-neoplastic properties and is well tolerated by humans. This study was undertaken to determine the therapeutic effects of oleuropein through modulation of master oncomiRs (miR-21 and miR-155) in BC cells. The present study provides the first link between miRNA and oleuropein as a mechanism in BC. MCF-7 cells were tested with and without oleuropein and the cell viability, apoptosis, and migration were examined. The effect of oleuropein on miR-21 and miR-155 expression was assessed through qRT-PCR. It was found that oleuropein induced apoptosis and retarded cell migration and invasion in a dose-dependent manner in the human MCF7 BC cell line. It was observed that oleuropein significantly decreased expression of both miR-21 and miR-155 over time in a dose-dependent manner. These results demonstrate that oleuropein is a potential therapeutic and preventive agent for BC. Oleuropein exhibits an anti-cancer effect by modulation of tumor suppressor gene expression, which is targeted by oncomiRs.

[Targeted newborn screening for sickle-cell anemia: Sickling test (Emmel test) boundaries in the prenatal assessment in West African area]. / Dépistage néonatal ciblé de la drépanocytose : limites du test de falciformation (test d'Emmel) dans le bilan prénatal en zone ouest africaine.

BACKGROUND: Newborn screening for sickle cell anemia is necessary in Africa where the disease is more frequent. Hemoglobin electrophoresis is used for screening, but is limited by a high cost and difficult access. Sickling test (Emmel test), which is more affordable and technically more accessible, is often requested for prenatal assessment of pregnant women in West African areas to reserve screening for newborns from mothers in whom the positive sickling test attests the presence of hemoglobin S. This study aims to evaluate the number of undetected sickle cell anemia newborns by a screening policy targeting only newborns from mothers in whom a sickling test would have been positive. METHODS: From 2010 to 2012, in Bamako, Mali, West Africa, 2489 newborns were routinely screened for sickle cell anemia at the umbilical cord or heel by isoelectrofocusing and, if necessary, by high-performance liquid chromatography. These newborns were born from 2420 mothers whose hemoglobin was studied by isoelectrofocusing. The data was recorded and processed using Excel software version 14.0.0. We calculated the frequency of the sickle cell gene in mothers and newborns as well as the number of SCA newborns from heterozygous or C homozygous mothers. RESULTS: Of the 2489 newborns, 16 had sickle cell anemia (6 SS and 10 SC); 198 had the sickle cell trait; 139 were AC and 1 was CC. Of the 10 newborns with SC profile, 3 were born from mothers not carrying the S gene but the C gene of hemoglobin and in which an Emmel test would have been negative. CONCLUSION: Targeted newborn screening, based on the results of sickling test in pregnant women, would misdiagnose more than one of six sickle cell anemia newborns who would not benefit from early care. Cost-effectiveness studies of routine newborn screening for sickle cell anemia should lead to a better screening strategy in contexts where hemoglobin S and other hemoglobin defect genes coexist.