The density of calretinin striatal interneurons is decreased in 6-OHDA-lesioned mice.

Interneurons play a significant role in the functional organization of the striatum and some of them display marked plastic changes in dopamine-depleted conditions. Here, we applied immunohistochemistry on brain sections from 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's disease and sham animals to characterize the regional distribution and the morphological and neurochemical changes of striatal interneurons expressing the calcium-binding protein calretinin (CR). Two morphological subtypes of calretinin-immunostained (CR +) interneurons referred, respectively, as small- and medium-sized CR + interneurons were detected in 6-OHDA- and sham-lesioned animals. The small cells (9-12 µm) prevail in the anterior and dorsal striatal regions; they stain intensely for CR and display a single slightly varicose and moderately arborized process. The medium-sized CR + interneurons (15-20 µm) are more numerous than the small CR + cells and rather uniformly distributed within the striatum; they stain weakly for CR and display 2-3 long, slightly varicose and poorly branched dendrites. The density of medium CR + interneurons is significantly decreased in the dopamine-depleted striatum (158 ± 15 neurons/mm3), when compared to sham animals (370 ± 41 neurons/mm3), whereas that of the small-sized CR + interneurons is unchanged (174 ± 46 neurons/mm3 in 6-OHDA-lesioned striatum and 164 ± 22 neurons/mm3 in sham-lesioned striatum). The nucleus accumbens is populated only by medium-sized CR + interneurons, which are distributed equally among the core and shell compartments and whose density is unaltered after dopamine denervation. Our results provide the first evidence that the medium-sized striatal interneurons expressing low level of CR are specifically targeted by dopamine denervation, while the small and intensely immunoreactive CR + cells remain unaffected. These findings suggest that high expression of the calcium-binding protein CR might protect striatal interneurons against an increase in intracellular calcium level that is believed to arise from altered glutamate corticostriatal transmission in Parkinson's disease.

Phenotypic and molecular characterization of macrolide resistance mechanisms among Streptococcus pneumoniae isolated in Tunisia.

Introduction. Streptococcus pneumoniae is responsible for many community infections, with the main ones being pneumonia and meningitis. Pneumococcus has developed increased resistance to multiple classes of antibiotics. The evolution of antibiotic resistance in pneumococcus was influenced by changes in serotype distribution under vaccine selection pressure.Aim. The aim of this study was to determine the genes involved in macrolide resistance, the antimicrobial susceptibility, the serotype distribution and the spread of international antibiotic-resistant clones among clinical isolates of S. pneumoniae.Methodology. We investigated 86 erythromycin-resistant S. pneumoniae strains isolated from respiratory (n=74) or non-respiratory (n=12) samples in Tunisia. Antimicrobial susceptibility was tested using the disk diffusion method. Macrolide-resistant strains were analysed by polymerase chain reaction (PCR) for ermA, ermB, mefA and msrD. We also investigated the macrolide resistance mechanisms in eight isolates (9.3%) by sequencing the L4 and L22 riboprotein-coding genes, plus relevant segments of the three 23S rRNA genes. Capsular serotypes were detected by multiplex PCR. Sequence types (STs) were explored using multilocus sequence typing (MLST).Results. Among the 86 studied strains, 70 (81.4 %) were resistant to penicillin G. The prevalent serotypes were 19F, 14, 19A and 23F. We observed that the cMLSB phenotype (66/86, 76.7%) was the most common in these pneumococci. In addition, ermB was the most frequent resistance gene. No mutation in ribosomal protein L22 or L4 or 23S rRNA was detected. Overall, 44 STs were identified in this study, including 16 that were described for the first time. Resistance to lincomycin, tetracycline and trimethoprim/sulfamethoxazole was observed in 55 (64 %), 34 (39.5 %) and 31 (36 %) isolates, respectively. Furthermore, an increase in fluoroquinolone use in particular may lead to the emergence of levofloxacin-resistant strains. Multidrug resistance was observed in 83 isolates (96.5%). Three global antibiotic-resistant clones were identified: Denmark14 ST230, Portugal19F ST177 and Spain9V ST156.Conclusion. This study shows that macrolide resistance among S. pneumoniae isolated in Tunisia is mainly related to target site modification. Our observations demonstrate a high degree of genetic diversity and capsular types among strains resistant to macrolides.

Genetic diversity of Streptococcus pneumoniae in Tunisia.

OBJECTIVES: This study aimed to explore the genetic diversity of Streptococcus pneumoniae isolates in a Tunisian pneumology hospital. METHODS: A total of 141 S. pneumoniae strains isolated between 2009-2016 in the microbiology laboratory at A. Mami Hospital of Pneumology were investigated. Antimicrobial susceptibility testing was performed the disk diffusion method. MICs of penicillin G, amoxicillin and cefotaxime were determined by Etest. Serotyping was inferred from the results of multiplex PCR targeting 40 serotypes. Sequence types (STs) were determined by multilocus sequence typing (MLST). RESULTS: Among the 141 S. pneumoniae isolates, 98 (69.5%) were resistant to erythromycin. Evaluation of ß-lactam susceptibility showed that 90 strains (63.8%) were non-susceptible to penicillin, whereas 48 (34.0%) had decreased susceptibility to amoxicillin and 21 (14.9%) to cefotaxime. Twenty-five serotypes were detected, and 10 isolates were classified as non-typeable. Vaccine coverage was 56.7%, 60.3% and 75.2% for pneumococcal conjugate vaccine 7 (PCV7), PCV10 and PCV13, respectively. Overall, 73 STs were identified, including 23 described for the first time. The most frequent STs were ST179 (n = 17), ST3772 (n = 14), ST2918 (n = 10) and ST4003 (n = 5), related to serotypes 19F, 19A, 14 and 23F, respectively. Moreover, 110 strains were classified within 45 STs. Three international antimicrobial-resistant clones were found, including Denmark14-ST230 (n = 22), Spain9V-ST156 (n = 22) and Portugal19F-ST177 (n = 20). CONCLUSION: This study emphasises the clonal and international dissemination of antimicrobial-resistant S. pneumoniae clones. Significant differences in genetic variation were documented by MLST within the various serotypes identified.

Is sequencing better than phenotypic tests for the detection of pyrazinamide resistance?

SETTING: Phenotypic tests used to detect pyrazinamide (PZA) resistance are slow and have a high rate of false resistance. OBJECTIVE: To evaluate the accuracy of pncA sequencing for the detection of PZA resistance in Mycobacterium tuberculosis strains isolated in Tunisia. DESIGN: A total of 82 isolates, 41 resistant and 41 susceptible to PZA on BACTEC™ MGIT™ 960, were sequenced for pncA. Whole genome sequencing was performed for strains that were phenotypically resistant and had wild-type pncA in addition to MGIT retesting with a modified protocol. RESULTS: Twenty-three strains resistant to PZA with negative pyrazinamidase (PZase) activity harboured a mutation in the promoter or coding region of pncA. However, 18 strains resistant to PZA did not present any mutation. Repeat MGIT 960 showed that 16 of 18 M. tuberculosis isolates were falsely resistant to PZA. Compared with MGIT, PZase activity assay and pncA sequencing both presented a sensitivity of 92.0% (95%CI 73.9-99.0) and a specificity of respectively 96.5% (positive predictive value [PPV] 92.0%, negative predictive value [NPV] 96.5%) and 100.0% (PPV 100.0%, NPV 96.6%). CONCLUSION: The standard MGIT assay showed a high rate of false resistance to PZA, and the PZase activity assay is slow. pncA sequencing could therefore represent a rapid, accurate, alternative test to detect PZA resistance.

[New methods of diagnosis in tuberculosis]. / Nouvelles méthodes de diagnostic de la tuberculose.

Bacteriological diagnosis of tuberculosis has benefited in recent years from many technological advances to improve rapidity and sensitivity of the techniques. Thus, new LED fluorescence microscopes are in the process of replacing the optical microscopes and the Ziehl-Neelsen technique, making the examination more precise, faster and easier. The manual and automatic liquid culture has improved Lowenstein-Jensen culture and helped shorten antibiotic sensitivity test, allowing appropriate management of patients. The development and standardization of molecular biology methods led to the rapid detection and identification of mycobacterium directly in clinical samples but also of resistance genes for early diagnosis of MDR-TB and dealing with them quickly. However, the performance of these techniques does not sufficiently cover the diagnosis of smear-negative tuberculosis, extrapulmonary forms, children- and immune-compromised tuberculosis where sensitivity is limited. The diagnosis of latent tuberculosis is reinforced by the in vitro release testing of gamma interferon overcoming the lack of specificity of the tuberculin skin test. Despite considerable progress, more amelioration is still needed to improve these techniques in order to extend them to the paucibacillary tuberculosis and to facilitate their access to low-resource countries.

[Management of multidrug-resistant tuberculosis]. / Prise en charge de la tuberculose multirésistante.

The emergence of drug-resistant TB in many countries has become a major public health problem and an obstacle to effective tuberculosis control. Multidrug-resistant tuberculosis (MDR-TB), which is most often the result of poor adherence, is a particularly dangerous form of tuberculosis because it is caused by bacilli resistant to at least isoniazid and rifampicin, the two most effective anti-tuberculosis drugs. Techniques for rapid diagnosis of resistance have greatly improved the care of patients by allowing early treatment which remains complex and costly establishment, and requires skills and resources. The treatment is not standardized but it includes in all cases attack phase with five drugs (there must be an injectable agent and a fluoroquinolone that form the basis of the regimen) for eight months and a maintenance phase (without injectable agent) with a total duration of 20 months on average. Surgery may be beneficial as long as the lesions are localized and the patient has a good cardiorespiratory function. Evolution of MDR-TB treated is less favorable than tuberculosis with germ sensitive. The cure rate varies from 60 to 75% for MDR-TB, and drops to 30 to 40% for XDR-TB. Mortality remains high, ranging from 20 to 40% even up to 70-90% in people co-infected with HIV.

WITHDRAWN: Bearing multi-faults diagnosis based on stator current bi-spectrum features and support vector machines.

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Diagnosis of broken-bars fault in induction machines using higher order spectral analysis.

Detection and identification of induction machine faults through the stator current signal using higher order spectra analysis is presented. This technique is known as motor current signature analysis (MCSA). This paper proposes two higher order spectra techniques, namely the power spectrum and the slices of bi-spectrum used for the analysis of induction machine stator current leading to the detection of electrical failures within the rotor cage. The method has been tested by using both healthy and broken rotor bars cases for an 18.5 kW-220 V/380 V-50 Hz-2 pair of poles induction motor under different load conditions. Experimental signals have been analyzed highlighting that bi-spectrum results show their superiority in the accurate detection of rotor broken bars. Even when the induction machine is rotating at a low level of shaft load (no-load condition), the rotor fault detection is efficient. We will also demonstrate through the analysis and experimental verification, that our proposed proposed-method has better detection performance in terms of receiver operation characteristics (ROC) curves and precision-recall graph.

["On and off" hypoxaemia]. / Hypoxémie « on-off ¼

INTRODUCTION: A right to left shunt caused by a patent foramen ovale (PFO) must be considered when patients present with symptoms of platypnoea-orthodeoxia. The most useful investigation is saline contrast transthoracic or transoesophageal echocardiography. CASE REPORT: We report a case of an eighty-year-old woman with the platypnoea-orthodeoxia syndrome, but without signs of a right to left shunt caused by a PFO. (99m)Tc-macroaggregated albumin lung scintigraphy and saline contrast transthoracic echocardiography were considered normal in the supine position. The clinical suspicion of PFO was so strong that the examinations were repeated in the upright position. This revealed a systemic uptake of the isotope on lung scintigraphy, confirmed by saline contrast echocardiography. The atrial septal defect was due to displacement of the interatrial septum by an aneurysm of the ascending aortic. In the upright position blood flowed directly from the inferior cava vena through a PFO into the left atrium. CONCLUSION: The diagnosis of PFO may be difficult and it is important to repeat saline contrast echocardiography in the upright position when it is negative supine. It is possible to confirm the diagnosis by contrast infusion through the femoral veins.

[Effect of citrate on oxidative status of rats tissues in experimental toxic hepatitis].

The effect of citrate free-radical oxidation intensity and aconitate hydratase, superoxide dismutase and catalase activities in liver and blood serum of rats with experimental toxic hepatitis has been investigated. Citrate administration to rats with hepatitis decreased biochemiluminescence parameters and conjugated diene content in rats tissues, increased under conditions of CCl4-induced liver damage. At the same time aconitase activity, decreased at the pathology, increases. The superoxide dismutase and catalase activities increased in at experimental toxic hepatitis, tended towards control values after citrate administration.

[Twinkling artifact on Doppler US: clinical presentations]. / L'artefact de scintillement en écho-Doppler et situations cliniques.

Twinkling artifact characterized by a rapidly fluctuating mixture of Doppler signals occurs behind a strongly reflecting granular interface such as urinary tract stones or gallstones. It may occurs in association with several clinical situations, and may sometimes be helpful for diagnosis while it may sometimes be a pitfall that must be recognized by the sonographer. After reviewing the technical nature of this artifact, several cases will be presented to illustrate the advantages and pitfalls related to this artifact.

[Molecular comparison of Legionella pneumophila serogroup 1 isolated in Tunisia]. / Comparaison moléculaire de Legionella pneumophila sérogroupe 1 isolées en Tunisie.

Legionella pneumophila is a common cause of hospital and community-acquired pneumonia, being transmitted by inhalation of aqueous aerosols. Most outbreaks are linked to contaminated hot water systems and cooling towers. Our study was about the molecular typing of 35 strains of L. pneumophila including four clinical isolates and 31 environmental strains isolated from the distribution systems of 14 hotels. Among the clinical strains, two have the same pattern, however, all were different from the studied environmental strains. For the 31 environmental strains, ten patterns were obtained. Among which, a same pulsotype was found for four strains isolated from four different establishments. In addition, two different pulsotypes were found for strains isolated from the same establishment. The pulsed-field gel electrophoresis showed the existence of various patterns. Although cases of legionellosis were declared in these hotels, there are no epidemiological links between the clinical and environmental strains.

[Acute stent thrombosis due to resistance to clopidogrel ? A case report]. / Implication de la résistance au clopidogrel dans la thrombose aiguë de stent ? A propos d'un cas.

The authors report the case of a 65 year old man who presented with an acute coronary syndrome without ST elevation due to acute stent thrombosis 12 hours after implantation. Recent reports in the literature suggest the role of resistance to antiplatelet drugs in acute, subacute or late stent thrombosis. This patient was included in a protocol studying the response to antiplatelet drugs in patients undergoing coronary stenting and fulfilled the criteria of resistance to clopidogrel. This clinical case illustrates the possible role of "resistance" to antiplatelet drugs in stent thromboses.

[Beneficial effect of a loading dose of 600 mg of clopidogrel on platelet parameters in patients admitted for acute coronary syndrome]. / Bénéfice d'une dose de charge de 600 mg de clopidogrel sur les paramètres plaquettaires chez les patients admis pour syndrome coronaire aigu.

INTRODUCTION: Despite the beneficial effect of an aspirin-clopidogrel combination in acute coronary syndrome, the incidence of ischaemic recurrences remains significant and very probably implicates a variability in the response to anti-platelet agents. OBJECTIVE: We sought to demonstrate the evidence for a beneficial effect, in terms of anti-platelet effect, of a higher loading dose of 600 mg of clopidogrel compared to the usual 300 mg in patients admitted to our centre with acute coronary syndrome. MATERIALS AND METHODS: Platelet reactivity was evaluated with the ADP 10_mol test and the degree of platelet activation by the expression of P-selectin. 178 consecutive patients admitted for acute coronary syndrome received 250 mg of intravenous aspirin together with either a loading dose of 300 mg of clopidogrel (n = 104) or 600 mg (n = 74) administered 12 to 24 hours prior to coronary angiography. RESULTS: The patients who received 600 mg of clopidogrel had an average aggregation intensity to ADP and a rate of platelet high reactivity post treatment that was significantly lower [48+20 vs 58+18, p = 0.0011 and 11 patients (15%) vs 26 patients (25%), p = 0.0003 respectively]. The degree of platelet activation evaluated with P-selectin was significantly lower in patients receiving 600mg [0.33 + 0.17 vs 0.50+0.29, p < 0.001]. CONCLUSION: Our study provides evidence for a beneficial effect of a loading dose of 600mg of clopidogrel compared to the usual 300 mg in terms of platelet reactivity and platelet activation post treatment.

[Endomyocardial fibrosis: a rare case of restrictive cardiomyopathy in a Caucasian female]. / Fibrose endomyocardique: une cause rare de cardiomyopathie restrictive chez une patiente caucasienne.

The authors report the case of endomyocardial fibrosis diagnosed in a young Caucasian female presenting with progressive congestive cardiac failure. The diagnosis was suspected on the echocardiographic, magnetic resonance imaging and cardiac catheterisation findings in association with the clinical presentation. After a short course of symptomatic medical therapy, the patient underwent the only curative treatment of this pathology, surgical endocardectomy and combined valvular surgery. The confirmation of the diagnosis was obtained a posteriori by histopathological examination of the operative findings which showed appearances of endomyocardial fibrosis similar to those observed in tropical regions. The patient was discharged on the eighth postoperative day, much improved clinically, and follow-up at one year was very satisfactory.

An explanation for observed estrogen receptor binding to single-stranded estrogen-responsive element DNA.

Estrogen-inducible genes contain an enhancer called the estrogen response element (ERE), a double-stranded inverted repeat. The estrogen receptor (ER) is generally thought to bind to the double-stranded ERE. However, some reports provide evidence that an ER homodimer can bind a single strand of the ERE and suggest that single-stranded ERE binding is the preferred binding mode for ER. Since these two models describe quite different mechanisms of receptor action, we have attempted to reconcile the observations. Analyzing DNA structure by nuclease sensitivity, we found that two identical molecules of a single strand of DNA containing the ERE sequence can partially anneal in an antiparallel manner. Bimolecular annealing produces double-stranded inverted repeats, with adjacent unannealed tails. The amount of annealing correlates exactly with the ability of ER to bind bimolecular EREs. Either strand of an ERE could anneal to itself in a way that would bind ER. We conclude that ER binds only the annealed double-stranded ERE both in vitro and in vivo.