Sampling strategy for bacteriological diagnosis of intrathoracic tuberculosis.

BACKGROUND: Pulmonary tuberculosis (TB) is the most frequent site of TB and the one leading its spread worldwide. Multiple specimens are commonly collected for TB diagnosis including those requiring invasive procedures. This study aimed to review the sampling strategy for the microbiological diagnosis of pulmonary TB. METHODS: A retrospective analysis of collected samples from September 1st 2014 to May 1st 2016 in the Bacteriology laboratory of Pitié-Salpêtrière Hospital (Paris, France) was performed. All the samples collected in patients aged over 18 years for the bacteriological diagnosis of pulmonary TB were included. RESULTS: A total of 6267 samples were collected in 2187 patients. One hundred and twenty-six patients (6%) had a culture confirmed pulmonary TB. Among them, multiple sputum collections were sufficient for TB diagnosis in 63.5%, gastric lavages permitted to avoid bronchoscopy in only 7.1%, and bronchoscopy was necessary in 29.4%. The culture positivity of sputa (8.6%) was higher than that of bronchial aspirations (3.1%), bronchiolo-alveolar lavages (BAL) (2.3%) or gastric lavages (4.8%) (P<0.001). From its 70.0% theoretical PPV value, the 46.1% selection in bronchial aspirations allocated to molecular test increased PPV up to 88.9%. CONCLUSIONS: Based on our data, we suggest to collect sputum consistently. If smear negative a bronchoscopy should be performed and molecular diagnosis be performed on a subset of bronchial aspirations based on expertise of the bronchoscopist.

Infective endocarditis due to Neisseria elongata: A case report and literature review.

INTRODUCTION: Neisseria elongata (NE), a Gram-negative, rod-shaped organism, was previously thought to be non-pathogenic. However, in recent years it has become increasingly recognized as a rare cause of infective endocarditis. In this paper, we report a case of NE infective endocarditis and provide a review of the literature. OBJECTIVES: To describe a case of NE endocarditis, and to review the literature in search of any similar cases of this rare condition. CASE REPORT: Our patient is a 77-year-old, otherwise healthy female patient who was found to have mitral valve endocarditis with valve regurgitation. DISCUSSION: NE endocarditis is a rare condition that typically affects the left cardiac chambers and is associated with high risk of embolization. A literature review retrieved 35 other cases. CONCLUSIONS: Our report underlines the rarity of NE endocarditis, insofar as relatively few cases have been reported. The bacterium presents similarities with HACEK organisms and can potentially cause infective endocarditis.

The impact of psoriasis on professional life: PsoPRO, a French national survey.

BACKGROUND: The physical, social and mental burden of psoriasis is well known, but its occupational impact has been less investigated. OBJECTIVE: To assess the impact of psoriasis on the working life of patients compared with the general population. METHODS: A national survey compared people with and without psoriasis using online questionnaires. In addition to the demographic, medical and professional characteristics, data on recent absenteeism and presenteeism were captured using the validated WPAI-PSO questionnaire. RESULTS: The patient sample comprised 714 with psoriasis (PsO), including 81 treated with systemic therapies (PsoST), and 84 with associated psoriatic arthritis (PsO + PsA). The control sample comprised 604 active subjects representative of the French population. Compared to controls, the impact of the disease on working life was no greater in PsO patients. Conversely, unemployment within the past 5 years and mean number of sick leaves within the previous year were more frequent in PsO + PsA. In patients with active psoriasis skin lesions, all aspects of the WPAI questionnaire were negatively impacted in PsoST and PsO + PsA patients, but not in PsO patients: Levels of absenteeism were 3.3% in controls, 5.6% in PsO (NS), 8.3% in PsoST (P < 0.05) and 13.0% in Ps0 + PsA (P < 0.05); impairment in presenteeism reached 27.0%, 21.2% (NS), 43.5% (P < 0.05) and 53.2% (P < 0.05), respectively, while overall work impairment was 27.9%, 22.2% (NS), 46.3% (P < 0.05) and 57.6% (P < 0.05), respectively. Nevertheless, a higher proportion of PsoST and PsO + PsA patients reported that work was more important than any other activity in their life. CONCLUSION: The occupational impact of psoriasis is important and significant in patients who receive systemic therapy or have concurrent PsA but minimal or absent in other psoriasis patients. The findings show that psoriasis patients have a high level of motivation to work.

Extrinsic mechanical forces mediate retrograde axon extension in a developing neuronal circuit.

To form functional neural circuits, neurons migrate to their final destination and extend axons towards their targets. Whether and how these two processes are coordinated in vivo remains elusive. We use the zebrafish olfactory placode as a system to address the underlying mechanisms. Quantitative live imaging uncovers a choreography of directed cell movements that shapes the placode neuronal cluster: convergence of cells towards the centre of the placodal domain and lateral cell movements away from the brain. Axon formation is concomitant with lateral movements and occurs through an unexpected, retrograde mode of extension, where cell bodies move away from axon tips attached to the brain surface. Convergence movements are active, whereas cell body lateral displacements are of mainly passive nature, likely triggered by compression forces from converging neighbouring cells. These findings unravel a previously unknown mechanism of neuronal circuit formation, whereby extrinsic mechanical forces drive the retrograde extension of axons.How neuronal migration and axon growth coordinate during development is only partially understood. Here the authors use quantitative imaging to characterise the morphogenesis of the zebrafish olfactory placode and report an unexpected phenomenon, whereby axons extend through the passive movement of neuron cell bodies away from tethered axon tips.

Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort.

BACKGROUND: Diagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC. PATIENTS AND METHODS: All patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded. RESULTS: 253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0-1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20-100). Median overall survival was 15.6 (13.6-17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE>2 upper limit of normal [ULN]; HR = 3.2), CgA>2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72). CONCLUSIONS: We report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.

Comparative study of non-invasive force and stress inference methods in tissue.

In the course of animal development, the shape of tissue emerges in part from mechanical and biochemical interactions between cells. Measuring stress in tissue is essential for studying morphogenesis and its physical constraints. For that purpose, a possible new approach is force inference (up to a single prefactor) from cell shapes and connectivity. It is non-invasive and can provide space-time maps of stress in a whole tissue, unlike existing methods. To validate this approach, three force-inference methods, which differ in their approach of treating indefiniteness in an inverse problem between cell shapes and forces, were compared. Tests using two artificial and two experimental data sets consistently indicate that our Bayesian force inference, by which cell-junction tensions and cell pressures are simultaneously estimated, performs best in terms of accuracy and robustness. Moreover, by measuring the stress anisotropy and relaxation, we cross-validated the force inference and the global annular ablation of tissue, each of which relies on different prefactors. A practical choice of force-inference methods in different systems of interest is discussed.

The diffusion constant of a labeled protein sliding along DNA.

Long ago inferred by biochemists, the linear diffusion of proteins along DNA has recently been observed at a single-molecule level using fluorescence microscopy. This imaging technique requires labeling the protein of interest with a fluorophore, usually an organic nanosized dye that is not supposed to impact the dynamics of the protein. Yet individual proteins can also be tracked using much larger labels, like quantum dots or beads. We investigate here the impact of such a large label on the protein diffusion along DNA. Solving a Fokker-Planck equation, we estimate the diffusion constant of a protein-label complex diffusing in a periodic potential that mimics the DNA-protein interaction, the link between the protein and the label being modeled as a Hookean spring. Our results indicate that the diffusion constant can generally be calculated by considering that the motion of the protein in the DNA potential is decoupled from the Brownian motion of the label. Our conclusions are in good agreement with the experimental results we obtained with the restriction enzyme EcoRV, assuming a rotation-coupled diffusion of the enzyme along DNA.

In vitro and in vivo efficacy of sulfo-carrabiose, a sugar-based cosmetic ingredient with anti-cellulite properties.

Most of adult women exhibit cellulite on the hips, buttock and thighs. Although extracellular matrix and lymphatic system disorders can increase its appearance, cellulite basically results from an excessive fat storage in the adipose tissue which exerts considerable pressure on the surrounding skin tissue and creates a dimpled irregular appearance. Caffeine, the most widely used anti-cellulite ingredient, favours fat break-down by inhibiting the phosphodiesterase enzyme and encouraging a high intracellular level of cAMP. A series of studies has shown that spermine and spermidine, two ubiquitous polyamines, encouraged fat storage and slowed fat break-down in the adipose tissue. Besides, it was shown that heparan sulfate glycosaminoglycans had a strong affinity for polyamines. To design a new cosmetic ingredient with anti-cellulite properties, we used molecular modelling to screen several ingredients with a structure similar to that of heparan sulfate glycosaminoglycans. This way, we identified sulfo-carrabiose as a potent molecule for trapping spermine and spermidine. These virtual results were first confirmed in tubo where sulfo-carrabiose was shown to dose-dependently inactivate spermine and spermidine. In vitro, adipocytes cultured with sulfo-carrabiose exhibited a significant reduction of lipogenesis and a significant increase of lipolysis. When sulfo-carrabiose was incorporated in a cosmetic formula, significant improvements were observed in thigh circumference, with better results than those obtained with caffeine after 28 days of use. Furthermore, a combination of caffeine and sulfo-carrabiose led to results significantly better than those obtained with caffeine alone. As measured by fringe projection, thigh volume was also significantly reduced after sulfo-carrabiose treatment. Finally, the appearance of cellulite assessed by clinical evaluation was also significantly reduced within 28 days.

Quantifying hopping and jumping in facilitated diffusion of DNA-binding proteins.

Facilitated diffusion of DNA-binding proteins is known to speed up target site location by combining three dimensional excursions and linear diffusion along the DNA. Here we explicitly calculate the distribution of the relocation lengths of such 3D excursions, and we quantify the short-range correlated excursions, also called hops, and the long-range uncorrelated jumps. Our results substantiate recent single-molecule experiments that reported sliding and 3D excursions of the restriction enzyme EcoRV on elongated DNA molecules. We extend our analysis to the case of anomalous 3D diffusion, likely to occur in a crowded cellular medium.

Release of antimicrobial actives from microcapsules by the action of axillary bacteria.

We describe the use of unique microcapsules that may be degraded by the actions of bacteria. These microcapsules are approximately 35 mum in diameter, are composed of natural protein, and may be filled with a variety of actives. We describe the use of antimicrobial actives such as farnesol and methylparaben to demonstrate that their release by the degradative actions of axillary bacteria such as Corynebacterium minutissimum, C. urealyticum, and Staphylococcus epidermidis leads to their demise. These microcapsules may be used in consumer products such as deodorants and antiperpirants that may, under actual use conditions, control malodor.

Synthesis and characterization of polyurethane and poly(ether urethane) nanocapsules using a new technique of interfacial polycondensation combined to spontaneous emulsification.

Polyurethane polymers and poly(ether urethane) copolymers were chosen as drug carriers for alpha-tocopherol. This active ingredient is widely used as a strong antioxidant in many medical and cosmetic applications, but is rapidly degraded, because of its light, heat and oxygen sensitivity. Polyurethane and poly(ether urethane)-based nanocapsules were synthesized by interfacial reaction between two monomers. Interfacial polycondensation combined with spontaneous emulsification is a new technique for nanoparticles formation. Nanocapsules were characterized by studying particle size (150-500 nm), pH, yield of encapsulation and morphologies. Polyurethanes (PUR) were obtained from the condensation of diisocyanate (isophorone diisocyanate: IPDI) and polyol: 1,2-ethanediol (EG), 1,4-butanediol (BD), 1,6-hexanediol (HD). Poly(ether urethane) copolymers were obtained by replacing diols by polyethylene glycol oligomers (PEG) M(w) 200, 300, 400 and 600. Molecular weights of di- and polyols have a considerable influence on nanocapsules characteristics cited above. The increase of molecular weight of polyols tends to increase the mean size of nanocapsules from (232+/-3)nm using EG to (615+/-39)nm using PEG 600, and led to the apparition of a population of agglomerate particles. We also noted that the yield of encapsulation increases with the increase of polyol length (from 85.6 to 92.2% w/w). Microscopic observations confirmed particle size analysis, but cannot predict the membrane structure owing the small size of the particles.

[Dementia and extrapyramidal problems caused by long-term valproic acid]. / Démence et troubles extra-pyramidaux sous acide valproïque au long cours.

Among the side-effects attributed to valproic acid (VPA), the occurrence of Parkinsonian syndromes and cognitive impairment is very uncommonly reported. We describe five cases of reversible associated Parkinsonism. These cases were observed in epileptic patients, 57 to 74 years old, two women and three men. Extrapyramidal disorders appeared after various durations of treatment (from 6 months to 10 years). Dementia characterized by an insidious onset was associated in three cases and bradypsychia in one case. Brain pseudoatrophy was present in three patients. In all cases the signs and symptoms improved some weeks or months after discontinuation of VPA. In the literature some cases, usually in young adults or children, have been reported. In a prospective study, Armon et al. found various abnormal symptoms and signs related to motor and cognitive function impairment in patients with long-term VPA therapy. These side-effects may be related to a disturbance in the gabaergic pathways in the basal ganglia system. It is of interest to consider that delta 2-valproic acid, a metabolite of VPA, is especially accumulated in selected areas of the brain: the substantia nigra, superior and inferior colliculus, hippocampus and medulla.

Acquired immunity to TNF: effects on intestinal wound healing.

Increased concentrations of tumor necrosis factor (TNF) damage normal tissue and produce a shock-like syndrome--changes that can be prevented with anti-body-specific antisera. These findings suggest that TNF-stimulated immunity should protect normal tissue and promote wound healing. To test this hypothesis, 30 Fischer 344 rats (150-200 g) were serially immunized against TNF (20 micrograms/kg). Convalescent sera assayed (micro-ELISA) for circulating antibodies revealed titers (2.54 +/- 0.08 au) significantly higher (P < 0.00001) in immunized animals than in nonimmunized controls (0.11 +/- 0.06 au). Following this, 10 immunized (Group I), 10 nonimmunized (Group II), and 10 control rats underwent partial cecectomy with primary anastomosis. Animals from Groups I and II received TNF (25 micrograms/kg) while controls received saline intravenously on Postoperative Days 1, 3, and 5. Animals were then sacrificed to determine: (1) hydroxyproline content of the anastomosis, (2) mitochondrial respiratory control ratio, and (3) pyruvate dehydrogenase activity of the muscle. We found that (1) exposure to increased concentrations of TNF (Group II) depresses (P < 0.01) biologic markers of wound healing and (2) acquired immunity to TNF (Group I) eliminates this response. In conclusion, acquired immunity to TNF protects the healing intestinal anastomosis from the effects of exposure to increased levels of TNF.

Contaminated wounds: the effect of initial management on outcome.

Delayed primary closure has been advocated as the optimal method of management in the presence of wound contamination. The present study was performed to determine whether surgeons have accepted this standard. A total of 918 surgical wounds were evaluated and classified according to the level of contamination and type of wound management used. We found that 150 patients had a Class III or Class IV contaminated wound; however, only 21 per cent were treated with delayed primary closure. The 118 patients treated with primary closure and antibiotics had an aggregate wound infection rate of 27 per cent (Class III-29%; Class IV-24%). Only one (3%) of the wounds managed by delayed primary closure developed an infection. If infection did not occur, there was no difference in the length of stay between patients managed with primary closure and delayed primary closure. However, there was a significantly longer length of stay in the primary closure group if infection occurred. Benefit risk analysis of the patients with contaminated wounds confirmed that in this clinical setting, delayed primary closure remains the optimal method of management for the wound.

[Intramuscular hematoma simulating a pseudomalignant tumor]. / Hématome intramusculaire évoluant comme une tumeur pseudo-maligne.

One case of a large post-traumatic cystic haematoma of the thigh presenting with a pseudotumoral aspect, and resulting in a femoral filling defect and a spontaneous fracture 7 years later, is reported by the authors. Relationships between its pathophysiology and its consequences on bone are stressed.

[Surgery of the lower limbs in Duchenne's muscular dystrophy]. / La chirurgie des membres inférieurs dans la dystrophie musculaire de Duchenne.

Seventy-one children had surgical procedures on hips and/or knees and/or feet contractures before or after the age of loosing gait. Gait has been continued on 1 year and 7 months to 3 years and 8 months according to the evolving type of Duchenne Muscular Dystrophy (DMD). After analysis of results of the surgery upon contractures, surgical procedures have been determined for each joint. Before loosing gait, but when contractures were all present, surgery prolonged on gait without orthosis and relieved of physiotherapy. During the 6 months after loosing gait, surgery allowed to recover same walking ability more often with orthesis. After loosing gait, surgery gave a better comfort of life to the child and his family.