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O’Neill’s recent Review on Antimicrobial Resistance expressed the view that by 2020 high-income countries should make it mandatory to support antimicrobial prescribing with rapid diagnostic evidence whenever possible.

•Two main strategies are commonly used for p-PBPK models building.•More and more time-varying parameters specific to pregnancy in PBPK models.•Data required to better characterize placental transfers and fetal distribution.•p-PBPK models are key tools for fetal exposure assessment in a DOHaD context.

ABSTRACTHaemophilus influenzaeis a significant causative agent of respiratory tract infections (RTI) worldwide. The development of a rapid H. influenzaediagnostic assay that would allow for the implementation of infection control measures and also improve antimicrobial stewardship for patients is required. A number of nucleic acid diagnostics approaches that detect H. influenzaein RTIs have been described in the literature; however, there are reported specificity and sensitivity limitations for these assays. In this study, a novel real-time PCR diagnostic assay targeting the smpBgene was designed to detect all serogroups of H. influenzae. The assay was validated using a panel of well-characterized Haemophilusspp. Subsequently, 44 Haemophilusclinical isolates were collected, and 36 isolates were identified as H. influenzaeusing a gold standard methodology that combined the results of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and a fucKdiagnostic assay. Using the novel smpBdiagnostic assay, 100% concordance was observed with the gold standard, demonstrating a sensitivity of 100% (95% confidence interval [CI], 90.26% to 100.00%) and a specificity of 100% (95% CI, 63.06% to 100.00%) when used on clinical isolates. To demonstrate the clinical utility of the diagnostic assay presented, a panel of lower RTI samples (n= 98) were blindly tested with the gold standard and smpBdiagnostic assays. The results generated were concordant for 94/98 samples tested, demonstrating a sensitivity of 90.91% (95% CI, 78.33% to 97.47%) and a specificity of 100% (95% CI, 93.40% to 100.00%) for the novel smpBassay when used directly on respiratory specimens.

Reference scattering curves for polarization and intensity produced by aggregates and agglomerates of ethylene and kerosene soot are obtained for scattering angles in the 10–170° range. The polarization measurements were obtained with the Propriétés Optiques des Grains Astronomiques et Atmosphériques instrument for particles that levitate in microgravity during parabolic flights and on the ground by an air draught technique. The intensity measurements were obtained also on the ground with a Laboratoire de Metéorologie Physique nephelometer. The maximum polarization is of the order of 80% at a scattering angle of 80° at λ = 632.8 nm and approximately 75% at an angle of 90° at λ = 543.5 nm. The polarization increases by approximately 10% when the size of the agglomerate increases from 10 μm to a few hundred micrometers. The intensity curve exhibits a strong increase at small scattering angles. These reference curves will be used in the near future for the detection of stratospheric soot by remote-sensing measurement techniques.

The cytochemical demonstration of acetylcholinesterase is theoretically and experimentally evaluated with a model system. The model is an artificial proteic membrane in which acetylcholinesterase homogeneously is immobilized chemically by a bifunctional agent, glutaraldehyde. The copper-thiocholine histochemical method is studied kinetically and the system is simulated by computer calculations based on experimental kinetic parameters and numerical analysis methods. In addition, the corresponding electron micrographs are presented. These studies lead to the conclusions that the system is ruled by diffusional constraints and that enzyme distribution and repartition of the insoluble electron dense product are not circumscribed by any specific conditions.

A histochemical model dealing with an immobilized bienzyme system (glucose oxidase-peroxidase) is presented. The model is an artificial proteic membrane obtained by a previously described co-cross-linking process. The kinetic properties of free and immobilized horseradish peroxidase were studied when 3,3'-diaminobenzidine is used as a hydrogen donor substrate. A new direct method was developed for immobilized enzyme activity measurements. Computer simulation based on experimental kinetic parameters was performed in order to discuss electron microscopy results. By changing diffusion limitations, various profiles of insoluble product were visualized inside the proteic film and no geometrical similarity was seen between enzyme distributions and insoluble osmiophilic product patterns.

Over a period of 6 years, we have treated 1,310 patients in 2,284 sessions using a neodymium–yttrium aluminum garnet laser. Indications are more often palliative than curative, with the primary goal to relieve an obstructed airway in a single treatment. The effectiveness of such resections is widely recognized, but indications for such a technique with its limitations deserve emphasis. The use of a rigid bronchoscope is important to provide satisfactory operating conditions and especially to manage hemorrhage rapidly while maintaining a satisfactory airway.

The mitochondrial derivative of the sperm cell of the Gastropod Helix is endowed with a compartment loaded with glycogen (Personne et André, 1964). The aim of this work is to establish whether this mitochondrial glycogen is synthesized in the mitochondrial derivative itself or elsewhere in the cell. For this purpose, living sperm were first incubated in a medium containing glucose 1-phosphate, then fixed, sectioned, and stained specifically for polysaccharides by the phosphotungstic acid technique or the periodic acid-thiosemicarbazide-silver proteinate technique. Comparison with controls shows that a synthesis of glycogen occurred during the time of incubation. It can be inferred from this result that an amylophosphorylase system controlling the metabolism of polysaccharides is present in the mitochondrial derivative itself. Results obtained with the iodine technique indicate that the original glycogen molecules are elongated during the experiment. It seems probable that the amylophosphorylase system demonstrated here accounts for at least a part of the proteinaceous coat morphologically detectable around each individual glycogen particle.

With the periodic acid-thiosemicarbazide-silver proteinate procedure for the detection of polysaccharides in thin sections, glycogen is localized in the cavities of centrioles and basal bodies, within the axoneme (and surrounding it), in mitochondria, and in the "packing" cytoplasm of the middle piece of spermatozoa of several invertebrate and vertebrate species. The cytochemical localization of glycogen is verified by extraction with α-amylase solution. These findings establish the existence of stored glycogen in sperm. The polysaccharide presumably serves as an endogenous source of energy in the absence of extracellular metabolites, under either aerobic or anaerobic conditions. Other hypotheses on the physiological significance of intracellular glycogen stores in sperm are discussed. Sperm that store glycogen contain some enzymes of glycogen metabolism. In the presence of glucose-1-phosphate, ATP, and Mg++ ions, an amylophosphorylase catalyzes the in vivo synthesis of glycogen. The newly formed product resembles γ-particles, and is digestible with α-amylase.

By electron-microscope cytochemistry, succinate- and NADH2-tetrazolium reductase activities have been demonstrated in spermatozoa of the pulmonate gastropods, Testacella and Helix. Enzyme reaction product is restricted to the mitochondrial compartment named the secondary helix; this compartment is derived from the matrix of typical mitochondria. ‘Mitochondrial metamorphosis’ during spermiogenesis accomplishes the segregation of dehydrogenases to this matrical compartment.

The morphology of “primitive” and “modified” sperm types in molluscs is reviewed. The cytochemical localizations of glycogen reserves and enzymes related to the metabolism of glyocogen are discussed in relation to their roles in sperm motility and the iiltrastructure of the mid-piece of molluscan spermatozoa.

A new technique for the management of tracheal or bronchial lesions (tumours or stenosis) using the NdYAG laser and bronchoscopy, was used in 55 patients without complications. The anaesthetic problems are discussed. In some circumstances the procedure may be performed using sedation and topical anaesthesia. In most, general anaesthesia was used, controlled ventilation being achieved through the bronchoscope using a modification of the Sander's injector with a mixture of 50% nitrogen and oxygen to avoid the risk of fire.