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GLP test facility management refers to the proper management and organization of a facility that conducts studies according to GLP regulations. Compliance with GLP regulations is necessary for data generated in such facilities to be accepted by regulatory authorities. According to GLP Principles, Test facility management (TFM) is responsible for a wide range of tasks and responsibilities to ensure the smooth and efficient operation of the facility. The framework in which the TFM operates within the Test Facility is certainly much more complex than in the early days of the GLP, and moreover it is unlikely that anything will change from a scientific and technological point of view in the years to come. Several aspects have changed from a scientific and technological point of view, and we know that innovation is very rapid. From the above considerations emerges the need for a major change in the performance of the TFM's role. • Test Facility Management (TFM) is responsible for GLP compliance of the test facility. • There is the need for a TFM more open to scientific and technological innovation. • TFM should be more open to the collaboration with other quality systems. [ABSTRACT FROM AUTHOR]

This work improves the systematic approach proposed in previous papers, aimed at defining design criteria specific for powder metallurgy (PM) parts subject to wear in application. Dry rolling-sliding tests have been performed on PM steels obtained under different process conditions, and the results have been used as a knowledge base in the proposed design procedure to evaluate the effect of the material variables (porosity and microhardness) and geometrical parameters (contact length) on wear resistance. The failure criterion considered here to ensure the functionality provides to compare the wear thickness with a value deriving from the dimensional tolerances. If the failure criterion is not matched, then a change in the material variables and/or geometrical parameters is proposed. The occurrence of plastic deformation and/or brittle contact at the surface region is also considered. Examples of application show that the most significant improvement is obtained by modifying both material variables and geometrical parameters. [ABSTRACT FROM AUTHOR]

Background.: Mask ventilation and tracheal intubation are basic techniques for airway management and mutually inclusive rescue measures to restore ventilation. The aim of this study was to compare the effectiveness of mask ventilation between two commonly used techniques of two-handed mask ventilation in obese unconscious apnoeic adults.Methods.: Eighty-one obese adults received mask ventilation after induction using C-E clamp and modified V-E clamp techniques in a randomized crossover manner. Mechanical ventilation was provided using a pressure-control mode, at a rate of 10 bpm, with an inspiratory-to-expiratory time ratio of 1:2 and a pre-set plateau airway pressure of 20 cm H 2 O. The primary outcome was expired tidal volume.Results.: The BMI for the subjects was 37 ( sd 4.9) kg m -2 . The failure rates for mask ventilation (tidal volume≤anatomical dead space) were 44% for the C-E technique and 0% for the V-E technique ( P <0.001). Tidal volume was significantly lower for the C-E than the V-E technique [371 ( sd 345) vs 720 (244) ml, P <0.001]. The peak airway pressures were 21 ( sd 1.5) cm H 2 O for the C-E technique and 21 (1.3) cm H 2 O for the V-E technique.Conclusions.: Mask ventilation using the modified V-E technique is more effective than with the C-E technique in unconscious obese apnoeic adults. Subjects who fail ventilation with the C-E technique can be ventilated effectively with the V-E technique.Clinical Trial Registration.: NCT02580526. [ABSTRACT FROM AUTHOR]

Abstract: Prolonged exposure to nicotine, as occurs in smokers, results in up-regulation of all the neuronal nicotinic acetylcholine receptor subtypes studied so far, the only differences residing in the extent and time course of the up-regulation. α6β2*-Nicotinic acetylcholine receptors are selectively enriched in the mesostriatal dopaminergic system and may play a crucial role in nicotine dependence. Here we show that chronic nicotine treatment (3mg/kg/day for two weeks, via s.c. osmotic minipumps) caused a significant decrease (36% on average) in the binding of [125I]Y0-α-conotoxin MII (a selective ligand for α6β2*-nicotinic acetylcholine receptors in this system) to all the five regions of the rat dopaminergic pathway analyzed in this study. After one week of withdrawal, binding was still lower than control in striatal terminal regions (namely the caudate putamen and the accumbens shell and core). In somatodendritic regions (the ventral tegmental area and the substantia nigra) the decrease was significant at the end of the treatment and recovered within one day of withdrawal. This effect was not due to displacement of [125I]Y0-α-conotoxin MII binding by residual nicotine. In fact the binding was not changed by 565 ng/g nicotine (obtained with a single injection of nicotine), a concentration much higher than that found in the brain of rats chronically treated with nicotine (240 ng/g). In addition, consistent with previous studies reporting an up-regulation of other subtypes of nicotinic acetylcholine receptors, we found that nicotine exposure significantly increased (40% on average) the binding of [125I]epibatidine (a non-selective agonist at most neuronal heteromeric nicotinic acetylcholine receptors) in three up to five regions containing only α-conotoxin MII-insensitive [125I]epibatidine binding sites, namely the primary motor, somatosensory and auditory cortices. In conclusion, this work is the first to demonstrate that α6β2*-nicotinic acetylcholine receptors, unique within the nicotinic acetylcholine receptor family, are down-regulated following chronic nicotine treatment in rat dopaminergic mesostriatal pathway, a finding that may shed new light in the complex mechanisms of nicotine dependence. [Copyright &y& Elsevier]

Infrared thermography in nondestructive testing provides images (thermograms) in which zones of interest (defects) appear sometimes as subtle signatures. In this context, raw images are not often appropriate since most will be missed. In some other cases, what is needed is a quantitative analysis such as for defect detection and characterization. In this paper, presentation is made of various methods of data analysis required either at preprocessing and/or processing images. References from literature are provided for briefly discussed known methods while novelties are elaborated in more details within the text which include also experimental results. [Copyright &y& Elsevier]

The article talks about bullous pemphigoid (BP) is a major autoimmune blistering skin disorder. It is mentioned that in BP majority of the autoantibodies (autoAbs) target the juxtamembranous extracellular NC16A domain of hemidesmosomal collagen XVII (COL17). The article discusses the connection between between BP and diabetes mellitus (DM) and how Dipeptidyl peptidase (DPP)-IV inhibitors causes BP.

This article describes a case control study evaluating the relationship between cutaneous melanoma and the residential use of pesticides. A hospital-based study of melanoma was conducted on subjects aged more than 18 years who were admitted in a hospital of central south Italy, Rome, during the period of May 2001 to May 2003. A total of 304 patient, with new histologically confirmed diagnosis of primary malignant cutaneous melanoma, were studied. In a multivariate model, considering sun exposure, phenotypic traits, number of nevi and the use of pesticides, duration of pesticides use was associated with 4 times the risk for melanoma.