Notes

[Pediatric intervertebral disc calcification: A hard-to-find cause of acquired torticollis. Case report].
splinting on mandibular overdentures.Facial allotransplantation (FA) is an emerging alternative modality following severe loss of hard and soft tissues. Although there are vast numbers of publications on the surgical aspects of this technique, limited information is available in the literature with regard to the long-term dental care of affected patients following postoperative stabilization and return to their locally based clinical milieu. The objective of this report is to review patient demographics, etiologies, structural graft components, immunosuppressive strategies, donor tissue pathogenicity, neurologic recovery, potential complications, and present clinical guidelines for dental management. Additionally, a brief discussion of the preparation of the donor mask, and cutaneous and intraoral images of allograft rejection have been provided.An alternative approach was used to increase the buccal vestibular depth of two edentulous patients, using free epithelialized palatal grafts. Two edentulous patients presented with shallow vestibules and inadequate keratinized tissue width in the mandibular anterior region. These sites were treated with vestibuloplasty followed by placement of an epithelialized palatal graft. In order to minimize graft movement and possible mechanical trauma to the area, the graft was covered with the buccal flap during the initial stages of healing. The patients maintained an increase in the vestibular depth as well as the keratinized tissue width at 14 months and 5 years postoperatively. Successful outcomes in terms of increase in vestibular depth can be achieved with the use of epithelialized palatal graft that is covered during the initial stage of healing. The dental practitioner fabricating the complete denture should be aware of the advantages offered by this alternative surgical technique.OBJECTIVES Hydrogen peroxide (HP) accounts for 15% of the total global chemical revenue. According to the National Institute of Occupational Safety and Health, the HP concentration immediately dangerous to human life or health is 75 ppm. Operators exposed to HP should pay attention when choosing the monitoring technique that should be specific and sensitive enough to discriminate the exposure levels from background concentrations. In order to assess the long- and short-term exposure to HP in disinfection processes, the authors compared 6 industrial hygiene monitoring methods to evaluate their efficiency in measuring airborne HP concentrations. MATERIAL AND METHODS Airborne HP concentrations were evaluated using an on-fiber triphenylphosphine solid-phase microextraction method, and they were compared with those obtained using a 13-mm Swinnex titanium oxysulfate filter holder and 4 portable direct-reading electrochemical sensors. A survey carried out in wood pulp bleaching, food and beverage disinfection processing, and in a hospital department to reduce the risk of spreading nosocomial infections, was performed during routine operations to access the risk of HP occupational exposure. RESULTS Through the generation of HP gaseous dynamic atmospheres (0.1-85 ppm), the authors evaluated the consistency of the results obtained using the 6 methods described. The monitoring campaigns showed that the increase in HP could be relatively high (until 67 ppm) in food and beverage processing. CONCLUSIONS In the authors' opinion, the current 8-h time-weighted average limits of 1 ppm for HP do not reflect the actual risk; a short-term exposure limit would, therefore, provide a much better protection. 2020;33(2)137-50. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.OBJECTIVES Various indirect or direct airway challenge tests are used to measure nonspecific bronchial hyper-responsiveness (NSBHR). The evaluation of NSBHR in diagnosing occupational asthma (OA) is performed, e.g., to monitor the specific inhalation challenge test (SICT). The aim of this study was to preliminarily compare the results of methacholine and mannitol inhalation challenge tests in SICT monitoring in bakers with work-related airway symptoms. MATERIAL AND METHODS Four bakery workers with a suspicion of OA underwent single-blind placebo-controlled SICTs involving workplace allergens, accompanied by the evaluation of NSBHR with mannitol and methacholine, both before and after SICTs. Clinical examinations, spirometry tests, skin prick tests (SPTs) to common aeroallergens and occupational allergens, as well as tests to determine serum specific IgE antibodies to occupational aeroallergens were also performed. RESULTS Positive SPTs results to occupational aeroallergens were found in all bakery workers, and specific IgE antibodies to flour were detected in 2 subjects. Three patients displayed positive SICT reactions. In all of these 3 patients, airway responsiveness to methacholine increased significantly. In 2 patients, airway reaction to mannitol was significant, whereas in 1 subject there was no increase in NSBHR after mannitol inhalation. The patient with a negative SICT result did not reveal any changes in NSBHR before and after the test, either to methacholine or mannitol. CONCLUSIONS The data obtained by the authors show that there is no clear correlation between the methacholine and mannitol inhalation challenge tests in SICT monitoring. Preliminary results indicate the need for further investigations to evaluate the usefulness of the mannitol challenge test in the diagnostics of OA. Int J Occup Med Environ Health. 2020;33(2)235-9. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.Cholinesterase inhibitors, the current frontline symptomatic treatment for Alzheimer's disease (AD), are associated with low efficacy and adverse effects. M1 muscarinic acetylcholine receptors (M1 mAChRs) represent a potential alternate therapeutic target; however, drug discovery programs focused on this G protein-coupled receptor (GPCR) have failed, largely due to cholinergic adverse responses. BMS-387032 molecular weight Employing novel chemogenetic and phosphorylation-deficient, G protein-biased, mouse models, paired with a toolbox of probe molecules, we establish previously unappreciated pharmacologically targetable M1 mAChR neurological processes, including anxiety-like behaviors and hyper-locomotion. link2 By mapping the upstream signaling pathways regulating these responses, we determine the importance of receptor phosphorylation-dependent signaling in driving clinically relevant outcomes and in controlling adverse effects including 'epileptic-like' seizures. We conclude that M1 mAChR ligands that promote receptor phosphorylation-dependent signaling would protect against cholinergic adverse effects in addition to driving beneficial responses such as learning and memory and anxiolytic behavior relevant for the treatment of AD.Ferroptotic death is the penalty for losing control over three processes-iron metabolism, lipid peroxidation and thiol regulation-that are common in the pro-inflammatory environment where professional phagocytes fulfill their functions and yet survive. We hypothesized that redox reprogramming of 15-lipoxygenase (15-LOX) during the generation of pro-ferroptotic signal 15-hydroperoxy-eicosa-tetra-enoyl-phosphatidylethanolamine (15-HpETE-PE) modulates ferroptotic endurance. Here, we have discovered that inducible nitric oxide synthase (iNOS)/NO•-enrichment of activated M1 (but not alternatively activated M2) macrophages/microglia modulates susceptibility to ferroptosis. Genetic or pharmacologic depletion/inactivation of iNOS confers sensitivity on M1 cells, whereas NO• donors empower resistance of M2 cells to ferroptosis. In vivo, M1 phagocytes, in comparison to M2 phagocytes, exert higher resistance to pharmacologically induced ferroptosis. This resistance is diminished in iNOS-deficient cells in the pro-inflammatory conditions of brain trauma or the tumour microenvironment. The nitroxygenation of eicosatetraenoyl (ETE)-PE intermediates and oxidatively truncated species by NO• donors and/or suppression of NO• production by iNOS inhibitors represent a novel redox mechanism of regulation of ferroptosis in pro-inflammatory conditions.The retrograde transport inhibitor Retro-2 has a protective effect on cells and in mice against Shiga-like toxins and ricin. Retro-2 causes toxin accumulation in early endosomes and relocalization of the Golgi SNARE protein syntaxin-5 to the endoplasmic reticulum. The molecular mechanisms by which this is achieved remain unknown. Here, we show that Retro-2 targets the endoplasmic reticulum exit site component Sec16A, affecting anterograde transport of syntaxin-5 from the endoplasmic reticulum to the Golgi. The formation of canonical SNARE complexes involving syntaxin-5 is not affected in Retro-2-treated cells. By contrast, the interaction of syntaxin-5 with a newly discovered binding partner, the retrograde trafficking chaperone GPP130, is abolished, and we show that GPP130 must indeed bind to syntaxin-5 to drive Shiga toxin transport from the endosomes to the Golgi. We therefore identify Sec16A as a druggable target and provide evidence for a non-SNARE function for syntaxin-5 in interaction with GPP130.Ferroptosis is widely involved in degenerative diseases in various tissues including kidney, liver and brain, and is a targetable vulnerability in multiple primary and therapy-resistant cancers. Accumulation of phospholipid hydroperoxides in cellular membranes is the hallmark and rate-limiting step of ferroptosis; however, the enzymes contributing to lipid peroxidation remain poorly characterized. Using genome-wide, CRISPR-Cas9-mediated suppressor screens, we identify cytochrome P450 oxidoreductase (POR) as necessary for ferroptotic cell death in cancer cells exhibiting inherent and induced susceptibility to ferroptosis. By genetic depletion of POR in cancer cells, we reveal that POR contributes to ferroptosis across a wide range of lineages and cell states, and in response to distinct mechanisms of ferroptosis induction. Using systematic lipidomic profiling, we further map POR's activity to the lipid peroxidation step in ferroptosis. Hence, our work suggests that POR is a key mediator of ferroptosis and potential druggable target for developing antiferroptosis therapeutics.Although viruses are extremely diverse in shape and size, evolution has led to a limited number of viral classes or lineages, which is probably linked to the assembly constraints of a viable capsid. Viral assembly mechanisms are restricted to two general pathways, (i) co-assembly of capsid proteins and single-stranded nucleic acids and (ii) a sequential mechanism in which scaffolding-mediated capsid precursor assembly is followed by genome packaging. Cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), which are revolutionizing structural biology, are central to determining the high-resolution structures of many viral assemblies as well as those of assembly intermediates. This wealth of cryo-EM data has also led to the development and redesign of virus-based platforms for biomedical and biotechnological applications. link3 In this Review, we will discuss recent viral assembly analyses by cryo-EM and cryo-ET showing how natural assembly mechanisms are used to encapsulate heterologous cargos including chemicals, enzymes, and/or nucleic acids for a variety of nanotechnological applications.
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