Pyoderma gangrenosum: an updated review Ruocco, E; Sangiuliano, S; Gravina, AG ...
Journal of the European Academy of Dermatology and Venereology,
September 2009, Letnik:
23, Številka:
9
Journal Article
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Pyoderma gangrenosum is a rare, ulcerative, cutaneous condition. First described in 1930, the pathogenesis of pyoderma gangrenosum remains unknown, but it is probably related to a hyperergic ...reaction. There are various clinical and histological variants of this disorder. Pyoderma gangrenosum often occurs in association with a systemic disease such as inflammatory bowel disease, rheumatologic disease, paraproteinaemia, or haematological malignancy. The diagnosis, mainly based on the clinical presentation and course, is confirmed through a process of elimination of other causes of cutaneous ulcers. Local treatment may be sufficient for mild disease, while for severe cases, systemic immunosuppressants are the mainstay. Long‐term treatment with these agents is often required, but this can expose patients to adverse side‐effects.
Conflicts of interest
None declared.
Abstract Introduction Several gender differences have been reported in Parkinson's Disease (PD). We evaluated the burden of non-motor symptoms (NMS) in PD and the possible gender differences in their ...occurrence. Methods The FRAGAMP study is a large multicenter case-control study. PD patients and controls underwent a face-to-face interview and a neurological examination performed by trained neurologists. Presence of NMS was investigated using a standardized questionnaire; cognitive impairment and depression were assessed using the Mini Mental State Examination and the Hamilton Depression Rating Scale respectively. Results 585 PD patients (59.5% men) and 481 controls (34.9% men) were enrolled in the study. All NMS were significantly more frequent among PD patients than controls. PD women showed a significantly higher frequency of depression and urinary disturbances than parkinsonian men; a close frequency among PD women and men was recorded for hallucination, cognitive impairment and sleep disorders. Nonetheless, with respect to the control population, according to logistic regression stratified by sex and adjusted by age, PD men showed a stronger positive significant association with almost all NMS compared to women, excepting for urinary disturbances. The strongest association among PD men was recorded for cognitive impairment (adjusted OR 5.44 for men and 2.82 for women) and depression (adjusted OR 30.88 for men and 12.72 for women). Conclusions With respect to the general population, presence of NMS was stronger associated with male gender. Our data suggest that the presence of NMS among PD men is more strictly due to the neurodegenerative processes related to PD.
In an airplane, varieties of stress factors superimpose themselves and generate unusual failure mechanisms to electronics. Additional and very specific difficulties are given in aircraft electronics ...supply chains, which mainly result from its characteristic as a low-volume production. This article highlights these issues more in detail and shows some illustrative failure analysis and failure anamnesis case studies from civil aircraft electronics. This work has been made under the precondition that our clients requested anonymization. Therefore, in some of the case studies, no photographs or only small parts of them are shown.
Several lines of evidence point to a compromised proteostasis associated with a reduction of the Ubiquitin Proteasome System (UPS) activity in patients affected by Alzheimer's Disease (AD) and ...suggest that the amyloid β peptide (Aβ) is an important player in the game. Inspired also by many reports, underlining the presence of ubiquitin (Ub) in the amyloid plaques of AD brains, here we set out to test whether Ub may bind the Aβ peptide and have any effect on its clearance pathways. By using an integrated array of MALDI-TOF/UPLC-HRMS, fluorescence, NMR, SPR, Microscale Thermophoresis (MST) and molecular dynamics studies, we consistently demonstrated that Aβ40 binds Ub with a 1 : 1 stoichiometry and
K
d
in the high micromolar range. In particular, we show that the N-terminal domain of the Aβ peptide (through residues D1, E3 and R5) interacts with the C-terminal tail of Ub (involving residues K63 and E64), inducing the central region of Aβ (
14
HQKLVFFAEDVGSNK
28
) to adopt a mixed α-helix/β-turn structure. ELISA assays, carried out in neuroblastoma cell lysates, suggest that Aβ competitively binds Ub also in the presence of the entire pool of cytosolic Ub binding proteins. Ub-bound Aβ has a lower tendency to aggregate into amyloid-like fibrils and is more slowly degraded by the Insulin Degrading Enzyme (IDE). Finally, we observe that the water soluble fragment Aβ1-16 significantly inhibits Ub chain growth reactions. These results evidence how the non-covalent interaction between Aβ peptides and Ub may have relevant effects on the regulation of the upstream events of the UPS and pave the way to future
in vivo
studies addressing the role played by Aβ peptide in the malfunction of proteome maintenance occurring in AD.
Appetite for ubiquitin: a gushy travel companion in the intracellular journey of the amyloid β peptide.
Orthognathic surgery and the Le Fort I osteotomy result in noticeable alterations to the nasal/nasolabial anatomy. The alar base cinch technique is a surgical technique to control lateralization of ...the base of the nose and is well described in the literature. The aim of this scoping review was to identify every unique alar cinch suture technique reported in orthognathic surgery and to propose a classification for the different techniques described. A search was conducted in the PubMed, Cochrane Library, and Scopus electronic databases covering the period May 1980 to July 2020, which identified 10 articles that were eligible for this review. Among these, there were several proposals for modifications to the technique, and different studies to show the effectiveness of one type among all others. Despite observing multiple techniques and variations of these while performing this review, the lack of a classification for alar cinch suture was noticed. Therefore, we propose a classification of the alar cinch suture that includes four types, which cover all of the cinching techniques described. It is believed that the use of a standardized classification may be useful to avoid duplicate publishing of techniques and to set a standard for further studies.
Abstract We investigated the antimicrobial resistance profile and the occurrence of Klebsiella pneumoniae carbapenemase (KPC)–producing Gram-negative rods in sewage samples obtained from a Brazilian ...teaching hospital and from the wastewater treatment plant (WWTP) that receives it for treatment. We identified multidrug-resistant bacteria as well as KPC-2–producing Aeromonas spp. and several Enterobacteriaceae species, including Kluyvera spp., in the hospital effluent and in different sites of the WWTP. Most isolates showed the blaKPC-2 gene harbored on a transposon that was carried by conjugative plasmids. The presence of KPC production among Aeromonas spp., Kluyvera spp., and other Enterobacteriaceae indicates the adaptability of such isolates to aquatic environments, not only in the hospital effluent but also throughout the WWTP. Although secondary treatment seems to decrease the amount of KPC producers in sewage, multidrug-resistant isolates are continually disposed in the urban river. Thus, sewage treatment regulations are urgently needed to decelerate the evolution of antimicrobial resistance beyond hospitals.
Liberalization and privatization have made the regulatory environment more market-friendly throughout the OECD. However using a large new dataset on product market regulation, we show that regulatory ...policies in OECD nations have become more dissimilar in relative terms, even as all nations have liberalized. This seemingly contradictory finding is explained by different starting points and different reform speeds. Our data also show that this divergence in the regulatory settings lines up with the divergent growth performance of OECD nations, in particular the poor performance of large Continental economies relative to that of the US. The data, which tracks various types of product market regulation in manufacturing and service industries for 18 OECD economies over the past two decades, allows us to explore this link in detail. We find that productivity growth is boosted by reforms that promote private corporate governance and competition (where these are viable). Moreover, our detailed findings suggest how product market regulation and productivity growth are linked. In manufacturing, the productivity gains from liberalization are greater the further a given country is from the technology leader. This indicates that entry-limiting regulation may hinder the adoption of existing technologies, possibly by reducing competitive pressures, technology spillovers, or the entry of new high-tech firms. These results offer an interpretation of poor Continental performance. Strict product market regulations -- and lack of regulatory reforms -- appear to underlie the meagre productivity performance of some European countries, especially in those industries where Europe has accumulated a technology gap (e.g. industries producing or using information and communication technologies).
In this paper, a new perspective of food packaging design is proposed by using the Life Cycle Assessment (LCA) approach, in which shelf life and food loss probability were taken into account. The ...study focused on twenty-four scenarios of packaging of a ripened cheese obtained from sheep milk, in order to analyze the environmental implications of different packaging systems in terms of potential food loss. The aim is to provide an eco-indicator able to quantify the environmental indirect effects related to the different choices in the food packaging. Results highlighted that, by considering only the direct inputs and outputs of the packaging system, thinner and recyclable packaging materials sealed in air are more sustainable from an environmental point of view. On the contrary, if indirect effects of food loss probability are also taken into account (e.g. production and transport of cheese in order to reconstruct the stockpile), multilayer systems under modified headspace conditions are preferred packaging solutions. This is consequence of the fact that cheese production brings about high environmental impacts if compared to the other phases of the life cycle, therefore, the environmental implications of the choices adopted for the packaging phase are more affected from the capacity of reducing food losses than from the production and disposing of packaging materials.
•A new perspective of food packaging design is proposed.•The approach utilized was based on Life Cycle Assessment (LCA).•The novelty consists of taking into account both product shelf life and food loss probability.•The best packaging are able to guarantee high shelf life and low food loss probability.
Objectives The aim of this study was to evaluate the presence of carbapenemases in a Klebsiella pneumoniae collection and the performance of the modified Hodge test (MHT) to correctly identify this ...phenotype. Methods Twenty-eight K. pneumoniae clinical isolates with reduced susceptibility to carbapenems were evaluated. Antimicrobial susceptibility and molecular typing were performed by agar dilution and PFGE, respectively. The MHT was performed using both standard and high inoculum of test organisms. Imipenem hydrolysis was investigated by spectrophotometric assays and carbapenemase-encoding genes were identified by PCR and amplicon sequencing. Porin loss was investigated by both PCR and SDS–PAGE. Results Susceptibility rates for imipenem, meropenem and ertapenem were 93%, 57% and 11%, respectively. The PFGE analysis showed seven unrelated genotypes. By testing standard inoculum and ertapenem or meropenem discs, 25% (n = 7) and 21% (n = 6) of the isolates were classified as carbapenemase producers, respectively. When a higher inoculum was employed, these rates increased to 54% (n = 15) and 43% (n = 12), respectively. No imipenem hydrolysis was detected. PCRs identified blaCTX-M in 27 (96%) isolates, of which 2 isolates also carried blaGES-1. SDS–PAGE and PCR assays revealed that all isolates had lost at least one outer membrane protein, except for a single isolate that was found to express both OmpK35 and OmpK36. Conclusions False detection of carbapenemase production was observed by the MHT possibly as a result of extended-spectrum β-lactamase (ESBL) production coupled with porin loss as reported before. Clinical laboratories must be aware of this fact, especially in geographical areas where ESBL-producing isolates are highly prevalent.
Identification of patient selection criteria and understanding of the potential mechanisms involved in the development of resistance are crucial for an appropriate and successful design of clinical ...trials with anti-insulin-like growth factor (IGF)-1R therapies. Few Ewing's sarcomas are highly sensitive to IGF-1R targeting and understanding the reason why, may hold the secret to improve successful treatments. In this paper, we show that a major mechanism of resistance to highly specific inhibitors of IGF-1R, either antibodies or tyrosine kinase inhibitors may involve enhanced insulin receptor (IR)-A homodimer formation and IGF-2 production. Resistant cells are able to switch from IGF-1/IGF-1R to IGF-2/IR-A dependency to maintain sustained activation of AKT and ERK1/2, proliferation, migration and metastasis. These cells also showed higher proliferative response to insulin, in keeping with a switch towards insulin pathways sustaining proliferation and malignancy, rather than metabolism. Our findings demonstrate a role for IR-A in eliciting intrinsic and adaptive resistance to anti-IGF-1R therapies. Thus, we indicate that tumors with low IGF-1R:IR ratio are unlikely to greatly benefit from anti-IGF-1R therapies and that the efficacy of anti-IGF-1R therapies should be evaluated in relationship to the IR-A:IGF-1R ratio in cancer cells. Moreover, we provide evidences supporting IR-A as an important target in sarcoma therapy.
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