Description of the relationship between NOHL classification in drug-induced sleep endoscopy and initial AHI in patients with moderate to severe OSAS, and evaluation of the results obtained with oral appliance therapy

Descrizione della relazione tra Classificazione NOHL definita durante la Drug-Induced Sleep Endoscopy e AHI iniziale in pazienti con OSAS da moderato a grave, e valutazione dei risultati ottenuti con dispositivi orali

Extra-small gold nanospheres decorated with a thiol-functionalized biodegradable and biocompatible linear polyamidoamine as nanovectors of anticancer molecules

Gold nanoparticles are elective candidate for cancer therapy. Current efforts are devoted to developing innovative methods for their synthesis. Besides, understanding their interaction with cells have become increasingly important for their clinical application. This work aims to describe a simple approach for the synthesis of extra-small gold nanoparticles for breast cancer therapy. In brief, a biocompatible and biodegradable polyamidoamine (named AGMA1-SH), bearing 20%, on a molar basis, thiol-functionalized repeat units, is employed to stabilize and coat extra-small gold nanospheres of different sizes (2.5, 3.5, and 5 nm in gold core), and to generate a nanoplatform for the link with Trastuzumab monoclonal antibody for HER2-positive breast cancer targeting. Dynamic light scattering, transmission electron microscopy, ultraviolet visible spectroscopy, X-ray powder diffraction, circular dichroism, protein quantification assays are used for the characterization. The targeting properties of the nanosystems are explored to achieve enhanced and selective uptake of AGMA1-SH-gold nanoparticles by in vitro studies against HER-2 overexpressing cells, SKBR-3 and compared to HER-2 low expressing cells, MCF-7, and normal fibroblast cell line, NIH-3T3. In vitro physicochemical characterization demonstrates that gold nanoparticles modified with AGMA1-SH are more stable in aqueous solution than the unmodified ones. Additionally, the greater gold nanoparticles size (5-nm) is associated with a higher stability and conjugation efficiency with Trastuzumab, which retains its folding and anticancer activity after the conjugation. In particular, the larger Trastuzumab functionalized nanoparticles displays the highest efficacy (via the pro-apoptotic protein increase, anti-apoptotic components decrease, survival-proliferation pathways downregulation) and internalization (via the activation of the classical clathrin-mediated endocytosis) in HER-2 overexpressing SKBR-3 cells, without eliciting significant effects on the other cell lines. The use of biocompatible AGMA1-SH for producing covalently stabilized gold nanoparticles to achieve selective targeting, cytotoxicity and uptake is completely novel, offering an important advancement for developing new anticancer conjugated-gold nanoparticles

From exercise intolerance to functional improvement: The second wind phenomenon in the identification of McArdle disease

McArdle disease is the most common of the glycogen storage diseases. Onset of symptoms is usually in childhood with muscle pain and restricted exercise capacity. Signs and symptoms are often ignored in children or put down to 'growing pains' and thus diagnosis is often delayed. Misdiagnosis is not uncommon because several other conditions such as muscular dystrophy and muscle channelopathies can manifest with similar symptoms. A simple exercise test performed in the clinic can however help to identify patients by revealing the second wind phenomenon which is pathognomonic of the condition. Here a patient is reported illustrating the value of using a simple 12 minute walk test.RSS is funded by Ciências sem Fronteiras/CAPES Foundation. The authors would like to thank the Association for Glycogen Storage Disease (UK), the EUROMAC Registry funded by the European Union, the Muscular Dystrophy Campaign, the NHS National Specialist Commissioning Group and the Myositis Support Group for funding

ACTH-producing tumorlets and carcinoids of the lung: clinico-pathologic study of 63 cases and review of the literature.

Adrenocorticotropic hormone (ACTH)-secreting lung carcinoids represent the principal cause of ectopic Cushing syndrome, but the prevalence of ACTH expression and the association between ACTH production and Cushing syndrome in lung carcinoids have scarcely been investigated. In addition, available information on the prognostic meaning of ACTH production is controversial. The aims of this multicentric retrospective study, also including a review of the literature, were to describe the clinico-pathologic features of ACTH-producing lung carcinoids, to assess recurrence and specific survival rates, and to evaluate potential prognostic factors. To identify ACTH production in 254 unselected and radically resected lung carcinoids, we used a double approach including RT-PCR (mRNA encoding for pro-opiomelanocortin) and immunohistochemistry (antibodies against ACTH and β-endorphin). Sixty-three (24.8%) tumors produced ACTH and 11 of them (17.4%), representing 4.3% of the whole series, were associated with Cushing syndrome. The median follow-up time was 71 months. The 10-year overall and specific survival rates were 88.5% and 98.2%, respectively, with difference neither between functioning and nonfunctioning tumors nor between ACTH-positive and ACTH-negative carcinoids. At univariate analysis, histological type (typical or atypical) and Ki67 index significantly correlated with tumor recurrence. The literature review identified 172 previously reported patients with functioning ACTH-secreting lung carcinoids, and the meta-analysis of survival showed that 92% of them were alive after a mean follow-up time of 50 months. Our results demonstrate that ACTH-producing lung carcinoids are not rare, are not always associated with Cushing syndrome, and do not represent an aggressive variant of lung carcinoid

Public service markets: their economics, institutional oversight and regulation

Public services in the UK have been transformed over the past 25 years with the introduction of market oriented solutions into their provision. This has been characterised by a shift away from state provision to independent providers, and by the introduction of competition and choice. This shift was partly ideologically motivated and partly driven by budget cutting considerations following the financial crisis. As such it has been lacking a comprehensive economic justification or method of analysis. It is now commonly accepted that the language of economic markets is essential to frame arguments about how effectively public services are achieving their intended outcomes. Using market language and concepts may not always be comfortable for those from a traditional policy-making background. It can nevertheless be very useful when designing investigations into the effectiveness and value for money in the mechanisms of delivery of such services, whenever these services entail a degree of user choice as is currently the case in large parts of health, social care and education (referred to as competition in the market). Our paper wants to provide a conceptual basis on the way of thinking in these terms. We provide a description of the current state and then comment on the desirability of this quasi market approach. Uniquely in the literature, we analyse the expected and desired developments by distinguishing between choice and compulsory merit goods. In choice merit goods markets many users are unable to choose effectively because of the existence of a number of demand side or supply side market failures. Moreover, conflicts may exist between how service users actually make choices, and policy objectives such as universality or equity which may not be achieved simply by ‘leaving it to the market’. The users of compulsory merit goods are typically a minority and unable to internalise the full social benefits of their actions; hence it may be welfare-enhancing for society to coerce them ‘consume’ these services. As choice cannot be an objective, the commissioning (competition for the market) or direct provision by the state of such goods may meet public policy objectives more effectively than the market mechanism alone. Building on these foundations the paper discusses when public service markets are likely to be an effective method of achieving public policy objectives, and when they may not be. Our paper analyses the implications for the institutional and legal framework, funding oversight and regulation of public service markets as a result of their transformation into quasi-markets. The paper concludes with some suggestions for those charged with overseeing public service markets in practice based on this analysis

Angioside: The role of Angiogenesis and Hypoxia in Lung Neuroendocrine Tumours According to Primary Tumour Location in Left or Right Parenchyma

Well-differentiated lung neuroendocrine tumours (Lu-NETs), classified as typical (TC) and atypical (AC) carcinoids, represent 30% of NETs. Angiogenesis plays an essential role in NET development and progression. A higher vascular network is a marker of differentiation, with positive prognostic implications. Materials and Methods: We retrospectively evaluated microvessel density (MVD) by CD34 immunohistochemical (IHC) staining and hypoxia by IHC staining for Hypoxia-inducible factor 1α (HIF-1α), comparing right- and left-lung parenchyma in 53 lung NETs. Results: The median age was 66 years (39–81), 56.6% males, 24.5% AC, 40.5% left-sided tumours and 69.8% TNM stage I. The mitotic count was <2/10 per 10 HPF in 79.2%, and the absence of necrosis in 81.1%, 39.6% with Ki67, was ≤2%. The MVD, the number of vessels and the average vessel area median values were significantly higher in the right than the left parenchyma (p: 0.025, p: 0.019, p: 0.016, respectively). Hypoxia resulted present in 14/19 (73.6%) left tumours and in 10/20 (50%) right tumours in the parenchyma (p: 0.129). Conclusions: This study suggests a biological rationale for a different angiogenesis and hypoxia according to the Lu-NETs’ location. In our study, left primary tumours were less vascularized and most likely to present hypoxia than right primary tumours. This finding could have potentially useful prognostic and predictive implications for Lu-NETs

high resolution study of epigenetic processes new insights into methylation and demethylation

n/