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It is known that lymphocytopenia is one of the most negative biomarkers in cancer patients, being an expression of cancer-related immunosuppression. Today it is known that, despite its complexity, the antitumor immunity is mainly mediated by dendritic cell-T lymphocyte system and suppressed by the macrophage-regulatory T lymphocyte system. Then, lymphocyte-to-monocyte ratio (LMR) has been proven to represent a more appropriate prognostic clinical index than the simple lyphocytopenia alone. Because of the fundamental role of lymphocytes in mediating tumor cell destruction, the correction of cancer-related lymphocytopenia could influence the clinical history of the neoplastic disease. At present, the only cytokine able to induce a clear in vivo lymphocytosisis IL-2. However, it has been demonstrated that the immune system is physiologically under a neuroendocrine control, and that the pineal hormone MLT may stimulate T lymphocyte proliferation and activation. On these bases, we have evaluated the effect of highdose MLT therapy in metastatic solid tumor patients with persistent lymphocytopenia and abnormally low values of LMR. The study included 14 patients, and the results were compared to those found in a control group of 20 lymphocytopenic untreatable metastatic cancer patients treated with the only best supportive care alone. Patients received MLT at a dose of 100 mg/day orally in the evening for 3 consecutive months. Lymphocyte mean count increases on MLT therapy, and the values observed after two months of therapy were significantly higher than the pretreatment ones, with a normalization of lymphocyte number in 4/14 (29%) patients, whereas no spontaneous lymphocyte rise occurred in the control group. On the other hand, monocyte count rapidly diminished on MLT therapy, and LMR mean values observed after only one month of treatment was significantly higher than that found prior to therapy, whereas it significantly decreases in controls. This preliminary study shows that high-dose MLT may improve the immune status of cancer patients, and be effective in the treatment of disseminated cancer-related lymphocytopenia.

Background: The endogenous signals leading to microglial activation represent central components of neuroinflammatory cascades. Given ATP release accompanies mechanical strain to neural tissue, and the P2X7R for ATP is expressed on microglial cells, we examined the morphological and molecular consequences of P2X7R stimulation in vivo and in vitro in detail to enhance understanding of the response. Methods: IL-1β release was determined with ELISA. Expression of mRNA used qPCR. ATP release was determined with the luciferin/luciferase assay while fura-2 indicated cytoplasmic calcium. Microglial migration used Boyden chambers. Morphological changes were quantified from Iba1-immunostained cells. Results: Sholl analysis of Iba1-stained cells showed retraction of microglial ramifications one day after injection of P2X7R agonist BzATP into mouse retinae. Mean branch length also decreased, while cell body size and expression of Nos2, Tnfa, Arg1, Chil3 increased. BzATP induced similar morphological changes in ex vivo tissue isolated from Cx3CR1-GFP mice, suggesting cell recruitment was unnecessary. Primary microglial cultures were developed to investigate the autonomous nature of the response. Isolated microglial cells expressed P2X7R, while increased intracellular Ca 2+ triggered by BzATP and blocked by antagonist A839977 confirmed functional expression. BzATP induced process retraction and cell body enlargement within minutes in isolated microglial cells, and increased expression of Nos2 and Arg1 . BzATP both increased expression of IL-1β, and triggered a substantial release, suggesting P2X7R both primes and activates the NLRP3 inflammasome. ATP increased microglial migration, but this required P2Y12R, not P2X7R involvement. As ATP release often accompanies mechanical strain, responses to intraocular pressure elevation were determined. Transient elevation increased ATP release and led to microglial process retraction, cell body enlargement and gene upregulation resembling the responses to BzATP injection. These pressure-dependent changes to microglia were reduced in P2X7R -/- mice. Critically, the loss of retinal ganglion cell neurons accompanying increased pressure was correlated with microglial activation in C57Bl/6J, but not P2X7R -/- mice.Conclusions: P2X7R stimulation induced morphological and molecular markers of activation in retinal microglial cells in vivo and in vitro , affecting IL-1β release and rapid process retraction but not cell migration. Parallel responses accompanied transient pressure elevation, suggesting ATP release and P2X7R stimulation contribute to the microglial response to rising pressure.

The global COVID-19 pandemic demonstrated the vulnerability of healthcare delivery to patients worldwide and challenged healthcare providers—not only in treating patients with coronavirus but also in trying to maintain optimal care for non-COVID patients at the same time. But challenging times often provide a fertile environment for innovation, and we have certainly seen major transformation in health care this year, via technology and global models, with the goal to democratize health care and provide greater access and more efficient and effective delivery of healthcare services to patients, regardless of their income or geography. Some of the world’s top leaders and influencers in healthcare delivery transformation and health technologies, including blockchain and telehealth, converged at the 4th Annual CONV2X 2020 Symposium held virtually from November 10 to 12, to talk about healthcare transformation. By far, one of the most widely discussed topics in the many sessions that took place over the 2-day event was virtual health.

During our 2019 ConVerge2Xcelerate (ConV2X) conference in Boston, we focused on the theme "Proving Market Value with Pragmatic Innovation in Healthcare" (see https://conv2x-2019.eventcreate.com/). This year, along with BHTY editorial board members, conference speakers were invited to join with Tory Cenaj, Publisher of BHTY, to contribute their expertise and share insights for the near-term landscape of blockchain in healthcare.

In 2020, Blockchain in Healthcare Today (BHTY) begins its third year of publication. We thank our global community of passionate leaders and early adopters for their support and diligence in making technology innovation in healthcare attainable for both the healthcare consumers who are the key stakeholders in patient-centered care and the broader healthcare system.

AIMS Dysplasia in colonic sessile serrated adenomas (SSAs)/sessile serrated polyps often shows loss of MLH1 expression as determined with immunohistochemistry, but the significance of loss of MLH1 expression in non-dysplastic crypts in these polyps is less well studied. The purpose of this study was to evaluate the prevalence of loss of MLH1 expression in non-dysplastic crypts in SSAs, and to evaluate its significance with regard to progression of these polyps. METHODS AND RESULTS Four hundred SSAs, including 158 SSAs without dysplasia, 219 SSAs with dysplasia (SSAD), and 23 SSAs with invasive adenocarcinoma (SSAC), were evaluated immunohistochemically for loss of MLH1 expression in both non-dysplastic and dysplastic portions of the polyps. Seventy-one of 400 (18%) SSAs showed loss of MLH1 expression in non-dysplastic crypts. The prevalence of MLH1-deficient non-dysplastic crypts was higher in polyps with dysplasia or carcinoma (7%, 22%, and 52% in SSAs, SSADs, and SSACs, respectively; P

To review blockchain lessons learned in 2018 and near-future predictions for blockchain in healthcare, Blockchain in Healthcare Today (BHTY) asked the world's blockchain in healthcare experts to share their insights. Here, our internationally-renowned BHTY peer-review board discusses their major predictions.Based on their responses, presented in detail below, ten major themes (Table ) for the future of blockchain in healthcare will emerge over the 12 months. CORRIGENDUM: This following paragraph has been corrected (page 3, first paragraph) from: "Fourth, with over 1000 insurance companies in the country, filling out paperwork to documentprovider training and licensure is a nightmare. The Synaptic Health Alliance aims to simplifythis process by putting all credentialing information on a distributed public ledger for all stakeholders to access.1" To: "Fourth, keeping health care provider directories maintained by health plans up-to-date is a critical, complex issue facing organizations across the health care system. The first project of the Synaptic Health Alliance aims to simplify this process by putting provider demographic information on a permissioned blockchain for Alliance members to access and maintain.1"

No abstract available.

It is believed that sessile serrated adenomas/polyps lead to the development of microsatellite unstable cancer via a dysplasia-carcinoma sequence. Little is known regarding the morphologic and biologic features, and outcome of sessile serrated adenomas/polyps with dysplasia, or of its specific dysplasia subtypes (intestinal versus serrated). The aims of this study were to analyze and compare the clinical, pathologic, and outcome characteristics of sessile serrated adenomas/polyps with serrated versus intestinal dysplasia. The study included 86 patients with sessile serrated adenomas/polyps with dysplasia (50 serrated dysplasia, 22 intestinal dysplasia, 14 mixed serrated and intestinal dysplasia). The clinical and pathologic features, and the prevalence rate of prior, concurrent, and future neoplastic lesions, were compared between sessile serrated adenomas/polyps with intestinal versus serrated dysplasia and with matched control patients with ≥1 conventional adenoma. The mean age of the patients, polyp size, and prevalence of adenocarcinoma within the polyps were significantly higher in sessile serrated adenomas/polyps with high versus low-grade dysplasia. Sessile serrated adenomas/polyps with intestinal dysplasia showed a significantly higher rate of adenocarcinoma (23%) compared with those with serrated dysplasia (6%, P=0.05), and the high-grade lesions occurred at a significantly younger age in the former compared with the latter (65 versus 76 years, P=0.05). Compared with patients with conventional adenomas, patients with sessile serrated adenomas/polyps with dysplasia showed a significantly higher rate of invasive carcinoma within the polyps (12 versus 0%, P=0.01) and a significantly lower association with prior or future conventional adenomas. Sessile serrated adenomas/polyps with dysplasia should be considered high-risk neoplastic precursor lesions, particularly those with intestinal dysplasia. Cancer may develop from sessile serrated adenomas/polyps with either type of dysplasia.

Purpose Accumulation of lysosomal waste is linked to neurodegeneration in multiple diseases, and pharmacologic enhancement of lysosomal activity is hypothesized to reduce pathology. An excessive accumulation of lysosomal-associated lipofuscin waste and an elevated lysosomal pH occur in retinal pigment epithelial cells of the ABCA4-/- mouse model of Stargardt's retinal degeneration. As treatment with the P2Y12 receptor antagonist ticagrelor was previously shown to lower lysosomal pH and lipofuscin-like autofluorescence in these cells, we asked whether oral delivery of ticagrelor also prevented photoreceptor loss. Methods Moderate light exposure was used to accelerate photoreceptor loss in albino ABCA4-/- mice as compared to BALB/c controls. Ticagrelor (0.1%-0.15%) was added to mouse chow for between 1 and 10 months. Photoreceptor function was determined with electroretinograms, while cell survival was determined using optical coherence tomography and histology. Results Protection by ticagrelor was demonstrated functionally by using the electroretinogram, as ticagrelor-treated ABCA4-/- mice had increased a- and b-waves compared to untreated mice. Mice receiving ticagrelor treatment had a thicker outer nuclear layer, as measured with both optical coherence tomography and histologic sections. Ticagrelor decreased expression of LAMP1, implicating enhanced lysosomal function. No signs of retinal bleeding were observed after prolonged treatment with ticagrelor. Conclusions Oral treatment with ticagrelor protected photoreceptors in the ABCA4-/- mouse, which is consistent with enhanced lysosomal function. As mouse ticagrelor exposure levels were clinically relevant, the drug may be of benefit in preventing the loss of photoreceptors in Stargardt's disease and other neurodegenerations associated with lysosomal dysfunction.

From the point of view of diversity of large sports and enthusiasm sports to people around the world, football is an impact phenomenal, which spectacle and attractiveness of extraordinary keeps to himself the interest and enthusiasm of billions of people of different ages and gender all over the planet.. The specific characteristics of football game of football activities require assessing in the content aspect of technique and tactics prerequisite for motor activity. According to some authors, technical player’s actions express a special process of expression of specific skills and are exclusively dependent on the level of motor skills players. Football is a sport that kind of game is always connected with the participation of two teams. The aim of the game is in accordance with the rules of competition to score more goals in the opponent's gate and take victory. Typical for the football game are actions that are performed especially in the lower limbs and less in other parts of the body. It is forbidden to play with hands except goalkeeper and prescribed in a particular area. Player who controls the ball aims succeeding his players through collective action and the efforts of all the team players to pass the field areas in order to reach the gate of the opposing team to score a goal. In general football as a collective game it provides excellent opportunities for personal and collective expression of the intellectual motor skills of people of different ages. DOI: 10.5901/ajis.2016.v5n3s1p565

Advances in our understanding of the pathobiology of gastrointestinal stromal tumor (GIST) have led to an increasingly refined classification of a molecularly heterogeneous group of tumors and the discovery of clinicopathologically distinct subtypes with critical implications for therapeutics, prognosis, and genetic counseling. Histomorphology, immunohistochemistry, and mutational analysis continue to play an exceedingly important role, not only in diagnosis, but also in the clinical management and achievement of optimal outcomes in patients with GIST. This chapter reviews diagnostic advances and the key histologic features of GIST, in conjunction with clinical and molecular correlates.

Bulgaria is a country that is positioned in the south-east Europe and north-west of the Balkan Peninsula. Bulgaria in the east it borders on the Black Sea, to the south are Turkey and Greece, on the west by Macedonia and Romania in the north-west. Since 1999 the region of Bulgaria is divided into 28 regions. The total area of Bulgaria is 110.910 km2 and has a population of about eight million people. Many different economical studies have been realized in Bulgaria area these last years. This study provides some financial data about some financial projects, during years ahead of EU membership, provided the latter. The goal of this paper is to present the correlation between comparative analyses of three financial projects on different periods of time. For this purpose we have received financial data from three respective projects during the four years of the study. Economical data for this country will presented for the first time in this scientific international activity. Financial data are presented, according to the comparative analyses we found out several interesting data that showed clearly the real contribution to the economy and development of the country. Comparing these data we found out that, financial investment has an unquestionable importance for advancing economic life and the EU provides adequate funding to achieve this goal. DOI: 10.5901/ajis.2015.v4n2s2p67