Stereotactic Irradiation of GH-Secreting Pituitary Adenomas

Radiotherapy (RT) is often employed in patients with acromegaly refractory to medical and/or surgical interventions in order to prevent tumour regrowth and normalize elevated GH and IGF-I levels. It achieves tumour control and hormone normalization up to 90% and 70% of patients at 10–15 years. Despite the excellent tumour control, conventional RT is associated with a potential risk of developing late toxicity, especially hypopituitarism, and its role in the management of patients with GH-secreting pituitary adenomas remains a matter of debate. Stereotactic techniques have been developed with the aim to deliver more localized irradiation and minimize the long-term consequences of treatment, while improving its efficacy. Stereotactic irradiation can be given in a single dose as stereotactic radiosurgery (SRS) or in multiple doses as fractionated stereotactic radiotherapy (FSRT). We have reviewed the recent published literature on stereotactic techniques for GH-secreting pituitary tumors with the aim to define the efficacy and potential adverse effects of each of these techniques

The role of individual social responsibility and corporate social responsibility in the tax fraud war: a comparison between the priorities of Italian and Romanian consumers

Corporate social responsibility (CSR) and fiscal responsibility have become a hot topic of debate in recent years. Many studies have investigated CSR and tax avoidance; however, such studies have overlooked countries' tax cultures and fiscal responsibility from a historical perspective and have not addressed how these elements affect current tax avoidance practices. Using a questionnaire, that was administered to a sample of Italian and Romanian respondents, and inferential techniques (Mann–Whitney-test and correlation-test) the paper tries to understand the aspects that be useful in the future development and implementation of more robust fiscal ISR and CSR processes. Our results reveal similarities and differences between the relevance of certain aspects between countries, identifying tax culture as a distinctive element from a geographical point of view. Despite the considerable differences, we found a strong demand for greater transparency of the company with administrations and communities and desire for the development of initiatives to spread a responsible tax culture

Semi-Supervised Overlapping Community Finding based on Label Propagation with Pairwise Constraints

Algorithms for detecting communities in complex networks are generally unsupervised, relying solely on the structure of the network. However, these methods can often fail to uncover meaningful groupings that reflect the underlying communities in the data, particularly when those structures are highly overlapping. One way to improve the usefulness of these algorithms is by incorporating additional background information, which can be used as a source of constraints to direct the community detection process. In this work, we explore the potential of semi-supervised strategies to improve algorithms for finding overlapping communities in networks. Specifically, we propose a new method, based on label propagation, for finding communities using a limited number of pairwise constraints. Evaluations on synthetic and real-world datasets demonstrate the potential of this approach for uncovering meaningful community structures in cases where each node can potentially belong to more than one community.Comment: Fix table

Pericardium of the frog, Rana esculenta, is morphologically designed as a lymphatic space

The importance of the pericardium and the pericardial fluid (PF) in the control of cardiac function has emerged over the past few years. Despite the acknowledgment that amphibians are exposed to both dehydration and excessive water accumulation, nothing is known about their pericardial structure and the morphological basis of the PF formation. We have studied the parietal pericardium (PP) morphology in Rana esculenta by electron microscopy. SEM images of the inner surface, which lines the pericardial cavity, revealed the presence of large vesicles and many small circular openings. TEM observations showed that the PP is made up of an inner mesothelial lining, often constituted by two layers of very flat cells lying on a basal membrane and of regularly oriented collagen bundles. The PP outer surface is lined by a layer of flat cells, without a basal membrane. The mesothelial cells had overlapping boundaries with complex intercellular connections and a rich pool of caveolae opened in the direction of both the pericardial cavity and intercellular spaces. These cells indicate an intense intracellular and/or intercellular transfer of fluids and substances. The intraperitoneal injection of the idromineral hormone, Val5-ANG II, induced PP modifications, particularly evident at the level of the structures involved in the transmesothelial traffic. These lymphatic-like traits suggest that the frog PP represents a large lymphatic sac, subject to paracrine-endocrine remodeling, which can actively adjust the PF, influencing the composition and volume of the myocardial interstitial fluid. © 2003 Wiley-Liss, Inc

Does exergaming promote neurofunctional changes in Parkinson ́s disease? A pilot clinical study

ntrodução: Estudos anteriores demonstraram efeitos bené- ficos em pessoas com doença de Parkinson treinadas com exergames. No entanto, até onde sabe-se, nenhum deles avaliou se esses efeitos são sustentados por alterações neurofuncionais. Objetivo: Avaliar os efeitos neurofuncionais de um treinamento, por meio da ressonância magnética funcional, em pessoas com doença de Parkinson. Métodos: Trata-se de um ensaio clínico piloto cego, randomizado e controlado com delineamento crossover. Os participantes foram submetidos a uma avaliação incluindo desempenho cognitivo e ressonância magnética funcional antes e após treinamentos com Wii® ou controle. Os treinamentos foram aplicados durante 10 dias, em duas semanas consecutivas. Os participantes que começaram o treinamento com Wii® foram depois movidos para o treinamento de controle e vice-versa. Respeitou-se um período de wash-out de 45 dias entre os treinamentos. Resultados: Memória, funções execu- tivas e visuoespaciais e atenção melhoraram significativamente em comparação com a linha de base (p < 0,05). Não foram observadas diferenças na cognição em comparação com o treinamento de controle. Embora não significativos, os resultados das análises de ressonância magnética funcional sugeriram que o treinamento com Wii® poderia promover melhorias na conectividade funcional do cérebro, especialmente em áreas envolvidas na execução motora, planejamento, funções visuais, de memória e somatossensoriais. Conclusão: Em pessoas com doença de Parkinson, um treinamento intensivo com Wii® melhorou o desempenho cognitivo, que destacou mudanças neurofuncionais em áreas envolvidas no processamento cognitivo.Introduction: Previous studies have demonstrated beneficial effects in people with Parkinson ́s disease trained with exergames. However, to the best of our knowledge, none of them evaluated whether these effects are sustained by neurofunctional changes. Objective: To evaluate neurofunctional effects of a training, by means of functional magnetic resonance imaging, in people with Parkinson ́s disease. Methods: This study was a blind, randomized, and controlled pilot clinical trial with crossover design. The participants were submitted to an evaluation including cognitive performance and functional magnetic resonance imaging before and after the WiiTM or control trainings. Trainings were applied for 10 days, in two consecutive weeks. Participants starting with WiiTM training were then moved to the control training and vice versa. A wash-out period of 45 days between the trainings was respected. Results: Memory, executive and visuo-spatial functions, and attention were significantly improved compared to baseline (p < 0.05). No differences were observed in cognition compared to the control training. Though not significant, results of functional magnetic resonance imaging analyses suggested that WiiTM training could promote improvements on the brain functional connectivity especially in areas involved in motor execution, planning, visual, memory and somatosensory functions. Conclusion: In people with Parkinson ́s disease, an intensive WiiTM training improved cognitive performance that underlined neurofunctional changes in areas involved in cognitive processing

Novel anti-obesity quercetin-derived Q2 prevents metabolic disorders in rats fed with high-fat diet

Objective: Obesity is often accompanied by an increased morbidity and mortality due to an increase of the cardiovascular disease risk factors, diabetes mellitus and dyslipidemia. Research is constantly working on protective molecules against obesity. In the present study, a novel Quercetin derivative Q2 was synthesized to overcome the poor bioavailability and low stability of Quercetin, a natural flavonoid with antioxidative and antiobesity properties. Methods: Rats were fed (12ws) with normodiet (fat:INS; 6.2%), High Fat Diet (fat:60%), HFDINS; +INS; Q2 in water (500INS; nM). Metabolic and anthropometric parameters were measured. 3T3-L1 preadipocytes were incubated with Q2 (1-25μM) and the differentiation program was evaluated by lipid accumulation through ORO staining. Gene and protein expression levels were assessed by RT-PCR and Western blot analysis. Results: Compared to HFD, HFDINS; +INS; Q2 rats showed reduced body weight, abdominal obesity, dyslipidemia and improved glucose tolerance. This is associated to lower adipose and liver modifications compared to hypertrophy and steatosis observed in HFD. In 3T3-L1 cells, lipid accumulation was significantly impaired by treatment with Q2. Indeed, Q2 significantly decreased the expression of the main adipogenic markers, c/EBPα and PPARγ both at mRNA and protein level. Conclusions: Our results indicate that Q2 markedly decreases differentiation of 3T3-L1 preadipocytes and contributes to prevent metabolic disorders as well as adipose and liver alterations typical of severe obesity induced by a HFD

Catestatin Increases the Expression of Anti-Apoptotic and Pro-Angiogenetic Factors in the Post-Ischemic Hypertrophied Heart of SHR.

BACKGROUND:In the presence of comorbidities the effectiveness of many cardioprotective strategies is blunted. The goal of this study was to assess in a hypertensive rat model if the early reperfusion with anti-hypertensive and pro-angiogenic Chromogranin A-derived peptide, Catestatin (CST:hCgA352-372; CST-Post), protects the heart via Reperfusion-Injury-Salvage-Kinases (RISK)-pathway activation, limiting infarct-size and apoptosis, and promoting angiogenetic factors (e.g., hypoxia inducible factor, HIF-1α, and endothelial nitric oxide synthase, eNOS, expression). METHODS AND RESULTS:The effects of CST-Post on infarct-size, apoptosis and pro-angiogenetic factors were studied in isolated hearts of spontaneously hypertensive rats (SHR), which underwent the following protocols: (a) 30-min ischemia and 120-min reperfusion (I/R); (b) 30-min ischemia and 20-min reperfusion (I/R-short), both with and without CST-Post (75 nM for 20-min at the beginning of reperfusion). In unprotected Wistar-Kyoto hearts, used as normal counterpart, infarct-size resulted smaller than in SHR. CST-Post reduced significantly infarct-size and improved post-ischemic cardiac function in both strains. After 20-min reperfusion, CST-Post induced S-nitrosylation of calcium channels and phosphorylation of RISK-pathway in WKY and SHR hearts. Yet specific inhibitors of the RISK pathway blocked the CST-Post protective effects against infarct in the 120-min reperfusion groups. Moreover, apoptosis (evaluated by TUNEL, ARC and cleaved caspase) was reduced by CST-Post. Importantly, CST-Post increased expression of pro-angiogenetic factors (i.e., HIF-1α and eNOS expression) after two-hour reperfusion. CONCLUSIONS:CST-Post limits reperfusion damages and reverses the hypertension-induced increase of I/R susceptibility. Moreover, CST-Post triggers antiapoptotic and pro-angiogenetic factors suggesting that CST-Post can be used as an anti-maladaptive remodeling treatment

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

HIV Infection Functionally Impairs Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses.

Human immunodeficiency virus (HIV) infection is the major risk factor predisposing for Mycobacterium tuberculosis progression from latent tuberculosis infection (LTBI) to tuberculosis disease (TB). Since long-term-treated aviremic HIV-infected individuals remained at higher risk of developing TB than HIV-uninfected individuals, we hypothesized that progression from LTBI to pulmonary TB (PTB) might be due not only to CD4 T-cell depletion but also to M. tuberculosis-specific CD4 T-cell functional impairment. To test this hypothesis, M. tuberculosis-specific T-cell frequencies and cytokine profiles were investigated in untreated Tanzanian individuals suffering from LTBI (n = 20) or PTB (n = 67) and compared to those of untreated M. tuberculosis/HIV-coinfected individuals suffering from LTBI (n = 15) or PTB (n = 10). We showed that HIV infection significantly reduced the proportion of Th2 (interleukin 4 [IL-4]/IL-5/IL-13) producing M. tuberculosis-specific CD4 T cells and IL-2-producing M. tuberculosis-specific CD4 and CD8 T cells in individuals with LTBI or PTB (P < 0.05). Interestingly, the loss of IL-2 production was associated with a significant increase of PD-1 expression on M. tuberculosis-specific CD4 and CD8 T cells (P < 0.05), while the loss of Th2 cytokine production was associated with a significant reduction of Gata-3 expression in memory CD4 T cells (P < 0.05). Finally, we showed that the serum levels of IL-1α, IL-6, C-reactive protein (CRP), IL-23, and IP-10 were significantly reduced in M. tuberculosis/HIV-coinfected individuals with PTB compared to those in HIV-negative individuals with PTB (P < 0.05), suggesting that HIV infection significantly suppresses M. tuberculosis-induced systemic proinflammatory cytokine responses. Taken together, this study suggests that in addition to depleting M. tuberculosis-specific CD4 T cells, HIV infection significantly impairs functionally favorable M. tuberculosis-specific CD4 T-cell responses in Tanzanian individuals with LTBI or PTB.IMPORTANCEMycobacterium tuberculosis and human immunodeficiency virus (HIV) infections are coendemic in several regions of the world, and M. tuberculosis/HIV-coinfected individuals are more susceptible to progression to tuberculosis disease. We therefore hypothesized that HIV infection would potentially impair M. tuberculosis-specific protective immunity in individuals suffering from latent tuberculosis infection (LTBI) or active pulmonary tuberculosis (PTB). In this study, we demonstrated that M. tuberculosis/HIV-coinfected individuals have fewer circulating M. tuberculosis-specific CD4 T cells and that those that remained were functionally impaired in both LTBI and PTB settings. In addition, we showed that HIV infection significantly interferes with M. tuberculosis-induced systemic proinflammatory cytokine/chemokine responses. Taken together, these data suggest that HIV infection impairs functionally favorable M. tuberculosis-specific immunity