Ιατρικά Άρθρα

Παρασκευή 20 Ιανουαρίου 2017

Effects of polyphenol compounds melanin on NAFLD/NASH prevention

Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Natalia Belemets, Nazarii Kobyliak, Oleksandr Virchenko, Tetyana Falalyeyeva, Tsyryuk Olena, Petro Bodnar, Oleksiy Savchuk, Tetyana Galenova, Martin Caprnda, Luis Rodrigo, Lubomir Skladany, Delian Delev, Radka Opatrilova, Peter Kruzliak, Tetyana Beregova, Lyudmyla Ostapchenko
BackgroundOne of the pathogenic mechanisms of the progression non-alcoholic liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is the accumulation of reactive oxygen species (ROS). So, antioxidant therapy is necessary for successful treatment of the liver injury. We have paid attention to melanin produced by yeast Nadsoniella nigra strain X-1 as novel antioxidant and anti-inflammatory agents with low toxicity. In current study we aimed to investigate the preventive effect of melanin on the monosodium glutamate (MSG) induced NAFLD model in rats.MethodsThe study was carried out on 45 Wistar rats that were divided into 3 groups: intact, MSG- and MSG+melanin groups (n=15 in each group). Newborn rats of MSG- and MSG+melanin groups were administered with MSG (4mg/g, 8μl/g, subcutaneously) at 2nd–10th days of life. Since the age of 1 month, rats of MSG-group were treated with water (0.25ml/100g), rats of MSG+melanin groups—with melanin (1mg/kg) dissolved in water (0.25ml/100g).Introductionhad been performed intermittently (two-week courses alternated with two-week breaks) for 3 months. In 4-month rats anthropometrical parameters and visceral adipose tissue (VAT) mass were estimated. To assess morphological changes in liver we used NAS (NAFLD activity score). The content of pro-inflammatory cytokines (interleukin (IL)-1β, IL-12Bp40, interferon (INF)-γ) and anti-inflammatory cytokines (IL-4, IL-10, tumor growth factor (TGF)-β) were measured by ELISA.ResultsWe found significantly lower total score (1.0±0.19 vs 3.33±0.36, p<0.001), degree of steatosis (0.73±0.18 vs 1.80±0.17, p<0.001) and manifestation of lobular inflammation (0.27±0.11 vs 1.20±0.17, p<0.001) due to NAFLD activity score in MSG+melanin group compared to MSG-obesity. NASH we confirmed only in 33.3% of rats with MSG-obesity that was significantly higher than after melanin (6.7%) administration (p=0.033). Melanin administration reduce amount of visceral fat on 44.5% (p<0.001) as compared to MSG-obesity group. Melanin reduced the content of IL-1β in rat serum and restored the level of anti-inflammatory cytokines (IL-10, TGF-β) to the control values.ConclusionThus, the administration of melanin can prevent development of NAFLD/NASH in rats with MSG-induced obesity and can be considered as possible novel therapeutic agents but further studies to confirm its action needed.

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MicroRNA-200c binding to FN1 suppresses the proliferation, migration and invasion of gastric cancer cells

Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Hengchun Zhang, Zhiguo Sun, Yan Li, Dong Fan, Hao Jiang
We aimed to investigate the effects of miR-200c binding to fibronectin 1 (FN1) on proliferation, migration and invasion of gastric cancer (GC) cells. A total of 52 GC tissues and their corresponding normal adjacent tissue samples were collected. Then, miR-200c and FN1 were tested using quantitative real-time RT-PCR in the clinical specimens and GC cells, while immunohistochemistry and western blotting assay were carried out to detect FN1 expressions. Dual luciferase reporter gene assay was used to assess the effect of miR-200c on the luciferase activity of FN1 3′UTR. BGC-823 cells were transfected with miR-200c mimics, miR-200c inhibitors and FN1 siRNA, respectively. The effects of miR-200c inhibitors and FN1 siRNA on cellular proliferation, migration and invasion were detected through MTT assay and Transwell assay. Compared to normal tissues and cells, miR-200c was significantly down-regulated and FN1 was significantly up-regulated (P<0.01). Dual luciferase reporter gene assay showed that miR-200c could specifically bind to the 3′-UTR of FN1 and significantly repress the luciferase activity (P<0.01). Both mRNA and protein expressions of FN1 were decreased significantly in GC cells when miR-200c was over expressed. The proliferation, migration and invasion of GC cells could be suppressed by over-expression of miR-200c or down-regulation of FN1. In conclusion, miR-200c was significantly down-regulated in both GC tissues and cell lines, while FN1 presented the opposite trends. Besides, miR-200c inhibited the proliferation, migration and invasion of GC cells through binding to FN1.

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Effects of osteogenic protein-1 on intervertebral disc regeneration: A systematic review of animal studies

Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Pei Li, Ruijie Zhang, Yibo Gan, Liyuan Wang, Chen Zhao, Lei Luo, Chengmin Zhang, Qiang Zhou
Osteogenic protein (OP)-1 delivery into discs has achieved some success in disc regeneration in animals, though conflicting outcomes exist. This study aimed to systematically review the animal studies that assessed the effect of OP-1 on disc regeneration. Relevant literature was searched in the following databases: PubMed, MEDLINE, EMBASE, the Cochrane Library, China National Knowledge Internet (CNKI) and Chinese BioMedical Literature Database (CBM). Animal species, disc degeneration model, OP-1 delivery method, and follow-up methodology including disc histology, disc matrix alteration, disc height, MRI T2 signal intensity and OP-1 treatment complications were extracted and reviewed. Among 15 eligible studies, direct OP-1 protein injection into the disc was reported in 10 studies whereas cell-based or viral-based OP-1 gene transfer into the disc was reported in 5 studies. Although one study using a spontaneous canine disc degeneration model reported negative findings, all other studies (10 in rabbit, 1 in canine and 3 in rat) indicated that OP-1 delivery was effective in retarding disc degeneration and regenerating discs. The adverse effect of OP-1 delivery (i.e., extradiscal new bone formation) was reported in one study. In conclusion, OP-1 delivery offers a feasible option to biologically treat degenerated discs in animals, especially in rodent rabbit and rat models. However, more animal studies are needed to test the safety of the current OP-1 delivery means. Additionally, care should be taken when OP-1 delivery is used to treat human disc degeneration due to the differences between human and animal discs.

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The cardioprotective effect of total flavonoids on myocardial ischemia/reperfusion in rats

Publication date: April 2017
Source:Biomedicine & Pharmacotherapy, Volume 88
Author(s): Dongling Lv, Xiaohu Cheng, Lingyi Tang, Meng Jiang
The flowers of Abelmoschus manihot (L.) Medic is a traditional Chinese medicine used for the treatment of ischemic diseases. The present study is to investigate whether total flavones (TA) of extracted from Abelmoschus manihot L. Medic has the potential cardioprotective effect on myocardial ischemia/reperfusion (I/R) damage in rats. The index of myocardial injury, inflammatory biomarkers and NLRP3-related parameters were measured, respectively. The results demonstrated that compared to I/R group, TA reduced myocardial infarction area, declined serum creatinine kinase (CK), lactate dehydrogenase (LDH) levels, attenuated serum interleukin-6 (IL-6), IL-1β and tumour necrosis factor (TNF-α) production. Moreover, TA markedly enhanced the activities of superoxide dismutase (SOD) and reduced the amounts of malondialdehyde (MDA) in I/R rats. In addition, TA reduced myocardial I/R induced injury in rats by inhibiting NLRPR3 inflammasome. Thus, it is assumed that TA could significantly improve myocardial I/R injury in rats partially through suppressing NLRP3 activtion.

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Food acid content and erosive potential of sugar-free confections

Abstract

Background

Dental erosion is an increasingly prevalent problem associated with frequent consumption of acidic foods and beverages. The aim of this study was to measure the food acid content and the erosive potential of a variety of sugar-free confections.

Methods

Thirty sugar-free confections were selected and extracts analysed to determine pH, titratable acidity, chemical composition and apparent degree of saturation with respect to apatite. The effect of the sugar-free confections in artificial saliva on human enamel was determined in an in vitro dental erosion assay using change in surface microhardness.

Results

The change in surface microhardness was used to categorise the confections as high, moderate or low erosive potential. Seventeen of the thirty sugar-free confections were found to contain high concentrations of food acids, exhibit low pH and high titratable acidity and have high erosive potential. Significant correlations were found between the dental erosive potential (change in enamel surface microhardness) and pH and titratable acidity of the confections. Ten of these high erosive potential confections displayed dental messages on the packaging suggesting they were safe for teeth.

Conclusions

Many sugar-free confections, even some with "Toothfriendly" messages on the product label contain high contents of food acids and have erosive potential.

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Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo

Publication date: Available online 19 January 2017
Source:Cell Stem Cell
Author(s): Nuno Guimarães-Camboa, Paola Cattaneo, Yunfu Sun, Thomas Moore-Morris, Yusu Gu, Nancy D. Dalton, Edward Rockenstein, Eliezer Masliah, Kirk L. Peterson, William B. Stallcup, Ju Chen, Sylvia M. Evans
Pericytes are widely believed to function as mesenchymal stem cells (MSCs), multipotent tissue-resident progenitors with great potential for regenerative medicine. Cultured pericytes isolated from distinct tissues can differentiate into multiple cell types in vitro or following transplantation in vivo. However, the cell fate plasticity of endogenous pericytes in vivo remains unclear. Here, we show that the transcription factor Tbx18 selectively marks pericytes and vascular smooth muscle cells in multiple organs of adult mouse. Fluorescence-activated cell sorting (FACS)-purified Tbx18-expressing cells behaved as MSCs in vitro. However, lineage-tracing experiments using an inducible Tbx18-CreERT2 line revealed that pericytes and vascular smooth muscle cells maintained their identity in aging and diverse pathological settings and did not significantly contribute to other cell lineages. These results challenge the current view of endogenous pericytes as multipotent tissue-resident progenitors and suggest that the plasticity observed in vitro or following transplantation in vivo arises from artificial cell manipulations ex vivo.

Graphical abstract

Teaser

Guimarães-Camboa et al. permanently labeled pericytes and vascular smooth muscle of multiple organs in vivo and followed the fate of these cells in aging and injury models. Their analyses showed that, in vivo, pericytes did not behave as stem cells, challenging the current view of pericytes as tissue-resident multipotent progenitors.

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Human iPSC-Derived Cerebral Organoids Model Cellular Features of Lissencephaly and Reveal Prolonged Mitosis of Outer Radial Glia

Publication date: Available online 19 January 2017
Source:Cell Stem Cell
Author(s): Marina Bershteyn, Tomasz J. Nowakowski, Alex A. Pollen, Elizabeth Di Lullo, Aishwarya Nene, Anthony Wynshaw-Boris, Arnold R. Kriegstein
Classical lissencephaly is a genetic neurological disorder associated with mental retardation and intractable epilepsy, and Miller-Dieker syndrome (MDS) is the most severe form of the disease. In this study, to investigate the effects of MDS on human progenitor subtypes that control neuronal output and influence brain topology, we analyzed cerebral organoids derived from control and MDS-induced pluripotent stem cells (iPSCs) using time-lapse imaging, immunostaining, and single-cell RNA sequencing. We saw a cell migration defect that was rescued when we corrected the MDS causative chromosomal deletion and severe apoptosis of the founder neuroepithelial stem cells, accompanied by increased horizontal cell divisions. We also identified a mitotic defect in outer radial glia, a progenitor subtype that is largely absent from lissencephalic rodents but critical for human neocortical expansion. Our study, therefore, deepens our understanding of MDS cellular pathogenesis and highlights the broad utility of cerebral organoids for modeling human neurodevelopmental disorders.

Graphical abstract

Teaser

Bershteyn and colleagues show that cerebral organoid modeling of lissencephaly using iPSCs derived from Miller-Dieker syndrome patients can characterize cellular and neurodevelopmental disease phenotypes and identify a mitotic defect in outer radial glia, a cell type that is particularly important for human cortical development.

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RNA Helicase DDX5 Inhibits Reprogramming to Pluripotency by miRNA-Based Repression of RYBP and its PRC1-Dependent and -Independent Functions

Publication date: Available online 19 January 2017
Source:Cell Stem Cell
Author(s): Huanhuan Li, Ping Lai, Jinping Jia, Yawei Song, Qing Xia, Kaimeng Huang, Na He, Wangfang Ping, Jiayu Chen, Zhongzhou Yang, Jiao Li, Mingze Yao, Xiaotao Dong, Jicheng Zhao, Chunhui Hou, Miguel A. Esteban, Shaorong Gao, Duanqing Pei, Andrew P. Hutchins, Hongjie Yao
RNA-binding proteins (RBPs), in addition to their functions in cellular homeostasis, play important roles in lineage specification and maintaining cellular identity. Despite their diverse and essential functions, which touch on nearly all aspects of RNA metabolism, the roles of RBPs in somatic cell reprogramming are poorly understood. Here we show that the DEAD-box RBP DDX5 inhibits reprogramming by repressing the expression and function of the non-canonical polycomb complex 1 (PRC1) subunit RYBP. Disrupting Ddx5 expression improves the efficiency of iPSC generation and impedes processing of miR-125b, leading to Rybp upregulation and suppression of lineage-specific genes via RYBP-dependent ubiquitination of H2AK119. Furthermore, RYBP is required for PRC1-independent recruitment of OCT4 to the promoter of Kdm2b, a histone demethylase gene that promotes reprogramming by reactivating endogenous pluripotency genes. Together, these results reveal important functions of DDX5 in regulating reprogramming and highlight the importance of a Ddx5-miR125b-Rybp axis in controlling cell fate.

Graphical abstract

Teaser

RNA-binding proteins have poorly defined roles in somatic cell reprogramming. Li et al. show that the RNA-binding protein DDX5 erects an epigenetic barrier to reprogramming. DDX5 controls RYBP through microRNA-125b to suppress specific somatic genes through deposition of H2AK119ub1 while activating an OCT4-KDM2B pluripotent gene program.

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Factors associated with electronic cigarette use among current cigarette-smoking adolescents in the Republic of Korea

Publication date: June 2017
Source:Addictive Behaviors, Volume 69
Author(s): Sunhee Park, Haein Lee, Soyoon Min
ObjectiveDespite a rapid increase in electronic cigarette (e-cigarette) use and substantial dual use of cigarettes and e-cigarettes among adolescents, little is currently known about adolescent e-cigarette use. Thus, this study aimed to investigate (a) rates of e-cigarette use and (b) significant factors associated with e-cigarette use among current cigarette users in adolescence.MethodsWe analyzed secondary data collected from a nationally representative sample of Korean adolescents. Our study sample included 6307 current smokers. Our dependent variable was e-cigarette use and consisted of three categories (nonuse, former use, and current use); independent variables included demographics, perceived stress, parental and friends' smoking, three characteristics of cigarette smoking, and other health risk behaviors. Descriptive statistics was used for the first aim; multinomial logistic regression analysis was performed for the second aim.ResultsOf current cigarette users, 20% smoked e-cigarettes in their lifetime but not within the past 30days (former users), and 42% smoked e-cigarettes in their lifetime and within the past 30days (current users). Both former and current e-cigarette use were significantly associated with male gender, higher grades, higher weekly allowance, residence in urban areas, friends' smoking, daily smoking, a higher number of cigarettes smoked, and quit attempts. In addition, current e-cigarette use was significantly associated with at-risk drinking, lifetime drug use, and lifetime sexual intercourse.ConclusionsE-cigarette use should be included in intervention strategies for smoking prevention and cessation. Strict regulations should be implemented in order to prohibit easy access to e-cigarettes and forbid advertising of e-cigarettes as well.

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Evaluation of the robotic approach concerning pitfalls in rectal surgery

Publication date: Available online 19 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Julia K. Baukloh, Matthias Reeh, Giuseppe Spinoglio, Andrea Corratti, Ilenia Bartolini, Vita M. Mirasolo, Fabio Priora, Jakob R. Izbicki, Manuel Gómez Fleitas, Manuel Gomez Ruiz, Daniel R. Perez
IntroductionThe feasibility and advantages of robotic rectal surgery (RRS) in comparison to conventional open or laparoscopic rectal resections have been postulated in several reports. But well-known challenges and pitfalls of minimal invasive rectal surgery have not been evaluated by a prospective, multicenter setting so far. Aim of this study was to analyze the perioperative outcome of patients following RRS especially in regard to the pitfalls such as obesity, male patients and low tumors by a European multicenter setting.MethodsThis prospective study included 348 patients undergoing robotic surgery due to rectal cancer in six major European centers. Clinicopathological parameters, morbidity, perioperative recovery and short-term outcome were analyzed.ResultsA total of 283 restorative surgeries and 65 abdominoperineal resections were carried out. The conversion rate was 4.3 %, mean blood loss was 191 ml, and mean operative time was 315 minutes. Postoperative complications with a Clavien-Dindo score >2 were observed in 13.5%. Obesity and low rectal tumors showed no significant higher rates of major complications or impaired oncological parameters. Male patients had significant higher rates of major complications and anastomotic leakage (p=0.048 and p=0.007, respectively).DiscussionRRS is a promising tool for improvement of rectal resections. The well-known pitfalls of minimal-invasive rectal surgery like obesity and low tumors were sufficiently managed by RRS. However, RRS showed significantly higher rates of major complications and anastomotic leakage in male patients, which has to be evaluated by future randomized trials.

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The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery

Publication date: Available online 19 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Iris J.G. Rutten, Jorne Ubachs, Roy F.P.M. Kruitwagen, David P.J. van Dijk, Regina G.H. Beets-Tan, Leon F.A.G. Massuger, Steven W.M. Olde Damink, Toon Van Gorp
BackgroundSarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary debulking surgery (PDS).MethodsOvarian cancer patients (n=216) treated with PDS were enrolled retrospectively. Total skeletal muscle surface area was measured on axial computed tomography at the level of the third lumbar vertebra. Optimum stratification was used to find the optimal skeletal muscle index cut-off to define sarcopenia (≤38.73 cm²/m²). Cox-regression and Kaplan-Meier analysis were used to analyse the relationship between sarcopenia and OS. The effect of sarcopenia on the development of major surgical complications was studied with logistic regression.ResultsKaplan-Meier analysis showed a significant survival disadvantage for patients with sarcopenia compared to patients without sarcopenia (p=0.010). Sarcopenia univariably predicted OS (HR 1.536 (95%CI 1.105-2.134), p=0.011) but was not significant in multivariable Cox-regression analysis (HR 1.362 (95%CI 0.968-1.916) p=0.076). Significant predictors for OS in multivariable Cox-regression analysis were complete PDS, treatment in a specialised centre and the development of major complications. Sarcopenia was not predictive of major complications.ConclusionSarcopenia was not predictive of OS or major complications in ovarian cancer patients undergoing primary debulking surgery. However a strong trend towards a survival disadvantage for patients with sarcopenia was seen. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival. Complete cytoreduction remains the strongest predictor of ovarian cancer survival.

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Efficacy of preoperative immunonutrition in locally advanced pancreatic cancer undergoing irreversible electroporation (IRE)

Publication date: Available online 19 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): R.C.G. Martin, S. Agle, M. Schlegel, T. Hayat, C.R. Scoggins, K.M. McMasters, P. Philips
BackgroundImproved preoperative immunonutrition has been shown to decrease the length of stay (LOS) and complications among patients undergoing elective gastrointestinal cancer surgeries. The purpose of this study was to determine whether preoperative immunonutrition supplementation decreases postoperative LOS, infectious complications, and morbidity in patients undergoing irreversible electroporation (IRE) surgery for locally advanced pancreatic cancer (LAPC).MethodsAt a regional hepatopancreatobiliary referral center within an academic medical center 71 patients receiving IRE treatment of LAPC were included in the study. The participants were divided into those receiving preoperative immunonutrition (n=44) and those receiving no supplemental preoperative immunonutrition (n=27). Main outcomes and measures were LOS, postoperative complications, nutritional risk index (NRI), and albumin levels.ResultsPatients in both groups were similar for preoperative nutrition parameters and operative therapy. Patients in the immunonutrition group experienced a statistically significant decrease in postoperative complications (p=0.05) and LOS (10.7 vs. 17.4, p=0.01), and less of a decrease in nutritional risk index (-12.6 vs. -16.2, p=0.03) and albumin levels (-1.1 vs. -1.5, p<0.01).ConclusionPreoperative immunonutrition was clinically significant in decreasing postoperative complications, LOS, and improving post-surgery NRI and albumin levels in patients receiving elective IRE treatment of non-resectable pancreatic cancer. These results indicate that preoperative immunonutrition is effective and feasible in this subset of cancer patients.

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Prognostic heterogeneity of the seventh edition of UICC Stage III gallbladder carcinoma: which patients benefit from surgical resection?

Publication date: Available online 19 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): J. Sakata, T. Kobayashi, T. Ohashi, Y. Hirose, K. Takano, K. Takizawa, K. Miura, H. Ishikawa, K. Toge, K. Yuza, D. Soma, T. Ando, T. Wakai
BackgroundThis study sought to evaluate the prognostic heterogeneity of Stage III (Union for International Cancer Control, seventh edition) gallbladder carcinoma.MethodsOf 175 patients enrolled with gallbladder carcinoma who underwent radical resection, 22 were classified with Stage IIIA disease (T3N0M0) and 46 with Stage IIIB disease (T2N1M0 [n = 23] and T3N1M0 [n = 23]). The median number of retrieved lymph nodes per patient was 18.ResultsThis staging system failed to stratify outcomes between Stages IIIA and IIIB; survival after resection was better for patients with Stage IIIB disease than for patients with Stage IIIA disease, with 5-year survival of 54.9% and 41.0%, respectively (p = 0.366). Multivariate analysis for patients with Stage III disease revealed independently better survival for patients with T2N1M0 than for patients with T3N0M0 (p = 0.016) or T3N1M0 (p = 0.001), with 5-year survival of 77.0%, 41.0%, and 31.0%, respectively. When N1 status was subdivided according to the number of positive nodes, 5-year survival in patients with T2M0 with 1-2 positive nodes, T2M0 with ≥ 3 positive nodes, T3M0 with 1-2 positive nodes, and T3M0 with ≥ 3 positive nodes was 83.3%, 50.0%, 45.8%, and 0%, respectively (p < 0.001).ConclusionsThe prognosis of T2N1M0 disease was better than that of T3N0/1M0 disease, suggesting that not all node-positive patients will have uniformly poor outcomes after resection of gallbladder carcinoma. T2M0 with 1-2 positive nodes leads to a favorable outcome after resection, whereas T3M0 with ≥ 3 positive nodes indicates a dismal prognosis.

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Surgical management of primary thyroid tumours

Publication date: Available online 19 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Panagiotis Asimakopoulos, Iain J. Nixon
The majority of patients who present with well differentiated thyroid cancer will require surgery, but decisions on the appropriate primary procedure will depend on information relating to patient, tumour and surgical factors. As the incidence of thyroid cancer continues to rise, it is critical that clinicians involved in the management of these cases understand the factors which underpin surgical decision making for individual patients. Reporting outcomes in well differentiated thyroid carcinoma (WDTC) has always been challenging due to the low recurrence and mortality rate of the disease. Although early data supported total thyroidectomy for all patients with >1cm WDTC, more recent evidence has supported lobectomy in selected, low risk patients. As a result we have seen a change in the approach of international guidelines from a blanket statement that total thyroidectomy should be the treatment for all patients towards a more selective approach to therapy. When selecting the most appropriate surgical approach to WDTC, the primary aim is to minimize the chance of death from disease or further recurrence. Additionally the impact of potential side effects of treatment (laryngeal nerve injury and hypocalcaemia) must also be weighed in the balance. In this review of surgical management of WDTC we aim to present a historical perspective on this subject and explore the arguments for and against total thyroidectomy and thyroid lobectomy in the low-risk patient group.

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Childhood leukodystrophies: A literature review of updates on new definitions, classification, diagnostic approach and management

Publication date: Available online 20 January 2017
Source:Brain and Development
Author(s): Mahmoud Reza Ashrafi, Ali Reza Tavasoli
Childhood leukodystrophies are a growing category of neurological disorders in pediatric neurology practice. With the help of new advanced genetic studies such as whole exome sequencing (WES) and whole genome sequencing (WGS), the list of childhood heritable white matter disorders has been increased to more than one hundred disorders. During the last three decades, the basic concepts and definitions, classification, diagnostic approach and medical management of these disorders much have changed. Pattern recognition based on brain magnetic resonance imaging (MRI), has played an important role in this process. We reviewed the last Global Leukodystrophy Initiative (GLIA) expert opinions in definition, new classification, diagnostic approach and medical management including emerging treatments for pediatric leukodystrophies.

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Editorial Board/Aims and Scope

Publication date: 7 February 2017
Source:Vaccine, Volume 35, Issue 6

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Heterochromatin remodeling in embryonic stem cells proceeds through stochastic de-stabilization of regional steady-states

Publication date: Available online 20 January 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Anastasia Christogianni, Eleftheria Chatzantonaki, Katerina Soupsana, Ioannis Giannios, Aggeliki Platania, Anastasia S. Politou, Spyros Georgatos
Cell differentiation is associated with progressive immobilization of chromatin proteins, expansion of heterochromatin, decrease of global transcriptional activity and induction of lineage-specific genes. However, how these processes relate to one another remains unknown. We show here that the heterochromatic domains of mouse embryonic stem cells (ESCs) are dynamically distinct and posesses a mosaic sub-structure. Although random spatio-temporal fluctuations reshuffle continously the chromatin landscape, each heterochromatic territory maintains its dynamic profile, exhibiting robustness and resembling a quasi-steady state. Transitions towards less dynamic states are detected sporadically as ESCs downregulate Nanog and exit the self-renewal phase. These transistions increase in frequency after lineage-commitment, but evolve differently depending on cellular context and transcriptional status. We propose that chromatin remodeling is a step-wise process, which involves stochastic de-stabilization of regional steady states and formation of new dynamic ensembles in coordination to changes in the gene expression program.

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Postradiation-associated sclerosing mediastinitis diagnosed in fine needle aspiration specimen: A cytological–pathological correlation

Publication date: Available online 19 January 2017
Source:Annals of Diagnostic Pathology
Author(s): Tamar Giorgadze, June H. Koizumi, Shira Ronen, Michael Chaump, Cynthia M. Magro
Sclerosing mediastinitis (SM) is an aggressive fibroproliferative process in the mediastinum that may lead to encasement of mediastinal structures within a dense fibrotic mass. This disease may cause significant clinical complications, morbidity, and even mortality. The etiology and pathogenesis of SM is unclear and in more than one third of cases remains idiopathic. Among the known causes of SM, granulomatous infection is the commonest. Association of SM with radiation therapy has been rarely reported. Herein, we are reporting a case of postradiation sclerosing mediastinitis diagnosed in fine needle aspiration (FNA) specimen. To our knowledge, this is the first reported case of postradiation sclerosing mediastinitis with unusual striking intracytoplasmic glycogen accumulation. Having high index of suspicion and awareness of the fact that this entity may be also associated with radiation therapy, will be helpful in avoiding diagnostic pitfalls in FNA specimens and guiding proper clinical management.

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Warthin-like papillary renal cell carcinoma: Clinicopathologic, morphologic, immunohistochemical and molecular genetic analysis of 11 cases

Publication date: Available online 19 January 2017
Source:Annals of Diagnostic Pathology
Author(s): Faruk Skenderi, Monika Ulamec, Tomas Vanecek, Petr Martinek, Reza Alaghehbandan, Maria Pane Foix, Iva Babankova, Delia Perez Montiel, Isabel Alvarado-Cabrero, Marian Svajdler, Pavol Dubinský, Dana Cempirkova, Michal Pavlovsky, Semir Vranic, Ondrej Daum, Ondrej Ondic, Kristyna Pivovarcikova, Kvetoslava Michalova, Milan Hora, Pavla Rotterova, Adela Stehlikova, Martin Dusek, Michal Michal, Ondrej Hes
Oncocytic papillary renal cell carcinoma (PRCC) is a distinct subtype of PRCC, listed as a possible new variant of PRCC in the 2016 WHO classification. It is composed of papillae aligned by large single-layered eosinophilic cells showing linearly arranged oncocytoma-like nuclei.We analyzed clinicopathologic, morphologic, immunohistochemical and molecular-genetic characteristics of 11 oncocytic PRCCs with prominent tumor lymphocytic infiltrate, morphologically resembling Warthin's tumor.The patients were predominantly males (8/11, 73%), with an average age of 59years (range 14–76), and a mean tumor size of 7cm (range 1–22cm). Tumors had the features of oncocytic PRCCs with focal pseudostratification in 8/11 cases and showed dense stromal inflammatory infiltration in all cases. Papillary growth pattern was predominant, comprising more than 60% of tumor volume. Tubular and solid components were present in 5 and 3 cases, respectively. Uniform immunohistochemical positivity was found for AMACR, PAX-8, MIA, vimentin, and OSCAR. Tumors were mostly negative for carboanhydrase 9, CD117, CK20, and TTF-1. Immunohistochemical stains for DNA mismatch repair proteins MLH1 and PMS2 were retained in all cases, while MSH2 and MSH6 were negative in 1 case. The lymphocytic infiltrate (TILs) consisted of both B and T cells. Chromosomal copy number variation analysis showed great variability in 5 cases, ranging from a loss of one single chromosome to complex genome rearrangements. Only one case showed gains of chromosomes 7 and 17, among other aberrations. In 4 cases no numerical imbalance was found. Follow up data was available for 9 patients (median 47.6months, range 1–132). In 6 patients no lethal progression was noted, while 3 died of disease.In conclusion, Warthin-like PRCC is morphologically very close to oncocytic PRCC, from which it differs by the presence of dense lymphoid stroma. Chromosomal numerical aberration pattern of these tumors is variable; only one case showed gains of chromosomes 7 and 17. Warthin-like PRCC is a potentially aggressive tumor since a lethal outcome was recorded in 3/9 cases.

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Dose–effect analysis of radiation induced rib fractures after thoracic SBRT

Publication date: Available online 19 January 2017
Source:Radiotherapy and Oncology
Author(s): Barbara Stam, Erik van der Bijl, Heike Peulen, Maddalena M.G. Rossi, José S.A. Belderbos, Jan-Jakob Sonke
Background and purposeTo determine a dose–effect relation for radiation induced rib fractures after stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC). Automatic rib delineation has enabled the analysis of a large patient group.Material and methodsFour-hundred and sixty-six patients with stage I/II NSCLC received SBRT with a median of 54Gy in 3 fractions. The optimal EQD2-corrected dose parameter to predict (a)symptomatic fractures was found using Cox regression. Three normal tissue complication probability (NTCP) models based on this optimal parameter were constructed: (1) at a median follow up (FU) of 26months, (2) for all data, with time to toxicity taken into account and (3) at a FU of 26months, excluding low dose ribs.ResultsThe median time to fracture was 22 (range 5–51) months. Maximum rib dose best predicted fractures. The TD50 (dose with 50% complication) of the second NTCP model was 375Gy. The TD50 was significantly higher for the other models indicating an under-estimation of the dose effect at the median follow-up time and/or when excluding low dose ribs.ConclusionsThe risk of symptomatic rib fractures after SBRT was significantly correlated to dose, and was <5% at 26months when Dmax<225Gy.

http://ift.tt/2jUkSYT

Patterns of failure for patients with glioblastoma following O-(2-[18F]fluoroethyl)-L-tyrosine PET- and MRI-guided radiotherapy

Publication date: Available online 19 January 2017
Source:Radiotherapy and Oncology
Author(s): Michael Lundemann, Junia Cardoso Costa, Ian Law, Svend Aage Engelholm, Aida Muhic, Hans Skovgaard Poulsen, Per Munck af Rosenschold
Background and purposeTo evaluate the patterns of failure following clinical introduction of amino-acid O-(2-[¹⁸F]fluoroethyl)-L-tyrosine (FET)-PET-guided target definition for radiotherapy (RT) of glioblastoma patients.Materials and methodsThe first 66 consecutive patients with confirmed histology, scanned using FET-PET/CT and MRI were selected for evaluation. Chemo-radiotherapy was delivered to a volume based on both MRI and FET-PET (PETvol). The volume of recurrence (RV) was defined on MRI data collected at the time of progression according to RANO criteria.ResultsFifty patients were evaluable, with median follow-up of 45months. Central, in-field, marginal and distant recurrences were observed for 82%, 10%, 2%, and 6% of the patients, respectively. We found a volumetric overlap of 26%, 31% and 39% of the RV with the contrast-enhancing MR volume, PETvol and the composite MRPETvol, respectively. MGMT-methylation (p=0.03), larger PETvol (p<0.001), and less extensive surgery (p<0.001), were associated with larger PETvol overlap.ConclusionThe combined MRPETvol had a stronger association with the recurrence volume than either of the modalities alone. Larger overlap of PETvol and RV was observed for patients with MGMT-methylation, less extensive surgery, and large PETvol on the RT-planning scans.

http://ift.tt/2j1zwPD

Bidirectional relationship of mast cells-neurovascular unit communication in neuroinflammation and its involvement in POCD

Publication date: 30 March 2017
Source:Behavioural Brain Research, Volume 322, Part A
Author(s): Nana Li, Xiang Zhang, Hongquan Dong, Youli Hu, Yanning Qian
Postoperative cognitive dysfunction (POCD) has been hypothesized to be mediated by surgery-induced neuroinflammation, which is also a key element in the pathobiology of neurodegenerative diseases, stroke, and neuropsychiatric disorders. There is extensive communication between the immune system and the central nervous system (CNS). Inflammation resulting from activation of the innate immune system cells in the periphery can impact central nervous system behaviors, such as cognitive performance. Mast cells (MCs), as the"first responders" in the CNS, can initiate, amplify, and prolong other immune and nervous responses upon activation. In addition, MCs and their secreted mediators modulate inflammatory processes in multiple CNS pathologies and can thereby either contribute to neurological damage or confer neuroprotection. Neuroinflammation has been considered to be linked to neurovascular dysfunction in several neurological disorders. This review will provide a brief overview of the bidirectional relationship of MCs-neurovascular unit communication in neuroinflammation and its involvement in POCD, providing a new and unique therapeutic target for the adjuvant treatment of POCD.

http://ift.tt/2j1IKLr

Inhibition of iNOS alleviates cognitive deficits and depression in diabetic mice through downregulating the NO/sGC/cGMP/PKG signal pathway

Publication date: 30 March 2017
Source:Behavioural Brain Research, Volume 322, Part A
Author(s): Xiao yan Zhou, Fang Zhang, Chang jiang Ying, Jing Chen, Ling Chen, Jing Dong, Yue Shi, Mang Tang, Xiao tong Hu, Zhi hua Pan, Na na Xu, Kui yang Zheng, Ren xian Tang, Yuan jian Song
Diabetes mellitus often results in a number of complications involving impaired brain function, including cognitive deficits and depression. However, the potential mechanisms for diabetes-related cognitive deficits and depression are not fully understood. Neurons in the hippocampal, cortical and amygdala functional regions are more susceptible to damage during hyperglycemia. Neuroprotection in the brain can rescue cognitive deficits and depression induced by hyperglycemia. This study investigated the potential mechanisms underlying diabetes-related congnitive deficits and depression, determined whether the inflammatory factor inducible nitric oxide synthase (iNOS) and the nitric oxide (NO)/soluble guanylyl cyclases (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway, play key roles in cognitive deficits and depression associated. In the present study, diabetic animal models were induced by streptozotocin (STZ, 150mg/kg) in mice, and aminoguanidine (AG), a selective inhibitor of iNOS, was given by intraperitoneal injection for 10 weeks. Blood glucose, activities of NOS and the levels of NO in serum and brain regions were measured. The spatial memory was detected using the Morris water maze test, depressive behavior was evaluated by the tail suspension test (TST), forced swimming test (FST), closed field test (CFT) and open field test (OFT). We also detected neuronal survival and cleaved caspase-3 positive ratios in three brain regions and the levels of iNOS, sGC, cGMP and PKG in hippocampus and frontal cortex. Data indicated that diabetic mice exerted impairments in spatial memory, decreased locomotor activity and increased immobile time in diabetic mice. In addition, diabetic mice had significantly decreased surviving neuronal density and showed signs of obvious neuronal injury in the hippocampus, frontal cortex and amygdala. iNOS overexpression and its associated signaling pathway NO/sGC/cGMP/PKG in the hippocampus and frontal cortex were implicated during hyperglycemia. However, AG improved the behavior disorders, reduced the activity of iNOS, protected nerve cells and inhibited the level of iNOS, sGC, PKG and cleaved caspase-3 in the hippocampus and cortex. These results suggested that iNOS/NO/sGC/cGMP/PKG signal pathway is a key feature of cognitive deficits and depression associated with diabetes. AG ameliorated cognitive deficits and depression in diabetic mice by exerting anti-inflammatory and neuroprotective effects by suppressing iNOS-associated signaling pathways.

http://ift.tt/2iSmwIz

Carcinogenic risk and Bisphenol A exposure: A focus on molecular aspects in endoderm derived glands.

Publication date: Available online 19 January 2017
Source:Molecular and Cellular Endocrinology
Author(s): Danila Cuomo, Immacolata Porreca, Gilda Cobellis, Roberta Tarallo, Giovanni Nassa, Geppino Falco, Antonio Nardone, Francesca Rizzo, Massimo Mallardo, Concetta Ambrosino
Epidemiological and experimental evidence associates the exposure to Bisphenol A with the increase of cancer risk in several organs, including prostate. BPA targets different pathways involved in carcinogenicity including the Nuclear Receptors (i.e. estrogen and androgen receptors), stress regulated proteins and, finally, epigenetic changes.Here, we analyse BPA-dependent carcinogenesis in endoderm-derived glands, thyroid, liver, pancreas and prostate focusing on cell signalling, DNA damage repair pathways and epigenetic modifications. Mainly, we gather molecular data evidencing harmful effects at doses relevant for human risk (low-doses). Since few molecular data are available, above all for the pancreas, we analysed transcriptomic data generated in our laboratory to suggest possible mechanisms of BPA carcinogenicity in endoderm-derived glands, discussing the role of nuclear receptors and stress/NF-kB pathways. We evidence that an in vitro toxicogenomic approach might suggest mechanisms of toxicity applicable to cells having the same developmental origin.Although we cannot draw firm conclusions, published data summarized in this review suggest that exposure to BPA, primarily during the developmental stages, represents a risk for carcinogenesis of endoderm-derived glands.

http://ift.tt/2j1ynrc

Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo

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Teaser

Human iPSC-Derived Cerebral Organoids Model Cellular Features of Lissencephaly and Reveal Prolonged Mitosis of Outer Radial Glia

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RNA Helicase DDX5 Inhibits Reprogramming to Pluripotency by miRNA-Based Repression of RYBP and its PRC1-Dependent and -Independent Functions

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Changes in Provider Prescribing Patterns After Implementation of an Emergency Department Prescription Opioid Policy

Publication date: Available online 19 January 2017
Source:The Journal of Emergency Medicine
Author(s): Scott R. Osborn, Julianna Yu, Barbara Williams, Maria Vasilyadis, C. Craig Blackmore
BackgroundPrescription opioid-associated abuse and overdose is a significant cause of morbidity and mortality in the United States. Opioid prescriptions generated from emergency departments (EDs) nationwide have increased dramatically over the past 20 years, and opioid-related overdose deaths have become an epidemic, according to the Centers for Disease Control and Prevention.ObjectiveOur aim was to determine the effectiveness of implementing a prescription policy for opioids on overall opioid prescribing patterns in a hospital ED.MethodsThe ED provider group of an academic, non-university–affiliated urban hospital with 23,000 annual patient visits agreed to opioid prescribing guidelines for chronic pain with the goal of limiting prescriptions that may be used for abuse or diversion. These guidelines were instituted in the ED through collaborative staff meetings and educational and training sessions. We used the electronic medical record to analyze the number and type of opioid discharge prescriptions during the study period from 2006–2014, before and after the prescribing guidelines were instituted in the ED.ResultsThe number of patients discharged with a prescription for opioids decreased 39.6% (25.7% to 15.6%; absolute decrease 10.2%; 95% confidence interval [CI] 9.6–10.7; p < 0.001) after the intervention. The improvements were sustained 2.5 years after the intervention. Decreases were seen in all major opioids (hydrocodone, oxycodone, hydromorphone, and codeine). The number of pills per prescription also decreased 14.8%, from 19.5% to 16.6% (absolute decrease 2.9; 95% CI 2.6–3.1; p < 0.001).ConclusionsImplementation of an ED prescription opioid policy was associated with a significant reduction in total opioid prescriptions and in the number of pills per prescription.

http://ift.tt/2iSq9y3

Standardized Direct Observation Assessment Tool: Using a Training Video

Publication date: Available online 19 January 2017
Source:The Journal of Emergency Medicine
Author(s): Kathleen E. Kane, Kevin R. Weaver, Gavin C. Barr, Gary Bonfante, Nicole L. Bendock, Brian M. Berry, Stephanie L. Goren-Garcia, Marc B. Lewbart, Allison L. Raines, Gregory Smeriglio, Bryan G. Kane
BackgroundWe developed a DVD training tool to educate physicians evaluating emergency residents on accurate Standardized Direct Observation Assessment Tool (SDOT) application.ObjectiveOur goal was to assess whether this training video improved attendings' and senior residents' SDOT use.MethodsParticipants voluntarily completed SDOT evaluations based on a scripted "test" video. A DVD with "positive" and "negative" scenarios of proper SDOT use was viewed. It included education on appropriate recording of 26 behaviors. The test scenario was viewed again and follow-up SDOTs submitted. Performances by attendings and residents on the pre- and post-test SDOTs were compared.ResultsTwenty-six attendings and 26 senior residents participated. Prior SDOT experience was noted for 8 attendings and 11 residents. For 20 anchors, participants recorded observed behaviors with statistically significant difference on one each of the pretest (no. 20; p = 0.034) and post-test (no. 14; p = 0.041) SDOTs. On global competency assessments, pretest medical knowledge (p = 0.016) differed significantly between groups. The training intervention changed one anchor (no. 5; p = 0.035) and one global assessment (systems-based practice; p = 0.031) more negatively for residents. Recording SDOTs with exact agreement occurred 48.73% for attendings pretest and 54.41% post-test; resident scores were 45.86% and 49.55%, respectively. DVD exposure slightly raised attending scores (p = 0.289) and significantly lowered resident scores (p = 0.046).ConclusionsExposure to an independently developed SDOT training video tended to raise attending scores, though without significance, while at the same time lowered senior resident scores statistically significantly. Emergency attendings' and senior residents' SDOT scoring rarely differed with significance; about half of anchor behaviors were recorded with exact agreement. This suggests senior residents, with appropriate education, may participate in SDOT assessment.

http://ift.tt/2jUiS2w

Enabling Donation after Cardiac Death in the Emergency Department: Overcoming Clinical, Legal, and Ethical Concerns

Publication date: Available online 19 January 2017
Source:The Journal of Emergency Medicine
Author(s): Michael Dailey, Sean P. Geary, Stefan Merrill, Marleen Eijkholt
BackgroundIn light of the growing gap between candidates for organ donation and the actual number of organs available, we present a unique case of organ donation after cardiac death. We hope to open a discussion regarding organ procurement from eligible donors in the prehospital and emergency department setting.CaseThis case study, involving an otherwise healthy man who, after suffering an untimely death, was able to successfully donate his organs, highlights the need to develop an infrastructure to make this type of donation a viable and streamlined option for the future.DiscussionGiven the departure from traditional practice in United States transplantation medicine, we bring forth legal and ethical considerations regarding organ donation in the emergency department. We hope that this case discussion inspires action and development in the realm of transplant medicine, with the aim of honoring the wishes of donors and the families of those who wish to donate in a respectful way, while using our medical skills and technologies to afford candidates who are waiting for organs a second chance.ConclusionsWe believe that this case shows that donation after cardiac death from the emergency department, while resource-intensive is feasible. We recognize that in order for this to become a more attainable goal, additional resources and systems development is required.

http://ift.tt/2j1Br6H

Primary orbital mantle cell lymphoma: Flow cytometric immunophenotyping as an adjunct to fine-needle aspiration cytology for diagnosis

Sangeeta Verma, Nalini Gupta, Satyawati Mohindra, Manupdesh Singh Sachdeva, Arvind Rajwanshi

CytoJournal 2017 14(1):2-2

http://ift.tt/2jfyfSI

Evaluation of polymerase chain reaction in space-occupying lesions of liver reported as granulomatous inflammation/tuberculosis on fine-needle aspiration cytology

Kusum Sharma, Nalini Gupta, Kapil Goyal, Ajay Kumar Duseja, Aman Sharma, Arvind Rajwanshi

CytoJournal 2017 14(1):1-1

Background: Tubercular involvement of the liver is uncommon, but is a serious consideration in differential diagnosis of granulomatous conditions, especially in endemic regions like India. Objective: To assess the role of polymerase chain reaction (PCR) done on archival cytological material in diagnosing tuberculosis (TB) in cases reported as granulomatous inflammation/TB in liver lesions. Materials and Methods: This was a retrospective study including a total of 17 cases of liver space-occupying lesions (SOLs) reported as granulomatous inflammation (n = 12) and TB (n = 5). The smears were retrieved from the archives of the department and were reviewed for the cytomorphologic features. Air-dried smears stained with May–Grünwald–Giemsa (MGG) stain were assessed for the representative material in the form of epithelioid granulomas and giant cells. One/two MGG smears from each case were destained and the material was used for performing PCR for Mycobacterium tuberculosis by amplification of 123 bp fragment of the IS6110 insertion element. Results: The age of the patients ranged from 3 to 61 years. There were 12 females and 5 males. The patients presented with solitary/multiple liver SOLs. DNA could be extracted from 10/17 cases from archival MGG smears. PCR positivity was noted in 8/10 cases (including four acid-fast bacilli smear-positive cases), confirming a diagnosis of TB. Conclusion: Cytomorphology alone may not be sufficient for differentiating various granulomatous lesions reported in liver SOLs. DNA can be extracted from the archival cytological MGG-stained smears. PCR should be carried out if Ziehl–Neelsen staining is negative in granulomatous lesions, especially when material has not been submitted for culture.

http://ift.tt/2kabzay

Hypoxia-inducing factor (HIF)-1α-derived peptide capable of inducing cancer-reactive cytotoxic T lymphocytes from HLA-A24+ patients with renal cell carcinoma

Publication date: March 2017
Source:International Immunopharmacology, Volume 44
Author(s): Takafumi Minami, Naoki Matsumura, Koichi Sugimoto, Nobutaka Shimizu, Marco De Velasco, Masahiro Nozawa, Kazuhiro Yoshimura, Nanae Harashima, Mamoru Harada, Hirotsugu Uemura
Hypoxic tumor microenvironment makes cancer cells to be therapy-resistant and hypoxia-inducing factors (HIFs) play a central role in hypoxic adaptation. Especially, renal cell carcinoma (RCC) is often associated with von Hippel-Lindau (VHL) gene mutations, leading to up-regulation of HIFs. However, from a different point of view, this suggests the possibility that HIFs could be promising targets in anti-cancer therapy. In this study, we searched for HIF-1α-derived peptides that are able to induce RCC-reactive cytotoxic T lymphocytes (CTLs) from HLA-A24⁺ RCC patients. Among five peptides derived from HIF-1α, which were prepared based on the binding motif to the HLA-A24 allele, a HIF-1α278–287 peptide induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24⁺ RCC patients most effectively. In immunoblot assays, the expression of HIF-1α was lowly detected in whole and nuclear lysates of RCC cell lines even under normoxia (20% O2), and their expression in whole lysates was increased under hypoxia (1% O2). Additionally, HIF-1α278–287 peptide-stimulated T cells showed a higher cytotoxicity against HLA-A24⁺ HIF-1α-expressing RCC cells than against HLA-A24⁻ HIF-1α-expressing RCC cells. The cytotoxicity was inhibited by the addition of HIF-1α278–287 peptide-pulsed cold target cells. Altogether, these results indicate that the HIF-1α278–287 peptide could be a candidate for peptide-based anti-cancer vaccines for HLA-A24⁺ RCC patients.

http://ift.tt/2jUfa9d

Primary acinic cell carcinoma of the lung with psammoma bodies: A case report and review of literature

Publication date: Available online 19 January 2017
Source:Pathology - Research and Practice
Author(s): Xiu-Peng Zhang, Gui-Yang Jiang, Qing-Fu Zhang, Hong-Tao Xu, Qing-Chang Li, En-Hua Wang
Salivary gland-type tumors are rare in the lung. Primary acinic cell carcinoma of the lung is extremely rare. Here, we report a case of primary acinic cell carcinoma of the lung with prominent psammoma bodies. A 31-year-old man came to our hospital with a tumor in the basal segment of the lower lobe of the right lung. The tumor tissue displayed solid, acinar, or microcystic structures at different regions. A large amount of psammoma bodies were scattered in more than half of the tumor. The majority of the tumor cells were round or polygonal in shape, with abundant acidophilic granular or vacuolated cytoplasm. The results of tumor tissue tests were positive for periodic acid Schiff (PAS), broad-spectrum cytokeratin, and cytokeratin 7 staining, but negative for P63, TTF-1, CD56, synaptophysin, HMB45, and PR staining. Based on the clinical information, histological features, and the immunohistochemical staining profile, the tumor was diagnosed as a primary acinic cell carcinoma of the lung. This is the first report of primary acinic cell carcinoma with prominent psammoma bodies in the lung.

http://ift.tt/2k86D1D

Primary multiple tumor with affection of the thyroid gland, uterus, urinary bladder, mammary gland and other organs

Publication date: Available online 19 January 2017
Source:Pathology - Research and Practice
Author(s): А. Romaniuk, M. Lyndin, V. Smiyanov, Vl. Sikora, A. Rieznik, Y. Kuzenko, H. Budko, Yu. Moskalenko, L. Karpenko, Vol. Sikora, O. Gladchenko
BackgroundNowadays multiple primary tumor is characterized by growth and development of two or more tumors in one patient. The total world sickness rate ranges from 1% to 37%. The presence of four or more tumors in one patient is rare case and presented as casuistry.Case presentationWe showed a case of multiple primary tumor with metahronic lesion of the thyroid, uterus and breast, followed by synchronous benign tumors of the subcutaneous fat, urinary bladder and gallbladder was considered. The development of all malignant tumors in all cases was accompanied by the presence of benign precancerous processes. Analysis of neoplasia histology shows the predominance of poorly differentiated forms of cancers in women with increased aggressiveness of cancerous tissue in each subsequent case and the growth of metastatic ability. The influence of heredity on the tumors progress is confirmed by immunohistochemical characteristics of cancer cells. Steroid-sensitive tissue of the uterus and breast in both cases didn't express ER and PR, in all cases the tissue had overexpression of Ki-67, p53, bax and bcl-2 receptors. The results of DNA testing for determination the Lynch syndrome revealed the presence of microsatellite instability in genetic material. The results of studies revealed the absence of mutations in these genes (MLH1, MSH2 and MSH6). Despite the negative results of the study, it doesn't exclude the possibility of Lynch syndrome for 100%, and its presence may be caused by the mutations of other genes (PMS1, PMS2 and MLH3), responsible for DNA repair. Unfortunately there wasn't any opportunity to study their mutations.ConclusionsWhile studying the anamnesis of life and disease of women it was revealed that she had multiple primary tumor with lesions of the breast, urinary bladder, thyroid, uterus and other organs. This study shows that neoplastic tissue in all cases had high rates of cell proliferation, their antiapoptotic stability, expression of prognostically unfavorable-receptors, and absence of favorable prognostic markers. Histological study revealed high rates of malignant neoplastic tissue. It indicates to the existence of common mechanisms of malignant tumors and their genetic predisposition that can be clearly observed in many generations of patient.

http://ift.tt/2iJ9r9e

Immunohistochemical expression of galectin-3 is significantly associated with grade, stage and differentiation of endometrial carcinomas

Publication date: Available online 19 January 2017
Source:Pathology - Research and Practice
Author(s): Jaudah Al-Maghrabi, Amer Shafie Abdelrahman, Tawfik Ghabrah, Nadeem Shafique Butt, Basim Al-Maghrabi, Mohamad Nidal Khabaz
This study describes galectin-3 immunohistochemical phenotype and its association with clinicopathological factors in the carcinoma of endometrium. Seventy one cases of endometrial carcinoma and 30 cases of benign and normal endometrium were employed for the detection of galectin-3 protein using tissue microarrays and immunohistochemistry staining. Thirty nine (55%) cases, including 54.2% of endometrioid adenocarcinomas and 55.5% serous carcinomas, were positively stained for galectin-3. Brown granular expression of this glycoprotein was detected in transformed epithelial cells of 36 cases including 28 cases with membranous and cytoplasmic staining and 8 cases with only cytoplasmic staining; nuclear expression was present in stromal cells of the remaining 3 cases. Twenty-four (80%) control cases showed granular cytoplasmic and membranous expression, and six control cases were negative. Tumor grade, stage and differentiation were significantly associated with galectin-3 immunoreactivity (p-values are 0.043, 0.016, and 0.044 respectively), cases with membranous and cytoplasmic staining is significantly associated with grade I and stage II, while cases with loss of staining are more frequent in grade II, III and poorly differentiated tumors. No significant association of galectin-3 staining was observed with age, diagnosis, recurrence and alive status. The current study supports the tumor suppression role of galectin-3 in endometrial carcinoma. Greater galectin-3 immunostaining has been found in control endometrial tissues compared to endometrial tumors. Loss or decreased galectin-3 immunoexpression gives a sign for poor prognoses in endometrial carcinoma patients.

http://ift.tt/2k7WZfw

From molecular insight to therapeutic strategy: the holistic approach for treating Triple Negative Breast Cancer

Publication date: Available online 19 January 2017
Source:Pathology - Research and Practice
Author(s): Rittwika Bhattacharya, Koyel Banerjee, Nupur Mukherjee, Minakshi Sen, Ashish Mukhopadhyay

http://ift.tt/2iJ9t0W

Immunoglobulin G4-Related Thyroid Diseases.

Immunoglobulin G4-Related Thyroid Diseases.

Eur Thyroid J. 2016 Dec;5(4):231-239

Authors: Kottahachchi D, Topliss DJ

Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a new disease category involving many organ systems, including the endocrine system in general and the thyroid in particular. Since an initial association was made between hypothyroidism and autoimmune (IgG4-related) pancreatitis, more forms of IgG4-related thyroid disease (IgG4-RTD) have been recognized. Four subcategories of IgG4-RTD have so far been identified: Riedel thyroiditis (RT), fibrosing variant of Hashimoto thyroiditis (FVHT), IgG4-related Hashimoto thyroiditis, and Graves disease with elevated IgG4 levels. Although a male predominance is seen for IgG4-RD in general, RT and FVHT have a female preponderance. The pathogenesis of IgG4-RD is not completely understood; however, genetic factors, antigen-antibody reactions, and an allergic phenomenon have been described. Diagnosis of IgG4-RD requires a combination of clinical features, serological evidence, and histological features. Histology is the mainstay of diagnosis, with IgG4 immunostaining. Although serum IgG4 levels are usually elevated in IgG4-RD, raised serum IgG4 is neither necessary nor adequate for diagnosis. Imaging supports the diagnosis and is a useful tool in disease monitoring. Management of IgG4-RTD is both medical and surgical. Steroids are the first-line treatment and may produce a swift response. Tamoxifen and rituximab are second-line agents used in steroid-resistant patients. Surgical debulking is carried out in RT solely as a procedure to relieve obstruction. Other endocrine associations described with IgG4-RD are hypophysitis and Hashimoto encephalopathy. IgG4-RTD is an uncommon disease entity, and prompt diagnosis and treatment can improve outcomes.

PMID: 28101487 [PubMed - in process]

http://ift.tt/2jGntbw

Serine Is an Essential Metabolite for Effector T Cell Expansion

Publication date: Available online 19 January 2017
Source:Cell Metabolism
Author(s): Eric H. Ma, Glenn Bantug, Takla Griss, Stephanie Condotta, Radia M. Johnson, Bozena Samborska, Nello Mainolfi, Vipin Suri, Hannah Guak, Maria L. Balmer, Mark J. Verway, Thomas C. Raissi, Harmony Tsui, Giselle Boukhaled, Sofia Henriques da Costa, Christian Frezza, Connie M. Krawczyk, Adam Friedman, Mark Manfredi, Martin J. Richer, Christoph Hess, Russell G. Jones
During immune challenge, T lymphocytes engage pathways of anabolic metabolism to support clonal expansion and the development of effector functions. Here we report a critical role for the non-essential amino acid serine in effector T cell responses. Upon activation, T cells upregulate enzymes of the serine, glycine, one-carbon (SGOC) metabolic network, and rapidly increase processing of serine into one-carbon metabolism. We show that extracellular serine is required for optimal T cell expansion even in glucose concentrations sufficient to support T cell activation, bioenergetics, and effector function. Restricting dietary serine impairs pathogen-driven expansion of T cells in vivo, without affecting overall immune cell homeostasis. Mechanistically, serine supplies glycine and one-carbon units for de novo nucleotide biosynthesis in proliferating T cells, and one-carbon units from formate can rescue T cells from serine deprivation. Our data implicate serine as a key immunometabolite that directly modulates adaptive immunity by controlling T cell proliferative capacity.

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Teaser

Activated lymphocytes reprogram their metabolism to support rapid growth and proliferation. Ma et al. reveal an essential role for the non-essential amino acid serine in T cell-mediated immune responses and show that serine metabolism is required for optimal T cell proliferation by fueling one-carbon metabolism and nucleotide biosynthesis.

http://ift.tt/2jTUpui

A Non-invasive Method to Assess Hepatic Acetyl-CoA In Vivo

Publication date: Available online 19 January 2017
Source:Cell Metabolism
Author(s): Rachel J. Perry, Liang Peng, Gary W. Cline, Kitt Falk Petersen, Gerald I. Shulman
Acetyl-coenzyme A (acetyl-CoA) is a critical metabolic signaling molecule that regulates gluconeogenesis, pyruvate oxidation, protein acetylation, and steroid and fatty acid biosynthesis; however, measurements of this metabolite using standard biochemical approaches are technically demanding, and there is currently no method to non-invasively assess hepatic acetyl-CoA content in vivo. To this end, we developed and validated a method to non-invasively detect differences in hepatic acetyl-CoA content in vivo across a 5-fold range of physiological acetyl-CoA concentrations by assessing the turnover of [¹³C4]β-hydroxybutyrate (β-OHB). Here, we show a strong correlation (R² = 0.86, p < 0.0001) between hepatic acetyl-CoA content and β-OHB turnover in rats with varying degrees of fasting hyperglycemia and insulin resistance. These studies demonstrate that β-OHB turnover can be used as a surrogate to non-invasively assess hepatic acetyl-CoA content, thereby allowing researchers to further elucidate the role of this metabolite in the regulation of hepatic gluconeogenesis and other metabolic processes in vivo.

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Levels of acetyl-CoA, a key metabolite in metabolism and signaling, are technically challenging to measure. Perry et al. present a novel method to non-invasively assess hepatic acetyl-CoA content in vivo by assessing rates of β-OHB turnover, validating this approach in rats with varying degrees of fasting hyperglycemia and insulin resistance.

http://ift.tt/2jTMMnA

Publication date: January 2017
Source:Neoplasia, Volume 19, Issue 1

http://ift.tt/2j1pqxZ

GALNT6 Stabilizes GRP78 Protein by O-glycosylation and Enhances its Activity to Suppress Apoptosis Under Stress Condition

Publication date: January 2017
Source:Neoplasia, Volume 19, Issue 1
Author(s): Jiaying Lin, Suyoun Chung, Koji Ueda, Koichi Matsuda, Yusuke Nakamura, Jae-Hyun Park
We previously reported that overexpression of an O-type glycosyltransferase, GALNT6 (polypeptide N-acetylgalactosaminyltransferase 6) played critical roles in mammary carcinogenesis. To further investigate the biological function of GALNT6, we screened a substrate protein(s) of GALNT6 using a VVA (Vicia villosa agglutinin) lectin (specific to GalNAc-Ser/Thr) pull-down method followed by mass spectrometry analysis. Here we report GRP78 (glucose-regulated protein 78, also known as HSPA5, heat shock 70 kDa protein 5), which is highly expressed in cancer cells and indicated to play important roles in various cellular processes including ER (endoplasmic reticulum) stress and autophagy, as a novel substrate of GALNT6. We found that GALNT6-induced O-glycosylation is critical for the stability of GRP78, its subcellular localization in ER, and its anti-apoptotic function. Furthermore, we demonstrated that overexpression of GRP78 could be important for Golgi-to-ER relocation of GALNT6. Collectively, our study revealed biological significances of O-glycosylation of GRP78 protein, which might play significant roles in the survival of cancer cells, and thus provided a new insight in cancer cell death and useful information for development of anti-cancer treatment targeting the GALNT6-GRP78 pathway.

http://ift.tt/2iRVfpw

Gaseous mercury flux from salt marshes is mediated by solar radiation and temperature

Publication date: March 2017
Source:Atmospheric Environment, Volume 153
Author(s): Tom Sizmur, Gordon McArthur, David Risk, Robert Tordon, Nelson J. O'Driscoll
Salt marshes are ecologically sensitive ecosystems where mercury (Hg) methylation and biomagnification can occur. Understanding the mechanisms controlling gaseous Hg flux from salt marshes is important to predict the retention of Hg in coastal wetlands and project the impact of environmental change on the global Hg cycle. We monitored Hg flux from a remote salt marsh over 9 days which included three cloudless days and a 4 mm rainfall event. We observed a cyclical diel relationship between Hg flux and solar radiation. When measurements at the same irradiance intensity are considered, Hg flux was greater in the evening when the sediment was warm than in the morning when the sediment was cool. This is evidence to suggest that both solar radiation and sediment temperature directly influence the rate of Hg(II) photoreduction in salt marshes. Hg flux could be predicted from solar radiation and sediment temperature in sub-datasets collected during cloudless days (R² = 0.99), and before (R² = 0.97) and after (R² = 0.95) the rainfall event, but the combined dataset could not account for the lower Hg flux after the rainfall event that is in contrast to greater Hg flux observed from soils after rainfall events.

http://ift.tt/2jU31Rx

Air pollutants and toxic emissions of various mileage motorcycles for ECE driving cycles

Publication date: March 2017
Source:Atmospheric Environment, Volume 153
Author(s): Jiun-Horng Tsai, Pei-Hsiu Huang, Hung-Lung Chiang
Motorcycles were selected to determine their fuel consumption and exhaust emissions following ECE driving cycles. Exhaust constituents including CO2, CO, NOx, total hydrocarbons (THC) and hydrocarbon species (27 paraffins, 9 olefins, 16 aromatics and 15 carbonyls) were investigated for this work. The age of 10– 90% of the selected motorcycles ranged from 2.5 to 12.4 years, and their mileage ranged from 5400 to 39,300 km. CO emission ranged from 1.4 to 6.4 g/km (median value: 2.98 g/km), THC from 0.41 to 1.54 g/km (median value: 0.98 g/km), NOx from 0.16 to 0.28 g/km (median value: 0.21 g/km), CO2 from 58.9 to 62.2 g/km (median value: 60.5 g/km) and fuel consumption from 30.7 to 36.4 km/L (median value: 33.4 km/L), corresponding to the percentage cumulative data from 10 to 90% of the selected motorcycles. Results indicated that the motorcycle exhaust emission and fuel consumption depended on their mileage and ages. An increase in mileage of 1000 km resulted in an increase of 103 mg for CO emission and 14.7 mg for hydrocarbon emission and a reduction of 1.52 mg NOx emission and 0.11 km per liter fuel consumption. For various VOC groups, a mileage increase of 1000 km corresponding to the increased exhaust emission of paraffins was 6.71 mg, olefins 1.90 mg, aromatics 7.04 mg, carbonyls 0.283 mg and 67 VOC species 15.9 mg. Fuel consumption and emissions of CO and hydrocarbon increased in motorcycles over the guaranteed mileage of 15,000 km.

http://ift.tt/2iIQsf2

Growing season methane emissions from a permafrost peatland of northeast China: Observations using open-path eddy covariance method

Publication date: March 2017
Source:Atmospheric Environment, Volume 153
Author(s): Xueyang Yu, Changchun Song, Li Sun, Xianwei Wang, Fuxi Shi, Qian Cui, Wenwen Tan
The mid-high latitude permafrost peatlands in the Northern Hemisphere is a major natural source of methane (CH4) to the atmosphere. Ecosystem scale CH4 emissions from a typical permafrost peatland in the Great Hing'an Mountains were observed during the growing season of 2014 and 2015 using the open-path eddy covariance method. Relevant environmental factors such as temperature and precipitation were also collected. There was a clear diurnal variation in methane emissions in the second half of each growing season, with significantly higher emission rates in the wet sector of study area. The daily CH4 exchange ranged from 1.8 mg CH4 m⁻² d⁻¹ to 40.2 mg CH4 m⁻² d⁻¹ in 2014 and ranged from −3.9 to 15.0 mg CH4 m⁻² d⁻¹ in 2015. There were no peaks of CH4 fluxes during the spring thawing period. However, large peaks of CH4 emission were found in the second half of both growing seasons. The CH4 emission after Jul 25th accounted for 77.9% of total growing season emission in 2014 and 85.9% in 2015. The total CH4 emission during the growing season of 2014 and 2015 was approximately 1.52 g CH4 m⁻² and 0.71 g CH4 m⁻², respectively. CH4 fluxes during the growing seasons were significantly correlated with thawing depth (R² = 0.71, P < 0.01) and soil temperatures (R² = 0.75, P < 0.01) at 40 cm depth. An empirical equation using these two major variables was modified to estimate growing season CH4 emissions in permafrost peatlands. Our multiyear observations indicate that the time-lagged volume of precipitation during the growing season is a key factor in interpreting locally inter-annual variations in CH4 emissions. Our results suggested that the low temperature in the deep soil layers effectively restricts methane production and emission rates; these conditions may create significant positive feedback under global climate change.

http://ift.tt/2iIQiVa

Letter to the editor: Critical assessments of the current state of scientific knowledge, terminology, and research needs concerning the ecological effects of elevated atmospheric nitrogen deposition in China

Publication date: March 2017
Source:Atmospheric Environment, Volume 153
Author(s): Yuepeng Pan, Yongwen Liu, Gregory R. Wentworth, Lin Zhang, Yuanhong Zhao, Yi Li, Xuejun Liu, Enzai Du, Yunting Fang, Hongwei Xiao, Hongyuan Ma, Yuesi Wang
In a publication in Atmospheric Environment (http://ift.tt/2iINV4t), Gu et al. (2015) estimated that "the total nitrogen (N) deposition in 2010 was 2.32 g N m⁻² yr⁻¹" in China. This value is comparable with previous estimations based on a synthesized dataset of wet/bulk inorganic N deposition observations, which underestimates the total N deposition since their algorithm (equations (2) and (3) in their paper) does not account for dry deposition of NH3, HNO3, NOx and wet/dry deposition of HONO and organic nitrogen (e.g. amines, amides, PAN). Indeed, Gu et al. (2015) mixed the terminology of wet/bulk deposition and total deposition. Another flawed assumption by Gu et al. (2015) is that all inorganic N in precipitation estimated by their algorithm originates from fertilizer and coal combustion. This is incorrect and almost certainly causes biases in the spatial and temporal distribution of estimated wet/bulk inorganic N deposition (Fig. 5 in their paper), further considering the fact that they neglected important N sources like livestock and they did not consider the nonlinearity between various sources and deposition. Besides the input data on N deposition, the model validation (Sect. 2.3.2) described in their paper also requires clarification because the detailed validation information about the time series of observational dataset versus modeling results was not given. As a result of these combined uncertainties in their estimation of N deposition and the lack of detail for model-measurement comparison, their estimates of the impacts of N deposition on carbon storage in Chinese forests may need further improvement. We suggest the clarification of the terminology regarding N deposition, especially for wet deposition, bulk deposition, gaseous and particulate dry deposition or total deposition since the accurate distinction between these terms is crucial to investigating and estimating the effects of N deposition on ecosystems.

http://ift.tt/2jTRZfd

Endorectal brachytherapy boost after external beam radiotherapy in elderly or medically inoperable patients with rectal cancer: primary outcomes of the phase I HERBERT study

Publication date: Available online 20 January 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): E.C. Rijkmans, A. Cats, R.A. Nout, H.J.G.D. van den Bongard, M. Ketelaars, J. Buijsen, T. Rozema, J.H. Franssen, L.A. Velema, B. van Triest, C.A.M. Marijnen
PurposeThis study evaluated toxicity and efficacy of the combination of external beam radiotherapy (EBRT) followed by high dose rate endorectal brachytherapy (HDREBT) boost in elderly and medically inoperable patients with rectal cancer.Material and MethodsA phase I dose escalation study was performed. Treatment consisted of EBRT (13x3 Gy) followed by three weekly brachytherapy applications six weeks later. HDREBT dose started at 5 Gy per fraction, increasing with 1 Gy per fraction if dose limiting toxicity (DLT, defined as > grade 3 proctitis < 6 weeks after HDREBT) occurred in ≤ 2 patients per dose level. The primary endpoint was the maximum tolerated dose, defined as one dose-level below the dose were three patients experienced DLT. Secondary endpoints were severe treatment-related late toxicity, clinical tumor response, freedom from local progression (FFLP) and local progression free and overall survival (L-PFS and OS).ResultsThirty-eight patients with a median age of 83 years were included in the study. Thirty-two were evaluable for DLT and late toxicity and 33 for response evaluation. Maximum delivered dose was 8 Gy per fraction resulting in a recommended dose of 7 Gy per fraction. Response occurred in 29 of 33 patients (87.9%) with 60% complete response (CR). L-PFS and OS were 42% and 63% at two years. Patients with CR showed a significant improved L-PFS (60% at 2 yrs, p=0.006) and a trend in improved OS (80% at 2 yrs, p=0.11). Severe late toxicity occurred in 10/32 patients.ConclusionHDREBT after EBRT results in a high overall response rate, with improved local progression free survival for patients with a CR. The high observed rate of severe late toxicity requires further evaluation of the risks and benefits of a HDREBT boost.

http://ift.tt/2k7UJ7W

Concomitant Behavioral and PFC Neuronal Activity Recorded Following Dose-Response Protocol of MPD in Adult Male Rats

Publication date: Available online 19 January 2017
Source:Brain Research Bulletin
Author(s): Sidish S. Venkataraman, Catherine Claussen, Michael Joseph, Nachum Dafny
The use of methylphenidate (MPD), a commonly prescribed drug to treat attention-deficit hyperactivity disorder (ADHD), has steadily increased over the past 25 years. This trend has been accompanied by more MPD abuse by ordinary individuals for its cognitive enhancing effects. Therefore, understanding the effects of MPD on the prefrontal cortex (PFC), a brain area involved in higher cortical processing such as executive function, language, planning, and attention regulation, is of particular importance. The goal of this study is to investigate the effects of acute and chronic dose-response characteristics following MPD exposure on both the PFC neuronal population and behavioral activity in freely behaving animals implanted previously with permanent electrodes within the PFC. Four groups of animals were used: saline (control), 0.6, 2.5, and 10.0mg/kg MPD. It was observed that the same dose of either 0.6, 2.5, or 10.0mg/kg repetitive (chronic) MPD exposure elicited behavioral sensitization in some animals and behavioral tolerance in others, and that the majority of PFC units recorded from animals expressing behavioral sensitization to chronic MPD exposure responded to MPD by increasing their neuronal firing rate, whereas the majority of PFC neurons recorded from animals expressing behavioral tolerance in response to chronic MPD responded by decreasing their neuronal firing rate. This data suggests that in animals that display behavioral sensitization, chronic MPD exposure causes an increase in the number of post-synaptic D1 dopamine receptors leading to an increase in behavioral and neuronal firing rate, while in animals that display behavioral tolerance, chronic MPD exposure causes an increase in the number of post-synaptic D2 dopamine receptors leading to a decrease in behavioral and neuronal firing rate. This dichotomy needs to be further investigated.

http://ift.tt/2jfkQtw

Possible involvement of the CA1 GABAergic system on harmaline induced memory consolidation deficit

Publication date: Available online 19 January 2017
Source:Brain Research Bulletin
Author(s): Mohammad Nasehi, Naghmeh Saadati, Fatemeh Khakpai, Mohammad-Reza Zarrindast
Activation of the GABAB receptors inhibit learning and memory processes. The current research was designed to examine the role of dorsal hippocampal (CA1) GABAB receptors on harmaline induced memory consolidation deficit in mice. For this purpose, the effects induced by the GABAB antagonist phaclofen and the GABAB agonist baclofen on memory consolidation were assessed by using the step-down inhibitory avoidance task. Furthermore, the possible involvement of harmaline on GABAB receptor's effects was also assessed through using the same behavioral procedure. In a first dose response experiments, post-training intra-CA1 injections of phaclofen did not change while baclofen (0.1μg/mouse) impaired animals' performance in this task, suggesting a modulation of storage of information. Moreover, Post-training intra-peritoneal (i.p.) infusion of harmaline (2 and 5mg/kg) also decreased memory consolidation. Interestingly, phaclofen at the sub-threshold dose (0.001μg/mouse, intra-CA1), successfully antagonized the deficits on memory consolidation induced by the highest doses of harmaline (2 and 4mg/kg, i.p.). On the other hand, non significant dose of baclofenc (0.001μg/mouse, intra-CA1) potentiated impairment of memory consolidation induced by harmaline (2mg/kg, i.p.). In addition in all experiments, locomotor activity did not alter significantly. These results indicate a) that the CA1 GABAB receptors are involved in memory consolidation b) that harmaline interact with the CA1 GABAB receptors in modulation of memory consolidation.

http://ift.tt/2k9QAV6

Aesthetic nurses to take stand on Botox being administered by beauticians

An emergency motion condemning the injection of Botox and dermal fillers by non-health professionals, such as beauty therapists and hairdressers, is to be proposed at this year's 6th National...

http://ift.tt/2j0Wl5M

Tailoring Bi-Te based nanomaterials by electrodeposition: Morphology and crystalline structure

Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): M.P. Proenca, M. Rosmaninho, P.M. Resende, C.T. Sousa, J. Ventura, J.P. Araújo, L. Fernandes, P.B. Tavares, A.M. Pereira
Bi2Te3 is the most commonly used thermoelectric material in modern solid-state refrigerators and power generators based on this basic principle. Due to predictions of significant improvements in their efficiency by using nanostructured materials, a thorough study on thin films and nanowires deposited by the electrodeposition method are here presented. The study of the deposition applied potential effect on the morphology, stoichiometry and crystallinity of both thin films and nanowires has been conducted. The morphology and stoichiometry was found to highly depend on the deposition potential, where by increasing it one was able to accurately control the Te% content of the deposits. X-ray diffraction measurements have shown the presence of a strong relation between the material's crystallinity and the deposition potential, where samples ranged from monocrystalline, at very low potentials, to almost completely amorphous, at high potentials. Finally, nanowire diameters were seen to diminish with the applied potential, in conjunction with the general array.

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http://ift.tt/2iIBPIB

An experimental and numerical study on quasi-static and dynamic crashing behaviors for tailor rolled blank (TRB) structures

Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): Guangyong Sun, Huile Zhang, Guoxing Lu, Jianwen Guo, Junjia Cui, Qing Li
Design for lightweight and crashworthiness remains a fairly challenging issue in vehicle industry. These two performance characteristics often conflict with each other. While tailor rolled blank (TRB) structures, as a relatively newer configuration, are of potential to reduce the weight and improve the crashworthiness simultaneously; unfortunately there have been rare experimental investigations reported in literature for more extensive applications of TRB techniques. This paper aimed to explore the crashworthiness of the TRB top-hat (TRBTH) structures subjected to axial quasi-static/dynamic crash loading experimentally and numerically. First, three representative TRBTH configurations and the corresponding conventional top-hat structures with uniform thickness (THUT) were considered to conduct quasi-static/dynamic axial crashing experiments, respectively. The results revealed that TRBTH exhibited superior crashworthiness to the THUT counterpart with more stable deformation during the crushing process. Second, the finite element (FE) models of the TRBTH and THUT were established and validated experimentally. These FE simulation results agreed well with the testing results. Third, based on the validated FE models, the effects of the thickness distribution and position of transition zone on the crashworthiness of TRBTH were explored; and the results showed that they influenced the crashworthiness of TRBTH significantly. Furthermore, the crashworthiness of the TRBTH and corresponding THUT were compared; and the results indicated that the TRBTH is evidently superior to the conventional THTU in overall crashworthiness for the same weight. Therefore, the TRB technology is definitely effective and feasible for lightweighting design of vehicle, and the study is expected to provide some primary data and technical guidance for lightweight and crashworthiness design of TRB structures.

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http://ift.tt/2iIL77i

PRELIM II(EDI BOARD)

Publication date: January 2017
Source:Neuroscience Research, Volume 114

http://ift.tt/2jvyeLd

Editorial announcement – Welcome to the new journey of Neuroscience Research

Publication date: January 2017
Source:Neuroscience Research, Volume 114
Author(s): Hiroyuki Kamiguchi

http://ift.tt/2jFRLuQ

Prophylactic active immunization with a novel epitope vaccine improves cognitive ability by decreasing amyloid plaques and neuroinflammation in APP/PS1 transgenic mice

Publication date: Available online 19 January 2017
Source:Neuroscience Research
Author(s): Li Ding, Yuan Meng, Hui-Yi Zhang, Wen-Chao Yin, Yi Yan, Yun-Peng Cao
Both amyloid-β peptide (Aβ) deposition and neuroinflammation are considered to be early events that play pivotal roles in Alzheimer's disease (AD) pathogenesis and its associated cognitive impairment. Prophylactic anti-Aβ active immunotherapy is a promising therapeutic strategy for AD, if the Aβ-specific autoimmune responses to self T cell epitopes of Aβ can be avoided. This can be achieved by the use of antigen, which contains the B cell epitope of Aβ and excludes the Aβ-specific T cell epitope. In this study, we developed a novel peptide epitope vaccine, Aβ3-10-KLH, by coupling the B cell epitope Aβ3-10 to keyhole limpet hemocyanin (KLH) as the carrier protein, and subcutaneously injected it into 2.5-month-old APP/PS1 transgenic mice. Aβ3-10-KLH immunization induced high levels of anti-Aβ antibodies and significantly improved cognitive ability in APP/PS1 transgenic mice. Immunohistochemistry and immunofluorescence revealed that Aβ3-10-KLH immunization significantly reduced cerebral amyloid plaque formation and alleviated gliosis. The results indicate that Aβ3-10-KLH immunization successfully rescued cognitive impairment in APP/PS1 transgenic mice via decreasing cerebral Aβ deposition and neuroinflammation. Aβ3-10-KLH may potentially be safe and effective for prevention and treatment of AD.

http://ift.tt/2jvIMtX

Predictors of parent-reported quality of life of adolescents with cerebral palsy: A longitudinal study

Publication date: Available online 19 January 2017
Source:Research in Developmental Disabilities
Author(s): Marion Rapp, Nora Eisemann, Catherine Arnaud, Virginie Ehlinger, Jérôme Fauconnier, Marco Marcelli, Susan I. Michelsen, Malin Nystrand, Allan Colver, Ute Thyen
AimParent-reporting is needed to examine Quality of Life (QoL) of children with cerebral palsy (CP) across all severities. This study examines whether QoL changes between childhood and adolescence, and what predicts adolescent QoL.MethodSPARCLE is a European cohort study of children with CP, randomly sampled from population databases. Of 818 8–12-year-olds joining the study, 594 (73%) were revisited as 13–17-year-olds. The subject of this report is the 551 (316 boys, 235 girls) where the same parent reported QoL on both occasions using KIDSCREEN-52 (transformed Rasch scale, mean 50, SD 10 per domain). Associations were assessed using linear regression.ResultsBetween childhood and adolescence, average QoL reduced in six domains (1.3-3.8 points, p<0.01) and was stable in three (Physical wellbeing, Autonomy, Social acceptance). Socio-demographic factors had little predictive value. Childhood QoL was a strong predictor of all domains of adolescent QoL. Severe impairments of motor function, IQ or communication predicted higher adolescent QoL on some domains; except that severe motor impairment predicted lower adolescent QoL on the Autonomy domain. More psychological problems and higher parenting stress in childhood and their worsening by adolescence predicted lower QoL in five and eight domains respectively; contemporaneous pain in seven domains. The final model explained 30%–40% of variance in QoL, depending on domain.InterpretationIn general, impairment severity and socio-demographic factors were not predictors of lower adolescent QoL. However, pain, psychological problems and parenting stress were predictors of lower adolescent QoL in most domains. These are modifiable factors and addressing them may improve adolescent QoL.

http://ift.tt/2iRCtyx

Host–guest recognition on photo-responsive cell surfaces directs cell–cell contacts

Publication date: Available online 18 January 2017
Source:Materials Today
Author(s): Peng Shi, Enguo Ju, Jiasi Wang, Zhengqing Yan, Jinsong Ren, Xiaogang Qu
We developed an efficient cell surface engineering method based on lipid-insertion and host–guest recognition. With this methodology, we tailored cell membranes with β-cyclodextrin and subsequently manipulated cell behaviors through introducing photo-switchable guest molecule. Non-covalent nature afforded this method inherent reversibility. Furthermore, considering the remarkable molecular recognition property of aptamer, azobenzene-labeled aptamer was modified on cell surface through host–guest interaction and served as targeting ligand for selectively identifying target cells. Based on these, we designed a cell-based therapy for directing peripheral blood mononuclear cells to induce target cancer cell apoptosis. Our results provide new insights into engineering well-defined molecular recognition event on cell membrane to meet the demands of specific applications.

http://ift.tt/2iIznBL

Tissue engineering by decellularization and 3D bioprinting

Publication date: Available online 19 January 2017
Source:Materials Today
Author(s): Elena Garreta, Roger Oria, Carolina Tarantino, Mateu Pla-Roca, Patricia Prado, Francisco Fernández-Avilés, Josep Maria Campistol, Josep Samitier, Nuria Montserrat
Discarded human donor organs have been shown to provide decellularized extracellular matrix (dECM) scaffolds suitable for organ engineering. The quest for appropriate cell sources to satisfy the need of multiple cells types in order to fully repopulate human organ-derived dECM scaffolds has opened new venues for the use of human pluripotent stem cells (hPSCs) for recellularization. In addition, three-dimensional (3D) bioprinting techniques are advancing towards the fabrication of biomimetic cell-laden biomaterial constructs. Here, we review recent progress in decellularization/recellularization and 3D bioprinting technologies, aiming to fabricate autologous tissue grafts and organs with an impact in regenerative medicine.

http://ift.tt/2k7v4fE

Catalytically-etched hexagonal boron nitride flakes and their surface activity

Publication date: 30 April 2017
Source:Applied Surface Science, Volume 402
Author(s): Do-Hyun Kim, Minwoo Lee, Bora Ye, Ho-Kyun Jang, Gyu Tae Kim, Dong-Jin Lee, Eok-Soo Kim, Hong Dae Kim
Hexagonal boron nitride (h-BN) is a ceramic compound which is thermally stable up to 1000°C in air. Due to this, it is a very challenging task to etch h-BN under air atmosphere at low temperature. In this study, we report that h-BN flakes can be easily etched by oxidation at 350°C under air atmosphere in the presence of transition metal (TM) oxide. After selecting Co, Cu, and Zn elements as TM precursors, we simply oxidized h-BN sheets impregnated with the TM precursors at 350°C in air. As a result, microscopic analysis revealed that an etched structure was created on the surface of h-BN flakes regardless of catalyst type. And, X-ray diffraction patterns indicated that the air oxidation led to the formation of Co3O4, CuO, and ZnO from each precursor. Thermogravimetric analysis showed a gradual weight loss in the temperature range where the weight of h-BN flakes increased by air oxidation. As a result of etching, pore volume and pore area of h-BN flakes were increased after catalytic oxidation in all cases. In addition, the surface of h-BN flakes became highly active when the h-BN samples were etched by Co3O4 and CuO catalysts. Based on these results, we report that h-BN flakes can be easily oxidized in the presence of a catalyst, resulting in an etched structure in the layered structure.

Graphical abstract

http://ift.tt/2j0BO1e

PDGFRa amplification in multiple skin lesions of undifferentiated pleomorphic sarcoma (UPS): a clue for intimal sarcoma metastases

Abstract

A 62-year-old HIV-positive man was admitted for multiple cutaneous and subcutaneous nodules on his lower limbs, corresponding to an undifferentiated proliferation of spindle and pleomorphic cells, with irregular nuclei and numerous mitoses. The tumor cells were negative for a large panel of immunohistochemical markers, except CD10. MDM2 immunohistochemical staining was also negative, leading to the diagnosis of FNCLCC grade III Undifferentiated Pleomorphic Sarcoma (UPS). aCGH showed a highly complex karyotype, with amplification of the 4q12 region, an area that contains only the PDGFRa gene. This amplification of PDFGRa, molecular hallmark of Intimal Sarcoma (IS), led to the diagnosis of skin IS metastasis. A positron emission tomography (PET) showed a hypermetabolic mass protruding in the pre-aortic area, consistent with the diagnosis of aortic IS. Our study shows that a rare differential diagnosis in peripheral UPS can be IS skin metastasis, and underlines the importance of molecular analyses in UPS.

http://ift.tt/2iImvvs

Intraepidermal proliferation of Merkel cells within a seborrheic keratosis: Merkel cell carcinoma in-situ or Merkel cell hyperplasia?

Abstract

Intradepidermal proliferation of Merkel cells without any dermal component has been interpreted as either a hyperplastic process secondary to chronic ultraviolet radiation (UVR) or a neoplastic process, namely, Merkel cell carcinoma (MCC) in-situ. The recent criteria that have been proffered to diagnose MCC in-situ, unfortunately, are identical to those that have been applied to Merkel cell hyperplasia in the past, posing a diagnostic quandary when faced with an intraepidermal proliferation of Merkel cells. Most previously reported cases of MCC in-situ have occurred within associated epithelial lesion that includes solar (actinic) keratosis and squamous-cell carcinoma in-situ. Similarly, Merkel cell hyperplasia has been reported to occur in association with a variety of epithelial lesions as well as on chronically sun-damaged skin. Herein, a case of an intraepidermal proliferation of Merkel cells within a seborrheic keratosis is presented accompanied by a discussion on whether the proliferation represents another case of Merkel-cell carcinoma in-situ or an incidental hyperplastic process on chronically sun-damaged skin.

http://ift.tt/2k7lr0t

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