Developments in anaplastic large-cell lymphoma: targeting the anaplastic lymphoma kinase

Francesca Farina, Alessandra Stasia, Carlo Gambacorti-Passerini Department of Health Sciences, University of Milano Bicocca, Monza, Italy Abstract: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase protein implicated in a variety of hematological malignancies and solid tumors. ALK contributes to the development of cancers in different cell lineages through a variety of genetic mechanisms: gene fusions, activating point mutations, and possibly gene amplification. Recent developments led to significant therapeutic advances, including efficient diagnostic tests and ALK-targeting agents. This review addresses some therapeutic considerations with regard to the use of ALK inhibitors in ALK-positive lymphomas where, in spite of the advanced stage of the disease, long-lasting responses could be obtained in a substantial portion of heavily pretreated patients. Data and mechanisms for the development of resistance to ALK inhibitors will also be presented and discussed. Keywords: ALK, lymphoma, tyrosine kinase, targeted therapy, crizotini

FAKTOR-FAKTOR YANG BERHUBUNGAN DENGAN PERILAKU SEKSUAL BERISIKO PADA REMAJA DI SMP NEGERI 3 MANADO

Latar Belakang : Faktor-faktor yang mempengaruhi perilaku kesehatan reproduksi remaja yang mencakup pengetahuan, pemahaman tingkat agama, peranan keluarga dan pencarian informasi dapat mempengaruhi timbulnya masalah menyangkut kesehatan reproduksi. Mengingat besarnya potensi terjadinya perilaku seksual berisiko di kalangan pelajar maka perilaku tersebut harus segera ditangani dan diberikan perhatian khusus agar dapat mengurangi dampak negatifnya bagi kesehatan reproduki remaja. Tujuan penelitian ini dilakukan untuk mengetahui faktor-faktor yang berhubungan dengan perilaku seksual berisiko pada remaja di SMP Negeri 3 Manado. Metode penelitian yang digunakan yaitu kuantitatif dengan metode observasional analitik dan menggunakan pendekatan cross sectional yang dilakukan di SMP Negeri 3 Manado pada bulan November 2019 – Juli 2020. Populasi dalam penelitian ini yaitu pelajar kelas VIII di SMP Negeri 3 Manado. Jumlah sampel yaitu 167 responden. Teknik pengambilan sampel yaitu simple random sampling. Analisis data adalah analisis univariat dan bivariat. Hasil penelitian menunjukan hubungan antara pengetahuan dengan perilaku seksual berisiko remaja dengan  p value 0,037, pemahaman tingkat agama dengan perilaku seksual berisiko remaja dengan p value 0,005, peranan keluarga dengan perilaku seksual berisiko remaja dengan p value 0,004 dan pencarian informasi dengan perilaku seksual berisiko remaja dengan p value 0,008. Kesimpulan: penelitian ini menunjukkan bahwa terdapat hubungan antara pengetahuan, pemahaman tingkat agama, peranan keluarga dan pencarian informasi dengan perilaku seksual berisiko pada remaja di SMP Negeri 3 Manado. Saran: Ditujukan bagi pihak sekolah, bagi siswa, bagi orang tua dan bagi peneliti selanjutnya sehubungan dengan faktor-faktor lain yang mungkin dapat mempengaruhi perilaku seksual berisiko remaja. Kata Kunci : Pengetahuan, pemahaman tingkat agama, peranan keluarga, pencarian informasi, Perilaku seksual remaja ABSTRACT Background: The factors that influence teenager’s reproductive health behavior, such as knowledge, the levels of religious understanding, the role of family and information retrieval, can influence the emergence of problems concerning reproductive health. If the behavior is not treated immediately, it will bring negative impacts on teenager’s reproductive health. The purpose of this research is to finding the relation between these factors with the risky sexual behavior on teenagers at SMPN 3 Manado. The research method used is quantitative with analytic observational method and by using a cross sectional approach conducted at SMPN 3 Manado in November 2019 – July 2020. The population in this study were students of class VIII. The number of samples is 167 respondents. The sampling technique used was simple random sampling. The data were analyzed using univariate and bivariate analysis. From the results of this research show that there is a relation between knowledge and risky sexual behavior of teenager at a p value of 0.037, the levels of religious understanding with risky sexual behavior of teenager at a  p value of 0.005, the role of family with risky sexual behavior of teenager at a p value of 0.004 and information retrieval with risky sexual behavior of teenager at a p value of 0.008.Summary: The conclusion of this study, there is a relation between knowledge, the levels of religious understanding, the role of family and information retrieval with risky sexual behavior of teenagers at SMPN 3 Manado. Suggestions: So the suggestions for this research are expected for schools, students, parents, and also to future researchers. Keywords: Knowledge, the levels of religious understanding, the role of family, information retrieval, sexual behavio

Pedunculopontine arousal system physiology—Effects of psychostimulant abuse

This review describes the interactions between the pedunculopontine nucleus (PPN), the ventral tegmental area (VTA), and the thalamocortical system. Experiments using modulators of cholinergic receptors in the PPN clarified its role on psychostimulant-induced locomotion. PPN activation was found to be involved in the animal?s voluntary search for psychostimulants. Every PPN neuron is known to generate gamma band oscillations. Voltage-gated calcium channels are key elements in the generation and maintenance of gamma band activity of PPN neurons. Calcium channels are also key elements mediating psychostimulant-induced alterations in the thalamic targets of PPN output. Thus, the PPN is a key substrate for maintaining arousal and REM sleep, but also in modulating psychostimulant self-administrationFil: Urbano Suarez, Francisco Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Bisagno, Veronica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); ArgentinaFil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); ArgentinaFil: Rivero Echeto, Maria Celeste Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Muñiz, Javier A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); ArgentinaFil: Luster, Brennon. University Of Arkansas For Medical Sciences; Estados UnidosFil: D'onofrio, Stasia. University Of Arkansas For Medical Sciences; Estados UnidosFil: Mahaffey, Susan. University Of Arkansas For Medical Sciences; Estados UnidosFil: Garcia Rill, E. University Of Arkansas For Medical Sciences; Estados Unido

Northern Bobwhite Demographics and Resource Selection Are Explained by Prescribed Fire with Grazing and Woody Cover in Southwest Missouri

Understanding the effects of landscape management on northern bobwhite (Colinus virginianus; hereafter, bobwhite) population growth requires information about seasonal- and stage-specific demographic parameters linked across the annual cycle. We review results to date from 3 years (2016–2018) of an intensive field study evaluating drivers of bobwhite population dynamics and resource selection during the breeding and non-breeding season in southwest Missouri, USA using data from adult and juvenile bobwhite fitted with radio-transmitters. Land cover of our study sites ranged from large blocks of native grasslands maintained with prescribed fire and grazing to more traditional management resulting in small patches of grasslands interspersed with food plots, disked idle areas, and woody cover. During the breeding season, relative probability of selection by broods increased in relation to proportion of native grass managed by grazing and burning and proportion of cropland. Brood survival was also greatest on native grasslands burned and grazed within the past 2 growing seasons. During the fall and winter, relative probability of selection by adults increased as woody edge density increased. Fall and winter survival increased as distance from trees increased and decreased as distance to shrubs increased. Our integrated population model indicated that the number of young hatched per female and adult breeding season survival were greatest on sites with the most native grassland managed by prescribed fire with grazing. However, non-breeding season survival was greater on sites with more agriculture or food plots and woody cover. Abundance declined across all sites from 2016 to 2019. Our work suggests that native grasslands managed by prescribed fire with grazing can provide quail habitat superior to traditional management that strived for a mixture of agriculture, woody cover, and grassland. The combination of conservation grazing and fire in native grasslands interspersed with shrubs may provide the greatest chance for bobwhite populations to persist in southwest Missouri and similar landscapes

Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma

Emerging evidence suggests that both human stem cells and mature stromal cells can play an important role in the development and growth of human malignancies. In contrast to these tumor-promoting properties, we observed that in an in vivo model of Kaposi's sarcoma (KS), intravenously (i.v.) injected human mesenchymal stem cells (MSCs) home to sites of tumorigenesis and potently inhibit tumor growth. We further show that human MSCs can inhibit the in vitro activation of the Akt protein kinase within some but not all tumor and primary cell lines. The inhibition of Akt activity requires the MSCs to make direct cell–cell contact and can be inhibited by a neutralizing antibody against E-cadherin. We further demonstrate that in vivo, Akt activation within KS cells is potently down-regulated in areas adjacent to MSC infiltration. Finally, the in vivo tumor-suppressive effects of MSCs correlates with their ability to inhibit target cell Akt activity, and KS tumors engineered to express a constitutively activated Akt construct are no longer sensitive to i.v. MSC administration. These results suggest that in contrast to other stem cells or normal stromal cells, MSCs possess intrinsic antineoplastic properties and that this stem cell population might be of particular utility for treating those human malignancies characterized by dysregulated Akt

Nitrite Therapy After Cardiac Arrest Reduces Reactive Oxygen Species Generation, Improves Cardiac and Neurological Function, and Enhances Survival via Reversible Inhibition of Mitochondrial Complex I

Three-fourths of cardiac arrest survivors die prior to hospital discharge or suffer significant neurological injury. Excepting therapeutic hypothermia and revascularization, no novel therapies have been developed that improve survival or cardiac and neurological function after resuscitation. Nitrite (NO2−) increases cellular resilience to focal ischemia-reperfusion injury in multiple organs. We hypothesized that nitrite therapy may improve outcomes after the unique global ischemia-reperfusion insult of cardiopulmonary arrest

Corrigendum to "European contribution to the study of ROS:A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)" [Redox Biol. 13 (2017) 94-162]

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.The EU-ROS consortium (COST Action BM1203) was supported by the European Cooperation in Science and Technology (COST). The present overview represents the final Action dissemination summarizing the major achievements of COST Action BM1203 (EU-ROS) as well as research news and personal views of its members. Some authors were also supported by COST Actions BM1005 (ENOG) and BM1307 (PROTEOSTASIS), as well as funding from the European Commission FP7 and H2020 programmes, and several national funding agencies

Effects of surface chemistry on the porous structure of coal. Technical progress report, September 1994--October 1995

The primary objective of this work is to use {sup 129}Xe NMR to characterize the microporous structure of coals. As an aide in this characterization, another objective is to combine this technique with volumetric adsorption techniques and track the effect of controlled opening of the micropores in a microporous carbon by oxygen chemisorption/desorption. The primary goal of the NMR work is to measure the micropore sizes in coal; more broadly, it is to better tailor the {sup 129}Xe NMR method for use with coal, and to investigate other ways it may be used to describe pore structure in coal, with emphasis on determining whether micropores in coal are connected or isolated. In terms of the primary objectives of the project, the {sup 129}Xe NMR spectra with pressure variation have been completed for four coals, and N{sub 2} and C0{sub 2} adsorption isotherms with surface area measurement have been completed for three coals. A microporous carbon has been subjected to one oxygen chemisorption/desorption cycle and examined by {sup 129}Xe NMR