Digital Commons Network^™

Dual Action Of Mir-125b As A Tumor Suppressor And Oncomir-22 Promotes Prostate Cancer Tumorigenesis, William T. Budd, Sarah J. Seashols-Williams, Gene C. Clark, Danielle Weaver, Valerie Calvert, Emanuel Petricoin, Ema A. Dragoescu, Katherine O'Hanlon, Zendra E. Zehner

Biochemistry and Molecular Biology Publications

MicroRNAs (miRs) are a novel class of small RNA molecules, the dysregulation of which can contribute to cancer. A combinatorial approach was used to identify miRs that promote prostate cancer progression in a unique set of prostate cancer cell lines, which originate from the parental p69 cell line and extend to a highly tumorigenic/metastatic M12 subline. Together, these cell lines are thought to mimic prostate cancer progression in vivo. Previous network analysis and miR arrays suggested that the loss of hsa-miR-125b together with the overexpression of hsa-miR-22 could contribute to prostate tumorigenesis. The dysregulation of these two miRs was …

Dpy-17 And Mua-3 Interact For Connective Tissue-Like Tissue Integrity In Caenorhabditis Elegans: A Model For Marfan Syndrome, Pauline Fotopoulos, Jeongho Kim, Moonjung Hyun, Waiss Qamari, Inhwan Lee, Young-Jai You

Biochemistry and Molecular Biology Publications

mua-3 is a Caenorhabditis elegans homolog of the mammalian fibrillin1, a monogenic cause of Marfan syndrome. We identified a new mutation of mua-3 that carries an in-frame deletion of 131 amino acids in the extracellular domain, which allows the mutants to survive in a temperature-dependent manner; at the permissive temperature, the mutants grow normally without obvious phenotypes, but at the nonpermissive temperature, more than 90% die during the L4 molt due to internal organ detachment. Using the temperature-sensitive lethality, we performed unbiased genetic screens to isolate suppressors to find genetic interactors of MUA-3. From two independent screens, we isolated …

Dissection Of C. Elegans Behavioral Genetics In 3-D Environments, Namseop Kwon, Ara B. Hwang, Young-Jai You, Seung-Jae V. Lee, Jung Ho Je

Biochemistry and Molecular Biology Publications

The nematode Caenorhabditis elegans is a widely used model for genetic dissection of animal behaviors. Despite extensive technical advances in imaging methods, it remains challenging to visualize and quantify C. elegans behaviors in three-dimensional (3-D) natural environments. Here we developed an innovative 3-D imaging method that enables quantification of C. elegans behavior in 3-D environments. Furthermore, for the first time, we characterized 3-D-specific behavioral phenotypes of mutant worms that have defects in head movement or mechanosensation. This approach allowed us to reveal previously unknown functions of genes in behavioral regulation. We expect that our 3-D imaging method will facilitate new …

Network Modelling Reveals The Mechanism Underlying Colitis-Associated Colon Cancer And Identifies Novel Combinatorial Anti-Cancer Targets, Junyan Lu, Hanlin Zeng, Zhongjie Liang, Limin Chen, Liyi Zhang, Hao Zhang, Hong Liu, Hualiang Jiang, Bairong Shen, Ming Huang, Meiyu Geng, Sarah Spiegel, Cheng Luo

Biochemistry and Molecular Biology Publications

The connection between inflammation and tumourigenesis has been well established. However, the detailed molecular mechanism underlying inflammation-associated tumourigenesis remains unknown because this process involves a complex interplay between immune microenvironments and epithelial cells. To obtain a more systematic understanding of inflammation-associated tumourigenesis as well as to identify novel therapeutic approaches, we constructed a knowledge-based network describing the development of colitis-associated colon cancer (CAC) by integrating the extracellular microenvironment and intracellular signalling pathways. Dynamic simulations of the CAC network revealed a core network module, including P53, MDM2, and AKT, that may govern the malignant transformation of colon epithelial cells in a …

P. Falciparum And P. Vivax Epitope-Focused Vlps Elicit Sterile Immunity To Blood Stage Infections, David C. Whitacre, Diego A. Espinosa, Cory J. Peters, Joyce E. Jones, Amy E. Tucker, Darrell L. Peterson, Fidel P. Zavala, David R. Milich

Biochemistry and Molecular Biology Publications

In order to design P. falciparum preerythrocytic vaccine candidates, a library of circumsporozoite (CS) T and B cell epitopes displayed on the woodchuck hepatitis virus core antigen (WHcAg) VLP platform was produced. To test the protective efficacy of the WHcAg-CS VLPs, hybrid CS P. berghei/P. falciparum (Pb/Pf) sporozoites were used to challenge immunized mice. VLPs carrying 1 or 2 different CS repeat B cell epitopes and 3 VLPs carrying different CS non-repeat B cell epitopes elicited high levels of anti-insert antibodies (Abs). Whereas, VLPs carrying CS repeat B cell epitopes conferred 98% protection of the liver against …

Increased Eicosanoid Levels In The Sugen/Chronic Hypoxia Model Of Severe Pulmonary Hypertension, Aysar Al-Husseini, Dayanjan S. Wijesinghe, Laszlo Farkas, Donatas Kraskauskas, Jennifer I. Drake, Ben Van Tassel, Antonio Abbate, Charles E. Chalfant, Norbert F. Voelkel

Biochemistry and Molecular Biology Publications

Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not …

Nanocuration Workflows: Establishing Best Practices For Identifying, Inputting, And Sharing Data To Inform Decisions On Nanomaterials, Christina M. Powers, Karmann A. Mills, Stephanie A. Morris, Fred Klaessig, Sharon Gaheen, Nastassja Lewinski, Christine Ogilvie Hendren

Chemical and Life Science Engineering Publications

There is a critical opportunity in the field of nanoscience to compare and integrate information across diverse fields of study through informatics (i.e., nanoinformatics). This paper is one in a series of articles on the data curation process in nanoinformatics (nanocuration). Other articles in this series discuss key aspects of nanocuration (temporal metadata, data completeness, database integration), while the focus of this article is on the nanocuration workflow, or the process of identifying, inputting, and reviewing nanomaterial data in a data repository. In particular, the article discusses: 1) the rationale and importance of a defined workflow in nanocuration, 2) the …

Generation Of Multicellular Tumor Spheroids With Microwell-Based Agarose Scaffolds For Drug Testing, Xue Gong, Chao Lin, Jian Cheng, Jiansheng Su, Hang Zhao, Tianlin Liu, Xuejun Wen, Peng Zhao

Chemical and Life Science Engineering Publications

Three dimensional multicellular aggregate, also referred to as cell spheroid or microtissue, is an indispensable tool for in vitro evaluating antitumor activity and drug efficacy. Compared with classical cellular monolayer, multicellular tumor spheroid (MCTS) offers a more rational platform to predict in vivo drug efficacy and toxicity. Nevertheless, traditional processing methods such as plastic dish culture with nonadhesive surfaces are regularly time-consuming, laborious and difficult to provide uniform-sized spheroids, thus causing poor reproducibility of experimental data and impeding high-throughput drug screening. In order to provide a robust and effective platform for in vitro drug evaluation, we present an agarose scaffold …

Genome-Scale Resources For Thermoanaerobacterium Saccharolyticum, Devin H. Currie, Babu Raman, Christopher M. Gowen, Timothy J. Tschaplinski, Miriam L. Land, Steven D. Brown, Sean F. Covalla, Dawn M. Klingeman, Zamin K. Yang, Nancy L. Engle, Courtney M. Johnson, Miguel Rodriguez, A Joe Shaw, William R. Kenealy, Lee R. Lynd, Stephen S. Fong, Jonathan R. Mielenz, Brian H. Davison, David A. Hogsett, Christopher D. Herring

Chemical and Life Science Engineering Publications

Background

Thermoanaerobacterium saccharolyticum is a hemicellulose-degrading thermophilic anaerobe that was previously engineered to produce ethanol at high yield. A major project was undertaken to develop this organism into an industrial biocatalyst, but the lack of genome information and resources were recognized early on as a key limitation.

Results

Here we present a set of genome-scale resources to enable the systems level investigation and development of this potentially important industrial organism. Resources include a complete genome sequence for strain JW/SL-YS485, a genome-scale reconstruction of metabolism, tiled microarray data showing transcription units, mRNA expression data from 71 different growth conditions or timepoints …

The Optimization And Comparison Of A Cerium Salt-Based Phosphate Filtration System To Industry Standard Phosphate Removal Water Filtration Systems, Nicholas Seymour, Snehi Shrestha, Laura Viktoria Pretzman

Capstone Design Expo Posters

Phosphorous, being one of the fundamental building blocks of life, has been linked with the increase of cyanobacteria and algae growth. One of the main ways that phosphorous enters the marine ecosystem is through the form of runoff phosphates from fertilizers and industrial processes. In addition to disrupting the biology of ecosystems another drawback of excess of phosphates is the tendency for these chemical groups to form scale buildup on metal through the form of calcium phosphate.

The goal of our project is to investigate a novel way of removing phosphate groups from wastewater with the use of the rare …

Non-Invasive Blood Glucose Monitoring System, Brittany Martinez, Brittany Noah, David Decker

Capstone Design Expo Posters

The objective of this project is to create a non-invasive hypoglycemic alert system that will detect a drop in blood sugar in type 1 diabetics during sleep. This will be achieved by creating an algorithm that couples heart rate variability with skin conductance to increase the accuracy of hypoglycemia detection. The device will be housed in a torso strap that will include: electrodes located over the user’s rib cage, a skin conductance sensor placed in the user’s armpit, a microcontroller to collect and process the data, and vibrating motors that will awaken the patient if hypoglycemia is detected. Integrating the …

Dynamics Of Planar Systems That Model Stage-Structured Populations, N. Lazaryan, Hassan Sedaghat

Mathematics and Applied Mathematics Publications

We study a general discrete planar system for modeling stage-structured populations. Our results include conditions for the global convergence of orbits to zero (extinction) when the parameters (vital rates) are time and density dependent. When the parameters are periodic we obtain weaker conditions for extinction. We also study a rational special case of the system for Beverton-Holt type interactions and show that the persistence equilibrium (in the positive quadrant) may be globally attracting even in the presence of interstage competition. However, we determine that with a sufficiently high level of competition, the persistence equilibrium becomes unstable (a saddle point) and …

Green Tea Inhibited The Elimination Of Nephro-Cardiovascular Toxins And Deteriorated The Renal Function In Rats With Renal Failure, Yu-Hsuan Peng, Douglas H. Sweet, Shiuan-Pey Lin, Chung-Ping Yu, Pei-Dawn Lee Chao, Yu-Chi Hou

Pharmaceutics Publications

Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound nephro-cardiovascular toxins, which are not efficiently removed through hemodialysis. The renal excretions of IS and PCS were mediated by organic anion transporters (OATs) such as OAT1 and OAT3. Green tea (GT) is a popular beverage containing plenty of catechins. Previous pharmacokinetic studies of teas have shown that the major molecules present in the bloodstream are the glucuronides/sulfates of tea catechins, which are putative substrates of OATs. Here we demonstrated that GT ingestion significantly elevated the systemic exposures of endogenous …

Analysis Of Standard Dna Procedures On Feathers Of Late 19th To Late 20th Century Osprey (Pandion Haliaetus), Alia A. Hamdan, Catherine B. Viverette, Rodney J. Dyer

Rice Rivers Center Research Symposium

Species with well-documented demographic histories and well known perturbations to gene flow provide good models for understanding how historic events impact contemporary population genetic structure1,2. Osprey (Pandion haliaetus), a marine bird-of-prey, experienced steep declines after widespread organochloride pesticide (e.g. DDT) use in the mid-twentieth century 3, however, population genetic consequences remain unknown. Use of historic specimens can aid population genetic studies4,5, however, these samples can degrade over time impacting quantity and quality of extracted DNA5. We compared the concentrations of extracted DNA of Osprey feathers from museum and research collections to those of contemporary samples collected according to standard field …

Communicating The Overall Experience Of Research Through Various Approaches Using Art: A Case Study Of The Prothonotary Warbler, Hannah Huddle, Lesley P. Bulluck, Sarah E. Faris

Rice Rivers Center Research Symposium

Recommended Citation

In general, scientific research has publication of data as the end goal. The process and experience, which are of great importance in art disciplines, is not necessarily represented or valued. However, science has an inherent element of art to it, which deserves to be shown. I have been studying Prothonotary Warblers with a team from the VCU Biology Department to learn how I can reinterpret the research in a way that bridges the gap between the experience and typical scientific products. The research team measured spatial and temporal variation in warbler prey abundance (caterpillars and mayflies) and assessed …

Emergent Non-Consumptive Predator Effects Alter Habitat Colonization By Mosquitoes, Ethan G. Staats, Salvatore J. Agosta, James R. Vonesh

Rice Rivers Center Research Symposium

Top-down consumptive control (suppression) is an important driver of populations and communities of prey organisms. Diverse predator assemblages often yield non-linear suppression with respect to constituent species' effects (emergence); most often diversity enhances suppression. Predators also affect prey organisms non-consumptively through changes in prey physiological, physical, spatial, temporal, and behavioral responses to predators. Role of predator diversity in non-consumptive response by prey is relatively un-studied. Role of predator diversity in shaping prey populations and communities through habitat colonization is a novel question.

Il-4 Inhibits Il-1Β-Induced Depressive-Like Behavior And Central Neurotransmitter Alterations, Hyun-Jung Park, Hyun-Soo Shim, Kyungeh An, Angela Starkweather, Kyung Soo Kim, Insop Shim

School of Nursing Publications

It has been known that activation of the central innate immune system or exposure to stress can disrupt balance of anti-/proinflammatory cytokines. The aim of the present study was to investigate the role of pro- and anti-inflammatory cytokines in the modulation of depressive-like behaviors, the hormonal and neurotransmitter systems in rats. We investigated whether centrally administered IL-1β is associated with activation of CNS inflammatory pathways and behavioral changes and whether treatment with IL-4 could modulate IL-1β-induced depressive-like behaviors and central neurotransmitter systems. Infusion of IL-4 significantly decreased IL-1β-induced anhedonic responses and increased social exploration and …

Addition Of Interleukin-21 For Expansion Of T-Cells For Adoptive Immunotherapy Of Murine Melanoma, Christine Kathryn Zoon, Wen Wan, Laura Graham, Harry D. Bear

Surgery Publications

We previously demonstrated that interleukin (IL)-7/15 was superior to IL-2 for expansion of T cells in vitro for adoptive immunotherapy. We sought to ascertain whether IL-21 would further improve yield and therapeutic efficacy of T cells in culture. Naïve T cell receptor (TcR) transgenic splenocytes or antigen-sensitized lymph node cells were harvested from PMEL-1 mice and exposed to bryostatin-1 and ionomycin (B/I) for 18 h. Cells were then cultured in IL-2, IL-21, IL-7/15 or IL-7/15/21 for six days. Harvested cells were analyzed by flow cytometry and used to treat C57Bl/6 mice injected intravenously with B16 melanoma. Lungs were harvested and …

Metabolic Effects Of Fgf-21: Thermoregulation And Beyond, Bin Ni, Jared S. Farrar, Janina A. Vaitkus, Francesco S. Celi

Internal Medicine Publications

Fibroblast growth factor (FGF)-21, a member of the FGF family, is a novel hormone involved in the control of metabolism by modulating glucose homeostasis, insulin sensitivity, ketogenesis, and promoting adipose tissue “browning.” Recent studies demonstrated that brown adipose tissue is not only a target for FGF-21, but is also a potentially important source of systemic FGF-21. These findings support the hypothesis that FGF-21 plays a physiologic role in thermogenesis and thermogenic recruitment of white adipose tissue by an autocrine–paracrine axis. This review examines the role of FGF-21 in thermogenesis from the perspective of cell-based, animal model, and human studies. We …

Increased Eicosanoid Levels In The Sugen/Chronic Hypoxia Model Of Severe Pulmonary Hypertension, Aysar A. Al-Husseini, Dayanjan S. Wijesinghe, Laszlo Farkas, Donatas Kraskauskas, Jennifer I. Drake, Ben Van Tassel, Antonio Abbate, Charles E. Chalfant, Norbert F. Voelkel

Internal Medicine Publications

Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not …

Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation In Diet-Induced Nonalcoholic Fatty Liver Disease, Tommy Pacana, Sophie Cazanave, Aurora Verdianelli, Vaishali Patel, Hae-Ki Min, Faridoddin Mirshahi, Eoin Quinlivan, Arun J. Sanyal

Internal Medicine Publications

Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, …

An International Survey On Taking Up A Career In Cardiovascular Research: Opportunities And Biases Toward Would-Be Physician-Scientists, Giuseppe Biondi-Zoccai, Enrico Cerrato, Mariangela Peruzzi, Fabrizio D'Ascenzo, Elena De Falco, Isotta Chimenti, Sebastiano Sciarretta, Antonio G. M. Marullo, Elena Cavarretta, Ernesto Greco, Umberto Benedetto, Giulio Pompilio, Javier Escaned, Antonio Abbate, Alain Carpentier, Juan Carlos Chachques, Giacomo Frati

Internal Medicine Publications

Background

Cardiovascular research is the main shaper of clinical evidence underpinning decision making, with its cyclic progression of junior researchers to mature faculty members. Despite efforts at improving cardiovascular research training, several unmet needs persist. We aimed to appraise current perceptions on cardiovascular research training with an international survey.

Methods and Results

We administered a 20-closed-question survey to mentors and mentees belonging to different international institutions. A total of 247 (12%) surveys were available (out of 2,000 invitations). Overall, mentees and mentors were reasonably satisfied with the educational and research resources. Significant differences were found analyzing results according to gender, …

Thyroid Hormone Mediated Modulation Of Energy Expenditure, Janina A. Vaitkus, Jared S. Farrar, Francesco S. Celi

Internal Medicine Publications

Thyroid hormone (TH) has diverse effects on mitochondria and energy expenditure (EE), generating great interest and research effort into understanding and harnessing these actions for the amelioration and treatment of metabolic disorders, such as obesity and diabetes. Direct effects on ATP utilization are a result of TH’s actions on metabolic cycles and increased cell membrane ion permeability. However, the majority of TH induced EE is thought to be a result of indirect effects, which, in turn, increase capacity for EE. This review discusses the direct actions of TH on EE, and places special emphasis on the indirect actions of TH, …

Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation In Diet-Induced Nonalcoholic Fatty Liver Disease, Tommy Pacana, Sophie Cazanave, Aurora Verdianelli, Viashali Patel, Hae-Ki Min, Faridoddin Mirshahi, Eoin Quinlavin, Arun J. Sanyal

Internal Medicine Publications

Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, …

State Of The Art On The Evidence Base In Cardiac Regenerative Therapy: Overview Of 41 Systematic Reviews, Mariangela Peruzzi, Elena De Falco, Antonio Abbate, Giuseppe Biondi-Zoccai, Isotta Chementi, Marzia Lotrionte, Umberto Benedetto, Ronak Delewi, Antonino G. M. Marullo, Giacomo Frati

Internal Medicine Publications

Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum …

Intermittent Hypoxia In Childhood: The Harmful Consequences Versus Potential Benefits Of Therapeutic Uses, Tatiana V. Serebrovskaya, Lei Xi

Internal Medicine Publications

Intermittent hypoxia (IH) often occurs in early infancy in both preterm and term infants and especially at 36–44 weeks postmenstrual age. These episodes of IH could result from sleep-disordered breathing or may be temporally unrelated to apnea or bradycardia events. There are numerous reports indicating adverse effects of IH on development, behavior, academic achievement, and cognition in children with sleep apnea syndrome. It remains uncertain about the exact causative relationship between the neurocognitive and behavioral morbidities and IH and/or its associated sleep fragmentation. On the other hand, well-controlled and moderate IH conditioning/training has been used in sick children for treating …

Use Of Probe-Based Confocal Laser Endomicroscopy (Pcle) In Gastrointestinal Applications. A Consensus Report Based On Clinical Evidence, Kenneth K. Wang, David L. Carr-Locke, Satish K. Singh, Helmut Neumann, Helga Bertani, Jean-Paul Galmiche, Razvan I. Arsenescu, Fabrice Caillol, Kenneth J. Chang, Stanislas Chaussade, Emmanuel Coron, Guida Costamagna, Aldona Dlugosz, S Ian Gan, Marc Giovannini, Frank G. Gress, Oleh Haluszka, Khek Y. Ho, Michel Kahaleh, Vani J. Konda, Frederic Prat, Raj J. Shah, Prateek Sharma, Adam Slivka, Herbert C. Wolfsen, Alvin Zfass

Internal Medicine Publications

Background

Probe-based confocal laser endomicroscopy (pCLE) provides microscopic imaging during an endoscopic procedure. Its introduction as a standard modality in gastroenterology has brought significant progress in management strategies, affecting many aspects of clinical care and requiring standardisation of practice and training.

Objective

This study aimed to provide guidance on the standardisation of its practice and training in Barrett’s oesophagus, biliary strictures, colorectal lesions and inflammatory bowel diseases.

Methods

Initial statements were developed by five group leaders, based on the available clinical evidence. These statements were then voted and edited by the 26 participants, using a modified Delphi approach. After two …

Rational Combinations Of Targeted Agents In Aml, Prithviraj Bose, Steven Grant

Internal Medicine Publications

Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex …

State Of The Art On The Evidence Base In Cardiac Regenerative Therapy: Overview Of 41 Systematic Reviews, Mariangela Peruzzi, Elena De Falco, Antonio Abbate, Giuseppe Biondi-Zoccai, Isotta Chimenti, Marzia Lotrionte, Umberto Benedetto, Ronak Delewi, Antonino G. M. Marullo, Giacomo Frati

Internal Medicine Publications

Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median …

An International Survey On Taking Up A Career In Cardiovascular Research: Opportunities And Biases Toward Would-Be Physician-Scientists, Giuseppe Biondi-Zoccai, Enrico Cerrato, Mariangela Peruzzi, Fabrizio D'Ascenzo, Elena De Falco, Isotta Chimenti, Sebastiano Sciarretta, Antonino G. M. Marullo, Elena Cavarretta, Ernesto Greco, Umberto Benedetto, Giulio Pompilio, Javier Escaned, Antonio Abbate, Alain Carpentier, Juan Carlos Chachques, Giacomo Frati

Internal Medicine Publications

Background

Cardiovascular research is the main shaper of clinical evidence underpinning decision making, with its cyclic progression of junior researchers to mature faculty members. Despite efforts at improving cardiovascular research training, several unmet needs persist. We aimed to appraise current perceptions on cardiovascular research training with an international survey.

Methods and Results

We administered a 20-closed-question survey to mentors and mentees belonging to different international institutions. A total of 247 (12%) surveys were available (out of 2,000 invitations). Overall, mentees and mentors were reasonably satisfied with the educational and research resources. Significant differences were found analyzing results according to gender, …