Opportunities and challenges for successful use of bevacizumab in pediatrics

Bevacizumab (Avastin) has rapidly gained status as a broadly active agent for malignancies of several different histologies in adults. This activity has spawned a range of uses in pediatrics for both oncologic and non-oncologic indications. Early analyses indicate that pediatric cancers exhibit a spectrum of responses to bevacizumab that suggest its activity may be more limited than in adult oncology. Most exciting, is that for low grade tumors that threaten vision and hearing, there is not only evidence for objective tumor response but for recovery of lost function as well. In addition to oncological indications, there is a range of uses for non-oncologic disease for which bevacizumab has clear activity. Finally, a number of mechanisms have been identified as contributing to bevacizumb resistance in cancer. Elucidating these mechanisms will guide the development of future clinical trials of bevacizumab in pediatric oncology

When Bio Meets Technology: Biohybrid Neural Interfaces.

The development of electronics capable of interfacing with the nervous system is a rapidly advancing field with applications in basic science and clinical translation. Devices containing arrays of electrodes can be used in the study of cells grown in culture or can be implanted into damaged or dysfunctional tissue to restore normal function. While devices are typically designed and used exclusively for one of these two purposes, there have been increasing efforts in developing implantable electrode arrays capable of housing cultured cells, referred to as biohybrid implants. Once implanted, the cells within these implants integrate into the tissue, serving as a mediator of the electrode-tissue interface. This biological component offers unique advantages to these implant designs, providing better tissue integration and potentially long-term stability. Herein, an overview of current research into biohybrid devices, as well as the historical background that led to their development are provided, based on the host anatomical location for which they are designed (CNS, PNS, or special senses). Finally, a summary of the key challenges of this technology and potential future research directions are presented.The authors acknowledge funding from EPSRC (EP/S009000/1 and DTP program), European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 732032 (BrainCom) (G.G.M.) and from the King Abdullah University of Science and Technology (KAUST) Office of sponsored Research (OSR) under award No. OSR‑2016‑CRG5‑3003

Energy Expenditure and Enjoyment of Active Television Viewing

International Journal of Exercise Science 9(1): 64-76, 2016. This study examined energy expenditure and enjoyment during sedentary television viewing (SED-TV), stepping in place during television commercials (COMM-TV), and physical activity prompted by common character phrases/mannerisms within a television program (PA-TV). Adults (N=38, age: 27.0±8.0 years, BMI: 25.4±4.2 kg/m2) completed three 30-minute sessions in random order: SED-TV, COMM-TV, and PA-TV. Energy expenditure and heart rate were assessed during each session. Enjoyment was assessed after the initial experimental session and at completion of the study. Energy expenditure was greater in the active versus sedentary sessions (COMM-TV vs SED-TV: difference = 32.7±1.9 kcal, p3.0 METS was lower in SED-TV (median = 0 minutes) compared to COMM-TV [median = 4.0 minutes (Inter-Quartile Range: 0.8, 7.3)] (p50% of age-predicted maximal heart rate. Both COMM-TV and PA-TV were reported to be significantly more enjoyable than SED-TV. COMM-TV and PA-TV resulted in higher energy expenditure, more minutes of moderate intensity physical activity, and higher reported enjoyment compared to SED-TV. These findings have implications for reducing sedentary time during television viewing, which may impact health-related outcomes. Intervention trials are warranted to determine the effectiveness of these strategies

Pilot Feasibility Study of a Campaign Intervention for Weight Loss among Overweight and Obese Adults

Background: Behavioral interventions produce significant short-term weight loss. However, these interventions typically require regular in-person sessions, which may not be feasible for all individuals. Purpose: The purpose of this pilot study was to evaluate the feasibility of a 12-week campaign intervention (CI) compared to a standard on-site, group-based behavioral weight loss intervention (SBWL) among overweight/obese adults. Methods: SBWL participants (n=13; age: 42.5 ± 9.1 years; BMI: 33.4 ± 3.8 kg/m²) attended weekly group meetings, were prescribed a daily reduced caloric goal and 200 minutes of moderate-intensity physical activity per week. CI participants (n=13; age: 43.8 ± 9.0 years; BMI: 33.2 ± 3.8 kg/m²) received the same recommendations as the SBWL, attended in-person group meetings at weeks 0 and 12, and received e-mail messages weeks 2-11. Additional CI features included a thematic framework and an incentive-based point system targeting behavioral goals. Results: Significant weight loss was demonstrated for intention-to-treat (SBWL: -5.6 ± 2.9 kg; CI: -3.1 ± 3.4 kg) (

Novel chemical library screen identifies naturally occurring plant products that specifically disrupt glioblastoma-endothelial cell interactions

Tumor growth is not solely a consequence of autonomous tumor cell properties. Rather, tumor cells act upon and are acted upon by their microenvironment. It is tumor tissue biology that ultimately determines tumor growth. Thus, we developed a compound library screen for agents that could block essential tumor-promoting effects of the glioblastoma (GBM) perivascular stem cell niche (PVN). We modeled the PVN with three-dimensional primary cultures of human brain microvascular endothelial cells in Matrigel. We previously demonstrated stimulated growth of GBM cells in this PVN model and used this to assay PVN function. We screened the Microsource Spectrum Collection library for drugs that specifically blocked PVN function, without any direct effect on GBM cells themselves. Three candidate PVN-disrupting agents, Iridin, Tigogenin and Triacetylresveratrol (TAR), were identified and evaluated in secondary in vitro screens against a panel of primary GBM isolates as well as in two different in vivo intracranial models. Iridin and TAR significantly inhibited intracranial tumor growth and prolonged survival in these mouse models. Together these data identify Iridin and TAR as drugs with novel GBM tissue disrupting effects and validate the importance of preclinical screens designed to address tumor tissue function rather than the mechanisms of autonomous tumor cell growth

X-ray markers for thin film implants

Implantable electronic medical devices are used in functional mapping of the brain before surgery and to deliver neuromodulation for the treatment of neurological and neuropsychiatric disorders. Their electrode arrays are assembled by hand, and this leads to bulky form factors with limited flexibility and low electrode counts. Thin film implants, made using microfabrication techniques, are emerging as an attractive alternative, as they offer dramatically improved conformability and enable high density recording and stimulation. A major limitation of these devices, however, is that they are invisible to fluoroscopy, the most common method used to monitor the insertion of implantable electrodes. Here, the development of mechanically flexible X-ray markers using bismuth- and barium-infused elastomers is reported. Their X-ray attenuation properties in human cadavers are explored and it is shown that they are biocompatible in cell cultures. It is further shown that they do not distort magnetic resonance imaging images and their integration with thin film implants is demonstrated. This work removes a key barrier for the adoption of thin film implants in brain mapping and in neuromodulation

The Impact of Loneliness Post-Pandemic and Immersed in the Upcoming Political Election

The Real Chemistry Emerging Insights Lab emerged with a partnership between Real Chemistry and the Public Relations department at the S.I. Newhouse School of Public Communication and serves as a multidisciplinary research center focusing on analytics, artificial intelligence, digital and emerging media for a number of organizations regarding communications. Healthcare professionals and organizations are interested in identifying how mental health impacts different U.S. generational groups after the COVID-19 pandemic and the intersectionality of U.S. Politics. Our team focused on two generational cohorts – Generation X (1965-1980) and Generation Z (1997-2012) – as an entry point into navigating the impact of mental health postpandemic and in the aftermath of the U.S. 2020 election year and the upcoming U.S. presidential election in fall of 2024

Combined VEGF and CXCR4 antagonism targets the GBM stem cell population and synergistically improves survival in an intracranial mouse model of glioblastoma

Glioblastoma recurrence involves the persistence of a subpopulation of cells with enhanced tumor-initiating capacity (TIC) that reside within the perivascular space, or niche (PVN). Anti-angiogenic therapies may prevent the formation of new PVN but have not prevented recurrence in clinical trials, suggesting they cannot abrogate TIC activity. We hypothesized that combining anti-angiogenic therapy with blockade of PVN function would have superior anti-tumor activity. We tested this hypothesis in an established intracranial xenograft model of GBM using a monoclonal antibody specific for murine and human VEGF (mcr84) and a Protein Epitope Mimetic (PEM) CXCR4 antagonist, POL5551. When doses of POL5551 were increased to overcome an mcr84-induced improvement in vascular barrier function, combinatorial therapy significantly inhibited intracranial tumor growth and improved survival. Anti-tumor activity was associated with significant changes in tumor cell proliferation and apoptosis, and a reduction in the numbers of perivascular cells expressing the TIC marker nestin. A direct effect on TICs was demonstrated for POL5551, but not mcr84, in three primary patient-derived GBM isolates. These findings indicate that targeting the structure and function of the PVN has superior anti-tumor effect and provide a strong rationale for clinical evaluation of POL5551 and Avastin in patients with GBM

Febrile seizures: mechanisms and relationship to epilepsy.

Studies of febrile seizures have been driven by two major enigmas: first, how these most common of human seizures are generated by fever has not been known. Second, epidemiological studies have linked prolonged febrile seizures with the development of temporal lobe epilepsy, yet whether long or recurrent febrile seizures cause temporal lobe epilepsy has remained unresolved. To investigate these questions, a model of prolonged (complex) febrile seizures was developed in immature rats and mice, permitting mechanistic examination of the potential causal relationships of fever and seizures, and of febrile seizures and limbic epilepsy. Although the model relied on hyperthermia, it was discovered that the hyperthermia-induced secretion of endogenous fever mediators including interleukin-1beta, which contributed to the generation of these 'febrile' seizures. In addition, prolonged experimental febrile seizures provoked epilepsy in a third of the animals. Investigations of the mechanisms of this epileptogenesis demonstrated that expression of specific ion (HCN) channels and of endocannabinoid signaling, may be involved. These may provide novel drug targets for intervention in the epileptogenic process

Sedentary Behavior Research Network (SBRN) - Terminology Consensus Project process and outcome

Background: The prominence of sedentary behavior research in health science has grown rapidly. With this growth there is increasing urgency for clear, common and accepted terminology and definitions. Such standardization is difficult to achieve, especially across multi-disciplinary researchers, practitioners, and industries. The Sedentary Behavior Research Network (SBRN) undertook a Terminology Consensus Project to address this need. Method: First, a literature review was completed to identify key terms in sedentary behavior research. These key terms were then reviewed and modified by a Steering Committee formed by SBRN. Next, SBRN members were invited to contribute to this project and interested participants reviewed and provided feedback on the proposed list of terms and draft definitions through an online survey. Finally, a conceptual model and consensus definitions (including caveats and examples for all age groups and functional abilities) were finalized based on the feedback received from the 87 SBRN member participants who responded to the original invitation and survey. Results: Consensus definitions for the terms physical inactivity, stationary behavior, sedentary behavior, standing, screen time, non-screen-based sedentary time, sitting, reclining, lying, sedentary behavior pattern, as well as how the terms bouts, breaks, and interruptions should be used in this context are provided. Conclusion: It is hoped that the definitions resulting from this comprehensive, transparent, and broad-based participatory process will result in standardized terminology that is widely supported and adopted, thereby advancing future research, interventions, policies, and practices related to sedentary behaviors