The Commonwealth Medical College

About: The Commonwealth Medical College is a education organization based out in Scranton, Pennsylvania, United States. It is known for research contribution in the topics: Medicine & Population. The organization has 624 authors who have published 928 publications receiving 18739 citations.

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

The influence of lipophilicity in drug discovery and design

Abstract: Introduction: The role of lipophilicity in drug discovery and design is a critical one. Lipophilicity is a key physicochemical property that plays a crucial role in determining ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties and the overall suitability of drug candidates. There is increasing evidence to suggest that control of physicochemical properties such as lipophilicity, within a defined optimal range, can improve compound quality and the likelihood of therapeutic success. Areas covered: This review focuses on understanding lipophilicity, techniques used to measure lipophilicity, and summarizes the importance of lipophilicity in drug discovery and development, including a discussion of its impact on individual ADMET parameters as well as its overall influence on the drug discovery and design process, specifically within the past 15 years. Expert opinion: A current review of the literature reveals a continued reliance on the synthesis of novel structures with increased...

Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling

Abstract: Engineered iron nanoparticles are being explored for the development of biomedical applications and many other industry purposes. However, to date little is known concerning the precise mechanisms of translocation of iron nanoparticles into targeted tissues and organs from blood circulation, as well as the underlying implications of potential harmful health effects in human. The confocal microscopy imaging analysis demonstrates that exposure to engineered iron nanoparticles induces an increase in cell permeability in human microvascular endothelial cells. Our studies further reveal iron nanoparticles enhance the permeability through the production of reactive oxygen species (ROS) and the stabilization of microtubules. We also showed Akt/GSK-3β signaling pathways are involved in iron nanoparticle-induced cell permeability. The inhibition of ROS demonstrate ROS play a major role in regulating Akt/GSK-3β – mediated cell permeability upon iron nanoparticle exposure. These results provide new insights into the bioreactivity of engineered iron nanoparticles which can inform potential applications in medical imaging or drug delivery. Our results indicate that exposure to iron nanoparticles induces an increase in endothelial cell permeability through ROS oxidative stress-modulated microtubule remodeling. The findings from this study provide new understandings on the effects of nanoparticles on vascular transport of macromolecules and drugs.

Racial, Economic, and Health Inequality and COVID-19 Infection in the United States.

Abstract: There is preliminary evidence of racial and social economic disparities in the population infected by and dying from COVID-19. The goal of this study is to report the associations of COVID-19 with respect to race, health, and economic inequality in the United States. We performed an ecological study of the associations between infection and mortality rate of COVID-19 and demographic, socioeconomic, and mobility variables from 369 counties (total population, 102,178,117 [median, 73,447; IQR, 30,761–256,098]) from the seven most affected states (Michigan, New York, New Jersey, Pennsylvania, California, Louisiana, Massachusetts). The risk factors for infection and mortality are different. Our analysis shows that counties with more diverse demographics, higher population, education, income levels, and lower disability rates were at a higher risk of COVID-19 infection. However, counties with higher proportion with disability and poverty rates had a higher death rate. African Americans were more vulnerable to COVID-19 than other ethnic groups (1981 African American infected cases versus 658 Whites per million). Data on mobility changes corroborate the impact of social distancing. Our study provides evidence of racial, economic, and health inequality in the population infected by and dying from COVID-19. These observations might be due to the workforce of essential services, poverty, and access to care. Counties in more urban areas are probably better equipped at providing care. The lower rate of infection, but a higher death rate in counties with higher poverty and disability could be due to lower levels of mobility, but a higher rate of comorbidities and health care access.

Telemedicine, the current COVID-19 pandemic and the future: a narrative review and perspectives moving forward in the USA.

Abstract: A narrative review was conducted to examine the current state of the utilisation of telemedicine amid the current COVID-19 pandemic and to evaluate the benefits of continuing telemedicine usage in the future. A literature review was performed for articles related to telemedicine. Databases including PubMed, Google Scholar, Cochrane Library and Ovid MEDLINE were searched. Three reviewers independently performed article selection based on relevance to our topic. We included all articles between 1990 and 2020 related to telemedicine using the following keywords: 'telemedicine', 'telehealth', 'policy', 'COVID-19', 'regulation', 'rural', 'physical examination', 'future'. A total of 60 articles were identified, and through careful selection we narrowed the final number of articles to 42 based on relevance to our topic. Telemedicine has been rapidly evolving over the past several decades. Issues with regulation and reimbursement have prevented its full immersion into the healthcare system. During the current pandemic, Centers for Medicare and Medicaid services have expanded access to telemedicine services. The advantages of telemedicine moving forward include its cost-effectiveness, ability to extend access to specialty services and its potential to help mitigate the looming physician shortage. Disadvantages include lack of available technological resources in certain parts of the country, issues with security of patient data, and challenges in performing the traditional patient examination. It is critically important that changes are made to fully immerse telemedicine services into the healthcare landscape in order to be prepared for future pandemics as well as to reap the benefits of this service in the future.