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University of Louisiana at Monroe

UniversityMonroe, Louisiana, United States

Research output, citation impact, and the most-cited recent papers from University of Louisiana at Monroe (United States). Aggregated across the NobleBlocks index of 300M+ scholarly works.

Total works
5.1K
Citations
177.6K
h-index
150
i10-index
3.6K
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University of Louisiana at MonroeUniversité de Louisiane à Monroe

Top-cited papers from University of Louisiana at Monroe

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
Daniel J. Klionsky, Kotb Abdelmohsen, Akihisa Abe, Md. Joynal Abedin +4 more
2016· Autophagy6.0Kdoi:10.1080/15548627.2015.1100356

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. For example, a key point that needs to be emphasized is thatthere 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 versus those that measure flux through the autophagy pathway (i.e., the completeprocess including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increasedautophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost 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 manycases, 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. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. 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 forreviewers 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 multipleassays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagyrelated protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. 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 assays, we hope to encourage technical innovation in the field.

Epidemiology, diagnosis, and management of polycystic ovary syndrome
Susan M. Sirmans, Kirsten Pate
2013· Clinical Epidemiology1.3Kdoi:10.2147/clep.s37559

Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%-20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%-70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications.

ORGANOPHOSPHORUS PESTICIDES: DO THEY ALL HAVE THE SAME MECHANISM OF TOXICITY?
Carey Pope
1999· Journal of Toxicology and Environmental Health Part B647doi:10.1080/109374099281205

Organophosphorus (OP) pesticides are used extensively to control agricultural, household and structural pests. These pesticides constitute a diverse group of chemical structures exhibiting a wide range of physicochemical properties, with their primary toxicological action arising from inhibition of the enzyme acetylcholinesterase (AChE, EC 3.1.1.7). Historically, risk characterizations for these toxicants have been based on hazard and exposure data pertaining to individual chemicals. The Food Quality Protection Act of 1996 now requires, however, that combined risk assessments be performed with pesticides having a common mechanism of toxicity. It is therefore critical to consider whether OP pesticides all exert toxicity through a common mechanism. This brief review evaluates the comparative toxicity of the 38 OP AChE inhibitors currently registered for use as pesticides in the United States and examines the data which suggest that some OP pesticides have toxicologically relevant sites of action in addition to AChE. It is concluded that all OP anticholinesterases potentially have a mechanism of toxicity in common, that is, phosphorylation of AChE causing accumulation of acetylcholine, overstimulation of cholinergic receptors, and consequent clinical signs of cholinergic toxicity. Additional macromolecular targets for some OP pesticides, however, may alter the cascade of events following AChE phosphorylation and thereby modify that common mechanism. Furthermore, other macromolecular targets of some OP pesticides appear capable of altering noncholinergic neurochemical processes. These additional actions may contribute to qualitative and quantitative differences in toxicity sometimes noted in the presence of similar levels of AChE inhibition induced by different OP pesticides. Further investigation of these additional sites of action may allow subclassification and influence the decision to perform combined risk assessments on this class of pesticides based on common mechanism of toxicity.

Contribution of hydrogen bonds to protein stability
C. Nick Pace, Hailong Fu, Katrina Lee Fryar, John D. Landua +4 more
2014· Protein Science596doi:10.1002/pro.2449

Our goal was to gain a better understanding of the contribution of the burial of polar groups and their hydrogen bonds to the conformational stability of proteins. We measured the change in stability, Δ(ΔG), for a series of hydrogen bonding mutants in four proteins: villin headpiece subdomain (VHP) containing 36 residues, a surface protein from Borrelia burgdorferi (VlsE) containing 341 residues, and two proteins previously studied in our laboratory, ribonucleases Sa (RNase Sa) and T1 (RNase T1). Crystal structures were determined for three of the hydrogen bonding mutants of RNase Sa: S24A, Y51F, and T95A. The structures are very similar to wild type RNase Sa and the hydrogen bonding partners form intermolecular hydrogen bonds to water in all three mutants. We compare our results with previous studies of similar mutants in other proteins and reach the following conclusions. (1) Hydrogen bonds contribute favorably to protein stability. (2) The contribution of hydrogen bonds to protein stability is strongly context dependent. (3) Hydrogen bonds by side chains and peptide groups make similar contributions to protein stability. (4) Polar group burial can make a favorable contribution to protein stability even if the polar groups are not hydrogen bonded. (5) The contribution of hydrogen bonds to protein stability is similar for VHP, a small protein, and VlsE, a large protein.

A Broadly Implementable Research Course in Phage Discovery and Genomics for First-Year Undergraduate Students
Tuajuanda C. Jordan, Sandra H. Burnett, Susan D. Carson, Steven M. Caruso +4 more
2014· mBio515doi:10.1128/mbio.01051-13

UNLABELLED: Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been taken by over 4,800 students at 73 institutions. We show here that this alliance-sourced model not only substantially advances the field of phage genomics but also stimulates students' interest in science, positively influences academic achievement, and enhances persistence in science, technology, engineering, and mathematics (STEM) disciplines. Broad application of this model by integrating other research areas with large numbers of early-career undergraduate students has the potential to be transformative in science education and research training. IMPORTANCE: Engagement of undergraduate students in scientific research at early stages in their careers presents an opportunity to excite students about science, technology, engineering, and mathematics (STEM) disciplines and promote continued interests in these areas. Many excellent course-based undergraduate research experiences have been developed, but scaling these to a broader impact with larger numbers of students is challenging. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunting Advancing Genomics and Evolutionary Science (SEA-PHAGES) program takes advantage of the huge size and diversity of the bacteriophage population to engage students in discovery of new viruses, genome annotation, and comparative genomics, with strong impacts on bacteriophage research, increased persistence in STEM fields, and student self-identification with learning gains, motivation, attitude, and career aspirations.

The Effects of Cold and Lower Body Negative Pressure on Cardiovascular Homeostasis
David J. Kean, Corey A. Peacock, Gabriel J. Sanders, John McDaniel +2 more
2015· BioMed Research International491doi:10.1155/2015/728145

PURPOSE: The purpose of this study is to determine how cold exposure and lower body negative pressure effected cardiovascular variables. METHODS: Eleven males (20.3 years ± 2.7) underwent two 20-minute exposures to LBNP. During the 2 trials, the subjects were exposed to cold air (10°C) (COLD) and to ambient temperature (23°C) (AMB). The trials consisted of a 100-minute pre-LBNP period followed by a 20-minute exposure to LBNP and then a 15-minute recovery period. Cardiovascular variables were recorded every 30 minutes using bioimpedance. RESULTS: When LBNP was applied during the AMB trials, stroke volume immediately decreased. During the COLD trial, there was a five-minute delay before the decrease in stroke volume. Heart rate increased immediately after LBNP initiation during the AMB trials but there was a delay in the increase during the COLD trials. That same pattern was followed with mean arterial blood pressures. Cerebral oxygenation was significantly lower throughout the COLD trial as compared to the AMB trials. Six subjects reported symptoms of syncope or presyncope during the AMB trials but there were no reports of symptoms during the COLD trials. CONCLUSION: From analysis of this data, cold improved the subject's tolerance to LBNP.

Examining Factors Impacting Online Survey Response Rates in Educational Research: Perceptions of Graduate Students
Amany Saleh, Krishna Bista
2017· Journal of MultiDisciplinary Evaluation485doi:10.56645/jmde.v13i29.487

Background: In educational research, online survey has become one of the most popular methods of data collection. Academic researchers, including faculty and students, expect and require a good response rate to their research projects for reliable results. Purpose: In this paper, the authors examine a wide range of factors related to survey response rates in academic research. Examples include email checking habits, survey design, and attitudes toward research. Setting: An online survey environment Intervention: Not applicable. Research Design: A cross-sectional quantitative research method was used to analyze the factors that influence participants’ email survey response rate. Data were collected at a single point in time. The authors did not directly measure changes that come over time in this study. Data Collection and Analysis: After receiving the Institutional Research Board’s approval, the researchers distributed the survey via the American Educational Research Association (AERA) Graduate Student Discussion List subscribers. A sample of 454 responses was used in the final analysis-- with a 78.9 % response rate. The authors used descriptive statistics (percentage, average mean) and inferential statistics (chi-square and correlations) to report the data analysis and findings. Findings: Results indicated that research survey response rate was highly influenced by interests of participants, survey structure, communication methods, and assurance of privacy and confidentiality. The findings also suggested that male participants were more likely to respond to surveys if they received a reminder, and older participants were more likely to respond if they were promised a reward.

Does e-learning service quality influence e-learning student satisfaction and loyalty? Evidence from Vietnam
Long Pham, Yam B. Limbu, Trung K. Bui, Hien Thi Nguyen +1 more
2019· International Journal of Educational Technology in Higher Education460doi:10.1186/s41239-019-0136-3

Prior studies on e-learning service quality were conducted mainly in developed countries; however, little effort has been made in emerging countries. This study examines the relationships among e-learning service quality attributes, overall e-learning service quality, e-learning student satisfaction, and e-learning student loyalty in the context of Vietnam, an emerging country. Survey data collected from 1232 college students were analyzed by means of exploratory factor analysis, confirmatory factor analysis, and structural equation modeling using SPSS 25 and SmartPLS 3.0. The results indicated that e-learning service quality was a second-order construct comprising of three factors, namely, e-learning system quality, e-learning instructor and course materials quality, and e-learning administrative and support service quality. The e-learning system quality was the most important dimension of overall e-learning service quality, followed by e-learning instructor and course materials quality, and e-learning administrative and support service quality. In addition, the overall e-learning service quality was positively related to e-learning student satisfaction, which in turn positively influences e-learning student loyalty. Also, overall e-learning service quality has a direct effect on e-learning student loyalty. Implications for colleges and universities are discussed.

Optimization of the Tetrazolium Dye (MTT) Colorimetric Assay for Cellular Growth and Viability
Paul W. Sylvester
2011· Methods in molecular biology438doi:10.1007/978-1-61779-012-6_9

The MTT colorimetric assay is an established method of determining viable cell number in proliferation and cytotoxicity studies. This assay is based on the cleavage of the yellow tetrazolium salt, MTT, to form a soluble blue formazan product by mitochondrial enzymes, and the amount of formazan produced is directly proportional to the number of living, not dead cells, present during MTT exposure. Since the MTT assay is rapid, convenient, and economical, it has become a very popular technique for quantification of viable cells in culture. However, various parameters have been identified that can affect cellular metabolism and other factors, which significantly modify MTT-specific activity and can result in calculated false high or false low cell counts. Therefore, it is essential to establish assay parameters with the proper controls for each cell line and/or drug treatment in order to optimize assay conditions and minimize confounding effects. These parameters should include determining appropriate cell densities, culture medium, optimal concentrations and exposure times for MTT, fresh culture medium at the time of assay to avoid nutrient depletion, and controlling for drug treatment effects that may influence cellular metabolism. By controlling these important parameters, the MTT colorimetric assay provides accurate and reliable quantification of viable cell number.

Healthcare Transformation and Changing Roles for Nursing
Susan Salmond, Mercedes Echevarria
2017· Orthopaedic Nursing298doi:10.1097/nor.0000000000000308

Factors driving healthcare transformation include fragmentation, access problems, unsustainable costs, suboptimal outcomes, and disparities. Cost and quality concerns along with changing social and disease-type demographics created the greatest urgency for the need for change. Caring for and paying for medical treatments for patients suffering from chronic health conditions are a significant concern. The Affordable Care Act includes programs now led by the Centers for Medicare & Medicaid Services aiming to improve quality and control cost. Greater coordination of care-across providers and across settings-will improve quality care, improve outcomes, and reduce spending, especially attributed to unnecessary hospitalization, unnecessary emergency department utilization, repeated diagnostic testing, repeated medical histories, multiple prescriptions, and adverse drug interactions. As a nation, we have taken incremental steps toward achieving better quality and lower costs for decades. Nurses are positioned to contribute to and lead the transformative changes that are occurring in healthcare by being a fully contributing member of the interprofessional team as we shift from episodic, provider-based, fee-for-service care to team-based, patient-centered care across the continuum that provides seamless, affordable, and quality care. These shifts require a new or an enhanced set of knowledge, skills, and attitudes around wellness and population care with a renewed focus on patient-centered care, care coordination, data analytics, and quality improvement.

Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury
Selim Fakhruddin, Wael A. Alanazi, Keith E. Jackson
2017· Journal of Diabetes Research292doi:10.1155/2017/8379327

Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage. Interestingly, all these pathological changes are predominantly driven by diabetes-induced reactive oxygen species (ROS) and abnormal downstream signaling molecules. In diabetic kidney, NADPH oxidase (enzymatic) and mitochondrial electron transport chain (nonenzymatic) are the prominent sources of ROS, which are believed to cause the onset of albuminuria followed by progression to renal damage through podocyte depletion. Chronic hyperglycemia and consequent ROS production can trigger abnormal signaling pathways involving diverse signaling mediators such as transcription factors, inflammatory cytokines, chemokines, and vasoactive substances. Persistently, increased expression and activation of these signaling molecules contribute to the irreversible functional and structural changes in the kidney resulting in critically decreased glomerular filtration rate leading to eventual renal failure.

Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s Disease: In Vitro and in Vivo Studies
Alaa H. Abuznait, Hisham Qosa, Belnaser A. Busnena, Khalid A. El Sayed +1 more
2013· ACS Chemical Neuroscience258doi:10.1021/cn400024q

Oleocanthal, a phenolic component of extra-virgin olive oil, has been recently linked to reduced risk of Alzheimer's disease (AD), a neurodegenerative disease that is characterized by accumulation of β-amyloid (Aβ) and tau proteins in the brain. However, the mechanism by which oleocanthal exerts its neuroprotective effect is still incompletely understood. Here, we provide in vitro and in vivo evidence for the potential of oleocanthal to enhance Aβ clearance from the brain via up-regulation of P-glycoprotein (P-gp) and LDL lipoprotein receptor related protein-1 (LRP1), major Aβ transport proteins, at the blood-brain barrier (BBB). Results from in vitro and in vivo studies demonstrated similar and consistent pattern of oleocanthal in controlling Aβ levels. In cultured mice brain endothelial cells, oleocanthal treatment increased P-gp and LRP1 expression and activity. Brain efflux index (BEI%) studies of (125)I-Aβ40 showed that administration of oleocanthal extracted from extra-virgin olive oil to C57BL/6 wild-type mice enhanced (125)I-Aβ40 clearance from the brain and increased the BEI% from 62.0 ± 3.0% for control mice to 79.9 ± 1.6% for oleocanthal treated mice. Increased P-gp and LRP1 expression in the brain microvessels and inhibition studies confirmed the role of up-regulation of these proteins in enhancing (125)I-Aβ40 clearance after oleocanthal treatment. Furthermore, our results demonstrated significant increase in (125)I-Aβ40 degradation as a result of the up-regulation of Aβ degrading enzymes following oleocanthal treatment. In conclusion, these findings provide experimental support that potential reduced risk of AD associated with extra-virgin olive oil could be mediated by enhancement of Aβ clearance from the brain.

Tissue Repair: An Important Determinant of Final Outcome of Toxicant-Induced Injury
Harihara M. Mehendale
2005· Toxicologic Pathology235doi:10.1080/01926230590881808

Tissue repair is a dynamic compensatory cell proliferation and tissue regeneration response stimulated in order to overcome acute toxicity and recover organ/tissue structure and function. Extensive evidence in rodent models using structurally and mechanistically diverse hepatotoxicants such as acetaminophen (APAP), carbon tetrachloride (CCl4), chloroform (CHCl3), thioacetamide (TA), trichloroethylene (TCE), and allyl alcohol (AA) have demonstrated that tissue repair plays a critical role in determining the final outcome of toxicity, i.e., recovery from injury and survival or progression of injury leading to liver failure and death. Tissue repair is a complex process governed by intricate cellular signaling involving a number of chemokines, cytokines, growth factors, and nuclear receptors leading to promitogenic gene expression and cell division. Tissue repair also encompasses regeneration of hepatic extracellular matrix and angiogenesis, the processes necessary to completely restore the structure and function of the liver tissue lost to toxicant-induced initiation followed by progression of injury. New insights have emerged over the last quarter century indicating that tissue repair follows a dose response. Tissue repair increases with dose until a threshold dose, beyond which it is delayed and impaired due to inhibition of cellular signaling resulting in runaway secondary events causing tissue destruction, organ failure, and death. Prompt and adequately stimulated tissue repair response to toxic injury is critical for recovery from toxic injury. Tissue repair is modulated by a variety of factors including species, strain, age, nutrition, and disease condition causing marked changes in susceptibility and toxic outcome. This review focuses on the properties of tissue repair, different factors affecting tissue repair, and the mechanisms that govern tissue repair and progression of injury. It also highlights the significance of tissue repair as a target for drug development strategies and an important consideration in the assessment of risk from exposure to toxicants.

Antiproliferative and Apoptotic Effects of Tocopherols and Tocotrienols on Preneoplastic and Neoplastic Mouse Mammary Epithelial Cells
Barry Mcintyre, Karen P. Briski, Abdul Gapor, Paul W. Sylvester
2000· Proceedings of The Society for Experimental Biology and Medicine230doi:10.1111/j.1525-1373.2000.22434.x

Abstract. Studies were conducted to determine the comparative effects of tocopherols and tocotrienols on preneoplastic (CL‐S1), neoplastic (‐SA), and highly malignant (+SA) mouse mammary epithelial cell growth and viability in vitro . Over a 5‐day culture period, treatment with 0–120 μ M α‐ and γ‐tocopherol had no effect on cell proliferation, whereas growth was inhibited 50% (IC 50 ) as compared with controls by treatment with the following: 13, 7, and 6 μ M tocotrienol‐rich‐fraction of palm oil (TRF); 55, 47, and 23 μ M δ‐tocopherol; 12, 7, and 5 μ M α‐tocotrienol; 8, 5, and 4 μ M γ‐tocotrienol; or 7, 4, and 3 μ M δ‐tocotrienol in CL‐S1, ‐SA and +SA cells, respectively. Acute 24‐hr exposure to 0–250 μ M α‐ or γ‐tocopherol (CL‐S1, ‐SA, and +SA) or 0–250 μ M δ‐tocopherol (CL‐S1) had no effect on cell viability, whereas cell viability was reduced 50% (LD 50 ) as compared with controls by treatment with 166 or 125 μ M δ‐tocopherol in ‐SA and +SA cells, respectively. Additional LD 50 doses were determined as the following: 50, 43, and 38 μ M TRF; 27, 28, and 23 μ M α‐tocotrienol; 19, 17, and 14 μ M γ‐tocotrienol; or 16, 15, or 12 μ M δ‐tocotrienol in CL‐S1, ‐SA, and +SA cells, respectively. Treatment‐induced cell death resulted from activation of apoptosis, as indicated by DNA fragmentation. Results also showed that CL‐S1, ‐SA, and +SA cells preferentially accumulate tocotrienols as compared with tocopherols, and this may partially explain why tocotrienols display greater biopotency than tocopherols. These data also showed that highly malignant +SA cells were the most sensitive, whereas the preneoplastic CL‐S1 cells were the least sensitive to the antiproliferative and apoptotic effects of tocotrienols, and suggest that tocotrienols may have potential health benefits in preventing and/or reducing the risk of breast cancer in women.

Antiproliferative and Apoptotic Effects of Tocopherols and Tocotrienols on Preneoplastic and Neoplastic Mouse Mammary Epithelial Cells
Barry Mcintyre, Karen P. Briski, Abdul Gapor, Paul W. Sylvester
2000· Proceedings of The Society for Experimental Biology and Medicine206doi:10.1046/j.1525-1373.2000.22434.x

Studies were conducted to determine the comparative effects of tocopherols and tocotrienols on preneoplastic (CL-S1), neoplastic (-SA), and highly malignant (+SA) mouse mammary epithelial cell growth and viability in vitro. Over a 5-day culture period, treatment with 0-120 microM alpha- and gamma-tocopherol had no effect on cell proliferation, whereas growth was inhibited 50% (IC50) as compared with controls by treatment with the following: 13, 7, and 6 microM tocotrienol-rich-fraction of palm oil (TRF); 55, 47, and 23 microM delta-tocopherol; 12, 7, and 5 microM alpha-tocotrienol; 8, 5, and 4 microM gamma-tocotrienol; or 7, 4, and 3 microM delta-tocotrienol in CL-S1, -SA and +SA cells, respectively. Acute 24-hr exposure to 0-250 microM alpha- or gamma-tocopherol (CL-S1, -SA, and +SA) or 0-250 microM delta-tocopherol (CL-S1) had no effect on cell viability, whereas cell viability was reduced 50% (LD50) as compared with controls by treatment with 166 or 125 microM delta-tocopherol in -SA and +SA cells, respectively. Additional LD50 doses were determined as the following: 50, 43, and 38 microM TRF; 27, 28, and 23 microM alpha-tocotrienol; 19, 17, and 14 microM gamma-tocotrienol; or 16, 15, or 12 microM delta-tocotrienol in CL-S1, -SA, and +SA cells, respectively. Treatment-induced cell death resulted from activation of apoptosis, as indicated by DNA fragmentation. Results also showed that CL-S1, -SA, and +SA cells preferentially accumulate tocotrienols as compared with tocopherols, and this may partially explain why tocotrienols display greater biopotency than tocopherols. These data also showed that highly malignant +SA cells were the most sensitive, whereas the preneoplastic CL-S1 cells were the least sensitive to the antiproliferative and apoptotic effects of tocotrienols, and suggest that tocotrienols may have potential health benefits in preventing and/or reducing the risk of breast cancer in women.

Role and Therapeutic Targeting of the PI3K/Akt/mTOR Signaling Pathway in Skin Cancer: A Review of Current Status and Future Trends on Natural and Synthetic Agents Therapy
Jean Christopher Chamcheu, Tithi Roy, Mohammad B. Uddin, Sergette Banang‐Mbeumi +4 more
2019· Cells196doi:10.3390/cells8080803

The mammalian or mechanistic target of rapamycin (mTOR) and associated phosphatidyl-inositiol 3-kinase (PI3K)/protein kinase B (Akt) pathways regulate cell growth, differentiation, migration, and survival, as well as angiogenesis and metabolism. Dysregulation of these pathways is frequently associated with genetic/epigenetic alterations and predicts poor treatment outcomes in a variety of human cancers including cutaneous malignancies like melanoma and non-melanoma skin cancers. Recently, the enhanced understanding of the molecular and genetic basis of skin dysfunction in patients with skin cancers has provided a strong basis for the development of novel therapeutic strategies for these obdurate groups of skin cancers. This review summarizes recent advances in the roles of PI3K/Akt/mTOR and their targets in the development and progression of a broad spectrum of cutaneous cancers and discusses the current progress in preclinical and clinical studies for the development of PI3K/Akt/mTOR targeted therapies with nutraceuticals and synthetic small molecule inhibitors.

Multitarget therapeutic strategies for Alzheimer’s disease
MoustafaT. Gabr, MostafaM. Ibrahim
2018· Neural Regeneration Research192doi:10.4103/1673-5374.245463

Neurodegenerative diseases such as Alzheimer's, Huntington's and Parkinson's diseases have multifaceted nature because of the different factors contributing to their progression. The complex nature of neurodegenerative diseases has developed a pressing need to design multitarget-directed ligands to address the complementary pathways involved in these diseases. The major enzyme targets for development of therapeutics for Alzheimer's disease are cholinesterase and β-secretase enzymes. In this review, we discuss recent advances in profiling single target inhibitors based on these enzymes to multitarget-directed ligands as potential therapeutics for this devastating disease. In addition, therapeutics based on iron chelation strategy are discussed as well.

Overview of skin cancer types and prevalence rates across continents
Amdad Hossain Roky, Mohammed Murshedul Islam, Abu Mohammed Fuad Ahasan, Md Saqline Mostaq +3 more
2024· Cancer Pathogenesis and Therapy187doi:10.1016/j.cpt.2024.08.002

Skin cancer is one of the most prevalent cancers in the world, and its incidence and mortality rates are increasing continuously, mostly in regions with white-skinned inhabitants. The types of skin cancer vary in their origin and clinical appearances and also differ in their extensiveness. The continents of the world have different scenarios of skin cancer prevalence. This review aims to explore the different types of skin cancer, their clinical features, and their worldwide prevalence based on the literature. Literature from different electronic databases, including Google Scholar, ResearchGate, PubMed, Scopus, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Elsevier, and Springer, were collected through a literature search using specific keywords such as "skin cancer", "skin cancer types", "melanoma", "non-melanoma", "skin cancer continental prevalence" or similar keywords. The search included English publications from 2000 to 2024. Melanoma skin cancer (MSC) ranks 17th in global prevalence, with the highest incidence and deaths occurring in Europe, However, Australia and New Zealand record the highest incidence and mortality rates. Asia has a lower incidence rate of melanoma, but a higher mortality rate. Superficial spreading melanoma (SSM) is the most common type of MSC. Non-melanoma skin cancers (NMSCs) have the highest incidence in North America, with the highest number of deaths occurring in Asia, Australia and New Zealand have the highest incidence rates for basal cell carcinoma (BCC). BCC is the most commonly diagnosed skin cancer worldwide and the most prevalent form of NMSCs; however, squamous cell carcinoma is the most aggressive form of NMSCs, causing more deaths. NMSCs are the most prevalent cancers worldwide, causing most skin cancer-related deaths. The prevalence of skin cancer rising globally, with several continents experiencing higher incidence and mortality rates. The types and subtypes of skin cancer are becoming more common among clinically diagnosed cancers. This review comprehensively describes skin cancer types and their prevalence worldwide. However, the actual prevalence of skin cancer in these countries should be investigated. Further research on the prevalence of skin cancer across different continents is required to develop more effective cancer management strategies and control the spread of the disease.

Class II Non-Extraction Patients Treated with the Forsus Fatigue Resistant Device Versus Intermaxillary Elastics
Graham Jones, Peter H. Buschang, Ki Beom Kim, D.R. Oliver
2007· The Angle Orthodontist187doi:10.2319/030607-115.1

OBJECTIVE: To evaluate the Forsus Fatigue Resistant Device (FRD) as a compliance-free alternative to Class II elastics. MATERIALS AND METHODS: A sample of 34 (14 female, 20 male) consecutively treated nonextraction FRD patients (12.6 years of age) were matched with a sample of 34 (14 female, 20 male) consecutively treated nonextraction Class II elastics patients (12.2 years of age) based on four pretreatment variables (ANB, L1-GoMe, SN-GoMe, and treatment duration). Pretreatment and posttreatment cephalometric radiographs were traced and analyzed using the pitchfork analysis and a vertical cephalometric analysis. t-Tests were used to evaluate group differences. Group differences were evaluated using t-tests. RESULTS: No statistically significant differences were found in the treatment changes between the groups. There was a general trend for mesial movement of the maxilla, mandible, and dentition during treatment for both groups. The mandibular skeletal advancement and dental movements were greater than those in the maxilla, which accounted for the Class II correction. Lower incisor proclination was evident in both groups. Vertically, the maxillary and mandibular molars erupted during treatment in both groups, while lower incisors proclined. With the exception of lower molar mesial movements and total molar correction, which were significantly (P < .05) greater in the Forsus group, there were no statistically significant group differences in the treatment changes. CONCLUSIONS: The Forsus FRD is an acceptable substitute for Class II elastics for noncompliant patients.

The Relative Importance of Journals Used in Management Research: An Alternative Ranking
Arthur D. Sharplin, Rodney H. Mabry
1985· Human Relations178doi:10.1177/001872678503800204

The journals which contribute most to management research are identified and ranked based upon the number of citations they received during a recent four-year period in the two top management journals, Administrative Science Quarterly and The Academy of Management Journal. Rankings are provided based upon total citations, citations per article published annually, and citations per 10,000 words published annually. A final ranking of just the top ten management journals is based upon the last criterion.