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Med. Sci., Volume 6, Issue 1 (March 2018)

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Cover Story (view full-size image) Over half of all melanoma tumors express a mutant BRAF protein. We hypothesized that polyamines are [...] Read more.
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Open AccessArticle The Association between Body Mass Index and Health-Related Quality of Life in Treatment-Seeking Arab Adults with Obesity
Med. Sci. 2018, 6(1), 25; https://doi.org/10.3390/medsci6010025
Received: 3 February 2018 / Revised: 7 March 2018 / Accepted: 9 March 2018 / Published: 13 March 2018
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Abstract
Few studies have thus far been carried out on Health-Related Quality of Life (HRQoL) and obesity in Arab-speaking countries, an issue that we therefore set out to investigate in this study. HRQoL was assessed by the validated Arabic version of the ORWELL 97
[...] Read more.
Few studies have thus far been carried out on Health-Related Quality of Life (HRQoL) and obesity in Arab-speaking countries, an issue that we therefore set out to investigate in this study. HRQoL was assessed by the validated Arabic version of the ORWELL 97 questionnaire in 129 treatment-seeking individuals with obesity referred to the Nutritional and Weight Management Outpatient Clinic at the Department of Nutrition and Dietetics of Beirut Arab University (BAU) in Lebanon, and 129 normal-weight participants of similar age and gender. Participants with obesity, regardless of gender, displayed higher total ORWELL 97 scores when compared with normal-weight controls, indicating that obesity is associated with lower HRQoL. Linear regression analysis showed that a higher body mass index (BMI) is associated with an increase in ORWELL 97 scores, but only among female, not male, participants with obesity (β = 2.89, 95% confidence interval (CI) = 1.43–4.53, p < 0.001). Moreover, logistic regression analysis showed that a one unit increase in BMI increases the odds of an ORWELL 97 score ≥ 71.75—considered indicative of a clinically significant impairment of HRQoL—by nearly 23% (odds ratio (OR), 95% CI = 1.23, 1.09–1.40, p < 0.05). If confirmed, our findings should prompt clinicians operating in Arab countries to encourage patients with obesity to initiate and persevere in weight-loss programs at the earliest opportunity. Full article
(This article belongs to the Section Endocrinology and Metabolic Diseases)
Open AccessReview Cellular and Animal Model Studies on the Growth Inhibitory Effects of Polyamine Analogues on Breast Cancer
Med. Sci. 2018, 6(1), 24; https://doi.org/10.3390/medsci6010024
Received: 28 January 2018 / Revised: 4 March 2018 / Accepted: 6 March 2018 / Published: 13 March 2018
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Abstract
Polyamine levels are elevated in breast tumors compared to those of adjacent normal tissues. The female sex hormone, estrogen is implicated in the origin and progression of breast cancer. Estrogens stimulate and antiestrogens suppress the expression of polyamine biosynthetic enzyme, ornithine decarboxylate (ODC).
[...] Read more.
Polyamine levels are elevated in breast tumors compared to those of adjacent normal tissues. The female sex hormone, estrogen is implicated in the origin and progression of breast cancer. Estrogens stimulate and antiestrogens suppress the expression of polyamine biosynthetic enzyme, ornithine decarboxylate (ODC). Using several bis(ethyl)spermine analogues, we found that these analogues inhibited the proliferation of estrogen receptor-positive and estrogen receptor negative breast cancer cells in culture. There was structure-activity relationship in the efficacy of these compounds in suppressing cell growth. The activity of ODC was inhibited by these compounds, whereas the activity of the catabolizing enzyme, spermidine/spermine N1-acetyl transferase (SSAT) was increased by 6-fold by bis(ethyl)norspermine in MCF-7 cells. In a transgenic mouse model of breast cancer, bis(ethyl)norspermine reduced the formation and growth of spontaneous mammary tumor. Recent studies indicate that induction of polyamine catabolic enzymes SSAT and spermine oxidase (SMO) play key roles in the anti-proliferative and apoptotic effects of polyamine analogues and their combinations with chemotherapeutic agents such as 5-fluorouracil (5-FU) and paclitaxel. Thus, polyamine catabolic enzymes might be important therapeutic targets and markers of sensitivity in utilizing polyamine analogues in combination with other therapeutic agents. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Open AccessArticle Network-Based Identification of Altered Stem Cell Pluripotency and Calcium Signaling Pathways in Metastatic Melanoma
Med. Sci. 2018, 6(1), 23; https://doi.org/10.3390/medsci6010023
Received: 8 January 2018 / Revised: 22 February 2018 / Accepted: 2 March 2018 / Published: 8 March 2018
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Abstract
Malignancy of cancer has been linked to distinct subsets of stem-like cells, the so-called cancer stem cells (CSCs), which persist during treatment and seem to lead to drug-resistant recurrence. Metastatic spread of cancer cells is one of the hallmarks of malignancy and contributes
[...] Read more.
Malignancy of cancer has been linked to distinct subsets of stem-like cells, the so-called cancer stem cells (CSCs), which persist during treatment and seem to lead to drug-resistant recurrence. Metastatic spread of cancer cells is one of the hallmarks of malignancy and contributes to most human melanoma-related deaths. Recently, overlapping groups of proteins and pathways were shown to regulate stem cell migration and cancer metastasis, raising the question of whether genes/proteins involved in stem cell pluripotency may have important implications when applied to the biology of cancer metastasis. Furthermore, it is well known that ion channels and receptors, particularly those responsible for calcium (Ca2+) signal generation, are critical in determining the cellular fate of stem cells (SCs). In the present study, we searched for evidence of altered stem cell pluripotency and Ca2+ signaling-related genes in the context of melanoma metastasis. We did this by using network analysis of gene expression in tissue biopsies from three different independent datasets of patients. First, we created an in silico network model (“STEMCa” interactome) showing the landscape of interactions between stem cell pluripotency and Ca2+ signaling-related genes/proteins, and demonstrated that around 51% (151 out of 294) of the genes within this model displayed significant changes of expression (False Discovery Rate (FDR), corrected p-value < 0.05) in at least one of the datasets of melanoma metastasis when compared with primary tumor biopsies (controls). Analysis of the properties (degree and betweenness) of the topological network revealed 27 members as the most central hub (HB) and nonhub-bottlenecks (NH-B) among the 294 genes/proteins of the whole interactome. From those representative genes, CTNNB1, GNAQ, GSK3B, GSTP1, MAPK3, PPP1CC, PRKACA, and SMAD4 showed equal up- or downregulation (corrected p-value < 0.05) in at least 2 independent datasets of melanoma metastases samples and PTPN11 showed upregulation (corrected p-value < 0.05) in three of them when compared with control samples. We postulate that altered expression of stem cell pluripotency and Ca2+ signaling pathway-related genes may contribute to the metastatic transformation, with these central members being an optimal candidate group of biomarkers and in silico therapeutic targets for melanoma metastasis, which deserve further investigation. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
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Open AccessFeature PaperReview Role of Polyamines in Immune Cell Functions
Med. Sci. 2018, 6(1), 22; https://doi.org/10.3390/medsci6010022
Received: 16 January 2018 / Revised: 28 February 2018 / Accepted: 2 March 2018 / Published: 8 March 2018
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Abstract
The immune system is remarkably responsive to a myriad of invading microorganisms and provides continuous surveillance against tissue damage and developing tumor cells. To achieve these diverse functions, multiple soluble and cellular components must react in an orchestrated cascade of events to control
[...] Read more.
The immune system is remarkably responsive to a myriad of invading microorganisms and provides continuous surveillance against tissue damage and developing tumor cells. To achieve these diverse functions, multiple soluble and cellular components must react in an orchestrated cascade of events to control the specificity, magnitude and persistence of the immune response. Numerous catabolic and anabolic processes are involved in this process, and prominent roles for l-arginine and l-glutamine catabolism have been described, as these amino acids serve as precursors of nitric oxide, creatine, agmatine, tricarboxylic acid cycle intermediates, nucleotides and other amino acids, as well as for ornithine, which is used to synthesize putrescine and the polyamines spermidine and spermine. Polyamines have several purported roles and high levels of polyamines are manifest in tumor cells as well in autoreactive B- and T-cells in autoimmune diseases. In the tumor microenvironment, l-arginine catabolism by both tumor cells and suppressive myeloid cells is known to dampen cytotoxic T-cell functions suggesting there might be links between polyamines and T-cell suppression. Here, we review studies suggesting roles of polyamines in normal immune cell function and highlight their connections to autoimmunity and anti-tumor immune cell function. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Open AccessArticle Risk Factors Including Age, Stage and Anatomic Location that Impact the Outcomes of Patients with Synovial Sarcoma
Med. Sci. 2018, 6(1), 21; https://doi.org/10.3390/medsci6010021
Received: 3 January 2018 / Revised: 10 February 2018 / Accepted: 1 March 2018 / Published: 6 March 2018
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Abstract
Synovial sarcoma is a high-grade soft tissue sarcoma that inflicts mostly children and young adults with high mortality rate; however, the risk factors that impact the outcomes remain incompletely understood. We have identified the synovial sarcoma cases from the Kaiser Permanente Northern California
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Synovial sarcoma is a high-grade soft tissue sarcoma that inflicts mostly children and young adults with high mortality rate; however, the risk factors that impact the outcomes remain incompletely understood. We have identified the synovial sarcoma cases from the Kaiser Permanente Northern California cancer registry between 1981 and 2014. Kaplan–Meier plots were used to display disease-free survival (DFS) and overall survival (OS); log-rank tests and Cox proportional hazard models were used to determine the impact of clinical factors on DFS, OS, and disease-specific survival. Tumor size > 5.0 cm and age > 50 years were associated with higher risk of presenting with stage IV disease. Median OS for patients with stage IV was 1.3 years and 7.8 years for early-stage disease. For patients with early-stage disease, tumor size > 5.0 cm was significantly associated with worse DFS, sarcoma-specific morality, and OS. Compared to extremity primary, patients with head and neck and trunk primary had approximately three-fold higher sarcoma-specific mortality and lower OS. There was no significant difference in DFS or OS among three histologic subtypes. Pre-operative and/or post-operative chemotherapy was not associated with improvement in DFS or OS. Twenty-six patients relapsed with predominantly lung metastasis, thirteen of whom received metastatectomy with a median OS of 7.8 years, compared to 2.3 years for patients who did not receive metastatectomy. In conclusion, age older than 50 years and tumor size > 5.0 cm are risk factors for presenting with stage IV disease. For early-stage patients, trunk and head and neck primary as well as tumor size > 5.0 cm are risk factors for decreased OS. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
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Open AccessArticle Electrodermal Activity during Blood Pooling for Arterial Blood Gases Analysis in Sedated Adult Intensive Care Unit Patients
Med. Sci. 2018, 6(1), 20; https://doi.org/10.3390/medsci6010020
Received: 17 January 2018 / Revised: 26 February 2018 / Accepted: 1 March 2018 / Published: 6 March 2018
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Abstract
Electrodermal activity (EDA) is considered a measure of autonomous nervous system activity. This study performed an exploratory analysis of the EDA changes during blood pooling for arterial blood gas analysis in sedated adult critical care patients and correlated the variations to other monitored
[...] Read more.
Electrodermal activity (EDA) is considered a measure of autonomous nervous system activity. This study performed an exploratory analysis of the EDA changes during blood pooling for arterial blood gas analysis in sedated adult critical care patients and correlated the variations to other monitored parameters. EDA, along with other parameters, were monitored during 4 h routine daytime intensive care nursing and treatment in an adult ICU. 4 h measurements were divided into two groups based upon the sedation level. Selected recordings before and after blood pooling for arterial blood gases analysis (stress event) was performed. Nine stress events from Group A and 17 from Group B were included for further analysis. Patients’ demographics, laboratory exams, and severity scores were recorded. For both sedation levels, EDA changes are much greater than any other monitoring parameters used. The changes are noticed in both measurement (15 s and 60 s), even though in the 60 s measurement only selected EDA parameters are significantly changed after the start of the procedure. EDA measurements are more sensitive to a given stress event than cardiovascular or respiratory parameters. However, the present results could only be considered as a pilot study. More studies are needed in order to identify the real stress-load and clinical significance of such stimuli, which are considered otherwise painless in those patients. Full article
(This article belongs to the Section Neurosciences)
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Open AccessReview Artemisinin and Its Synthetic Derivatives as a Possible Therapy for Cancer
Med. Sci. 2018, 6(1), 19; https://doi.org/10.3390/medsci6010019
Received: 10 January 2018 / Revised: 15 February 2018 / Accepted: 22 February 2018 / Published: 27 February 2018
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Abstract
To assess the possibility of using the antimalarial drug artemisinin and its synthetic derivatives as antineoplastic drugs. A Pubmed and Google Scholar (1983–2018) search was performed using the terms artemisinin, cancer, artesunate and Artemisia annua. Case reports and original research articles, review articles,
[...] Read more.
To assess the possibility of using the antimalarial drug artemisinin and its synthetic derivatives as antineoplastic drugs. A Pubmed and Google Scholar (1983–2018) search was performed using the terms artemisinin, cancer, artesunate and Artemisia annua. Case reports and original research articles, review articles, and clinical trials in both humans and animals were evaluated. Both in vitro and in vivo clinical trials and case reports have shown promising activity of the artemisinin drug derivatives in treating certain types of cancer. However, the reported articles are few, and therefore not statistically significant. The minimal toxicity shown in clinical trials and case reports, along with the selective cytotoxic activity of the compounds, make them possible cancer therapies due to the emerging evidence of the drug’s effectiveness. Full article
(This article belongs to the Section Cancer and Cancer-Related Research)
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Open AccessArticle Assessment and Treatment of Pediatric Sleep Problems: Knowledge, Skills, Attitudes and Practices in a Group of Community Child Psychiatrists
Med. Sci. 2018, 6(1), 18; https://doi.org/10.3390/medsci6010018
Received: 4 January 2018 / Revised: 19 February 2018 / Accepted: 20 February 2018 / Published: 23 February 2018
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Abstract
As part of a university-based quality improvement project, we aimed to evaluate child psychiatrists’ knowledge, skills, attitudes, and practices regarding assessment and treatment of pediatric sleep problems. We developed a nine-question survey of knowledge, skills, attitudes, and practices regarding assessing for and treating
[...] Read more.
As part of a university-based quality improvement project, we aimed to evaluate child psychiatrists’ knowledge, skills, attitudes, and practices regarding assessment and treatment of pediatric sleep problems. We developed a nine-question survey of knowledge, skills, attitudes, and practices regarding assessing for and treating sleep complaints in pediatric patients, and administered this survey to child psychiatrists in training and in practice in the state of Missouri. Respondents reported sleep hygiene as the first-line treatment strategy, followed by the use of supplements or over-the-counter remedies. The most common barriers to evidence-based assessment and treatment of sleep problems were the lack of ability to obtain reliable history, and parental preference for medications over behavioral approaches for sleep concerns. These results suggest potential opportunities for enhancing knowledge regarding validated assessment tools and non-pharmacological treatment options for sleep problems. Additional research is needed to further assess the quality and type of sleep education provided in child psychiatry training programs. Full article
(This article belongs to the Special Issue Updates in Pediatric Sleep and Child Psychiatry)
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Open AccessArticle Diagnostic Utility of High Sensitivity Troponins for Echocardiographic Markers of Structural Heart Disease
Med. Sci. 2018, 6(1), 17; https://doi.org/10.3390/medsci6010017
Received: 25 January 2018 / Revised: 12 February 2018 / Accepted: 13 February 2018 / Published: 15 February 2018
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Abstract
The conventional use of high-sensitivity troponins (hs-troponins) is for diagnosing myocardial infarction however they also have a role in chronic disease management. This pilot study assessed the relationship of hs-troponins with echocardiographic markers of left ventricular hypertrophy (LVH) and structural heart disease (SHD).
[...] Read more.
The conventional use of high-sensitivity troponins (hs-troponins) is for diagnosing myocardial infarction however they also have a role in chronic disease management. This pilot study assessed the relationship of hs-troponins with echocardiographic markers of left ventricular hypertrophy (LVH) and structural heart disease (SHD). Patients undergoing computer gomography (CT) coronary angiogram for low-intermediate risk chest pain and healthy volunteers were recruited. Hs-troponins Singulex I, Abbott I and Roche T and N-terminal pro-brain natriuretic peptide (NT-proBNP) were evaluated in relation to SHD parameters including left ventricular hypertrophy (LVHEcho) and left atrial enlargement (LAEEcho) on echocardiography. 78 subjects who underwent echocardiography were included in this study. C-statistics (95% confidence interval) of the four biomarkers for predicting LVHEcho were 0.84 (0.72–0.92), 0.84 (0.73–0.92), 0.75 (0.63–0.85) and 0.62 (0.49–0.74); for LAEEcho 0.74 (0.6–0.85), 0.78 (0.66–0.88), 0.55 (0.42–0.67) and 0.68 (0.62–0.85); and composite SHD 0.79 (0.66–0.88), 0.87 (0.75–0.94), 0.62 (0.49–0.73) and 0.74 (0.62–0.84) respectively. Optimal cut points for SHD were >1.2 ng/L, >1.6 ng/L, >8 ng/L and >18 pmol/L respectively. These results advocate the potential role of hs-troponins as screening tools for structural heart disease with theranostic implications. Full article
(This article belongs to the Section Cardiovascular Disease)
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Open AccessFeature PaperReview Narcolepsy and Psychiatric Disorders: Comorbidities or Shared Pathophysiology?
Med. Sci. 2018, 6(1), 16; https://doi.org/10.3390/medsci6010016
Received: 3 January 2018 / Revised: 2 February 2018 / Accepted: 6 February 2018 / Published: 15 February 2018
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Abstract
Narcolepsy and psychiatric disorders have a significant but unrecognized relationship, which is an area of evolving interest, but unfortunately, the association is poorly understood. It is not uncommon for the two to occur co-morbidly. However, narcolepsy is frequently misdiagnosed initially as a psychiatric
[...] Read more.
Narcolepsy and psychiatric disorders have a significant but unrecognized relationship, which is an area of evolving interest, but unfortunately, the association is poorly understood. It is not uncommon for the two to occur co-morbidly. However, narcolepsy is frequently misdiagnosed initially as a psychiatric condition, contributing to the protracted time to accurate diagnosis and treatment. Narcolepsy is a disabling neurodegenerative condition that carries a high risk for development of social and occupational dysfunction. Deterioration in function may lead to the secondary development of psychiatric symptoms. Inversely, the development of psychiatric symptoms can lead to the deterioration in function and quality of life. The overlap in pharmaceutical intervention may further enhance the difficulty to distinguish between diagnoses. Comprehensive care for patients with narcolepsy should include surveillance for psychiatric illness and appropriate treatment when necessary. Further research is necessary to better understand the underlying pathophysiology between psychiatric disease and narcolepsy. Full article
(This article belongs to the Special Issue Updates in Pediatric Sleep and Child Psychiatry)
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Open AccessReview Traumatic Brain Injury, Sleep Disorders, and Psychiatric Disorders: An Underrecognized Relationship
Med. Sci. 2018, 6(1), 15; https://doi.org/10.3390/medsci6010015
Received: 28 December 2017 / Revised: 4 February 2018 / Accepted: 5 February 2018 / Published: 15 February 2018
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Abstract
Traumatic brain injury (TBI) is commonplace among pediatric patients and has a complex, but intimate relationship with psychiatric disease and disordered sleep. Understanding the factors that influence the risk for the development of TBI in pediatrics is a critical component of beginning to
[...] Read more.
Traumatic brain injury (TBI) is commonplace among pediatric patients and has a complex, but intimate relationship with psychiatric disease and disordered sleep. Understanding the factors that influence the risk for the development of TBI in pediatrics is a critical component of beginning to address the consequences of TBI. Features that may increase risk for experiencing TBI sometimes overlap with factors that influence the development of post-concussive syndrome (PCS) and recovery course. Post-concussive syndrome includes physical, psychological, cognitive and sleep–wake dysfunction. The comorbid presence of sleep–wake dysfunction and psychiatric symptoms can lead to a more protracted recovery and deleterious outcomes. Therefore, a multidisciplinary evaluation following TBI is necessary. Treatment is generally symptom specific and mainly based on adult studies. Further research is necessary to enhance diagnostic and therapeutic approaches, as well as improve the understanding of contributing pathophysiology for the shared development of psychiatric disease and sleep–wake dysfunction following TBI. Full article
(This article belongs to the Special Issue Updates in Pediatric Sleep and Child Psychiatry)
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Open AccessReview Skeletal Muscle Pathophysiology: The Emerging Role of Spermine Oxidase and Spermidine
Med. Sci. 2018, 6(1), 14; https://doi.org/10.3390/medsci6010014
Received: 30 November 2017 / Revised: 7 February 2018 / Accepted: 9 February 2018 / Published: 14 February 2018
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Abstract
Skeletal muscle comprises approximately 40% of the total body mass. Preserving muscle health and function is essential for the entire body in order to counteract chronic diseases such as type II diabetes, cardiovascular diseases, and cancer. Prolonged physical inactivity, particularly among the elderly,
[...] Read more.
Skeletal muscle comprises approximately 40% of the total body mass. Preserving muscle health and function is essential for the entire body in order to counteract chronic diseases such as type II diabetes, cardiovascular diseases, and cancer. Prolonged physical inactivity, particularly among the elderly, causes muscle atrophy, a pathological state with adverse outcomes such as poor quality of life, physical disability, and high mortality. In murine skeletal muscle C2C12 cells, increased expression of the spermine oxidase (SMOX) enzyme has been found during cell differentiation. Notably, SMOX overexpression increases muscle fiber size, while SMOX reduction was enough to induce muscle atrophy in multiple murine models. Of note, the SMOX reaction product spermidine appears to be involved in skeletal muscle atrophy/hypertrophy. It is effective in reactivating autophagy, ameliorating the myopathic defects of collagen VI-null mice. Moreover, spermidine treatment, if combined with exercise, can affect D-gal-induced aging-related skeletal muscle atrophy. This review hypothesizes a role for SMOX during skeletal muscle differentiation and outlines its role and that of spermidine in muscle atrophy. The identification of new molecular pathways involved in the maintenance of skeletal muscle health could be beneficial in developing novel therapeutic lead compounds to treat muscle atrophy. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Open AccessMeeting Report 23rd International Symposium on Infections in the Critically Ill Patient
Med. Sci. 2018, 6(1), 13; https://doi.org/10.3390/medsci6010013
Received: 6 February 2018 / Revised: 7 February 2018 / Accepted: 7 February 2018 / Published: 8 February 2018
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(This article belongs to the Section Pneumology and Respiratory Diseases)
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Open AccessReview Alpha-Difluoromethylornithine, an Irreversible Inhibitor of Polyamine Biosynthesis, as a Therapeutic Strategy against Hyperproliferative and Infectious Diseases
Med. Sci. 2018, 6(1), 12; https://doi.org/10.3390/medsci6010012
Received: 9 January 2018 / Revised: 2 February 2018 / Accepted: 5 February 2018 / Published: 8 February 2018
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Abstract
The fluorinated ornithine analog α-difluoromethylornithine (DFMO, eflornithine, ornidyl) is an irreversible suicide inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine biosynthesis. The ubiquitous and essential polyamines have many functions, but are primarily important for rapidly proliferating cells. Thus, ODC
[...] Read more.
The fluorinated ornithine analog α-difluoromethylornithine (DFMO, eflornithine, ornidyl) is an irreversible suicide inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine biosynthesis. The ubiquitous and essential polyamines have many functions, but are primarily important for rapidly proliferating cells. Thus, ODC is potentially a drug target for any disease state where rapid growth is a key process leading to pathology. The compound was originally discovered as an anticancer drug, but its effectiveness was disappointing. However, DFMO was successfully developed to treat African sleeping sickness and is currently one of few clinically used drugs to combat this neglected tropical disease. The other Food and Drug Administration (FDA) approved application for DFMO is as an active ingredient in the hair removal cream Vaniqa. In recent years, renewed interest in DFMO for hyperproliferative diseases has led to increased research and promising preclinical and clinical trials. This review explores the use of DFMO for the treatment of African sleeping sickness and hirsutism, as well as its potential as a chemopreventive and chemotherapeutic agent against colorectal cancer and neuroblastoma. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Open AccessReview Exploring Interventions for Sleep Disorders in Adolescent Cannabis Users
Med. Sci. 2018, 6(1), 11; https://doi.org/10.3390/medsci6010011
Received: 8 January 2018 / Revised: 2 February 2018 / Accepted: 5 February 2018 / Published: 8 February 2018
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Abstract
This review summarizes the available literature on the intersection of adolescent cannabis use and sleep disturbances, along with interventions for adolescent cannabis users who suffer sleep impairments. Adolescents are susceptible to various sleep disorders, which are often exacerbated by the use of substances
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This review summarizes the available literature on the intersection of adolescent cannabis use and sleep disturbances, along with interventions for adolescent cannabis users who suffer sleep impairments. Adolescents are susceptible to various sleep disorders, which are often exacerbated by the use of substances such as cannabis. The relationship between cannabis and sleep is bidirectional. Interventions to improve sleep impairments among adolescent cannabis users to date have demonstrated limited efficacy, although few studies indicating the benefits of behavioral interventions—such as Cognitive Behavior Therapy for Insomnia or Mindfulness Based Stress Reduction—appear promising in the treatment of sleep disorders, which are present for users of cannabis. Further research is necessary to elucidate the precise mechanisms by which cannabis use coexists with sleep impairments, along with effective interventions for those users who suffer sleep difficulties. Full article
(This article belongs to the Special Issue Updates in Pediatric Sleep and Child Psychiatry)
Open AccessArticle Conventional Chromosome Analysis of Fetuses with Central Nervous System Anomalies and Associated Anomalies: Is Anything Changed?
Med. Sci. 2018, 6(1), 10; https://doi.org/10.3390/medsci6010010
Received: 14 November 2017 / Revised: 19 December 2017 / Accepted: 1 February 2018 / Published: 6 February 2018
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Abstract
Central nervous system (CNS) abnormalities are often isolated but can accompany various genetic syndromes. In this study, we evaluated conventional karyotype results and associated findings of fetuses that were diagnosed with CNS abnormalities. Cases included in the study were diagnosed with fetal CNS
[...] Read more.
Central nervous system (CNS) abnormalities are often isolated but can accompany various genetic syndromes. In this study, we evaluated conventional karyotype results and associated findings of fetuses that were diagnosed with CNS abnormalities. Cases included in the study were diagnosed with fetal CNS anomalies and underwent conventional karyotyping. Conventional karyotype results of subjects were compared with karyotype results of fetal karyotyped patients as a result of maternal anxiety in a two-year period. In this period, 69 patients were diagnosed with fetal CNS anomalies and 64 of them underwent invasive fetal karyotyping. Of these, 32 patients had isolated CNS anomalies, while 32 were associated with other anomalies. There was no significant difference between karyotype results when compared with the control group (p = 0.76). Apart from some specific anomalies, the aneuploidy rate does not significantly differ between fetuses with CNS anomalies and the control group. Advanced genetic evaluation may provide additional diagnostic benefits, especially for this group. Full article
(This article belongs to the Section Gynecology)
Open AccessEditorial Immunotherapy: A New Strategy for the Treatment of Cervical Cancer. Interview with Dr. Christian Marth and Dr. Sharad Ghamande
Med. Sci. 2018, 6(1), 9; https://doi.org/10.3390/medsci6010009
Received: 22 January 2018 / Revised: 22 January 2018 / Accepted: 22 January 2018 / Published: 2 February 2018
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Abstract
At the European Gynecological Oncology Congress (ESGO) 2017, held in Vienna, a symposium on immunotherapy took place: A New Strategy for the Treatment of Cervical Cancer, sponsored by Advaxis, Inc. Full article
(This article belongs to the Section Gynecology)
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Open AccessFeature PaperArticle The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression
Med. Sci. 2018, 6(1), 8; https://doi.org/10.3390/medsci6010008
Received: 10 December 2017 / Revised: 7 January 2018 / Accepted: 9 January 2018 / Published: 19 January 2018
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Abstract
Invasive infections caused by Streptococcus pneumoniae, a commensal in the nasopharynx, pose significant risk to human health. Limited serotype coverage by the available polysaccharide-based conjugate vaccines coupled with increasing incidence of antibiotic resistance complicates therapeutic strategies. Bacterial physiology and metabolism that allows
[...] Read more.
Invasive infections caused by Streptococcus pneumoniae, a commensal in the nasopharynx, pose significant risk to human health. Limited serotype coverage by the available polysaccharide-based conjugate vaccines coupled with increasing incidence of antibiotic resistance complicates therapeutic strategies. Bacterial physiology and metabolism that allows pathogens to adapt to the host are a promising avenue for the discovery of novel therapeutics. Intracellular polyamine concentrations are tightly regulated by biosynthesis, transport and degradation. We previously reported that deletion of cadA, a gene that encodes for lysine decarboxylase, an enzyme that catalyzes cadaverine synthesis results in an attenuated phenotype. Here, we report the impact of cadA deletion on pneumococcal capsule and protein expression. Our data show that genes for polyamine biosynthesis and transport are downregulated in ∆cadA. Immunoblot assays show reduced capsule in ∆cadA. Reduced capsule synthesis could be due to reduced transcription and availability of precursors for synthesis. The capsule is the predominant virulence factor in pneumococci and is critical for evading opsonophagocytosis and its loss in ∆cadA could explain the reported attenuation in vivo. Results from this study show that capsule synthesis in pneumococci is regulated by polyamine metabolism, which can be targeted for developing novel therapies. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Open AccessEditorial Acknowledgement to Reviewers of Medical Sciences in 2017
Med. Sci. 2018, 6(1), 7; https://doi.org/10.3390/medsci6010007
Received: 15 January 2018 / Revised: 15 January 2018 / Accepted: 15 January 2018 / Published: 19 January 2018
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Abstract
Peer review is an essential part in the publication process, ensuring that Medical Sciences maintains high quality standards for its published papers.[...] Full article
Open AccessViewpoint The Side Effects of the Most Commonly Used Group of Antibiotics in Periodontal Treatments
Med. Sci. 2018, 6(1), 6; https://doi.org/10.3390/medsci6010006
Received: 27 October 2017 / Revised: 7 December 2017 / Accepted: 11 January 2018 / Published: 18 January 2018
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Abstract
Antibiotic combinations are preferred for the treatment of periodontal diseases, with the aim of hitting the bacterial flora, according to its characteristics—aerobic, anaerobic, gram-negative, and gram-positive—with certain antibiotics that act on certain bacteria. The aim of this study is to analyze the side
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Antibiotic combinations are preferred for the treatment of periodontal diseases, with the aim of hitting the bacterial flora, according to its characteristics—aerobic, anaerobic, gram-negative, and gram-positive—with certain antibiotics that act on certain bacteria. The aim of this study is to analyze the side effects of the antibiotics used. Data on the side effects (preferably expressed in percentages) of some antibiotics, the favorites in periodontal recipes, are gathered from the literature. These data are listed according to the antibiotic used. In the case of providing a periodontal prescription, the patient is at risk of allergy (5%), nephritis (3%), hematological problems (2–2.5%), gastrointestinal problems (5.5%), disturbance in the nervous system (2%), allergic signs on the skin (5.5%), and problems with electrolytes displayed in lower percentages. Interaction with different medications is present in almost all cases. The influence on the body systems is 4% in total, the maximum value of which is expressed on the skin, and the minimum value is expressed in the nervous system. Cross allergies are at a high value because of the expressed structural similarity of antibiotics. Given a recipe, we have a balance of the percentage of side effects, the percentage of bacterial resistance, and the percentage of the success of the recommended dose of antibiotics. Full article
Open AccessArticle Acute Traumatic Endotheliopathy in Isolated Severe Brain Injury and Its Impact on Clinical Outcome
Med. Sci. 2018, 6(1), 5; https://doi.org/10.3390/medsci6010005
Received: 28 November 2017 / Revised: 8 January 2018 / Accepted: 10 January 2018 / Published: 16 January 2018
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Abstract
Study design: Prospective observational cohort. Objective: To investigate the difference in plasma levels of syndecan-1 (due to glycocalyx degradation) and soluble thrombomodulin (due to endothelial damage) in isolated severe traumatic brain injury (TBI) patients with/without early coagulopathy. A secondary objective was to compare
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Study design: Prospective observational cohort. Objective: To investigate the difference in plasma levels of syndecan-1 (due to glycocalyx degradation) and soluble thrombomodulin (due to endothelial damage) in isolated severe traumatic brain injury (TBI) patients with/without early coagulopathy. A secondary objective was to compare the effects of the degree of TBI endotheliopathy on hospital mortality among patients with TBI-associated coagulopathy (TBI-AC). Methods: Data was prospectively collected on isolated severe TBI (sTBI) patients with Glasgow Coma Scale (GCS) ≤8 less than 12 h after injury admitted to a level I trauma centre. Isolated sTBI patients with samples withdrawn prior to blood transfusion were stratified by conventional coagulation tests as coagulopathic (prothrombin time (PT) ≥ 16.7 s, international normalized ratio (INR) ≥ 1.27, and activated partial thromboplastin time (aPTT) ≥ 28.8 s) and non-coagulopathic. Twenty healthy controls were also included. Plasma levels of thrombomodulin and syndecan-1 were estimated by ELISA. With receiver operating characteristic curve (ROC) analysis, we defined endotheliopathy as a syndecan-1 cut-off level that maximized the sum of sensitivity and specificity for predicting TBI-AC. Results: Inclusion criteria were met in 120 cases, with subjects aged 35.5 ± 12.6 years (88.3% males). TBI-AC was identified in 50 (41.6%) patients, independent of age, gender, and GCS, but there was an association with acidosis (60%; p = 0.01). Following isolated sTBI, we found insignificant changes in soluble thrombomodulin (sTM) levels between patients with isolated TBI and controls, and sTM levels were lower in coagulopathic compared to non-coagulopathic patients. Elevations in plasma syndecan-1 (ng/mL) levels were seen compared to control (31.1(21.5–30.6) vs. 24.8(18.5–30.6); p = 0.08). Syndecan-1(ng/mL) levels were significantly elevated in coagulopathic compared to non-coagulopathic patients (33.7(21.6–109.5) vs. 29.9(19.239.5); p = 0.03). Using ROC analysis (area under the curve = 0.61; 95% Confidence Interval (CI) 0.50 to 0.72), we established a plasma syndecan-1 level cutoff of ≥30.5 ng/mL (sensitivity % = 55.3, specificity % = 52.3), with a significant association with TBI-associated coagulopathy. Conclusion: Subsequent to brain injury, elevated syndecan-1 shedding and endotheliopathy may be associated with early coagulation abnormalities. A syndecan-1 level ≥30.5 ng/mL identified patients with TBI-AC, and may be of importance in guiding management and clinical decision-making. Full article
(This article belongs to the Section Neurosciences)
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Open AccessReview Role of Polyamines in Asthma Pathophysiology
Med. Sci. 2018, 6(1), 4; https://doi.org/10.3390/medsci6010004
Received: 12 December 2017 / Revised: 31 December 2017 / Accepted: 2 January 2018 / Published: 6 January 2018
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Abstract
Asthma is a complex disease of airways, where the interactions of immune and structural cells result in disease outcomes with airway remodeling and airway hyper-responsiveness. Polyamines, which are small-sized, natural super-cations, interact with negatively charged intracellular macromolecules, and altered levels of polyamines and
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Asthma is a complex disease of airways, where the interactions of immune and structural cells result in disease outcomes with airway remodeling and airway hyper-responsiveness. Polyamines, which are small-sized, natural super-cations, interact with negatively charged intracellular macromolecules, and altered levels of polyamines and their interactions have been associated with different pathological conditions including asthma. Elevated levels of polyamines have been reported in the circulation of asthmatic patients as well as in the lungs of a murine model of asthma. In various studies, polyamines were found to potentiate the pathogenic potential of inflammatory cells, such as mast cells and granulocytes (eosinophils and neutrophils), by either inducing the release of their pro-inflammatory mediators or prolonging their life span. Additionally, polyamines were crucial in the differentiation and alternative activation of macrophages, which play an important role in asthma pathology. Importantly, polyamines cause airway smooth muscle contraction and thus airway hyper-responsiveness, which is the key feature in asthma pathophysiology. High levels of polyamines in asthma and their active cellular and macromolecular interactions indicate the importance of the polyamine pathway in asthma pathogenesis; therefore, modulation of polyamine levels could be a suitable approach in acute and severe asthma management. This review summarizes the possible roles of polyamines in different pathophysiological features of asthma. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Open AccessArticle A Novel Polyamine-Targeted Therapy for BRAF Mutant Melanoma Tumors
Med. Sci. 2018, 6(1), 3; https://doi.org/10.3390/medsci6010003
Received: 29 November 2017 / Revised: 21 December 2017 / Accepted: 28 December 2017 / Published: 5 January 2018
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Abstract
Mutant serine/threonine protein kinase B-Raf (BRAF) protein is expressed in over half of all melanoma tumors. Although BRAF inhibitors (BRAFi) elicit rapid anti-tumor responses in the majority of patients with mutant BRAF melanoma, the tumors inevitably relapse after a short time. We hypothesized
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Mutant serine/threonine protein kinase B-Raf (BRAF) protein is expressed in over half of all melanoma tumors. Although BRAF inhibitors (BRAFi) elicit rapid anti-tumor responses in the majority of patients with mutant BRAF melanoma, the tumors inevitably relapse after a short time. We hypothesized that polyamines are essential for tumor survival in mutant BRAF melanomas. These tumors rely on both polyamine biosynthesis and an upregulated polyamine transport system (PTS) to maintain their high intracellular polyamine levels. We evaluated the effect of a novel arylpolyamine (AP) compound that is cytotoxic upon cellular entry via the increased PTS activity of melanoma cells with different BRAF mutational status. Mutant BRAF melanoma cells demonstrated greater PTS activity and increased sensitivity to AP compared to wild type BRAF (BRAFWT) melanoma cells. Treatment with an inhibitor of polyamine biosynthesis, α-difluoromethylornithine (DFMO), further upregulated PTS activity in mutant BRAF cells and increased their sensitivity to AP. Furthermore, viability assays of 3D spheroid cultures of mutant BRAF melanoma cells demonstrated greater resistance to the BRAFi, PLX4720, compared to 2D monolayer cultures. However, co-treatment with AP restored the sensitivity of melanoma spheroids to PLX4720. These data indicate that mutant BRAF melanoma cells are more dependent on the PTS compared to BRAFWT melanoma cells, resulting in greater sensitivity to the PTS-targeted cytotoxic AP compound. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Open AccessArticle The ODC 3′-Untranslated Region and 5′-Untranslated Region Contain cis-Regulatory Elements: Implications for Carcinogenesis
Med. Sci. 2018, 6(1), 2; https://doi.org/10.3390/medsci6010002
Received: 16 November 2017 / Revised: 7 December 2017 / Accepted: 15 December 2017 / Published: 22 December 2017
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Abstract
It has been hypothesized that both the 3′-untranslated region (3′UTR) and the 5′-untranslated region (5′UTR) of the ornithine decarboxylase (ODC) mRNA influence the expression of the ODC protein. Here, we use luciferase expression constructs to examine the influence of both UTRs in keratinocyte
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It has been hypothesized that both the 3′-untranslated region (3′UTR) and the 5′-untranslated region (5′UTR) of the ornithine decarboxylase (ODC) mRNA influence the expression of the ODC protein. Here, we use luciferase expression constructs to examine the influence of both UTRs in keratinocyte derived cell lines. The ODC 5′UTR or 3′UTR was cloned into the pGL3 control vector upstream or downstream of the luciferase reporter gene, respectively, and luciferase activity was measured in both non-tumorigenic and tumorigenic mouse keratinocyte cell lines. Further analysis of the influence of the 3′UTR on luciferase activity was accomplished through site-directed mutagenesis and distal deletion analysis within this region. Insertion of either the 5′UTR or 3′UTR into a luciferase vector resulted in a decrease in luciferase activity when compared to the control vector. Deletion analysis of the 3′UTR revealed a region between bases 1969 and 2141 that was inhibitory, and mutating residues within that region increased luciferase activity. These data suggest that both the 5′UTR and 3′UTR of ODC contain cis-acting regulatory elements that control intracellular ODC protein levels. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Open AccessReview Carbapenem Resistance: A Review
Med. Sci. 2018, 6(1), 1; https://doi.org/10.3390/medsci6010001
Received: 6 November 2017 / Revised: 25 November 2017 / Accepted: 5 December 2017 / Published: 21 December 2017
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Abstract
Carbapenem resistance is a major and an on-going public health problem globally. It occurs mainly among Gram-negative pathogens such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, and may be intrinsic or mediated by transferable carbapenemase-encoding genes. This type of resistance genes
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Carbapenem resistance is a major and an on-going public health problem globally. It occurs mainly among Gram-negative pathogens such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, and may be intrinsic or mediated by transferable carbapenemase-encoding genes. This type of resistance genes are already widespread in certain parts of the world, particularly Europe, Asia and South America, while the situation in other places such as sub-Saharan Africa is not well documented. In this paper, we provide an in-depth review of carbapenem resistance providing up-to-date information on the subject. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
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