Open AccessFeature PaperReview
Myc, Oncogenic Protein Translation, and the Role of Polyamines
Med. Sci. 2018, 6(2), 41; https://doi.org/10.3390/medsci6020041 (registering DOI) -
Abstract
Deregulated protein synthesis is a common feature of cancer cells, with many oncogenic signaling pathways directly augmenting protein translation to support the biomass needs of proliferating tissues. MYC’s ability to drive oncogenesis is a consequence of its essential role as a governor linking
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Deregulated protein synthesis is a common feature of cancer cells, with many oncogenic signaling pathways directly augmenting protein translation to support the biomass needs of proliferating tissues. MYC’s ability to drive oncogenesis is a consequence of its essential role as a governor linking cell cycle entry with the requisite increase in protein synthetic capacity, among other biomass needs. To date, direct pharmacologic inhibition of MYC has proven difficult, but targeting oncogenic signaling modules downstream of MYC, such as the protein synthetic machinery, may provide a viable therapeutic strategy. Polyamines are essential cations found in nearly all living organisms that have both direct and indirect roles in the control of protein synthesis. Polyamine metabolism is coordinately regulated by MYC to increase polyamines in proliferative tissues, and this is further augmented in the many cancer cells harboring hyperactivated MYC. In this review, we discuss MYC-driven regulation of polyamines and protein synthetic capacity as a key function of its oncogenic output, and how this dependency may be perturbed through direct pharmacologic targeting of components of the protein synthetic machinery, such as the polyamines themselves, the eukaryotic translation initiation factor 4F (eIF4F) complex, and the eukaryotic translation initiation factor 5A (eIF5A). Full article
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Open AccessFeature PaperArticle
Feasibility of Antimicrobial Stewardship (AMS) in Critical Care Settings: A Multidisciplinary Approach Strategy
Med. Sci. 2018, 6(2), 40; https://doi.org/10.3390/medsci6020040 (registering DOI) -
Abstract
Antimicrobial resistance is escalating and triggers clinical decision-making challenges when treating infections in patients admitted to intensive care units (ICU). Antimicrobial stewardship (AMS) may help combat this problem, but it can be difficult to implement in critical care settings. The implementation of multidisciplinary
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Antimicrobial resistance is escalating and triggers clinical decision-making challenges when treating infections in patients admitted to intensive care units (ICU). Antimicrobial stewardship (AMS) may help combat this problem, but it can be difficult to implement in critical care settings. The implementation of multidisciplinary AMS in ICUs could be more challenging than what is currently suggested in the literature. Our main goal was to analyze the reduction in duration of treatment (DOT) for the most commonly used antibacterial and antifungal agents during the first six months of 2014, and during the same period two years later (2016). A total of 426 and 424 patient encounters, respectively, were documented and collected from the intensive care unit’s electronic patient record system. Daily multidisciplinary ward rounds were conducted for approximately 30–40 min, with the goal of optimizing antimicrobial therapy in order to analyze the feasibility of implementing AMS. The only antimicrobial agent which showed a significant reduction in the number of prescriptions and in the duration of treatment during the second audit was vancomycin, while linezolid showed an increase in the number of prescriptions with no significant prolongation of the duration of treatment. A trend of reduction was also seen in the DOT for co-amoxiclavulanate and in the number of prescriptions of anidulafungin without any corresponding increases being observed for other broad-spectrum anti-infective agents (p-values of 0.07 and 0.05, respectively). Full article
Open AccessReview
Tools for Detection of Schistosomiasis in Resource Limited Settings
Med. Sci. 2018, 6(2), 39; https://doi.org/10.3390/medsci6020039 -
Abstract
Schistosomiasis is a debilitating disease affecting over 200 million people, with the highest burden of morbidity and mortality in African countries. Despite its huge impact on the health and socio-economic burden of the society, it remains a neglected tropical disease, with limited attention
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Schistosomiasis is a debilitating disease affecting over 200 million people, with the highest burden of morbidity and mortality in African countries. Despite its huge impact on the health and socio-economic burden of the society, it remains a neglected tropical disease, with limited attention from governments and stakeholders in healthcare. One of the critical areas that is hugely under-developed is the development of accurate diagnostics for both intestinal and urogenital schistosomiasis. Diagnosis of schistosomiasis is important for the detection and treatment of disease in endemic and non-endemic settings. A conclusive detection method is also an indispensable part of treatment, both in the clinic and during mass drug administration (MDA), for the monitoring efficacy of treatment. Here, we review the available diagnostic methods and discuss the challenges encountered in diagnosis in resource limited settings. We also present the available diagnostics and cost implications for deployment in resource limited settings. Lastly, we emphasize the need for more funding directed towards the development of affordable diagnostic tools that is affordable for endemic countries as we work towards the elimination of the disease. Full article
Open AccessArticle
Critical Appraisal of Advanced Glycation End Products (AGEs) and Circulating Soluble Receptors for Advanced Glycation End Products (sRAGE) as a Predictive Biomarkers for Cardiovascular Disease in Hemodialysis Patients
Med. Sci. 2018, 6(2), 38; https://doi.org/10.3390/medsci6020038 -
Abstract
The interaction of advanced glycation end products (AGE) and their receptors promote vascular complications of diabetes in hemodialysis (HD) patients. The soluble form of the receptor for the advanced glycation end-products (sRAGE) has been studied as a vascular biomarker in various diseases with
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The interaction of advanced glycation end products (AGE) and their receptors promote vascular complications of diabetes in hemodialysis (HD) patients. The soluble form of the receptor for the advanced glycation end-products (sRAGE) has been studied as a vascular biomarker in various diseases with controversial results. Our aim was to evaluate the association of the serum levels of the AGEs and their receptor sRAGE with cardiovascular disease (CVD) and the cardiovascular risk factors among HD patients. There were 130 HD patients and 80 age and gender matched control subjects were involved; 31.5% of the HD group were diabetic, which was an underlying cause of renal impairment; 36.1% had CVD, which was comprising 44.7% of diabetics and 55.3% of non-diabetic patients. The AGEs and sRAGE were assessed by enzyme linked immunosorbent assay (ELISA). In addition, the lipid profile, glycemic indices, pre-dialysis renal function tests, and hemoglobin % (Hb) were evaluated. The results show that the circulating AGEs and sRAGE levels were significantly higher in the HD patients. Those with underlying diabetes displayed higher sRAGE levels, which were positively correlated with hyperglycemia, HbA1C, and total cholesterol (TC). The HD patients with an increased serum sRAGE exhibited more cardiovascular risk factors (hypercholesterolemia and anemia) with a high prevalence of CVD. Using a linear regression analysis, we found a significant association of sRAGE with CVD and TC among HD patients, regardless of whether associating diabetes was an underlying cause of renal impairment. Overall, the HD patients displayed significantly higher serum AGEs with a concomitant increase in the circulating sRAGE levels, mainly in the diabetic HD, which were significantly associated with the CVD (independent predictors) and CV risk factors (hypercholesterolemia), mainly sRAGEs, regardless of the underlying diabetes mellitus. This highlights the prognostic role of AGEs and sRAGE in HD patients regardless of underlying cause in order to predict the risk for CVD. Full article
Open AccessArticle
Pituitary, Gonadal, Thyroid Hormones and Endocrine Disruptors in Pre and Postmenopausal Nigerian Women with ER-, PR- and HER-2-Positive and Negative Breast Cancers
Med. Sci. 2018, 6(2), 37; https://doi.org/10.3390/medsci6020037 -
Abstract
Breast cancer is broadly sub-divided into hormone responsive and non-hormone responsive subtypes. Estradiol has been associated with hormone responsive breast cancers. There is, however, a paucity of information on the role of sex hormones, gonadotropins, and thyroid hormone in non-hormone responsive breast cancer.
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Breast cancer is broadly sub-divided into hormone responsive and non-hormone responsive subtypes. Estradiol has been associated with hormone responsive breast cancers. There is, however, a paucity of information on the role of sex hormones, gonadotropins, and thyroid hormone in non-hormone responsive breast cancer. This study aimed to determine differences in the serum levels of sex hormones, gonadotropins, thyroid hormones, and endocrine disruptors (lead, cadmium, and arsenic) in Nigerian women with hormone responsive and non-hormone responsive breast cancers. Seventy-nine non-pregnant women aged 28–80 years with histologically confirmed breast cancer were recruited, pre-therapy, into this cross-sectional study. They comprised 52 premenopausal women and 27 postmenopausal women recruited from the Surgical Oncology Clinic of the Department of Surgery, University College Hospital, Ibadan. Comparison of biochemical parameters were based on the positivity (+) and negativity (−) of estrogen receptor (ER), progesterone receptor (PR) and human epithelial receptor-2 (HER-2). Estradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were determined using enzyme immunoassay (EIA). Serum lead, cadmium and arsenic were determined using atomic absorption spectrophotometry (AAS). Expression of ER, PR and HER2 were determined using immunohistochemistry. Data was analyzed using Mann-Whitney U-test and multiple regression, with p < 0.05 considered as being statistically significant. Estradiol and progesterone were significantly higher in breast cancer participants with ER and PR compared with those with ER+ and PR+ breast cancer (p < 0.05). Follicle stimulating hormone and LH levels were significantly higher in participants with ER+ and PR+ breast cancer compared with participants with ER and PR breast cancer (p < 0.05). Arsenic was inversely related with TSH in premenopausal participants with ER and PR (β = −0.305; β = −0.304, respectively). Sex hormones and gonadotropins appear to be involved in the pathogenesis of triple negative and luminal breast cancer, respectively. Full article
Open AccessArticle
Inhibition of Insulin Degrading Enzyme and Insulin Degradation by UV-Killed Lactobacillus acidophilus
Med. Sci. 2018, 6(2), 36; https://doi.org/10.3390/medsci6020036 -
Abstract
Probiotics have beneficial effects on management of type 2 diabetes (T2D). The major hallmarks of T2D are insulin deficiency and insulin resistance which emphasize insulin therapy in onset of disease. Lactobacilli such as Lactobacillus acidophilus (L. acidophilus) have well known properties
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Probiotics have beneficial effects on management of type 2 diabetes (T2D). The major hallmarks of T2D are insulin deficiency and insulin resistance which emphasize insulin therapy in onset of disease. Lactobacilli such as Lactobacillus acidophilus (L. acidophilus) have well known properties on prevention of T2D and insulin resistance but not on insulin degradation. Insulin-degrading enzyme (IDE) degrades insulin in the human body. We studied the effects of cell-free supernatant (CFS) and ultraviolet (UV)-killed L. acidophilus (ATCC 314) on IDE activity and insulin degradation in vitro. Cell growth inhibition by CFS and UV-killed L. acidophilus (ATCC 314) was studied and Western blotting and a fluoregenic assay was performed to determine IDE expression and its activity, respectively. Insulin degradation was evaluated by sandwich enzyme-linked immunosorbent assay(ELISA). IDE expression and activity was reduced by CFS and UV-killed L. acidophilus (ATCC 314). Although, decreased enzyme expression and activity was not significant for CFS in contrast to MRL (MRS with same pH as CFS). Also, reduction in IDE activity was not statistically considerable when compared to IDE expression. Insulin degradation was increased by CFS but decreased by UV-killed L. acidophilus (ATCC 314). Full article
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Open AccessReview
Characteristics and Management of Community-Acquired Pneumonia in the Era of Global Aging
Med. Sci. 2018, 6(2), 35; https://doi.org/10.3390/medsci6020035 -
Abstract
Community-acquired pneumonia (CAP) can occur at any time of life, but its incidence and risk of death are linked to increasing age. CAP in the elderly is a major health problem associated with high rates of readmission, morbidity, and mortality. Since the clinical
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Community-acquired pneumonia (CAP) can occur at any time of life, but its incidence and risk of death are linked to increasing age. CAP in the elderly is a major health problem associated with high rates of readmission, morbidity, and mortality. Since the clinical presentation of pneumonia in the elderly may be atypical, clinicians should suspect pneumonia in older patients presenting symptoms such as falls and altered mental status, fatigue, lethargy, delirium, anorexia, in order to avoid the complications associated with delayed diagnosis and therapy. Streptococcus pneumoniae remains the most frequently reported pathogen in this population. However, particular attention should be paid to patients with risk factors for multidrug resistant pathogens, because a large proportion of elderly persons present multimorbidity. Vaccination is one of the most important preventive approaches for CAP in the elderly. In addition, lifestyle-tailored interventions for different modifiable risk factors will help to reduce the risk of pneumonia in elderly persons. Surveillance of etiological pathogens may improve vaccination policies in this population. Full article
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Open AccessReview
The Role of Adipokines in Intervertebral Disc Degeneration
Med. Sci. 2018, 6(2), 34; https://doi.org/10.3390/medsci6020034 -
Abstract
Intervertebral disc degeneration (IDD) is an important cause of low back pain. Recent evidence suggests that in addition to abnormal and excessive mechanical loading, inflammation may be a key driver for both IDD and low back pain. Obesity, a known mechanical risk factor
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Intervertebral disc degeneration (IDD) is an important cause of low back pain. Recent evidence suggests that in addition to abnormal and excessive mechanical loading, inflammation may be a key driver for both IDD and low back pain. Obesity, a known mechanical risk factor of IDD, is now increasingly being recognized as a systemic inflammatory state with adipokines being postulated as likely inflammatory mediators. The aim of this review was to summarize the current literature regarding the inflammatory role of adipokines in the pathophysiology of IDD. A systematic literature search was performed using the OVID Medline, EMBASE and PubMed databases to identify all studies assessing IDD and adipokines. Fifteen studies were included in the present review. Leptin was the most commonly assessed adipokine. Ten of 15 studies were conducted in humans; three in rats and two in both humans and rats. Studies focused on a variety of topics ranging from receptor identification, pathway analysis, genetic associations, and proteonomics. Currently, data from both human and animal experiments demonstrate significant effects of leptin and adiponectin on the internal milieu of intervertebral discs. However, future studies are needed to determine the molecular pathway relationships between adipokines in the pathophysiology of IDD as avenues for future therapeutic targets. Full article
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Open AccessReview
Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives
Med. Sci. 2018, 6(2), 33; https://doi.org/10.3390/medsci6020033 -
Abstract
Myeloperoxidase (MPO) belongs to the family of heme-containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kDa) is the product of the MPO gene located on long arm of chromosome 17. The primary gene product undergoes several modifications, such as the
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Myeloperoxidase (MPO) belongs to the family of heme-containing peroxidases, produced mostly from polymorphonuclear neutrophils. The active enzyme (150 kDa) is the product of the MPO gene located on long arm of chromosome 17. The primary gene product undergoes several modifications, such as the removal of introns and signal peptides, and leads to the formation of enzymatically inactive glycosylated apoproMPO which complexes with chaperons, producing inactive proMPO by the insertion of a heme moiety. The active enzyme is a homodimer of heavy and light chain protomers. This enzyme is released into the extracellular fluid after oxidative stress and different inflammatory responses. Myeloperoxidase is the only type of peroxidase that uses H2O2 to oxidize several halides and pseudohalides to form different hypohalous acids. So, the antibacterial activities of MPO involve the production of reactive oxygen and reactive nitrogen species. Controlled MPO release at the site of infection is of prime importance for its efficient activities. Any uncontrolled degranulation exaggerates the inflammation and can also lead to tissue damage even in absence of inflammation. Several types of tissue injuries and the pathogenesis of several other major chronic diseases such as rheumatoid arthritis, cardiovascular diseases, liver diseases, diabetes, and cancer have been reported to be linked with MPO-derived oxidants. Thus, the enhanced level of MPO activity is one of the best diagnostic tools of inflammatory and oxidative stress biomarkers among these commonly-occurring diseases. Full article
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Open AccessReview
The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into “Old” Diseases
Med. Sci. 2018, 6(2), 32; https://doi.org/10.3390/medsci6020032 -
Abstract
The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production.
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The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota—depending on their composition—have disease-promoting effects but can also possess protective properties. This review focuses on disorders of metabolic syndrome, with special regard to obesity as a prequel to type 2 diabetes, type 2 diabetes itself, and type 1 diabetes. In all these conditions, differences in the composition of the gut microbiota in comparison to healthy people have been reported. Mechanisms of the interaction between microbiota and host that have been characterized thus far include an increase in energy harvest, modulation of free fatty acids—especially butyrate—of bile acids, lipopolysaccharides, gamma-aminobutyric acid (GABA), an impact on toll-like receptors, the endocannabinoid system and “metabolic endotoxinemia” as well as “metabolic infection.” This review will also address the influence of already established therapies for metabolic syndrome and diabetes on the microbiota and the present state of attempts to alter the gut microbiota as a therapeutic strategy. Full article
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Open AccessReview
Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells
Med. Sci. 2018, 6(2), 31; https://doi.org/10.3390/medsci6020031 -
Abstract
Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20–30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise
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Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20–30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse. Full article
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Open AccessArticle
Cimetidine: A Safe Treatment Option for Cutaneous Warts in Pediatric Heart Transplant Recipients
Med. Sci. 2018, 6(2), 30; https://doi.org/10.3390/medsci6020030 -
Abstract
Background and Objectives: Immunosuppressed individuals are at particularly increased risk for human papilloma virus-related infections. The primary objective of our study is to determine if there are any adverse effects associated with high-dose cimetidine treatment. A secondary objective is to report our
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Background and Objectives: Immunosuppressed individuals are at particularly increased risk for human papilloma virus-related infections. The primary objective of our study is to determine if there are any adverse effects associated with high-dose cimetidine treatment. A secondary objective is to report our experience with cimetidine in the treatment of cutaneous warts in pediatric heart transplant recipients. Methods and Results: This was a retrospective observational study. A total of 8 pediatric heart transplant recipients diagnosed with multiple recalcitrant warts were the subject of the study. All patients were treated with cimetidine (30–40 mg/kg/day) in two divided doses for 3 to 6 month durations. All patients had complete resolution of their lesions except 1 patient who had no clinical improvement. Of these 8 patients, one had recurrence of warts at one year follow-up, which resolved with restarting cimetidine therapy. One patient who had only 3 months of cimetidine therapy had immediate relapse after cimetidine was stopped. None of them had significant change in their tacrolimus trough, serum creatinine, and alanine transaminase levels. No adverse events were reported except one patient experienced mild gynecomastia. Conclusion: Cimetidine can be a safe and alternative treatment option for multiple warts in pediatric heart transplant recipients. Full article
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Open AccessReview
Clostridium Bacteria and Autism Spectrum Conditions: A Systematic Review and Hypothetical Contribution of Environmental Glyphosate Levels
Med. Sci. 2018, 6(2), 29; https://doi.org/10.3390/medsci6020029 -
Abstract
Nowadays, there seems to be a consensus about the multifactorial nature of autism spectrum disorders (ASD). The literature provides hypotheses dealing with numerous environmental factors and genes accounting for the apparently higher prevalence of this condition. Researchers have shown evidence regarding the impact
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Nowadays, there seems to be a consensus about the multifactorial nature of autism spectrum disorders (ASD). The literature provides hypotheses dealing with numerous environmental factors and genes accounting for the apparently higher prevalence of this condition. Researchers have shown evidence regarding the impact of gut bacteria on neurological outcomes, altering behavior and potentially affecting the onset and/or severity of psychiatric disorders. Pesticides and agrotoxics are also included among this long list of ASD-related environmental stressors. Of note, ingestion of glyphosate (GLY), a broad-spectrum systemic herbicide, can reduce beneficial bacteria in the gastrointestinal tract microbiota without exerting any effects on the Clostridium population, which is highly resistant to this herbicide. In the present study, (i) we performed a systematic review to evaluate the relationship between Clostridium bacteria and the probability of developing and/or aggravating autism among children. For that purpose, electronic searches were performed on Medline/PubMed and Scielo databases for identification of relevant studies published in English up to December 2017. Two independent researches selected the studies and analyzed the data. The results of the present systematic review demonstrate an interrelation between Clostridium bacteria colonization of the intestinal tract and autism. Finally, (ii) we also hypothesize about how environmental GLY levels may deleteriously influence the gut–brain axis by boosting the growth of Clostridium bacteria in autistic toddlers. Full article
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Open AccessArticle
Relationship between Response to PDE5 Inhibitors and Penile Duplex Doppler Ultrasound in Erectile Dysfunction
Med. Sci. 2018, 6(2), 28; https://doi.org/10.3390/medsci6020028 -
Abstract
The relationship between the results of penile duplex Doppler ultrasound (PDDU) and response to vardenafil was investigated in patients diagnosed with erectile dysfunction (ED). Data from 148 patients with ED were analyzed retrospectively. Patients who did not respond to therapy were classified in
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The relationship between the results of penile duplex Doppler ultrasound (PDDU) and response to vardenafil was investigated in patients diagnosed with erectile dysfunction (ED). Data from 148 patients with ED were analyzed retrospectively. Patients who did not respond to therapy were classified in to Group I (n = 32), those who responded partially were classified into Group II (n = 40), and complete responders were classified into Group III (n = 76). Age, comorbidities, and vascular and penile pathologies were compared among the three groups. While diabetes mellitus (DM) and dyslipidemia positivity adversely affected the response to treatment, the presence of hypertension (HT), Peyronie’s disease and priapism increased the therapeutic response to the treatment (p < 0.05). Arterial insufficiency was present in 20 (30.3%), 25 (37.9%) and 21 (31.8%) of the patients in Group I, Group II and Group III, respectively (p = 0.001). Venous insufficiency was observed in three (14.3%) patients in Group I and in eight (85.7%) patients in Group III (p = 0.001). Arterial/venous insufficiency was seen in 9 (30%), 14 (46.7%) and 7 (23.3%) of the patients in Group I, Group II and Group III, respectively (p = 0.001). The response rate to treatment was highest in normal patients according to PDDU, followed by patients with venous insufficiency. In addition, it was found that DM decreased the response to treatment, whereas the response increased in cases with HT, priapism and Peyronie’s disease. Full article
Open AccessReview
Live Bacterial Vectors—A Promising DNA Vaccine Delivery System
Med. Sci. 2018, 6(2), 27; https://doi.org/10.3390/medsci6020027 -
Abstract
Vaccination is one of the most successful immunology applications that has considerably improved human health. The DNA vaccine is a new vaccine being developed since the early 1990s. Although the DNA vaccine is promising, no human DNA vaccine has been approved to date.
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Vaccination is one of the most successful immunology applications that has considerably improved human health. The DNA vaccine is a new vaccine being developed since the early 1990s. Although the DNA vaccine is promising, no human DNA vaccine has been approved to date. The main problem facing DNA vaccine efficacy is the lack of a DNA vaccine delivery system. Several studies explored this limitation. One of the best DNA vaccine delivery systems uses a live bacterial vector as the carrier. The live bacterial vector induces a robust immune response due to its natural characteristics that are recognized by the immune system. Moreover, the route of administration used by the live bacterial vector is through the mucosal route that beneficially induces both mucosal and systemic immune responses. The mucosal route is not invasive, making the vaccine easy to administer, increasing the patient’s acceptance. Lactic acid bacterium is one of the most promising bacteria used as a live bacterial vector. However, some other attenuated pathogenic bacteria, such as Salmonella spp. and Shigella spp., have been used as DNA vaccine carriers. Numerous studies showed that live bacterial vectors are a promising candidate to deliver DNA vaccines. Full article
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Open AccessArticle
Socio-Economic Predictors and Distribution of Tuberculosis Incidence in Beijing, China: A Study Using a Combination of Spatial Statistics and GIS Technology
Med. Sci. 2018, 6(2), 26; https://doi.org/10.3390/medsci6020026 -
Abstract
Evidence shows that multiple factors, such as socio-economic status and access to health care facilities, affect tuberculosis (TB) incidence. However, there is limited literature available with respect to the correlation between socio-economic/health facility factors and tuberculosis incidence. This study aimed to explore the
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Evidence shows that multiple factors, such as socio-economic status and access to health care facilities, affect tuberculosis (TB) incidence. However, there is limited literature available with respect to the correlation between socio-economic/health facility factors and tuberculosis incidence. This study aimed to explore the relationship between TB incidence and socio-economic/health service predictors in the study settings. A retrospective spatial regression analysis was carried out based on new sputum smear-positive pulmonary TB cases in Beijing districts. Global Moran’s I analysis was adopted to detect the spatial dependency followed by spatial regression models (spatial lag model, and spatial error model) along with the ordinary least square model were applied to examine the correlation between TB incidence and predictors. A high incidence of TB was seen in densely populated districts in Beijing, e.g., Haidian, Mentougou, and Xicheng. After comparing the R2, log-likelihood, and Akaike information criterion (AIC) values among three models, the spatial error model (R2 = 0.413; Log Likelihood = −591; AIC = 1199.76) identified the best model fit for the spatial regression model. The study showed that the number of beds in health institutes (p < 0.001) and per capita gross domestic product (GDP) (p = 0.025) had a positive effect on TB incidence, whereas population density (p < 0.001) and migrated population (p < 0.001) had an adverse impact on TB incidence in the study settings. High TB incidence districts were detected in urban and densely populated districts in Beijing. Our findings suggested that socio-economic predictors influence TB incidence. These findings may help to guide TB control programs and promote targeted intervention. Full article
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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 -
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
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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
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 -
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).
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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
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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 -
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
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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
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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 -
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
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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
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