Open AccessFeature PaperArticle
Exacerbations in COPD Patients with Bronchiectasis
Med. Sci. 2017, 5(2), 7; doi:10.3390/medsci5020007 -
Abstract
There is evidence that coexisting bronchiectasis (BE) in patients with chronic obstructive pulmonary disease (COPD) aggravates the course of the disease. In this study, we aimed to evaluate the frequency and severity of bacterial exacerbations in COPD patients with BE. The frequency and
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There is evidence that coexisting bronchiectasis (BE) in patients with chronic obstructive pulmonary disease (COPD) aggravates the course of the disease. In this study, we aimed to evaluate the frequency and severity of bacterial exacerbations in COPD patients with BE. The frequency and duration of bacterial exacerbations treated in a 12‐month period, as well as the duration of the exacerbation‐free interval, were evaluated in 54 patients with COPD (Group D) who were diagnosed and assessed according to official recommendations. In 27 patients, BE was diagnosed by high‐resolution computed tomography (HRCT), whereas an equal number of COPD patients who were confirmed negative for BE by HRCT, served as controls. We found a significantly higher mean number of exacerbations in a 12‐month period in COPD patients with BE (2.9 ± 0.5), as compared to their mean number in controls (2.5 ± 0.3) (p = 0.0008). The mean duration of exacerbation, i.e. the mean number of days elapsed before complete resolution of the symptoms or their return to the baseline severity, was significantly longer in COPD patients with BE as compared to their mean duration in controls (6.9 ± 1.8 vs. 5.7 ± 1.4; p = 0.0085). In addition, the mean exacerbation‐free interval expressed in days, in patients with COPD with BE, was significantly shorter than in COPD patients in whom BE were excluded (56.4 ± 17.1 vs. 67.2 ± 14.3; p = 0.0149). Overall, our findings indicate that coexisting BE in COPD patients may lead to more frequent exacerbations with a longer duration. Full article
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Open AccessArticle
Efficacy of Pancreatic Endotherapy In Pancreatic Ascites And Pleural Effusion
Med. Sci. 2017, 5(2), 6; doi:10.3390/medsci5020006 -
Abstract
Pancreatic ascites and effusion is a challenging complication to manage, hence our aim was to evaluate the efficacy of pancreatic endotherapy in pancreatic ascites and pleural effusion. Endotherapy included endoscopic retrograde cholangiopancreatography (ERCP) with a pancreatogram and pancreatic stent placement across the leak
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Pancreatic ascites and effusion is a challenging complication to manage, hence our aim was to evaluate the efficacy of pancreatic endotherapy in pancreatic ascites and pleural effusion. Endotherapy included endoscopic retrograde cholangiopancreatography (ERCP) with a pancreatogram and pancreatic stent placement across the leak in patients with pancreatic ascites/effusion. A total of 53 patients were included after successful cannulation. The male:female ratio was 7.8:1. The pancreatogram revealed a leak from the pancreatic duct in 20/53 (37.73%) patients. The most common leak site was the pancreatic body in 10/53 (18.9%) patients followed by the tail in 6/53 (11.32%) patients and the genu in 4/53 (7.5%) patients. In 29/53 (54.7%) patients, stent was placed beyond the leak site. Sphincterotomy was done in 7/53 (13.2%) patients, and in five patients with an obscure leak site, stent was placed empirically. A total of 39/53 (73.6%) patients benefited in terms of achieving the complete resolution of ascites and pleural effusion. The factors which were significant for the success of pancreatic endotherapy in the multivariate analysis were the site of the pancreatic ductal leak (p value = 0.008) and the ability of the stent to cross the leak site (p value = 0.004). To sum up, bridging the pancreatic ductal leak by stent offers a high rate of success. Pancreatic endotherapy is less invasive and highly effective in managing pancreatic ascites/pleural effusion. Full article
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Open AccessFeature PaperArticle
A Prospective Randomized Trial of Postural Changes vs Passive Supine Lying during the Second Stage of Labor under Epidural Analgesia
Med. Sci. 2017, 5(1), 5; doi:10.3390/medsci5010005 -
Abstract
There exist very few studies comparing different postures or postural changes during labor in parturients with epidural analgesia. Aim: To disclose whether the intervention of a multidisciplinary nursing team including a physiotherapist during the second stage of labor improves the obstetric outcome in
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There exist very few studies comparing different postures or postural changes during labor in parturients with epidural analgesia. Aim: To disclose whether the intervention of a multidisciplinary nursing team including a physiotherapist during the second stage of labor improves the obstetric outcome in parturients with epidural analgesia. Design: Prospective randomized trial. Setting: University-affiliated hospital. Population: Women undergoing labor with epidural analgesia after a normal gestation. Methods: 150 women were randomized either to actively perform predefined postural changes during the passive phase of the second stage of labor under the guidance of the attending physiotherapist (study group), or to carry out the whole second stage of labor lying in the traditional supine position (control group). Results: There were significantly more eutocic deliveries (p = 0.005) and, conversely, significantly less instrumental deliveries (p < 0.05) and cesarean sections (p < 0.05) in the study group. The total duration of the second stage of labor was significantly shorter (p < 0.01) in the study group. This was at the expense of the passive phase of the second stage of labor (p < 0.01). Significantly less episiotomies were performed in the study group (31.2% vs 17.8%, p < 0.05). Conclusion: The intervention of a physiotherapist during the second stage of labor significantly improved the obstetric outcome. Full article
Open AccessCorrection
Correction: Hasona, N.A. and Elasbali, A. Evaluation of Electrolytes Imbalance and Dyslipidemia in Diabetic Patients. Med. Sci. 2016, 4, 7
Med. Sci. 2017, 5(1), 4; doi:10.3390/medsci5010004 -
Abstract
The authors wish to make the following correction to their paper [1]. In the discussion section, the sentence “Regarding the lipid profile, the present results revealed a significant increase (p < 0.001) in the serum levels of cholesterol, triglycerides and HDL-cholesterol in
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The authors wish to make the following correction to their paper [1]. In the discussion section, the sentence “Regarding the lipid profile, the present results revealed a significant increase (p < 0.001) in the serum levels of cholesterol, triglycerides and HDL-cholesterol in all diabetics relative to all non-diabetic subjects”. This should be changed to “Regarding the lipid profile, the present results revealed a significant increase (p < 0.001) in the serum levels of cholesterol and triglycerides and a significant decrease in HDL-cholesterol in all diabetics relative to all non-diabetic subjects”.[...] Full article
Open AccessEditorial
Acknowledgement to Reviewers of Medical Sciences in 2016
Med. Sci. 2017, 5(1), 3; doi:10.3390/medsci5010003 -
Abstract The editors of Medical Sciences would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...] Full article
Open AccessArticle
HLA Typing and Celiac Disease in Moroccans
Med. Sci. 2017, 5(1), 2; doi:10.3390/medsci5010002 -
Abstract
Genetic and environmental factors are responsible for differences in the prevalence of some diseases across countries. Human leukocyte antigen (HLA) allele frequencies in North African populations show some differences in their distribution compared to Europeans, Mediterraneans, and sub-Saharans, and some specific alleles and
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Genetic and environmental factors are responsible for differences in the prevalence of some diseases across countries. Human leukocyte antigen (HLA) allele frequencies in North African populations show some differences in their distribution compared to Europeans, Mediterraneans, and sub-Saharans, and some specific alleles and haplotypes could be clinically relevant. Celiac disease (CD) has been fast increasing in prevalence in North Africa; but few immunogenetic data are available for this area, in which a high prevalence of the disease has been described. In this report, we assess and discuss results of HLA class II (HLA-DQA1/DQB1/DRB1) typing in Moroccan patients with CD and compare them with a control population from Morocco—genetically well characterized—and with other North African, Mediterranean, and European populations. The classical HLA-DQ associations were confirmed in Moroccans with CD. The high frequency of DQ2.5 homozygosity (45.2%) found in Moroccans with CD was noteworthy as compared with other populations (23%–32%). The genetic risk gradient for CD, identified by previous studies, has been confirmed in Moroccans with some differences, mainly concerning DQ8 genotypes. This study provides the immunogenetic framework of CD in Moroccans and confirms the need to learn more about associations with additional HLA and non-HLA genetic factors. Full article
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Open AccessArticle
A Comparative Evaluation of Gait between Children with Autism and Typically Developing Matched Controls
Med. Sci. 2017, 5(1), 1; doi:10.3390/medsci5010001 -
Abstract
Anecdotal reports suggest children with autism spectrum disorder (ASD) ambulate differently than peers with typical development (TD). Little empirical evidence supports these reports. Children with ASD exhibit delayed motor skills, and it is important to determine whether or not motor movement deficits exist
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Anecdotal reports suggest children with autism spectrum disorder (ASD) ambulate differently than peers with typical development (TD). Little empirical evidence supports these reports. Children with ASD exhibit delayed motor skills, and it is important to determine whether or not motor movement deficits exist during walking. The purpose of the study was to perform a comprehensive lower-extremity gait analysis between children (aged 5–12 years) with ASD and age- and gender-matched-samples with TD. Gait parameters were normalized to 101 data points and the gait cycle was divided into seven sub-phases. The Model Statistic procedure was used to test for statistical significance between matched-pairs throughout the entire gait cycle for each parameter. When collapsed across all participants, children with ASD exhibited large numbers of significant differences (p < 0.05) throughout the gait cycle in hip, knee, and ankle joint positions as well as vertical and anterior/posterior ground reaction forces. Children with ASD exhibited unique differences throughout the gait cycle, which supports current literature on the heterogeneity of the disorder. The present work supports recent findings that motor movement differences may be a core symptom of ASD. Thus, individuals may benefit from therapeutic movement interventions that follow precision medicine guidelines by accounting for individual characteristics, given the unique movement differences observed. Full article
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Open AccessArticle
Iron Profile and Glycaemic Control in Patients with Type 2 Diabetes Mellitus
Med. Sci. 2016, 4(4), 22; doi:10.3390/medsci4040022 -
Abstract
Iron overload is increasingly being connected to insulin resistance in Type 2 Diabetes Mellitus (T2DM) patients. Free iron causes the assembly of reactive oxygen species that invariably steer the body’s homeostasis towards oxidative stress-mediated diabetic complications. This study aims to assess the serum
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Iron overload is increasingly being connected to insulin resistance in Type 2 Diabetes Mellitus (T2DM) patients. Free iron causes the assembly of reactive oxygen species that invariably steer the body’s homeostasis towards oxidative stress-mediated diabetic complications. This study aims to assess the serum iron, total iron binding capacity (TIBC), and percentage transferrin saturation (Tsat) of 150 subjects divided into three groups (I,II,III) of 50. Healthy individuals (controls) constituted Group I. Group II consisted of T2DM patients with optimal glycaemic control. T2DM patients with suboptimal glycaemic control formed group III. Mean serum free iron concentration was 105.34 ± 3.5, 107.33 ± 3.45, and 125.58 ± 3.45 μg/dL in Group I, Group II, and Group III, respectively. Mean serum TIBC concentration in Group I, Group II, and Group III was 311.39 ± 5.47, 309.63 ± 6.1, and 284.2 ± 3.18 μg/dL, respectively. Mean serum transferrin saturation (%) in Group I, Group II, and Group III was 34.17 ± 1.21, 35.02 ± 1.2, and 44.39 ± 1.07, respectively. The difference between TIBC, mean serum free iron concentration, and transferrin saturation between Group I and Group III (for all, p values <0.001), as well as between Group II and Group III (p values 0.0012, 0.0015, and <0.0001, respectively) was statistically significant. The fasting plasma glucose values of Groups II and III were significantly higher than those of Group I, (p < 0.0001). Glycated haemoglobin (HbA1c) values were also shown to increase from Group I to II and then III, and the increase was highly significant (all p values <0.0001). Thus, decreased glycaemic control and an increase in the glycation of haemoglobin was the key to elevation in serum iron values and alterations in other parameters. However, a significant correlation was absent between serum iron and HbA1c (r = 0.05) and transferrin saturation (r = 0.0496) in Group III. Full article
Open AccessReview
Why Oats Are Safe and Healthy for Celiac Disease Patients
Med. Sci. 2016, 4(4), 21; doi:10.3390/medsci4040021 -
Abstract
The water-insoluble storage proteins of cereals (prolamins) are called “gluten” in wheat, barley, and rye, and “avenins” in oat. Gluten can provoke celiac disease (CD) in genetically susceptible individuals (those with human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 serotypes). Avenins are present at a
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The water-insoluble storage proteins of cereals (prolamins) are called “gluten” in wheat, barley, and rye, and “avenins” in oat. Gluten can provoke celiac disease (CD) in genetically susceptible individuals (those with human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 serotypes). Avenins are present at a lower concentration (10%–15% of total protein content) in oat as compared to gluten in wheat (80%–85%). The avenins in the genus Avena (cultivated oat as well as various wild species of which gene bank accessions were analyzed) are free of the known CD immunogenic epitopes from wheat, barley, and rye. T cells that recognize avenin-specific epitopes have been found very rarely in CD patients. CD patients that consume oats daily do not show significantly increased levels of intraepithelial lymphocyte (EIL) cells. The safety and the positive health effects of the long-term inclusion of oats in the gluten-free diet have been confirmed in long-term studies. Since 2009 (EC 41/2009) and 2013 (FDA) oat products may be sold as gluten-free in several countries provided a gluten contamination level below 20 ppm. Introduction of oats in the gluten-free diet of celiac patients is advised after the recovery of the intestine. Health effects of oat consumption are reflected in European Food Safety Authority (EFSA)- and Food and Drug Administration (FDA)-approved health claims. Oats can form a healthy, nutritious, fiber-rich, and safe complement to the gluten-free diet. Full article
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Open AccessFeature PaperArticle
Evaluation of Multiple Diagnostic Indicators in Comparison to the Intestinal Biopsy as the Golden Standard in Diagnosing Celiac Disease in Children
Med. Sci. 2016, 4(4), 20; doi:10.3390/medsci4040020 -
Abstract
Celiac disease (CD) is a chronic small intestinal enteropathy triggered by gluten in genetically predisposed individuals. The susceptibility is strongly associated with certain human leukocyte antigen (HLA)-genes, but efforts are being made in trying to find non-HLA genes that are predictive for the
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Celiac disease (CD) is a chronic small intestinal enteropathy triggered by gluten in genetically predisposed individuals. The susceptibility is strongly associated with certain human leukocyte antigen (HLA)-genes, but efforts are being made in trying to find non-HLA genes that are predictive for the disease. The criteria for diagnosing CD were previously based primarily on histologic evaluation of small intestinal biopsies, but nowadays are often based only on blood tests and symptoms. In this context, we elucidated the accuracy of three diagnostic indicators for CD, alone or in combination. Genetic analyses of HLA-type and nine single nucleotide polymorphisms (SNPs) known to be associated with CD were performed in 177 children previously investigated for the suspicion of CD. CD was confirmed in 109 children, while 68 were considered non-celiacs. The antibodies and urinary nitrite/nitrate concentrations of all of them were measured. The combinations of all the variables used in the study would classify 93% of the study population in the correct diagnostic group. The single best predictors were antibodies (i.e., anti-endomysium immunoglobulin A (IgA) (EMA) and transglutaminase IgA (TGA)), followed by HLA-type and nitric oxide (NO)-metabolites. The nine SNPs used did not contribute to the right diagnoses. Although our control group consisted of children with mostly gastrointestinal symptoms, the presented methodology predicted a correct classification in more than 90% of the cases. Full article
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Open AccessBrief Report
Do Sex Differences in Respiratory Burst Enzyme Activities Exist in Human Immunodeficiency Virus-1 Infection?
Med. Sci. 2016, 4(4), 19; doi:10.3390/medsci4040019 -
Abstract
Studies have shown that human immunodeficiency virus type 1 (HIV-1) disproportionally affects more females than males. Affected individuals are susceptible to infections due to depressed immunity, qualitative defects in phagocytic function and altered phagocytosis as well as lowered oxidative burst capacity. This study
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Studies have shown that human immunodeficiency virus type 1 (HIV-1) disproportionally affects more females than males. Affected individuals are susceptible to infections due to depressed immunity, qualitative defects in phagocytic function and altered phagocytosis as well as lowered oxidative burst capacity. This study seeks to determine whether sex differences exist in serum activities of respiratory burst enzymes in HIV-1–infected female and male subjects. Serum myeloperoxidase, catalase and superoxide dismutase activities were assayed in 170 confirmed HIV-1 positive and 50 HIV-1 negative subjects using ELISA. Data were analyzed using Student’s t-test and p values of less than 0.05 were considered significant. The measured enzyme activities were significantly higher (p < 0.001) in females than males in HIV-1 negative subjects while no sex differences were observed in HIV-1 positive subjects. The absence of sex differences in the activities of respiratory burst enzymes in HIV-1 infection may be due to immune activation as a result of active phagocytic leukocytes, immune reactivity and inflammation. Full article
Open AccessArticle
Metoprolol Dose Equivalence in Adult Men and Women Based on Gender Differences: Pharmacokinetic Modeling and Simulations
Med. Sci. 2016, 4(4), 18; doi:10.3390/medsci4040018 -
Abstract
Recent meta-analyses and publications over the past 15 years have provided evidence showing there are considerable gender differences in the pharmacokinetics of metoprolol. Throughout this time, there have not been any research articles proposing a gender stratified dose-adjustment resulting in an equivalent total
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Recent meta-analyses and publications over the past 15 years have provided evidence showing there are considerable gender differences in the pharmacokinetics of metoprolol. Throughout this time, there have not been any research articles proposing a gender stratified dose-adjustment resulting in an equivalent total drug exposure. Metoprolol pharmacokinetic data was obtained from a previous publication. Data was modeled using nonlinear mixed effect modeling using the MONOLIX software package to quantify metoprolol concentration–time data. Gender-stratified dosing simulations were conducted to identify equivalent total drug exposure based on a 100 mg dose in adults. Based on the pharmacokinetic modeling and simulations, a 50 mg dose in adult women provides an approximately similar metoprolol drug exposure to a 100 mg dose in adult men. Full article
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Open AccessArticle
An Assessment of Oxidative Damage and Non-Enzymatic Antioxidants Status Alteration in Relation to Disease Progression in Breast Diseases
Med. Sci. 2016, 4(4), 17; doi:10.3390/medsci4040017 -
Abstract
The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydroxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E, and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant
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The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydroxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E, and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant increases in the level of the oxidative damage marker 8-OHdG and cell proliferation activity were observed in breast carcinoma patients in comparison to benign and normal controls, which were accompanied by a significant decrease in non-enzymatic antioxidants and TAS concentrations (p < 0.05). 8-OHdG and cell proliferation levels were negatively correlated with non-enzymatic antioxidants, namely, vitamin A, vitamin C, and vitamin E levels and total antioxidant activity. Altered levels of biomarkers of oxidative stress and cell proliferation activity among the malignant, the benign, and the controls suggest a correlation of increased oxidative stress and cell proliferation activity in the progression of disease in breast carcinoma patients. In conclusion, our results showed that the characterized biomarkers (i.e., low levels of vitamin A, C and D, and the TAS status; and high levels of 8-OHdG) could be used as a suitable method for detecting subjects with malignant and benign breast diseases. Full article
Open AccessReview
Combination of mTOR and MAPK Inhibitors—A Potential Way to Treat Renal Cell Carcinoma
Med. Sci. 2016, 4(4), 16; doi:10.3390/medsci4040016 -
Abstract
Renal cell carcinoma (RCC) is the most common neoplasm that occurs in the kidney and is marked by a unique biology, with a long history of poor response to conventional cancer treatments. In the past few years, there have been significant advancements to
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Renal cell carcinoma (RCC) is the most common neoplasm that occurs in the kidney and is marked by a unique biology, with a long history of poor response to conventional cancer treatments. In the past few years, there have been significant advancements to understand the biology of RCC. This has led to the introduction of novel targeted therapies in the management of patients with metastatic disease. Patients treated with targeted therapies for RCC had shown positive impact on overall survival, however, no cure is possible and patients need to undergo treatment for long periods of time, which raises challenges to manage the associated adverse events. Moreover, many patients may not respond to it and even response may not last long enough in the responders. Many inhibitors of the Mammalian target of Rapamycin (mTOR) signaling pathway are currently being used in treatment of advanced RCC. Studies showed that inhibitions of mTOR pathways induce Mitogen-Activated Protein Kinase (MAPK) escape cell death and cells become resistant to mTOR inhibitors. Because of this, there is a need to inhibit both pathways with their inhibitors comparatively for a better outcome and treatment of patients with RCC. Full article
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Open AccessArticle
Androgen Receptor Expression in Thai Breast Cancer Patients
Med. Sci. 2016, 4(3), 15; doi:10.3390/medsci4030015 -
Abstract
The aim of this study was to investigate prevalence and related factors of androgen receptor (AR) expression in Thai breast cancer patients. A descriptive study was done in 95 patients, who were admitted to Charoenkrung Pracharak Hospital, Bangkok (2011–2013). Statistical relationships were examined
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The aim of this study was to investigate prevalence and related factors of androgen receptor (AR) expression in Thai breast cancer patients. A descriptive study was done in 95 patients, who were admitted to Charoenkrung Pracharak Hospital, Bangkok (2011–2013). Statistical relationships were examined between AR protein expression, tumor status, and patient characteristics. Compared with those from Western countries, ethnic Thai patients were younger at age of diagnosis and had a higher proliferative index (high Ki-67 expression), which indicates unfavorable prognosis. In addition, 91% of the Thai breast tumors that were positive for any of the following receptors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) also expressed the AR protein, while in triple negative breast tumors only 33% were AR positive. ER and PR expression was positively related with AR expression, while AR expression was inversely correlated to Ki-67 expression. AR status was strongly correlated with ER and PR status in Thai patients. There is an inverse relationship between Ki-67 and AR, which suggests that AR may be a prognostic factor for breast cancer. Full article
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Open AccessReview
Neuroprotection by Endoplasmic Reticulum Stress-Induced HRD1 and Chaperones: Possible Therapeutic Targets for Alzheimer’s and Parkinson’s Disease
Med. Sci. 2016, 4(3), 14; doi:10.3390/medsci4030014 -
Abstract
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative disorders with a severe medical and social impact. Further insights from clinical and scientific studies are essential to develop effective therapies. Various stresses on the endoplasmic reticulum (ER) cause unfolded/misfolded proteins to aggregate, initiating
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Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative disorders with a severe medical and social impact. Further insights from clinical and scientific studies are essential to develop effective therapies. Various stresses on the endoplasmic reticulum (ER) cause unfolded/misfolded proteins to aggregate, initiating unfolded protein responses (UPR), one of which is the induction of neuronal cell death. Some of the pathogenic factors for AD and PD are associated with UPR. ER molecules such as ubiquitin ligases (E3s) and chaperones are also produced during UPR to degrade and refold aberrant proteins that accumulate in the ER. In this review, we examine the role of HMG-CoA reductase degradation protein 1 (HRD1) and the chaperone protein-disulfide isomerase (PDI), which are both produced in the ER in response to stress. We discuss the importance of HRD1 in degrading amyloid precursor protein (APP) and Parkin-associated endothelin receptor-like receptor (Pael-R) to protect against neuronal death. PDI and the chemical chaperone 4-phenyl-butyrate also exert neuroprotective effects. We discuss the pathophysiological roles of ER stress, UPR, and the induction and neuroprotective effects of HRD1 and PDI, which may represent significant targets for novel AD and PD therapies. Full article
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Open AccessArticle
Alteration to Dopaminergic Synapses Following Exposure to Perfluorooctane Sulfonate (PFOS), in Vitro and in Vivo
Med. Sci. 2016, 4(3), 13; doi:10.3390/medsci4030013 -
Abstract
Our understanding of the contribution exposure to environmental toxicants has on neurological disease continues to evolve. Of these, Parkinson’s disease (PD) has been shown to have a strong environmental component to its etiopathogenesis. However, work is still needed to identify and characterize environmental
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Our understanding of the contribution exposure to environmental toxicants has on neurological disease continues to evolve. Of these, Parkinson’s disease (PD) has been shown to have a strong environmental component to its etiopathogenesis. However, work is still needed to identify and characterize environmental chemicals that could alter the expression and function of the nigrostriatal dopamine system. Of particular interest is the neurotoxicological effect of perfluorinated compounds, such as perfluorooctane sulfonate (PFOS), which has been demonstrated to alter aspects of dopamine signaling. Using in vitro approaches, we have elaborated these initial findings to demonstrate the neurotoxicity of PFOS to the SH-SY5Y neuroblastoma cell line and dopaminergic primary cultured neurons. Using an in vivo model, we did not observe a deficit to dopaminergic terminals in the striatum of mice exposed to 10 mg/kg PFOS for 14 days. However, subsequent exposure to the selective dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly reduced the expression of dopamine transporter (DAT) and tyrosine hydroxylase (TH), and resulted in an even greater reduction in DAT expression in animals previously exposed to PFOS. These findings suggest that PFOS is neurotoxic to the nigrostriatal dopamine circuit and this neurotoxicity could prime the dopamine terminal to more extensive damage following additional toxicological insults. Full article
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Open AccessArticle
Novel Somatic Copy Number Alteration Identified for Cervical Cancer in the Mexican American Population
Med. Sci. 2016, 4(3), 12; doi:10.3390/medsci4030012 -
Abstract
Cervical cancer affects millions of Americans, but the rate for cervical cancer in the Mexican American is approximately twice that for non-Mexican Americans. The etiologies of cervical cancer are still not fully understood. A number of somatic mutations, including several copy number alterations
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Cervical cancer affects millions of Americans, but the rate for cervical cancer in the Mexican American is approximately twice that for non-Mexican Americans. The etiologies of cervical cancer are still not fully understood. A number of somatic mutations, including several copy number alterations (CNAs), have been identified in the pathogenesis of cervical carcinomas in non-Mexican Americans. Thus, the purpose of this study was to investigate CNAs in association with cervical cancer in the Mexican American population. We conducted a pilot study of genome-wide CNA analysis using 2.5 million markers in four diagnostic groups: reference (n = 125), low grade dysplasia (cervical intraepithelial neoplasia (CIN)-I, n = 4), high grade dysplasia (CIN-II and -III, n = 5) and invasive carcinoma (squamous cell carcinoma (SCC), n = 5) followed by data analyses using Partek. We observed a statistically-significant difference of CNA burden between case and reference groups of different sizes (>100 kb, 10–100 kb and 1–10 kb) of CNAs that included deletions and amplifications, e.g., a statistically-significant difference of >100 kb deletions was observed between the reference (6.6%) and pre-cancer and cancer (91.3%) groups. Recurrent aberrations of 98 CNA regions were also identified in cases only. However, none of the CNAs have an impact on cancer progression. A total of 32 CNA regions identified contained tumor suppressor genes and oncogenes. Moreover, the pathway analysis revealed endometrial cancer and estrogen signaling pathways associated with this cancer (p < 0.05) using Kyoto Encyclopedia of Genes and Genomes (KEGG). This is the first report of CNAs identified for cervical cancer in the U.S. Latino population using high density markers. We are aware of the small sample size in the study. Thus, additional studies with a larger sample are needed to confirm the current findings. Full article
Open AccessArticle
Relationship between Neutrophil-to-Lymphocyte Ratio and Inflammatory Markers in Sickle Cell Anaemia Patients with Proteinuria
Med. Sci. 2016, 4(3), 11; doi:10.3390/medsci4030011 -
Abstract
The renal functions and structure in sickle cell anaemia (SCA) patients may be affected by chronic haemodynamic changes and consequences of vaso-occlusive events in the renal medulla. Few reports on neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios in SCA patients in Africans exist in
[...] Read more.
The renal functions and structure in sickle cell anaemia (SCA) patients may be affected by chronic haemodynamic changes and consequences of vaso-occlusive events in the renal medulla. Few reports on neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios in SCA patients in Africans exist in the literature. This study correlates the values of NLR and PLR with measured traditional inflammatory markers in SCA patients with and without proteinuria and impaired kidney function (defined in this study as estimated glomerular filtration rate (eGFR), less than 60 mL/min/1.73 m2. Full blood count, C-reactive protein (CRP), and fibrinogen were assayed in 150 SCA patients and 50 control subjects using Coulter Haematology analyser (CELL DYE 37000) and ELISA method, respectively. The NLR and PLR were calculated by dividing absolute neutrophil or platelet counts by absolute lymphocyte count. Fibrinogen, CRP, NLR, and PLR increased progressively (p < 0.001) in SCA patients with or without proteinuria, with the highest values seen in those with impaired renal function. NLR correlated positively with CRP and fibrinogen in SCA patients without proteinuria (p < 0.001), with proteinuria (p < 0.001), and impaired renal function (p < 0.05). A positive relationship was also observed between NLR and fibrinogen in the control subjects. The need to determine cut-off values for these leukocyte ratios to be used in identifying those patients at risk and in the general management of SCA patients is suggested. Full article
Open AccessArticle
First Evidence for the Disease-Stage, Cell-Type, and Virus Specificity of microRNAs during Human Immunodeficiency Virus Type-1 Infection
Med. Sci. 2016, 4(2), 10; doi:10.3390/medsci4020010 -
Abstract
The potential involvement of host microRNAs (miRNAs) in HIV infection is well documented, and evidence suggests that HIV modulates and also dysregulates host miRNAs involved in maintaining the host innate immune system. Moreover, the dysregulation of host miRNAs by HIV also effectively interferes
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The potential involvement of host microRNAs (miRNAs) in HIV infection is well documented, and evidence suggests that HIV modulates and also dysregulates host miRNAs involved in maintaining the host innate immune system. Moreover, the dysregulation of host miRNAs by HIV also effectively interferes directly with the host gene expression. In this study, we have simultaneously evaluated the expression of host miRNAs in both CD4+ and CD8+ T-cells derived from HIV-positive (HIV+) individuals (viremic and aviremic individuals while receiving highly active antiretroviral therapy (HAART), therapy-naïve long-term non-progressors (LTNP), and HIV-negative (HIV–) healthy controls. miRNAs were run on Affymetrix V2 chips, and the differential expression between HIV+ and HIV− samples, along with intergroup comparisons, was derived using PARTEK software, using an FDR of 5% and an adjusted p-value < 0.05. The miR-199a-5p was found to be HIV-specific and expressed in all HIV+ groups as opposed to HIV– controls. Moreover, these are the first studies to reveal clearly the highly discriminatory miRNAs at the level of the disease state, cell type, and HIV-specific miRNAs. Full article