Open AccessArticle
The Association of Triiodothyronine-to-Thyroxine Ratio with Body Mass Index in Obese Nigerian Children and Adolescents
Med. Sci. 2017, 5(4), 36; doi:10.3390/medsci5040036 (registering DOI) -
Abstract
The interest in the relationship between thyroid dysfunction and obesity is on the increase. This study compares the triiodothyronine-to-thyroxine (T3/T4) ratio in obese and lean children and adolescents, and correlates thyroid hormones with body mass index (BMI) in obese Nigerian children. It is
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The interest in the relationship between thyroid dysfunction and obesity is on the increase. This study compares the triiodothyronine-to-thyroxine (T3/T4) ratio in obese and lean children and adolescents, and correlates thyroid hormones with body mass index (BMI) in obese Nigerian children. It is a retrospective study of records of 76 obese children and adolescents with a BMI of 31.7 ± 0.1 kg/m2 (26 males aged 10.9 ± 0.35 years, and 50 females aged 10.8 ± 0.4 years) that were referred to the laboratory for thyroid hormone evaluation because of their obese status. The controls were 20 age-matched non-obese apparently healthy subjects, with a mean age of 11.0 ± 0.47 years and a BMI of 20.2 ± 0.2 kg/m2. Serum T3, T4, and thyroid stimulating hormone (TSH) were determined using ELECSYS 1010 auto-analyzer (Roche Diagnostics, Penzberg, Germany). The BMI (p < 0.001), T3 (p < 0.01), TSH (p < 0.001) and T3/T4 ratio (p < 0.001) were significantly higher in obese than non-obese children and adolescents. Triiodothyronine (r = 0.230; p < 0.05), TSH (r = 0.272; p < 0.02), and T3/T4 ratio (r = 0.232; p < 0.05) correlated positively with BMI in obese children and adolescents. The T3/T4 ratio (p < 0.005) was significantly higher in obese boys than obese girls. Serum T3, TSH, and T3/T4 ratio correlated positive with BMI in obese Nigerian children and adolescents. Since thyroid dysfunction represents a continuum from asymptomatic to clinical symptomatic disease, it is suggested that obese children be counseled on the need to maintain ideal BMI in order to avoid the risks associated with obesity. Full article
Open AccessArticle
Pharmacoeconomic Analysis of Drugs Used in the Treatment of Pneumonia in Paediatric Population in a Tertiary Care Hospital in India—A Cost-of-Illness Study
Med. Sci. 2017, 5(4), 33; doi:10.3390/medsci5040033 -
Abstract
Aims and objectives: The cost of antibiotic therapy for the treatment of pneumonia in the inpatient paediatric population can have a major impact on the healthcare expenditure. We planned to assess the direct and indirect costs of diagnosis and medical treatment of paediatric
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Aims and objectives: The cost of antibiotic therapy for the treatment of pneumonia in the inpatient paediatric population can have a major impact on the healthcare expenditure. We planned to assess the direct and indirect costs of diagnosis and medical treatment of paediatric patients with community acquired pneumonia who are hospitalized in a tertiary care hospital in India. Methods: 125 children with a diagnosis of pneumonia who were admitted to the inpatient department of a paediatric hospital receiving antibiotic treatment were observed. Data on clinical presentation and resources consumed were collected and the costs of pneumonia treatment were calculated. Descriptive statistics (mean ± standard deviation (SD)) were used to evaluate data regarding demographics, drugs prescribed and cost (direct and indirect cost). Multivariate regression analysis was used to find out predictors of direct and indirect cost. Results: Among all pneumonia admissions, mild-to-moderate pneumonia constitutes 76.8%, and 23.2% children were admitted with severe pneumonia; 105 children out of 125 (84%) were suffering from associated disorders along with pneumonia. The majority of antibiotics prescribed belonged to beta lactams (52%) followed by aminoglycosides (19%), macrolides (13%) and peptides (11%). Parenteral routes of administration were used in a majority of patients as compared to oral. The average cost per patient in management of pneumonia was 12245 ± 593 INR ($187.34 ± 9.07). Full article
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Open AccessArticle
Histologic Grade Is Predictive of Incidence of Epidermal Growth Factor Receptor Mutations in Metastatic Lung Adenocarcinoma
Med. Sci. 2017, 5(4), 34; doi:10.3390/medsci5040034 -
Abstract
Activating epidermal growth factor receptor (EGFR) mutations in metastatic non-small cell lung cancer (NSCLC) are associated with a high response rate to EGFR tyrosine kinase inhibitor (TKI). The current guidelines recommend routine EGFR mutational analysis prior to initiating first line systemic therapy. The
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Activating epidermal growth factor receptor (EGFR) mutations in metastatic non-small cell lung cancer (NSCLC) are associated with a high response rate to EGFR tyrosine kinase inhibitor (TKI). The current guidelines recommend routine EGFR mutational analysis prior to initiating first line systemic therapy. The clinical characteristics including smoking status, histologic type, sex and ethnicity are known to be associated with the incidence of EGFR mutations. We retrospectively analyzed 277 patients with metastatic NSCLC within Kaiser Permanente Northern California (KPNC); among these patients, 83 were positive for EGFR mutations. We performed both univariate and multivariable logistic regressions to identify predictors of EGFR mutations. We found that histologic grade was significantly associated with the incidence of EGFR mutation, regardless of ethnicity, sex and smoking status. In grade I (well differentiated) and II (moderately differentiated), histology was associated with significantly higher incidence of EGFR mutations compared to grade II–III (moderate-to-poorly differentiated) and III (poorly differentiated). Ever-smokers with grade III lung adenocarcinoma had 1.8% incidence of EGFR mutations. This study indicates that histologic grade is a predictive factor for the incidence of EGFR mutations and suggests that for patients with grade II–III or III lung adenocarcinoma, prompt initiation of first-line chemotherapy or immunotherapy is appropriate while awaiting results of EGFR mutational analysis, particularly for patients with history of smoking. Full article
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Open AccessArticle
Investigation of Polyamine Metabolism and Homeostasis in Pancreatic Cancers
Med. Sci. 2017, 5(4), 32; doi:10.3390/medsci5040032 -
Abstract
Pancreatic cancers are currently the fourth leading cause of cancer-related death and new therapies are desperately needed. The most common pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). This report describes the development of therapies, which effectively deplete PDAC cells of their required polyamine
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Pancreatic cancers are currently the fourth leading cause of cancer-related death and new therapies are desperately needed. The most common pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). This report describes the development of therapies, which effectively deplete PDAC cells of their required polyamine growth factors. Of all human tissues, the pancreas has the highest level of the native polyamine spermidine. To sustain their high growth rates, PDACs have altered polyamine metabolism, which is reflected in their high intracellular polyamine levels and their upregulated import of exogenous polyamines. To understand how these cancers respond to interventions that target their specific polyamine pools, L3.6pl human pancreatic cancer cells were challenged with specific inhibitors of polyamine biosynthesis. We found that pancreatic cell lines have excess polyamine pools, which they rebalance to address deficiencies induced by inhibitors of specific steps in polyamine biosynthesis (e.g., ornithine decarboxylase (ODC), spermidine synthase (SRM), and spermine synthase (SMS)). We also discovered that combination therapies targeting ODC, SMS, and polyamine import were the most effective in reducing intracellular polyamine pools and reducing PDAC cell growth. A combination therapy containing difluoromethylornithine (DFMO, an ODC inhibitor) and a polyamine transport inhibitor (PTI) were shown to significantly deplete intracellular polyamine pools. The additional presence of an SMS inhibitor as low as 100 nM was sufficient to further potentiate the DFMO + PTI treatment. Full article
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Open AccessArticle
Sociodemographic Factors on Contraceptive Use among Ever-Married Women of Reproductive Age: Evidence from Three Demographic and Health Surveys in Bangladesh
Med. Sci. 2017, 5(4), 31; doi:10.3390/medsci5040031 -
Abstract
Contraceptive use among married women of reproductive age has showed a substantial progress over the last few decades in Bangladesh. This study explores the sociodemographic factors associated with contraceptive use among ever-married women of reproductive age in Bangladesh by utilizing the information extracted
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Contraceptive use among married women of reproductive age has showed a substantial progress over the last few decades in Bangladesh. This study explores the sociodemographic factors associated with contraceptive use among ever-married women of reproductive age in Bangladesh by utilizing the information extracted from three of the Bangladesh Demographic and Health Surveys (BDHSs) in 1993–1994, 2004 and 2014. Bivariate analysis was conducted by performing chi-squared test of independence to explore the relationship between selected sociodemographic factors and dependent variables. To know the adjusted effects of covariates, a popular binary logistic regression model was considered. Respondents’ current age, place residence, division religion, education, age at first marriage, family planning (FP) media exposure, ideal number of children and fertility preferences are the significant determinants according to the most recent survey, BDHS 2014. However, wealth index and a respondent’s current working status were found to be significant factors only in BDHS 2004. The results of the study strongly recommend efforts to increase the education level among poor people, particularly among women in Bangladesh. Program interventions, including health behavior education and family planning services and counselling, are especially needed for some categories of the population, including those living in rural areas, Sylhet, Chittagong and Dhaka divisions, as well as illiterate and Muslim ever-married women. Full article
Open AccessReview
Cognitive and Behavioral Consequences of Sleep Disordered Breathing in Children
Med. Sci. 2017, 5(4), 30; doi:10.3390/medsci5040030 -
Abstract
There is now a plethora of evidence that children with sleep disordered breathing (SDB) show deficits in neurocognitive performance, behavioral impairments, and school performance. The following review will focus on the neurobehavioral impacts of SDB, pediatric sleep investigation challenges, potential mechanisms of behavioral
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There is now a plethora of evidence that children with sleep disordered breathing (SDB) show deficits in neurocognitive performance, behavioral impairments, and school performance. The following review will focus on the neurobehavioral impacts of SDB, pediatric sleep investigation challenges, potential mechanisms of behavioral and cognitive deficits in children with SDB, and the impact of SDB treatment. Full article
Open AccessReview
Alzheimer’s Disease, Brain Injury, and C.N.S. Nanotherapy in Humans: Sonoporation Augmenting Drug Targeting
Med. Sci. 2017, 5(4), 29; doi:10.3390/medsci5040029 -
Abstract
Owing to the complexity of neurodegenerative diseases, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted nanoemulsion) are available. Versatile small-molecule drug(s) targeting multiple pathways of Alzheimer’s
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Owing to the complexity of neurodegenerative diseases, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted nanoemulsion) are available. Versatile small-molecule drug(s) targeting multiple pathways of Alzheimer’s disease pathogenesis are known. By incorporating such drug(s) into the targeted lipid-coated microbubble/nanoparticle-derived (LCM/ND) lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly scavenger receptor class B type I (SR-BI)), making it possible for various Alzheimer’s-related cell types to be simultaneously sought for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble (LCM) subpopulation (i.e., a stable LCM suspension); such LCM substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer’s patient. Full article
Open AccessFeature PaperReview
Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells
Med. Sci. 2017, 5(4), 28; doi:10.3390/medsci5040028 -
Abstract
Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal
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Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells. Full article
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Open AccessArticle
Evaluation of Polyamine Transport Inhibitors in a Drosophila Epithelial Model Suggests the Existence of Multiple Transport Systems
Med. Sci. 2017, 5(4), 27; doi:10.3390/medsci5040027 -
Abstract
Increased polyamine biosynthesis activity and an active polyamine transport system are characteristics of many cancer cell lines and polyamine depletion has been shown to be a viable anticancer strategy. Polyamine levels can be depleted by difluoromethylornithine (DFMO), an inhibitor of the key polyamine
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Increased polyamine biosynthesis activity and an active polyamine transport system are characteristics of many cancer cell lines and polyamine depletion has been shown to be a viable anticancer strategy. Polyamine levels can be depleted by difluoromethylornithine (DFMO), an inhibitor of the key polyamine biosynthesis enzyme ornithine decarboxylase (ODC). However, malignant cells frequently circumvent DFMO therapy by up-regulating polyamine import. Therefore, there is a need to develop compounds that inhibit polyamine transport. Collectively, DFMO and a polyamine transport inhibitor (PTI) provide the basis for a combination therapy leading to effective intracellular polyamine depletion. We have previously shown that the pattern of uptake of a series of polyamine analogues in a Drosophila model epithelium shares many characteristics with mammalian cells, indicating a high degree of similarity between the mammalian and Drosophila polyamine transport systems. In this report, we focused on the utility of the Drosophila epithelial model to identify and characterize polyamine transport inhibitors. We show that a previously identified inhibitor of transport in mammalian cells has a similar activity profile in Drosophila. The Drosophila model was also used to evaluate two additional transport inhibitors. We further demonstrate that a cocktail of polyamine transport inhibitors is more effective than individual inhibitors, suggesting the existence of multiple transport systems in Drosophila. Our findings reinforce the similarity between the Drosophila and mammalian transport systems and the value of the Drosophila model to provide inexpensive early screening of molecules targeting the transport system. Full article
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Open AccessReview
Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity
Med. Sci. 2017, 5(4), 26; doi:10.3390/medsci5040026 -
Abstract
Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter;
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Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords “subacute sclerosing panencephalitis” and “brainstem” using the National Library of Medicine PubMed database (March 1981–September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment. Full article
Open AccessArticle
Inflammatory Biomarkers of Cardiometabolic Risk in Obese Egyptian Type 2 Diabetics
Med. Sci. 2017, 5(4), 25; doi:10.3390/medsci5040025 -
Abstract
Inflammatory biomarkers provide a minimally invasive means for early detection and specific treatment of metabolic syndrome and related disorders. The objective of this work was to search for inflammatory biomarkers of cardiometabolic risk in obese type 2 diabetics. The study was performed on
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Inflammatory biomarkers provide a minimally invasive means for early detection and specific treatment of metabolic syndrome and related disorders. The objective of this work was to search for inflammatory biomarkers of cardiometabolic risk in obese type 2 diabetics. The study was performed on 165 persons attending the medical outpatient clinic of Ismailia General Hospital. Their mean age was (50.69 ± 10.15) years. They were divided into three groups. The control group was composed of 55 non-obese, non-diabetic healthy volunteers, 32 males and 23 females. Two study groups were included in this study: group 2 was composed of 55 obese, non-diabetic subjects, 25 males and 30 females matched for age and gender. All patients including the control were subjected to clinical history taking, a clinical examination for the measurement of body mass index (BMI). Investigations were carried out for fasting blood glucose, fasting serum insulin, insulin resistance (IR), the lipid profile, lipoprotein band lipoprotein phospholipase A2, and non-high-density lipoprotein cholesterol (non-HDL-C). Urea, albumin and creatinine analysis and liver function tests were performed, and a complete blood count (CBC) was taken. Hemoglobin A1C (HbA1C), serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were tested. There were statistically significant differences among the studied groups in terms of total cholesterol, non-HDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), lipoprotein-associated phospholipase A2 and apolipoprotein B. The inflammatory biomarkers hs-CRP, IL-6 and TNF-α were significantly statistically increased in the study groups by (1.62 ± 0.99, 2.32 ± 1.11), (1.73 ± 1.14, 2.53 ± 1.34), and (1.87 ± 1.09, 2.17 ± 0.89) respectively, where p < 0.01. Significant positive correlation was found between Homeostatic Model Assessment (HOMA)-IR, hs-CRP and IL-6. There was a significant positive correlation between non-HDL and hs-CRP, IL-6 and TNF-α and triglycerides and hs-CRP. In conclusion, in this study, CRP, IL-6, and TNF-α were significantly elevated in obese Egyptian type 2 diabetics and were positively correlated with insulin resistance, non-HDL and triglycerides. These inflammatory biomarkers could help in the premature identification of obese type 2 diabetic patients at high cardiometabolic risk. Additionally, these biomarkers are critical for providing prognostics and the validity of future potential anti-inflammatory therapeutic modalities. Full article
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Open AccessArticle
Assessment of Hepatitis B Viral Infection as a Predictor of Hepatic Enzymes and Compounds Alteration among Antenatal Patients
Med. Sci. 2017, 5(4), 24; doi:10.3390/medsci5040024 -
Abstract
Worldwide, hepatitis B viral (HBV) infection continues to be a major public health issue. The study was aimed at assessing HBV infection as a predictor of hepatic enzymes and compounds alteration among antenatal patients in Kano State, Nigeria. Sera were screened for HBV
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Worldwide, hepatitis B viral (HBV) infection continues to be a major public health issue. The study was aimed at assessing HBV infection as a predictor of hepatic enzymes and compounds alteration among antenatal patients in Kano State, Nigeria. Sera were screened for HBV markers using immunochromatograhy and ELISA. Serum levels of alkaline phosphatase (ALP), asphatate aminotransferase (AST), alanine aminotransferase (ALT), albumin and bilirubin were also determined. Out of the 160 patients, 6.9% and 31.3% tested positive for HBsAg and HBcAb, respectively. None tested positive for HBeAg. These markers also appeared in other combinations. Of the HBsAg seropositives, 72.7% showed abnormal levels of both AST and ALP, 36.7% showed abnormal levels of both total and direct bilirubin, 9.1% showed abnormal levels of albumin, and none showed abnormal levels of ALT. HBsAg seropositivity shows significant association with ALP elevation (p = 0.02).The study revealed that few subjects (1.3%) that tested positive for HBsAg and HBeAb with normal ALT were in the inactive carrier phase of chronic hepatitisand6.9% that were seronegatives for all HBV markers equally had altered hepatic enzymes. The presence of HBeAg in the serum during HBV infection seems to cause a marked elevation of ALT level, while the reverse happens if HBeAg is absent. HBV infection can alter levels of hepatic enzymes and compounds and thus serve as one of its predictors, however; pregnancy can also lead to some of these alterations, which makes it difficult to establish the origin of these alterations among antenatal patients. Full article
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Open AccessFeature PaperReview
Cytokine Signaling in Multiple Sclerosis and Its Therapeutic Applications
Med. Sci. 2017, 5(4), 23; doi:10.3390/medsci5040023 -
Abstract
Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known but it is widely accepted that it is autoimmune in nature. Disease onset is believed to be initiated by the activation of
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Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known but it is widely accepted that it is autoimmune in nature. Disease onset is believed to be initiated by the activation of CD4+ T cells that target autoantigens of the central nervous system (CNS) and their infiltration into the CNS, followed by the expansion of local and infiltrated peripheral effector myeloid cells that create an inflammatory milieu within the CNS, which ultimately lead to tissue damage and demyelination. Clinical studies have shown that progression of MS correlates with the abnormal expression of certain cytokines. The use of experimental autoimmune encephalomyelitis (EAE) model further delineates the role of these cytokines in neuroinflammation and the therapeutic potential of manipulating their biological activity in vivo. In this review, we will first present an overview on cytokines that may contribute to the pathogenesis of MS or EAE, and provide successful examples and roadblock of translating data obtained from EAE to MS. We will then focus in depth on recent findings that demonstrate the pathological role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in MS and EAE, and briefly discuss the potential of targeting effector myeloid cells as a treatment strategy for MS. Full article
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Open AccessFeature PaperArticle
Massively Parallel Sequencing of Genes Implicated in Heritable Cardiac Disorders: A Strategy for a Small Diagnostic Laboratory
Med. Sci. 2017, 5(4), 22; doi:10.3390/medsci5040022 -
Abstract
Sudden cardiac death (SCD) in people before the age of 35 years is a devastating event for any family. The causes of SCD in the young can be broadly divided into two groups: heritable cardiac disorders that affect the heart structure (cardiomyopathies) and
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Sudden cardiac death (SCD) in people before the age of 35 years is a devastating event for any family. The causes of SCD in the young can be broadly divided into two groups: heritable cardiac disorders that affect the heart structure (cardiomyopathies) and primary electrical disorders (cardiac ion channelopathies). Genetic testing is vital as those suffering from cardiac ion channelopathies have structurally normal hearts, and those with cardiomyopathies may only show subtle abnormalities in the heart and these signs may not be detected during an autopsy. Post-mortem genetic testing of SCD victims is important to identify the underlying genetic cause. This is important as family cascade screening may be undertaken to identify those who may be at risk and provide vital information about risk stratification and clinical management. The development of massively parallel sequencing (MPS) has made it possible for the simultaneous screening of multiple patients for hundreds of genes. In light of this, we opted to develop an MPS approach for SCD analysis that would allow us to screen for mutations in genes implicated in cardiomyopathies and cardiac ion channelopathies. The rationale behind this panel was to limit it to genes carrying the greatest mutation load. If no likely pathogenic gene variant were found then testing could cascade to whole exome/genome sequencing as a gene-discovery exercise. The overarching aim was to design and validate a custom-cardiac panel that satisfies the diagnostic requirements of LabPLUS (Auckland City Hospital, Auckland, NZ) and the guidelines provided by the Royal College of Pathologists of Australasia and the Association for Clinical Genetic Science. Full article
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Open AccessArticle
Quantification of Age‐Related Lung Tissue Mechanics under Mechanical Ventilation
Med. Sci. 2017, 5(4), 21; doi:10.3390/medsci5040021 -
Abstract
Elderly patients with obstructive lung diseases often receive mechanical ventilation to support their breathing and restore respiratory function. However, mechanical ventilation is known to increase the severity of ventilator‐induced lung injury (VILI) in the elderly. Therefore, it is important to investigate the effects
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Elderly patients with obstructive lung diseases often receive mechanical ventilation to support their breathing and restore respiratory function. However, mechanical ventilation is known to increase the severity of ventilator‐induced lung injury (VILI) in the elderly. Therefore, it is important to investigate the effects of aging to better understand the lung tissue mechanics to estimate the severity of ventilator‐induced lung injuries. Two age‐related geometric models involving human bronchioles from generation G10 to G23 and alveolar sacs were developed. The first is for a 50‐year‐old (normal) and second is for an 80‐year old (aged) model. Lung tissue mechanics of normal and aged models were investigated under mechanical ventilation through computational simulations. Results obtained indicated that lung tissue strains during inhalation (t = 0.2 s) decreased by about 40% in the alveolar sac (G23) and 27% in the bronchiole (G20), respectively, for the 80‐year‐old as compared to the 50‐year‐old. The respiratory mechanics parameters (work of breathing per unit volume and maximum tissue strain) over G20 and G23 for the 80‐year‐old decreased by about 64% (three‐fold) and 80% (four‐fold), respectively, during the mechanical ventilation breathing cycle. However, there was a significant increase (by about threefold) in lung compliance for the 80‐year‐old in comparison to the 50‐year‐old. These findings from the computational simulations demonstrated that lung mechanical characteristics are significantly compromised in aging tissues, and these effects were quantified in this study. Full article
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Open AccessArticle
Healthcare Cost and Utilization before and after Diagnosis of Pseudomonas aeruginosa among Patients with Non-Cystic Fibrosis Bronchiectasis in the U.S.
Med. Sci. 2017, 5(4), 20; doi:10.3390/medsci5040020 -
Abstract
Non-cystic fibrosis bronchiectasis (NCFBE) is a rare, chronic lung disease characterized by bronchial inflammation and permanent airway dilation. Chronic infections with P. aeruginosa have been linked to higher morbidity and mortality. To understand the impact of P. aeruginosa in NCFBE on health care
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Non-cystic fibrosis bronchiectasis (NCFBE) is a rare, chronic lung disease characterized by bronchial inflammation and permanent airway dilation. Chronic infections with P. aeruginosa have been linked to higher morbidity and mortality. To understand the impact of P. aeruginosa in NCFBE on health care costs and burden, we assessed healthcare costs and utilization before and after P. aeruginosa diagnosis. Using data from 2007 to 2013 PharMetrics Plus administrative claims, we included patients with ≥2 claims for bronchiectasis and >1 claim for P. aeruginosa; then excluded those with a claim for cystic fibrosis. Patients were indexed at first claim for P. aeruginosa and were required to have >12 months before and after the index P. aeruginosa. The mean differences in utilization and costs were assessed using paired Student’s t-tests for statistical significance. Mean total healthcare costs per patient were $36,213 pre-P. aeruginosa diagnosis versus $67,764 post-P. aeruginosa, an increase of 87% (p < 0.0001). Inpatient costs represented the largest proportion of total healthcare costs post-P. aeruginosa (54%) with an increase of four hospitalizations per patient (p < 0.0001). NCFBE patients with evidence of P. aeruginosa incur substantially greater healthcare costs and utilization after P. aeruginosa diagnosis. Future research should explore methods of earlier identification of NCFBE patients with P. aeruginosa, as this may lead to fewer severe exacerbations, thereby resulting in a reduction in hospitalizations and healthcare costs. Full article
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Open AccessFeature PaperCommunication
Molecular Characterization of Peripheral Extracellular Vesicles in Clinically Isolated Syndrome: Preliminary Suggestions from a Pilot Study
Med. Sci. 2017, 5(3), 19; doi:10.3390/medsci5030019 -
Abstract
Extracellular vesicles (EVs), nanoparticles originated from different cell types, seem to be implicated in several cellular activities. In the Central Nervous System (CNS), glia and neurons secrete EVs and recent studies have demonstrated that the intercellular communication mediated by EVs has versatile functional
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Extracellular vesicles (EVs), nanoparticles originated from different cell types, seem to be implicated in several cellular activities. In the Central Nervous System (CNS), glia and neurons secrete EVs and recent studies have demonstrated that the intercellular communication mediated by EVs has versatile functional impact in the cerebral homeostasis. This essential role may be due to their proteins and RNAs cargo that possibly modify the phenotypes of the targeted cells. Despite the increasing importance of EVs, little is known about their fluctuations in physiological as well as in pathological conditions. Furthermore, only few studies have investigated the contents of contemporary EVs subgroups (microvesicles, MVs and exosomes, EXOs) with the purpose of discriminating between their features and functional roles. In order to possibly shed light on these issues, we performed a pilot study in which MVs and EXOs extracted from serum samples of a little cohort of subjects (patients with the first clinical evidence of CNS demyelination, also known as Clinically Isolated Syndrome and Healthy Controls) were submitted to deep small-RNA sequencing. Data were analysed by an in-home bioinformatics platform. In line with previous reports, distinct classes of non-coding RNAs have been detected in both the EVs subsets, offering interesting suggestions on their origins and functions. We also verified the feasibility of this extensive molecular approach, thus supporting its valuable use for the analysis of circulating biomarkers (e.g., microRNAs) in order to investigate and monitor specific diseases. Full article
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Open AccessReview
The Association between Sleep and Theory of Mind in School Aged Children with ADHD
Med. Sci. 2017, 5(3), 18; doi:10.3390/medsci5030018 -
Abstract
Theory of Mind (ToM) is defined as the ability to infer a range of internal mental states of others, including beliefs, intentions, desires, and emotions. These abilities are associated with children’s ability to socialize effectively with peers. ToM impairments are associated with peer
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Theory of Mind (ToM) is defined as the ability to infer a range of internal mental states of others, including beliefs, intentions, desires, and emotions. These abilities are associated with children’s ability to socialize effectively with peers. ToM impairments are associated with peer rejection and psychiatric disorders such as Attention-Deficit/Hyperactivity Disorder (ADHD). Previous studies have found poor sleep negatively impacts executive functioning (EF) and emotional information processing, which are essential for the effective use of ToM. Youth with ADHD have EF deficits and sleep problems. However, the relationship between sleep, executive functioning, and ToM in children with ADHD has not been studied. In this review, we propose that the poor social and interpersonal skills characterizing individuals with ADHD could be explained by the impact of poor sleep on the emotional and cognitive mechanisms underlying ToM. Full article
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Open AccessArticle
VEGF-B Levels in the Vitreous of Diabetic and Non-Diabetic Patients with Ocular Diseases and Its Correlation with Structural Parameters
Med. Sci. 2017, 5(3), 17; doi:10.3390/medsci5030017 -
Abstract
Vascular endothelial growth factor B (VEGF-B) is one of the enigmatic members of the VEGF family. The knowledge gap about VEGF-B expression and how its levels are altered in diabetic eyes were the focus of this investigation that was addressed by comparing and
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Vascular endothelial growth factor B (VEGF-B) is one of the enigmatic members of the VEGF family. The knowledge gap about VEGF-B expression and how its levels are altered in diabetic eyes were the focus of this investigation that was addressed by comparing and correlating vitreous VEGF-B between diabetic and non-diabetic patients. VEGF-B levels were measured by enzyme-linked immunosorbent assay in vitreous samples (n = 33) from diabetic (n = 25) and non-diabetic (n = 8) patients. Results were compared between groups. Optical coherence tomography from diabetic patients was evaluated for central retinal thickness (CRT) and macular volume (MV). Mean vitreous VEGF-B concentration was higher in diabetic (18.82 ± 1.44 pg/mL ) vs. non-diabetic patients (17.90 ± 0.32 pg/mL) (p = 0.006), and in proliferative diabetic retinopathy (PDR) (19.03 ± 1.52 pg/mL) vs. non-PDR (NPDR) patients (18.18 ±0.96 pg/mL) (p = 0.025). In diabetic retinopathy (DR) patients, correlation between VEGF-B and CRT (μm) was positive and moderate: rs = 0.441 (p ≤ 0.05) and the correlation between VEGF-B and MV (mm3) was positive and robust: rs = 0.716 (p ≤ 0.01). VEGF-B levels are overexpressed in vitreous of diabetic patients, and the levels are higher in developed stages of DR. Correlation results show that CRT and MV increase with increased levels of VEGF-B. Targeting VEGF-B inhibition may have therapeutic beneficial implications. Full article
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Open AccessReview
Disparities in Brain Cancer in the United States: A Literature Review of Gliomas
Med. Sci. 2017, 5(3), 16; doi:10.3390/medsci5030016 -
Abstract
In the human body, the central regulatory system of homeostasis is maintained by the brain. Its complexity is mesmerizing and many of its functions are largely uncharted. Unfortunately, its functionality is often impaired through neoplastic growths, like gliomas, which are devastating to patients
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In the human body, the central regulatory system of homeostasis is maintained by the brain. Its complexity is mesmerizing and many of its functions are largely uncharted. Unfortunately, its functionality is often impaired through neoplastic growths, like gliomas, which are devastating to patients and their families. Annually, gliomas are the most common primary brain tumours affecting over 20,000 people in the United States. However, despite their status as the third most common cause of cancer related death for individuals between ages 20 and 39, the aetiology of gliomas remains unknown. This paper aims to review the latest information regarding the 2016 World Health Organization (WHO) 4th edition classifications of gliomas, their malignant effects, and disparities within these classifications, as well as identify areas for further research. These suggestions for future inquiry may contribute to a better understanding of the pathology of these cancers enabling improvement in prevention, screening, and treatment. Full article
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