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Med. Sci., Volume 6, Issue 3 (September 2018)

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Cover Story (view full-size image) Gut microbiota colonization during the first months of life is a complex and essential process that [...] Read more.
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Open AccessArticle Cardiac Magnetic Resonance Imaging (MRI) Findings in Arrhythmogenic Right Ventricular Dysplasia (ARVD) Compared with Echocardiography
Med. Sci. 2018, 6(3), 80; https://doi.org/10.3390/medsci6030080 (registering DOI)
Received: 6 July 2018 / Revised: 31 August 2018 / Accepted: 10 September 2018 / Published: 19 September 2018
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Abstract
Arrhythmogenic right ventricular dysplasia (ARVD) is an abnormality in the right side of the heart that may lead to sudden death. The study aims to compare cardiac MRI (magnetic resonance imaging findings) with echocardiography in patients with ARVD. For the cross-sectional study, patients
[...] Read more.
Arrhythmogenic right ventricular dysplasia (ARVD) is an abnormality in the right side of the heart that may lead to sudden death. The study aims to compare cardiac MRI (magnetic resonance imaging findings) with echocardiography in patients with ARVD. For the cross-sectional study, patients with ARVD that were diagnosed using Task Force criteria were included, and their cardiac MRI findings were evaluated. Additionally, the right ventricle was divided into three levels—basal, middle, and apical—and each of them was also subdivided into three secondary segments. Gadolinium enhancement was evaluated in each segment. Overall, 39 patients were studied. Thirty-one patients (81%) were men. The average age of female and male patients was 37.8 ± 4.6 and 32.48 ± 5.8, respectively. The average ejection fraction found was 43 ± 9.4 and 42.8 ± 8.5% by MRI and echocardiography, respectively. Additionally, 46 and 35.8% of the patients had hypokinesia in the right ventricle, found based on MRI and echocardiography, respectively. The right ventricular aneurysm was found in 20.5 and 5.1% of patients based on MRI and echocardiography, respectively. The cardiac MRI managed to diagnose some cases which echocardiography was not able to detect. Thus, MRI plays an important role in presenting diagnostic data for the management of patients with ARVD and also making the diagnosis in suspicious patients definitive. Full article
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Open AccessFeature PaperReview Gut–Liver Axis: How Do Gut Bacteria Influence the Liver?
Med. Sci. 2018, 6(3), 79; https://doi.org/10.3390/medsci6030079
Received: 17 July 2018 / Revised: 9 September 2018 / Accepted: 10 September 2018 / Published: 17 September 2018
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Abstract
Chronic liver diseases are a major cause of morbidity and mortality worldwide. Recently, gut dysbiosis was identified as an important factor in the pathogenesis of liver diseases. The relationship between gut microbiota and the liver is still not well understood; however, dysfunction of
[...] Read more.
Chronic liver diseases are a major cause of morbidity and mortality worldwide. Recently, gut dysbiosis was identified as an important factor in the pathogenesis of liver diseases. The relationship between gut microbiota and the liver is still not well understood; however, dysfunction of the gut mucosal barrier (“leaky gut”) and increased bacterial translocation into the liver via the gut–liver axis probably play crucial roles in liver disease development and progression. The liver is an important immunological organ, and, after exposure to gut-derived bacteria via portal circulation, it responds with activation of the innate and adaptive immune system, leading to hepatic injury. A better understanding of the pathophysiological links among gut dysbiosis, the integrity of the gut barrier, and the hepatic immune response to gut-derived factors is essential for the development of new therapies to treat chronic liver diseases. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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Open AccessReview Apolipoprotein E Epsilon 4 Genotype, Mild Traumatic Brain Injury, and the Development of Chronic Traumatic Encephalopathy
Med. Sci. 2018, 6(3), 78; https://doi.org/10.3390/medsci6030078
Received: 25 August 2018 / Revised: 4 September 2018 / Accepted: 12 September 2018 / Published: 14 September 2018
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Abstract
The annual incidence of mild traumatic brain injury (MTBI) is 3.8 million in the USA with 10–15% experiencing persistent morbidity beyond one year. Chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by accumulation of hyperphosphorylated tau, can occur with repetitive MTBI. Risk factors
[...] Read more.
The annual incidence of mild traumatic brain injury (MTBI) is 3.8 million in the USA with 10–15% experiencing persistent morbidity beyond one year. Chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by accumulation of hyperphosphorylated tau, can occur with repetitive MTBI. Risk factors for CTE are challenging to identify because injury mechanisms of MTBI are heterogeneous, clinical manifestations and management vary, and CTE is a postmortem diagnosis, making prospective studies difficult. There is growing interest in the genetic influence on head trauma and development of CTE. Apolipoprotein epsilon 4 (APOE-ε4) associates with many neurologic diseases, and consensus on the ε4 allele as a risk factor is lacking. This review investigates the influence of APOE-ε4 on MTBI and CTE. A comprehensive PubMed literature search (1966 to 12 June 2018) identified 24 unique reports on the topic (19 MTBI studies: 8 athletic, 5 military, 6 population-based; 5 CTE studies: 4 athletic and military, 1 leucotomy group). APOE-ε4 genotype is found to associate with outcomes in 4/8 athletic reports, 3/5 military reports, and 5/6 population-based reports following MTBI. Evidence on the association between APOE-ε4 and CTE from case series is equivocal. Refining modalities to aid CTE diagnosis in larger samples is needed in MTBI. Full article
(This article belongs to the Special Issue Traumatic Brain Injury)
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Open AccessReview It Takes a Village: Multidisciplinary Approach to Screening and Prevention of Pediatric Sleep Issues
Med. Sci. 2018, 6(3), 77; https://doi.org/10.3390/medsci6030077
Received: 31 July 2018 / Revised: 29 August 2018 / Accepted: 10 September 2018 / Published: 14 September 2018
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Abstract
Sleep is essential to human development. Poor sleep can have significant effects on cognition, learning and memory, physical and behavioral health, and social-emotional well-being. This paper highlights the prevalence of common pediatric sleep problems and posits that a multidisciplinary approach to the assessment
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Sleep is essential to human development. Poor sleep can have significant effects on cognition, learning and memory, physical and behavioral health, and social-emotional well-being. This paper highlights the prevalence of common pediatric sleep problems and posits that a multidisciplinary approach to the assessment and intervention of sleep problems is ideal. Primary care providers are often the first professionals to discuss sleep issues with youth and families. However, dentists, otolaryngologists, childcare providers, school personnel, and behavioral health providers have a vital role in screening and prevention, providing intervention, and monitoring the progress of daily functioning. The strengths of this approach include better provider-to-provider and provider-to-family communication, streamlined assessment and intervention, earlier identification of sleep issues with more efficient referral, and longer-term monitoring of progress and impact on daily functioning. Barriers to this approach include difficulty initiating and maintaining collaboration among providers, limited provider time to obtain the necessary patient permission to collaborate among all multidisciplinary providers, lack of financial support for consultation and collaboration outside of seeing patients face-to-face, geographic location, and limited resources within communities. Research investigating the utility of this model and the overall impact on pediatric patient sleep issues is warranted and strongly encouraged. Full article
(This article belongs to the Special Issue Updates in Pediatric Sleep and Child Psychiatry)
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Open AccessReview Relationship between Sleep and Psychosis in the Pediatric Population: A Brief Review
Med. Sci. 2018, 6(3), 76; https://doi.org/10.3390/medsci6030076
Received: 19 August 2018 / Revised: 9 September 2018 / Accepted: 10 September 2018 / Published: 14 September 2018
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Abstract
Sleep disorders are common in several psychiatric disorders, including schizophrenia. In the pediatric population, the relationship between sleep and psychosis is not completely understood due to limited research studies investigating the link. Insomnia is noted to be a predictor of psychosis, especially in
[...] Read more.
Sleep disorders are common in several psychiatric disorders, including schizophrenia. In the pediatric population, the relationship between sleep and psychosis is not completely understood due to limited research studies investigating the link. Insomnia is noted to be a predictor of psychosis, especially in ultrahigh risk adolescents. Sleep difficulties are also associated with a two to three-fold increase in paranoid thinking. Biological factors, such as decrease in thalamic volume, have been observed in children with schizophrenia and ultrahigh risk adolescents with associated sleep impairment. Objective studies have indicated possible actigraphy base measures to be the predictor of psychosis after a one year follow-up. The studies using polysomnography have rare and inconsistent results. In this brief review, we provide an overview of existing literature. We also posit that future research will be beneficial in understanding the initiation, course and progression of sleep disturbance in the high risk pediatric population with the goal of implementing interventions to alter the development of psychosis. Full article
(This article belongs to the Special Issue Updates in Pediatric Sleep and Child Psychiatry)
Open AccessArticle Classification of Tidal Breathing Airflow Profiles Using Statistical Hierarchal Cluster Analysis in Idiopathic Pulmonary Fibrosis
Med. Sci. 2018, 6(3), 75; https://doi.org/10.3390/medsci6030075
Received: 27 August 2018 / Accepted: 3 September 2018 / Published: 12 September 2018
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Abstract
In idiopathic pulmonary fibrosis (IPF) breathing pattern changes with disease progress. This study aims to determine if unsupervised hierarchal cluster analysis (HCA) can be used to define airflow profile differences in people with and without IPF. This was tested using 31 patients with
[...] Read more.
In idiopathic pulmonary fibrosis (IPF) breathing pattern changes with disease progress. This study aims to determine if unsupervised hierarchal cluster analysis (HCA) can be used to define airflow profile differences in people with and without IPF. This was tested using 31 patients with IPF and 17 matched healthy controls, all of whom had their lung function assessed using spirometry and carbon monoxide CO transfer. A resting tidal breathing (RTB) trace of two minutes duration was collected at the same time. A Euclidian distance technique was used to perform HCA on the airflow data. Four distinct clusters were found, with the majority (18 of 21, 86%) of the severest IPF participants (Stage 2 and 3) being in two clusters. The participants in these clusters exhibited a distinct minute ventilation (p < 0.05), compared to the other two clusters. The respiratory drive was greatest in Cluster 1, which contained many of the IPF participants. Unstructured HCA was successful in recognising different airflow profiles, clustering according to differences in flow rather than time. HCA showed that there is an overlap in tidal airflow profiles between healthy RTB and those with IPF. The further application of HCA in recognising other respiratory disease is discussed. Full article
(This article belongs to the Section Pneumology and Respiratory Diseases)
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Open AccessReview Shall We Focus on the Eosinophil to Guide Treatment with Systemic Corticosteroids during Acute Exacerbations of COPD?: PRO
Med. Sci. 2018, 6(3), 74; https://doi.org/10.3390/medsci6030074
Received: 12 July 2018 / Revised: 2 September 2018 / Accepted: 4 September 2018 / Published: 11 September 2018
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Abstract
In an era of precision medicine, it seems regressive that we do not use stratified approaches to direct treatment of oral corticosteroids during an exacerbation of chronic obstructive pulmonary disease (COPD). This is despite evidence suggesting that 40% of COPD patients have eosinophilic
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In an era of precision medicine, it seems regressive that we do not use stratified approaches to direct treatment of oral corticosteroids during an exacerbation of chronic obstructive pulmonary disease (COPD). This is despite evidence suggesting that 40% of COPD patients have eosinophilic inflammation and this is an indicator of corticosteroid response. Treatments with oral corticosteroids are not always effective and not without harm, with significant and increased risk of hyperglycemia, sepsis, and fractures. Eosinophils are innate immune cells with an incompletely understood role in the pathology of airway disease. They are detected at increased levels in some patients and can be measured using non-invasive methods during states of exacerbation and stable periods. Despite the eosinophil having an unknown mechanism in COPD, it has been shown to be a marker of length of stay in severe hospitalized exacerbations, a predictor of risk of future exacerbation and exacerbation type. Although limited, promising data has come from one prospective clinical trial investigating the eosinophil as a biomarker to direct systemic corticosteroid treatment. This identified that there were statistically significant and clinically worsened symptoms in patients with low eosinophil levels who were prescribed prednisolone, demonstrating the potential utility of the eosinophil. In an era of precision medicine our patients’ needs are best served by accurate diagnosis, correct identification of maximal treatment response and the abolition of harm. The peripheral blood eosinophil count could be used towards reaching these aims. Full article
(This article belongs to the Special Issue COPD Exacerbations)
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Open AccessReview Diagnosis of Idiopathic Pulmonary Fibrosis: Differential Diagnosis
Med. Sci. 2018, 6(3), 73; https://doi.org/10.3390/medsci6030073
Received: 5 July 2018 / Revised: 26 July 2018 / Accepted: 30 July 2018 / Published: 4 September 2018
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Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease of unknown origin with a characteristic imaging and histologic pattern called usual interstitial pneumonia (UIP). The diagnosis of IPF is a complex procedure that requires the support of various specialists,
[...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease of unknown origin with a characteristic imaging and histologic pattern called usual interstitial pneumonia (UIP). The diagnosis of IPF is a complex procedure that requires the support of various specialists, who must integrate clinical, radiological, and histological data. The multidisciplinary team (MDT) has become the new gold standard to diagnose and manage the disease, increasing the accuracy and agreement of the diagnosis between different centers. It is mandatory to exclude nonspecific interstitial pneumonia or other diseases that can cause the UIP pattern, particularly drugs or exposure diseases, including chronic hypersensitivity pneumonitis or systemic autoimmune disease. The role of the MDT is also to decide who could need a biopsy or to review patient diagnoses at regular intervals in those with additional information or unexpected evolution. This review provides updated information to achieve a proper IPF diagnosis. Full article
(This article belongs to the Special Issue Idiopathic Pulmonary Fibrosis)
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Open AccessReview Insomnia in Adolescence
Med. Sci. 2018, 6(3), 72; https://doi.org/10.3390/medsci6030072
Received: 3 August 2018 / Revised: 28 August 2018 / Accepted: 29 August 2018 / Published: 1 September 2018
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Abstract
Adolescent insomnia is a common condition that negatively impacts a developing young adult’s mental and physical health. While the treatment of adult insomnia has been standardized, the treatment of pediatric insomnia is very practitioner-dependent and few large-scale studies are available to determine a
[...] Read more.
Adolescent insomnia is a common condition that negatively impacts a developing young adult’s mental and physical health. While the treatment of adult insomnia has been standardized, the treatment of pediatric insomnia is very practitioner-dependent and few large-scale studies are available to determine a standard recommended practice. There is great hope that as the adolescent medicine and sleep medicine fields flourish, larger cohort analyses will be performed to determine the prevalence and precipitating factors of adolescent insomnia, allowing for standardized treatment recommendations and systematic efforts to make these recommendations available to all adolescents. Full article
(This article belongs to the Special Issue Updates in Pediatric Sleep and Child Psychiatry)
Open AccessReview Comorbidities and Complications in Idiopathic Pulmonary Fibrosis
Med. Sci. 2018, 6(3), 71; https://doi.org/10.3390/medsci6030071
Received: 23 July 2018 / Revised: 14 August 2018 / Accepted: 20 August 2018 / Published: 30 August 2018
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Abstract
Though idiopathic pulmonary fibrosis (IPF) is characterized by single-organ involvement, many comorbid conditions occur within other organ systems. Patients with IPF may present during evolution different complications and comorbidities that influence the prognosis and modify the natural course of their disease. In this
[...] Read more.
Though idiopathic pulmonary fibrosis (IPF) is characterized by single-organ involvement, many comorbid conditions occur within other organ systems. Patients with IPF may present during evolution different complications and comorbidities that influence the prognosis and modify the natural course of their disease. In this chapter, we highlight common comorbid conditions encountered in IPF, discuss disease-specific diagnostic modalities, and review the current treatment data for several key comorbidities. The diagnosis and treatment of these comorbidities is a challenge for the pulmonologist specialized in interstitial lung diseases (ILDs). We will focus on pulmonary emphysema, lung cancer, gastroesophageal reflux, pulmonary hypertension, obstructive sleep apnea (sleep disorders), and acute exacerbation of IPF. Full article
(This article belongs to the Special Issue Idiopathic Pulmonary Fibrosis)
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Open AccessReview Role of Transglutaminase 2 in Migration of Tumor Cells and How Mouse Models Fit
Med. Sci. 2018, 6(3), 70; https://doi.org/10.3390/medsci6030070
Received: 27 July 2018 / Revised: 20 August 2018 / Accepted: 27 August 2018 / Published: 30 August 2018
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Abstract
A search for the “magic bullet”, a molecule, the targeting abilities of which could stop the migration of tumor cells, is currently underway, but remains in the early stages. There are still many unknowns regarding the cell migration. The main approach is the
[...] Read more.
A search for the “magic bullet”, a molecule, the targeting abilities of which could stop the migration of tumor cells, is currently underway, but remains in the early stages. There are still many unknowns regarding the cell migration. The main approach is the employment of mouse models, that are sources of valuable information, but still cannot answer all of the questions. One of the molecules of interest is Transglutaminase 2 (TG2). It is a well-described molecule involved in numerous pathways and elevated in metastatic tumors. The question remains whether mice and humans can give the same answer considering TG2. Full article
(This article belongs to the Special Issue Transglutaminases in Health and Disease)
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Open AccessReview The Gut Microbiome in Multiple Sclerosis: A Potential Therapeutic Avenue
Med. Sci. 2018, 6(3), 69; https://doi.org/10.3390/medsci6030069
Received: 14 June 2018 / Revised: 27 July 2018 / Accepted: 22 August 2018 / Published: 24 August 2018
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Abstract
Recently, there has been a substantial increase in the number of studies focused upon connecting the gut microbiome with cases of central nervous system (CNS) autoimmunity. Multiple sclerosis (MS) is a neurodegenerative autoimmune disorder of the CNS. Recent experimental and clinical evidence suggests
[...] Read more.
Recently, there has been a substantial increase in the number of studies focused upon connecting the gut microbiome with cases of central nervous system (CNS) autoimmunity. Multiple sclerosis (MS) is a neurodegenerative autoimmune disorder of the CNS. Recent experimental and clinical evidence suggests the presence of microbial imbalances in the gut of MS sufferers. The gut microbiome is defined as the summation of all the microbial entities as well as their genes, proteins, and metabolic products in a given space and time. Studies show the MS gut microbiome as having general alterations in specific taxa, some associated with the promotion of inflammatory cytokines and overall inflammation. In conjunction with these findings, experimental models of the disease have reported that T regulatory (Treg) cells have deficits in their function as a result of the aberrant gut microbiota composition. The findings suggest that the interactions between the host and the microbiota are reciprocal, although more extensive work is required to confirm this. Moreover, evidence indicates that changes in microbiota composition may result in imbalances that could result in disease, with the gut as a potential novel therapeutic avenue. By understanding the biological effects of aberrant gut microbiome composition, it is possible to contemplate current therapeutic options and their efficacy. Ultimately, more research is necessary in this field, but targeting the gut microbiota may lead to the development of novel therapeutic strategies. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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Open AccessReview Lung Transplantation in Idiopathic Pulmonary Fibrosis
Med. Sci. 2018, 6(3), 68; https://doi.org/10.3390/medsci6030068
Received: 19 June 2018 / Revised: 9 August 2018 / Accepted: 10 August 2018 / Published: 23 August 2018
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Abstract
Despite the advances in recent years in the treatment of idiopathic pulmonary fibrosis (IPF), it continues to be a progressive disease with poor prognosis. In selected patients, lung transplantation may be a treatment option, with optimal results in survival and quality of life.
[...] Read more.
Despite the advances in recent years in the treatment of idiopathic pulmonary fibrosis (IPF), it continues to be a progressive disease with poor prognosis. In selected patients, lung transplantation may be a treatment option, with optimal results in survival and quality of life. Currently, pulmonary fibrosis is the main cause of lung transplantation. However, mortality on the waiting list of these patients is high, since many patients are referred to the transplant units with advanced disease. There is not a parameter that can predict the survival of a specific patient. Different variables are to be considered in order to decide the right time to send them to a transplant unit. It is also very difficult to decide when to include these patients on the waiting list. Every patient diagnosed with IPF, without contraindications for surgery, should be referred early to a transplant unit for assessment. A uni or bilateral transplantation will be decided based on the characteristics of the patient and the experience of each center. The post-transplant survival of recipients with IPF is lower than that observed in other diseases, such as cystic fibrosis or chronic obstructive pulmonary disease as a consequence of their older age and the frequent presence of associated comorbidity. Post-transplant follow-up must be tight in order to assure optimal level of immunosuppressive treatment, detect complications associated with it, and avoid graft rejection. The main cause of long-term mortality is late graft dysfunction as a consequence of chronic rejection. Other complications, such as infections and tumors, must be considered. Full article
(This article belongs to the Special Issue Idiopathic Pulmonary Fibrosis)
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Open AccessBrief Report Improving Blood Transfusion Practices in a Community Hospital Setting: Our Experience with Real-Time Clinical Decision Support
Med. Sci. 2018, 6(3), 67; https://doi.org/10.3390/medsci6030067
Received: 7 August 2018 / Revised: 13 August 2018 / Accepted: 17 August 2018 / Published: 22 August 2018
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Abstract
There is good evidence that 50% or more of red blood cell (RBC) transfusions are unnecessary. To curtail inappropriate RBC transfusions at our hospital, real-time clinical decision support was implemented in our electronic medical record (EMR) that alerts clinicians to the patient’s most
[...] Read more.
There is good evidence that 50% or more of red blood cell (RBC) transfusions are unnecessary. To curtail inappropriate RBC transfusions at our hospital, real-time clinical decision support was implemented in our electronic medical record (EMR) that alerts clinicians to the patient’s most recent pretransfusion hemoglobin value upon order entry and provides Best Practice Advisory. This is a soft pop-up alert which is activated when the hemoglobin exceeds 7 g/dL. The ordering clinician can either honor (by cancelling the order) or override the alert. We studied the impact of the alert on blood utilization during a 3-month period (November 2016 to January 2017). For patients who were transfused despite the alert, a retrospective review of the medical chart was performed to determine whether or not the transfusion was clinically indicated. During the study period, 178 of the 895 RBC transfusion orders (20%) triggered the alert. After excluding duplicates, 144 orders were included in our analysis. Most of these orders (124/144, 86%) were carried out despite the alert. According to our chart review, 48% of the alert transfusions could be considered inappropriate, with hemodynamically stable, asymptomatic anemia being the leading indication. Of clinical services, orthopedic surgery had the highest rate of overriding the alert with no clinical justification (70%). The number of RBC transfusions dropped from 313.5 units per month (preintervention period) to 293.2 units per month (postintervention period)—a 6.5% decrease. Real-time clinical decision support may reduce the number of inappropriate RBC transfusions in a community hospital setting, though in our study, the decrease in blood utilization (6.5%) did not reach statistical significance. Full article
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Open AccessPerspective The Future of Health Is Self-Production and Co-Creation Based on Apomediative Decision Support
Med. Sci. 2018, 6(3), 66; https://doi.org/10.3390/medsci6030066
Received: 18 July 2018 / Revised: 11 August 2018 / Accepted: 20 August 2018 / Published: 22 August 2018
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Abstract
Cultural changes are needed in medicine if the benefits of technological advances are to benefit healthcare users. The Digital Health Manifesto of ‘medical futurist’ doctor Bertalan Meskó and ‘e-patient’ Dave deBronkart, The Patient Will See You Now by Eric Topol and The Patient
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Cultural changes are needed in medicine if the benefits of technological advances are to benefit healthcare users. The Digital Health Manifesto of ‘medical futurist’ doctor Bertalan Meskó and ‘e-patient’ Dave deBronkart, The Patient Will See You Now by Eric Topol and The Patient as CEO by Robin Farmanfarmaian, are among the proliferating warnings of the approaching paradigm shift in medicine, resulting, above all, from technological advances that gives users independent access to exponentially increasing amounts of information about themselves. We question their messages only in suggesting they do not sufficiently shift the focus from ‘patient’ to ‘person’ and consequently fail to recognise the need for the credible, efficient, ethical and independent decision support that can ensure the ‘democratisation of knowledge’ is person empowering, not overpowering. Such decision support can ensure the ‘democratisation of decision,’ leading to higher quality decisions and fully-informed and preference-based consent to health provider actions. The coming paradigm will therefore be characterised by apomediative (‘direct-to-consumer’) decision support tools, engaged with by the person in the community to help them make health production decisions for themselves (including whether to consult a healthcare professional or provider), as well as intermediative (‘direct-from-clinician’) tools, delivered by a health professional in a ‘shared decision making’ or ‘co-creation of health’ process. This vision paper elaborates on the implementation of these preference-sensitive decision support tools through the technique of Multi-Criteria Decision Analysis. Full article
(This article belongs to the Special Issue Recent Advances in Health Improvement Strategies)
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Open AccessArticle Polyamine Biosynthetic Pathway as a Drug Target for Osteosarcoma Therapy
Med. Sci. 2018, 6(3), 65; https://doi.org/10.3390/medsci6030065
Received: 13 July 2018 / Revised: 9 August 2018 / Accepted: 13 August 2018 / Published: 16 August 2018
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Abstract
Osteosarcoma (OS) is the most common bone tumor in children. Polyamines (PAs) are ubiquitous cations involved in many cell processes including tumor development, invasion and metastasis. In other pediatric cancer models, inhibition of the PA biosynthesis pathway with ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine
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Osteosarcoma (OS) is the most common bone tumor in children. Polyamines (PAs) are ubiquitous cations involved in many cell processes including tumor development, invasion and metastasis. In other pediatric cancer models, inhibition of the PA biosynthesis pathway with ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine (DFMO) results in decreased cell proliferation and differentiation. In OS, the PA pathway has not been evaluated. DFMO is an attractive, orally administered drug, is well tolerated, can be given for prolonged periods, and is already used in pediatric patients. Three OS cell lines were used to study the cellular effects of PA inhibition with DFMO: MG-63, U-2 OS and Saos-2. Effects on proliferation were analyzed by cell count, flow cytometry-based cell cycle analysis and RealTime-Glo™ MT Cell Viability assays. Intracellular PA levels were measured with high-performance liquid chromatography (HPLC). Western blot analysis was used to evaluate cell differentiation. DFMO exposure resulted in significantly decreased cell proliferation in all cell lines. After treatment, intracellular spermidine levels were drastically decreased. Cell cycle arrest at G2/M was observed in U-2 OS and Saos-2. Cell differentiation was most prominent in MG-63 and U-2 OS as determined by increases in the terminal differentiation markers osteopontin and collagen 1a1. Cell proliferation continued to be suppressed for several days after removal of DFMO. Based on our findings, DFMO is a promising new adjunct to current osteosarcoma therapy in patients at high risk of relapse, such as those with poor necrosis at resection or those with metastatic or recurrent osteosarcoma. It is a well-tolerated oral drug that is currently in phase II clinical trials in pediatric neuroblastoma patients as a maintenance therapy. The same type of regimen may also improve outcomes in osteosarcoma patients in whom there have been essentially no medical advances in the last 30 years. Full article
(This article belongs to the Special Issue Polyamine Metabolism in Disease and Polyamine-Targeted Therapies)
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Open AccessReview Cell Therapy in Idiopathic Pulmonary Fibrosis
Med. Sci. 2018, 6(3), 64; https://doi.org/10.3390/medsci6030064
Received: 12 June 2018 / Revised: 2 August 2018 / Accepted: 8 August 2018 / Published: 13 August 2018
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Abstract
Idiopathic pulmonary fibrosis is a fatal disease with no effective or curative treatment options. In recent decades, cell-based therapies using stem cells or lung progenitor cells to regenerate lung tissue have experienced rapid growth in both preclinical animal models and translational clinical studies.
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Idiopathic pulmonary fibrosis is a fatal disease with no effective or curative treatment options. In recent decades, cell-based therapies using stem cells or lung progenitor cells to regenerate lung tissue have experienced rapid growth in both preclinical animal models and translational clinical studies. In this review, the current knowledge of these cell therapies is summarized. Although further investigations are required, these studies indicate that cell therapies are a promising therapeutic approach for the treatment of idiopathic pulmonary fibrosis. Full article
(This article belongs to the Special Issue Idiopathic Pulmonary Fibrosis)
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Open AccessReview Care Bundles after Discharging Patients with Chronic Obstructive Pulmonary Disease Exacerbation from the Emergency Department
Med. Sci. 2018, 6(3), 63; https://doi.org/10.3390/medsci6030063
Received: 20 June 2018 / Revised: 2 August 2018 / Accepted: 6 August 2018 / Published: 7 August 2018
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Abstract
Chronic obstructive pulmonary disease (COPD) is the second leading cause of emergency department (ED) admissions to hospital, and nearly a third of patients with acute exacerbation (AE) of COPD are re-admitted to hospital within 28 days after discharge. It has been suggested that
[...] Read more.
Chronic obstructive pulmonary disease (COPD) is the second leading cause of emergency department (ED) admissions to hospital, and nearly a third of patients with acute exacerbation (AE) of COPD are re-admitted to hospital within 28 days after discharge. It has been suggested that nearly a third of COPD admissions could be avoided through the implementation of evidence-based care interventions. A COPD discharge bundle is a set of evidence-based practices, aimed at improving patient outcomes after discharge from AE COPD; body of evidence supports the usefulness of discharge care bundles after AE of COPD, although there is a lack of consensus of what interventions should be implemented. On the other hand, the implementation of those interventions also involves different challenges. Important care gaps remain regarding discharge care bundles for patients with acute exacerbation of COPD discharged from EDs There is an urgent need for investigations to guide future implementation of care bundles for those patients discharged from EDs. Full article
(This article belongs to the Special Issue COPD Exacerbations)
Open AccessArticle Should Mumps Be Higher Up on the Public Health Agenda in India? A Concern for Global Health Security
Med. Sci. 2018, 6(3), 62; https://doi.org/10.3390/medsci6030062
Received: 21 June 2018 / Revised: 1 August 2018 / Accepted: 1 August 2018 / Published: 7 August 2018
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Abstract
Mumps is a public health problem on a global scale caused by mumps virus, a member of family paramyxoviridae. An effective form of vaccination exists and is incorporated into routine immunization schedules in over 100 countries, usually in the form of the Measles,
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Mumps is a public health problem on a global scale caused by mumps virus, a member of family paramyxoviridae. An effective form of vaccination exists and is incorporated into routine immunization schedules in over 100 countries, usually in the form of the Measles, Mumps and Rubella (MMR) vaccine. This is not the case in India, as mumps is not viewed as a significant enough public health problem by the government to warrant such an intervention. This original research paper discusses about outbreaks of mumps in Kashmir, India and aims to add to the body of literature to support the routine immunization with the mumps vaccine. From July to September 2017, there were 15 outbreaks and 260 cases of mumps recorded in the region by the Integrated Disease Surveillance Programme (IDSP). We conclude that the Indian Government should include the MMR vaccination in the Universal Immunization Programme. This would result in clinical and economic benefits by reducing outbreaks and associated morbidity of mumps, in addition to tackling the recognized morbidity and mortality of rubella and measles. To support the global health security, there is a great need to strengthen surveillance, adhere to the World Health Organization’s International Health Regulations (IHRs), and pay attention to emerging and re-emerging infectious agents, including paramyxovirus group. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
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Open AccessReview Contribution of Inhibitor of Differentiation and Estrogenic Endocrine Disruptors to Neurocognitive Disorders
Med. Sci. 2018, 6(3), 61; https://doi.org/10.3390/medsci6030061
Received: 7 July 2018 / Revised: 27 July 2018 / Accepted: 30 July 2018 / Published: 3 August 2018
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Abstract
The devastating growth in the worldwide frequency of neurocognitive disorders and its allied difficulties, such as decline in memory, spatial competency, and ability to focus, poses a significant psychological public health problem. Inhibitor of differentiation (ID) proteins are members of a family of
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The devastating growth in the worldwide frequency of neurocognitive disorders and its allied difficulties, such as decline in memory, spatial competency, and ability to focus, poses a significant psychological public health problem. Inhibitor of differentiation (ID) proteins are members of a family of helix-loop-helix (HLH) transcription factors. ID proteins have been demonstrated to be involved in neurodevelopmental and depressive diseases and, thus, may influence neurocognitive deficiencies due to environmental exposure. Previously, it has been demonstrated that environmental factors, such as estrogenic endocrine disruptors (EEDs), have played an essential role in the influence of various neurocognitive disorders such as Alzheimer’s, dementia, and Parkinson’s disease. Based on this increasing number of reports, we consider the impact of these environmental pollutants on ID proteins. Better understanding of how these ID proteins by which EED exposure can affect neurocognitive disorders in populations will prospectively deliver valuable information in the impediment and regulation of these diseases linked with environmental factor exposure. Full article
(This article belongs to the collection Advances in the Pathogenesis of Neurodegenerative Diseases)
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Open AccessArticle Occurrence of Surgical Site Infections at a Tertiary Healthcare Facility in Abuja, Nigeria: A Prospective Observational Study
Med. Sci. 2018, 6(3), 60; https://doi.org/10.3390/medsci6030060
Received: 11 June 2018 / Revised: 20 July 2018 / Accepted: 23 July 2018 / Published: 30 July 2018
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Abstract
Surgical site infection (SSI) is one of the most frequent complications of surgical interventions. Several factors have been identified as major determinants of occurrence of SSIs. The present study determined the occurrence and possible risk factors associated with SSIs at a tertiary healthcare
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Surgical site infection (SSI) is one of the most frequent complications of surgical interventions. Several factors have been identified as major determinants of occurrence of SSIs. The present study determined the occurrence and possible risk factors associated with SSIs at a tertiary healthcare facility in Abuja, Nigeria. All patients scheduled for operation in the hospital during the study period and who consented to participate willingly in the study were observed prospectively for the occurrence of SSI based on criteria stipulated by the United States Centre for Disease Control and Prevention (CDC). Data on sociodemographic characteristics, lifestyle, surgical procedure and co-morbidity were collected into a pre-tested data collection tool and analysed using IBM SPSS Statistics software v.24. Predictors of SSIs were identified using multivariate logistic regression model and p-value less than 0.05 was considered statistically significant. Of the 127 surgical patients that met the inclusion criteria comprising 65 (51.2%) females and 62 (48.8%) males between 1 and 83 years with mean age of 25.64 ± 1.66 years, 35 (27.56%; 95% Confidence Interval (CI): 0.205–0.360) developed SSIs. Prolonged post-operative hospital stays (p < 0.05), class of wound (p < 0.0001) and some comorbid conditions were found to be significantly associated with higher SSI rate. The SSI rate was highest among patients that had Kirschner-wire insertion (75.0%), followed by an unexpectedly high infection rate among patients that had mastectomy (42.9%), while lower percentages (33.3%) were recorded among patients that had exploratory laparotomy and appendicectomy. The overall magnitude of SSIs in this facility is high (27.6%; 95% CI: 0.205–0.360). Several factors were found to be independent predictors of occurrence of SSI. The findings thus highlight the need for improved surveillance of SSIs and review of infection control policies of the hospital. Full article
(This article belongs to the Section Immunology and Infectious Diseases)
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Open AccessReview Comorbidities, Complications and Non-Pharmacologic Treatment in Idiopathic Pulmonary Fibrosis
Med. Sci. 2018, 6(3), 59; https://doi.org/10.3390/medsci6030059
Received: 11 June 2018 / Revised: 11 July 2018 / Accepted: 17 July 2018 / Published: 24 July 2018
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Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease. The treatment is challenging and nowadays a comprehensive approach based not only in pharmacological strategies is necessary. Identification and control of comorbidities, non-pharmacological treatment, prevention and management of exacerbations as well as
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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease. The treatment is challenging and nowadays a comprehensive approach based not only in pharmacological strategies is necessary. Identification and control of comorbidities, non-pharmacological treatment, prevention and management of exacerbations as well as other areas of care (social, psychological) are fundamental for a holistic management of IPF. Gastroesophageal reflux, pulmonary hypertension, obstructive sleep apnea, combined with emphysema, lung cancer and cardiovascular involvement are the main comorbidities associated with IPF. Non-pharmacological treatment includes the use of oxygen in patients with rest or nocturnal hypoxemia and other support therapies such as non-invasive ventilation or even a high-flow nasal cannula to improve dyspnea. In some patients, lung transplant should be considered as this enhances survival. Pulmonary rehabilitation can add benefits in outcomes such control of dyspnea, exercise capacity distance and, overall, improve the quality of life; therefore it should be considered in patients with IPF. Also, multidisciplinary palliative care programs could help with symptom control and psychological support, with the aim of maintaining quality of life during the whole process of the disease. This review intends to provide clear information to help those involved in IPF follow up to improve patients’ daily care. Full article
(This article belongs to the Special Issue Idiopathic Pulmonary Fibrosis)
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Open AccessReview Causes of Pulmonary Fibrosis in the Elderly
Med. Sci. 2018, 6(3), 58; https://doi.org/10.3390/medsci6030058
Received: 29 May 2018 / Revised: 16 July 2018 / Accepted: 16 July 2018 / Published: 24 July 2018
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Abstract
Idiopathic pulmonary fibrosis (IPF) is the most common and most lethal type of idiopathic interstitial pneumonia. It is a chronic, aging-associated lung disease characterized by fibrotic foci and inflammatory infiltrates, with no cure and very limited therapeutic options. Although its etiology is unknown,
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Idiopathic pulmonary fibrosis (IPF) is the most common and most lethal type of idiopathic interstitial pneumonia. It is a chronic, aging-associated lung disease characterized by fibrotic foci and inflammatory infiltrates, with no cure and very limited therapeutic options. Although its etiology is unknown, several pathogenic pathways have been described that could explain this process, involving aging, environmental factors, genomic instability, loss of proteostasis, telomere attrition, epigenetic changes, mitochondrial dysfunction, cell senescence, and altered intercellular communication. One of the main prognostic factors for the development of IPF in broad epidemiological studies is age. The incidence increases with age, making this a disease that predominantly affects the elderly population, being exceptional under 45 years of age. However, the degree to which each of these mechanisms is involved in the etiology of the uncontrolled fibrogenesis that defines IPF is still unknown. Clarifying these questions is crucial to the development of points of intervention in the pathogenesis of the disease. This review briefly summarizes what is known about each possible etiological factor, and the questions that most urgently need to be addressed. Full article
(This article belongs to the Special Issue Idiopathic Pulmonary Fibrosis)
Open AccessArticle The Use of Biochemical and Biophysical Markers in Early Screening for Preeclampsia in Mongolia
Med. Sci. 2018, 6(3), 57; https://doi.org/10.3390/medsci6030057
Received: 1 June 2018 / Revised: 11 July 2018 / Accepted: 13 July 2018 / Published: 20 July 2018
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Abstract
Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality, particularly in developing countries. In Mongolia, preeclampsia and eclampsia have occurred among pregnancy complications at a rate of 25% in recent years. Recent studies in the literature have screened for
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Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality, particularly in developing countries. In Mongolia, preeclampsia and eclampsia have occurred among pregnancy complications at a rate of 25% in recent years. Recent studies in the literature have screened for preeclampsia by combining maternal factors with biomarkers. This study was conducted using prospective cohort research including 393 singleton pregnancies at 11–13+6 weeks. Maternal plasmas pregnancy-associated plasma protein-A (PAPP-A) and maternal serum placental growth factor (PlGF) were measured using Perkin Elmer time-resolved fluoroimmunoassay (DELFIA) kits, and the measurement of mean arterial pressure (MAP) was performed by automated devices and the uterine artery pulsatility index was measured by Doppler ultrasound. In the study population, there were 16.7% showing complicated preeclampsia. The receiver-operating characteristics (ROC) curve analysis showed a sensitivity of 71.21%, and a specificity of 75.54% when the mean arterial pressure cut-off was 89.5 mm; while a sensitivity of 33.36% and specificity of 77.68% were observed when the uterine artery mean pulsatility index (mPI) cut-off was 2.34; a sensitivity of 79.66% and specificity of 44.04% were observed when the PAPP-A cut-off was 529.1 mU/L; and a sensitivity of 74.58% and specificity of 46.6% were observed when the PlGF cut-off was 39.87 pg/mL. The detection rates following the combination of markers with the maternal history were as follows: 62.7% with mean arterial pressure, 69.5–82.9% with two markers 86.5% with three markers and 91.4% with four markers. In conclusion, the mean arterial pressure was highly sensitive and demonstrated its easy usage and cost-effectiveness as a predictive marker for the early screening of preeclampsia from other biomarkers. Full article
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Open AccessFeature PaperReview Gut Microbiota and Mucosal Immunity in the Neonate
Med. Sci. 2018, 6(3), 56; https://doi.org/10.3390/medsci6030056
Received: 8 June 2018 / Revised: 4 July 2018 / Accepted: 12 July 2018 / Published: 17 July 2018
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Abstract
Gut microbiota colonization is a complex, dynamic, and step-wise process that is in constant development during the first years of life. This microbial settlement occurs in parallel with the maturation of the immune system, and alterations during this period, due to environmental and
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Gut microbiota colonization is a complex, dynamic, and step-wise process that is in constant development during the first years of life. This microbial settlement occurs in parallel with the maturation of the immune system, and alterations during this period, due to environmental and host factors, are considered to be potential determinants of health-outcomes later in life. Given that host–microbe interactions are mediated by the immune system response, it is important to understand the close relationship between immunity and the microbiota during birth, lactation, and early infancy. This work summarizes the evidence to date on early gut microbiota colonization, and how it influences the maturation of the infant immune system and health during the first 1000 days of life. This review will also address the influence of perinatal antibiotic intake and the importance of delivery mode and breastfeeding for an appropriate development of gut immunity. Full article
(This article belongs to the Special Issue Therapeutic Potential of the Microbiome)
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Open AccessArticle Relationship between Atherogenic Indices and Carotid Intima-Media Thickness in Prediabetes: A Cross-Sectional Study from Central India
Med. Sci. 2018, 6(3), 55; https://doi.org/10.3390/medsci6030055
Received: 14 June 2018 / Revised: 29 June 2018 / Accepted: 2 July 2018 / Published: 5 July 2018
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Abstract
Prediabetes is the precursor stage of diabetes mellitus and is also considered to be a risk factor for the development of cardiovascular disease. Atherogenic indices have been used for assessment of risk for cardiovascular disease development. To date, there is no data on
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Prediabetes is the precursor stage of diabetes mellitus and is also considered to be a risk factor for the development of cardiovascular disease. Atherogenic indices have been used for assessment of risk for cardiovascular disease development. To date, there is no data on evaluating the relationship between atherogenic indices (cardiac risk ratio (CRR), atherogenic coefficient (AC), and atherogenic index of plasma (AIP)) and carotid intima-media thickness (CIMT) in prediabetes. Hence, we aimed to determine atherogenic indices (CRR, AC, and AIP) and CIMT in prediabetic subjects and then sought to evaluate the relationship between them. A total of 400 human subjects were included in the present study, out of which 200 were prediabetic subjects and 200 were normal healthy control subjects. For each subject, CRR, AC, and AIP were calculated from routine lipid parameters and carotid intima-media thickness was measured as well. Atherogenic indices, that is, CRR, AC, and AIP, were significantly increased in prediabetic subjects as compared to the controls (5.87 ± 0.87 vs. 4.23 ± 0.50, p < 0.001; 4.87 ± 0.87 vs. 3.23 ± 0.50, p < 0.001; and 0.29 ± 0.07 vs. 0.09 ± 0.09, p < 0.001, respectively). Moreover, a significant and positive correlation was observed between CIMT and AIP (r = 0.529, p < 0.01), CRR (r = 0.495, p < 0.01), and AC (r = 0.495, p < 0.01). Prediabetic subjects present abnormalities in atherogenic indices and CIMT, which indicate a greater propensity of prediabetes for the development of cardiovascular disease. Hence, atherogenic indices can be used in addition to routine lipid parameters for the better assessment of subclinical atherosclerosis in prediabetic subjects. Full article
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Open AccessReview Apoptosis: Activation and Inhibition in Health and Disease
Med. Sci. 2018, 6(3), 54; https://doi.org/10.3390/medsci6030054
Received: 12 June 2018 / Revised: 28 June 2018 / Accepted: 29 June 2018 / Published: 4 July 2018
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Abstract
There are many types of cell death, each involving multiple and complex molecular events. Cell death can occur accidentally when exposed to extreme physical, chemical, or mechanical conditions, or it can also be regulated, which involves a genetically coded complex machinery to carry
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There are many types of cell death, each involving multiple and complex molecular events. Cell death can occur accidentally when exposed to extreme physical, chemical, or mechanical conditions, or it can also be regulated, which involves a genetically coded complex machinery to carry out the process. Apoptosis is an example of the latter. Apoptotic cell death can be triggered through different intracellular signalling pathways that lead to morphological changes and eventually cell death. This is a normal and biological process carried out during maturation, remodelling, growth, and development in tissues. To maintain tissue homeostasis, regulatory, and inhibitory mechanisms must control apoptosis. Paradoxically, these same pathways are utilized during infection by distinct intracellular microorganisms to evade recognition by the immune system and therefore survive, reproduce and develop. In cancer, neoplastic cells inhibit apoptosis, thus allowing their survival and increasing their capability to invade different tissues and organs. The purpose of this work is to review the generalities of the molecular mechanisms and signalling pathways involved in apoptosis induction and inhibition. Additionally, we compile the current evidence of apoptosis modulation during cancer and Leishmania infection as a model of apoptosis regulation by an intracellular microorganism. Full article
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Open AccessArticle Elevated Proangiogenic Markers are Associated with Vascular Complications within Ghanaian Sickle Cell Disease Patients
Med. Sci. 2018, 6(3), 53; https://doi.org/10.3390/medsci6030053
Received: 14 May 2018 / Revised: 22 June 2018 / Accepted: 22 June 2018 / Published: 27 June 2018
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Abstract
Sickle cell disease (SCD) is an inherited blood disorder that can result in vasculopathy and end organ damage. Angiogenesis has been implicated as a key contributing factor to vascular mediated tissue injury in SCD. The relative plasma levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2),
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Sickle cell disease (SCD) is an inherited blood disorder that can result in vasculopathy and end organ damage. Angiogenesis has been implicated as a key contributing factor to vascular mediated tissue injury in SCD. The relative plasma levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) greatly influence angiogenesis. Dysregulation of these growth factors, leading to a pro-angiogenic state in SCD patients, has been documented in the developed world but there is very little data in Africa. There is the need, therefore, for studies in Ghanaian SCD patients. The aim of this study was to assess plasma levels of Ang-1, Ang-2, and VEGF in homozygous (HbSS) SCD patients with or without complications and healthy controls (HbAA) in Ghana. The study was a case-control study involving 544 participants: 396 HbSS SCD patients and 148 HbAA healthy controls. The study was conducted at the Center for Clinical Genetics (Sickle Cell Clinic) and Accra Area Blood Centre for National Blood transfusion at the Korle-Bu Teaching Hospital, Accra, Ghana. The plasma levels of Ang-1, Ang-2, and VEGF of study participants were measured with a double sandwich enzyme-linked immunosorbent assay (ELISA) technique. Complete blood count (CBC) was measured with an autoanalyser. The mean plasma Ang-1, Ang-2, and VEGF were significantly higher in HbSS SCD patients with or without complications than healthy controls (p < 0.001). The Ang-2/Ang-1 ratio was significantly lower in the controls than the HbSS patients (p < 0.001). The Ang-2/Ang-1 ratio was higher in the HbSS patients with leg ulcers as compared with patients with other complications and healthy controls (p < 0.001). There were higher leucocyte counts in HbSS patients than healthy controls. Overall, there was elevated plasma levels of Ang-1, Ang-2, and VEGF in SCD patients. The higher Ang-2/Ang-1 plasma levels in patients with leg ulcers suggests a possible ongoing angiogenesis and response to inflammatory stimuli. The study provides a first report on plasma levels of angiopoietin-1, angiopoietin-2, and vascular endothelial growth factors in homozygous sickle cell disease patients in Ghana. Full article
Open AccessReview Circadian Rhythm and Alzheimer’s Disease
Med. Sci. 2018, 6(3), 52; https://doi.org/10.3390/medsci6030052
Received: 10 May 2018 / Revised: 19 June 2018 / Accepted: 19 June 2018 / Published: 21 June 2018
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Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder with a growing epidemiological importance characterized by significant disease burden. Sleep-related pathological symptomatology often accompanies AD. The etiology and pathogenesis of disrupted circadian rhythm and AD share common factors, which also opens the perspective of viewing
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Alzheimer’s disease (AD) is a neurodegenerative disorder with a growing epidemiological importance characterized by significant disease burden. Sleep-related pathological symptomatology often accompanies AD. The etiology and pathogenesis of disrupted circadian rhythm and AD share common factors, which also opens the perspective of viewing them as a mutually dependent process. This article focuses on the bi-directional relationship between these processes, discussing the pathophysiological links and clinical aspects. Common mechanisms linking both processes include neuroinflammation, neurodegeneration, and circadian rhythm desynchronization. Timely recognition of sleep-specific symptoms as components of AD could lead to an earlier and correct diagnosis with an opportunity of offering treatments at an earlier stage. Likewise, proper sleep hygiene and related treatments ought to be one of the priorities in the management of the patient population affected by AD. This narrative review brings a comprehensive approach to clearly demonstrate the underlying complexities linking AD and circadian rhythm disruption. Most clinical data are based on interventions including melatonin, but larger-scale research is still scarce. Following a pathophysiological reasoning backed by evidence gained from AD models, novel anti-inflammatory treatments and those targeting metabolic alterations in AD might prove useful for normalizing a disrupted circadian rhythm. By restoring it, benefits would be conferred for immunological, metabolic, and behavioral function in an affected individual. On the other hand, a balanced circadian rhythm should provide greater resilience to AD pathogenesis. Full article
(This article belongs to the collection Advances in the Pathogenesis of Neurodegenerative Diseases)
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