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Diseases, Volume 6, Issue 4 (December 2018)

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Cover Story (view full-size image) Many studies have tried to unmask the "French paradox", which consists of low cardiovascular [...] Read more.
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Open AccessFeature PaperReview Strategic Syntheses of Vine and Wine Resveratrol Derivatives to Explore Their Effects on Cell Functions and Dysfunctions
Diseases 2018, 6(4), 110; https://doi.org/10.3390/diseases6040110
Received: 26 October 2018 / Revised: 6 December 2018 / Accepted: 7 December 2018 / Published: 11 December 2018
Cited by 1 | Viewed by 531 | PDF Full-text (2787 KB) | HTML Full-text | XML Full-text
Abstract
Trans-resveratrol, the most well-known polyphenolic stilbenoid, is found in grapes and accordingly in wine and it is considered to be beneficial for human health, especially towards the aging-linked cell alterations by providing numerous biological activities, such as anti-oxidant, antitumoral, antiviral, anti-inflammatory, neuroprotective, [...] Read more.
Trans-resveratrol, the most well-known polyphenolic stilbenoid, is found in grapes and accordingly in wine and it is considered to be beneficial for human health, especially towards the aging-linked cell alterations by providing numerous biological activities, such as anti-oxidant, antitumoral, antiviral, anti-inflammatory, neuroprotective, and platelet anti-aggregation properties. Although trans-resveratrol is a promising molecule, it cannot be considered as a drug, due to its weak bio-availability and fast metabolism. To overcome these weaknesses, several research teams have undertaken the synthesis of innovative trans-resveratrol derivatives, with the aim to increase its solubility in water and pharmacological activities towards cell targets. The aim of this review is to show the chronological evolution over the last 25 years of different strategies to develop more efficient trans-resveratrol derivatives towards organism physiology and, therefore, to enhance various pharmacological activities. While the literature on the development of new synthetic derivatives is impressive, this review will focus on selected strategies regarding the substitution of trans-resveratrol phenyl rings, first with hydroxy, methoxy, and halogen groups, and next with functionalized substituents. The effects on cell functions and dysfunctions of interesting resveratrol analogs will be addressed in this review. Full article
(This article belongs to the Special Issue Wine and Vine Components and Health)
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Open AccessFeature PaperReview Gut Microbiota, Fusobacteria, and Colorectal Cancer
Diseases 2018, 6(4), 109; https://doi.org/10.3390/diseases6040109
Received: 30 August 2018 / Revised: 9 November 2018 / Accepted: 4 December 2018 / Published: 11 December 2018
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Abstract
The gut microbiota has emerged as an environmental contributor to colorectal cancer (CRC) in both animal models and human studies. It is now generally accepted that bacteria are ubiquitous colonizers of all exposed human body surfaces, including the entire alimentary tract (5). Recently, [...] Read more.
The gut microbiota has emerged as an environmental contributor to colorectal cancer (CRC) in both animal models and human studies. It is now generally accepted that bacteria are ubiquitous colonizers of all exposed human body surfaces, including the entire alimentary tract (5). Recently, the concept that a normal bacterial microbiota is essential for the development of inflammation-induced carcinoma has emerged from studies of well-known colonic bacterial microbiota. This review explores the evidence for a role of fusobacteria, an anaerobic gram-negative bacterium that has repeatedly been detected at colorectal tumor sites in higher abundance than surrounding histologically normal tissue. Mechanistic studies provide insight on the interplay between fusobacteria, other gut microbiota, barrier functions, and host responses. Studies have shown that fusobacteria activate host inflammatory responses designed to protect against pathogens that promote tumor growth. We discuss how future research identifying the pathophysiology underlying fusobacteria colon colonization during colorectal cancer may lead to new therapeutic targets for cancer. Furthermore, disease-protective strategies suppressing tumor development by targeting the local tumor environment via bacteria represent another exciting avenue for researchers and are highlighted in this review. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
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Open AccessCase Report Delusional Parasitosis Impeding Delivery of Acute Care in a Cancer Patient
Diseases 2018, 6(4), 108; https://doi.org/10.3390/diseases6040108
Received: 18 November 2018 / Revised: 2 December 2018 / Accepted: 4 December 2018 / Published: 5 December 2018
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Abstract
Taking care of patients with delusional parasitosis can be challenging. This report illustrates the added management complexity and ethical dilemmas surrounding a patient who was newly diagnosed with an incurable lung cancer, while at the same time was suffering from delusional parasitosis. Her [...] Read more.
Taking care of patients with delusional parasitosis can be challenging. This report illustrates the added management complexity and ethical dilemmas surrounding a patient who was newly diagnosed with an incurable lung cancer, while at the same time was suffering from delusional parasitosis. Her delusion was so profound that she blamed flukes for her respiratory failure and refused treatment of her cancer. This paper emphasizes making the right decision with the greater good in mind, even if this meant “yielding” to a patient’s delusion and treating the non-existing parasitosis in order for her to allow us to also treat the cancer. Full article
(This article belongs to the Section Oncology)
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Open AccessArticle DOPS Adjuvant Confers Enhanced Protection against Malaria for VLP-TRAP Based Vaccines
Diseases 2018, 6(4), 107; https://doi.org/10.3390/diseases6040107
Received: 28 September 2018 / Revised: 12 November 2018 / Accepted: 16 November 2018 / Published: 21 November 2018
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Abstract
Vaccination remains the most effective and essential prophylactic tool against infectious diseases. Enormous efforts have been made to develop effective vaccines against malaria but successes remain so far limited. Novel adjuvants may offer a significant advantage in the development of malaria vaccines, in [...] Read more.
Vaccination remains the most effective and essential prophylactic tool against infectious diseases. Enormous efforts have been made to develop effective vaccines against malaria but successes remain so far limited. Novel adjuvants may offer a significant advantage in the development of malaria vaccines, in particular if combined with inherently immunogenic platforms, such as virus-like particles (VLP). Dioleoyl phosphatidylserine (DOPS), which is expressed on the outer surface of apoptotic cells, represents a novel adjuvant candidate that may confer significant advantage over existing adjuvants, such as alum. In the current study we assessed the potential of DOPS to serve as an adjuvant in the development of a vaccine against malaria either alone or combined with VLP using Plasmodium falciparum thrombospondin-related adhesive protein (TRAP) as a target antigen. TRAP was chemically coupled to VLPs derived from the cucumber mosaic virus fused to a universal T cell epitope of tetanus toxin (CuMVtt). Mice were immunized with TRAP alone or formulated in alum or DOPS and compared to TRAP coupled to CuMVtt formulated in PBS or DOPS. Induced immune responses, in particular T cell responses, were assessed as the major protective effector cell population induced by TRAP. The protective capacity of the various formulations was assessed using a transgenic Plasmodium berghei expressing PfTRAP. All vaccine formulations using adjuvants and/or VLP increased humoral and T cell immunogenicity for PfTRAP compared to the antigen alone. Display on VLPs, in particular if formulated with DOPS, induced the strongest and most protective immune response. Thus, the combination of VLP with DOPS may harness properties of both immunogenic components and optimally enhance induction of protective immune responses. Full article
(This article belongs to the Special Issue Vaccines as Allies in the Malaria Eradication Effort)
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Open AccessFeature PaperReview Polyphenol Extracts from Red Wine and Grapevine: Potential Effects on Cancers
Diseases 2018, 6(4), 106; https://doi.org/10.3390/diseases6040106
Received: 8 October 2018 / Revised: 13 November 2018 / Accepted: 16 November 2018 / Published: 18 November 2018
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Abstract
Wine has been popular worldwide for many centuries and currently remains an important component of our diet. Scientific interest in wine and its health effects has grown considerably since the 1990s with the emergence of the “French Paradox” concept, correlating moderate wine consumption, [...] Read more.
Wine has been popular worldwide for many centuries and currently remains an important component of our diet. Scientific interest in wine and its health effects has grown considerably since the 1990s with the emergence of the “French Paradox” concept, correlating moderate wine consumption, a characteristic of the Mediterranean diet, and low incidence of coronary heart diseases. Since then, the positive effects on health, health promotion, disease prevention, and disease prognosis of moderate wine consumption, in particular red wine, have been attributed to its polyphenolic compounds such as resveratrol, quercetin, and other flavonoids acting as antioxidants. Several epidemiological, in vivo and in vitro, studies have reported that moderate red wine or red wine polyphenolic extract consumption may be active in the prevention and treatment of chronic diseases such as cardiovascular disease, metabolic syndrome, degenerative pathologies, and cancer. The aim of this review is to summarize the current findings about the effects of red wine polyphenols on cancer and to discuss how the polyphenolic composition of red wine may influence its chemopreventive properties. Full article
(This article belongs to the Special Issue Wine and Vine Components and Health)
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Open AccessReview Is a Meal without Wine Good for Health?
Diseases 2018, 6(4), 105; https://doi.org/10.3390/diseases6040105
Received: 31 October 2018 / Accepted: 14 November 2018 / Published: 16 November 2018
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Abstract
Hippocrates, the father of medicine, had said: “Wine is a thing wonderfully appropriate to man if, in health as in disease, it is administered with appropriate and just measure according to the individual constitution.” Wine has always accompanied humanity, for religion or for [...] Read more.
Hippocrates, the father of medicine, had said: “Wine is a thing wonderfully appropriate to man if, in health as in disease, it is administered with appropriate and just measure according to the individual constitution.” Wine has always accompanied humanity, for religion or for health. Christians and Jews need wine for the liturgy. For Plato, wine was an indispensable element in society and the most important in the symposium. In this second part of the banquet, mixed with water, the wine gave the word. If the French paradox made a lot of ink flow; it was the wine that was originally responsible for it. Many researchers have tried to study alcohol and polyphenols in wine, in order to solve the mystery. Beyond its cardiovascular effects, there are also effects on longevity, metabolism, cancer prevention, and neuroprotection, and the list goes on. The purpose of this work is to make an analysis of the current knowledge on the subject. Indeed, if the paradigm of antioxidants is seductive, it is perhaps by their prooxidant effect that the polyphenols act, by an epigenetic process mediated by nrf2. Wine is a preserve of antioxidants for the winter and it is by this property that the wine acts, in an alcoholic solution. A wine without alcohol is pure heresy. Wine is the elixir that by design, over millennials, has acted as a pharmacopeia that enabled man to heal and prosper on the planet. From Alvise Cornaro to Serge Renaud, nutrition was the key to health and longevity, whether the Cretan or Okinawa diet, it is the small dose of alcohol (wine or sake) that allows the bioavailability of polyphenols. Moderate drinking gives a protection for diseases and a longevity potential. In conclusion, let us drink fewer, but drink better, to live older. Full article
(This article belongs to the Special Issue Wine and Vine Components and Health)
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Open AccessFeature PaperCase Report ST-Elevation Myocardial Infarction in Coronary Ectasia: A Case Report
Diseases 2018, 6(4), 104; https://doi.org/10.3390/diseases6040104
Received: 9 October 2018 / Revised: 30 October 2018 / Accepted: 15 November 2018 / Published: 16 November 2018
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Abstract
Coronary artery ectasia (CAE) is localized or diffuse dilatation of the coronary artery lumen exceeding the diameter of adjacent healthy reference segments by 1.5 times. It is a rare phenomenon and incidence ranges from 1 to 5% in patients undergoing angiography. We report [...] Read more.
Coronary artery ectasia (CAE) is localized or diffuse dilatation of the coronary artery lumen exceeding the diameter of adjacent healthy reference segments by 1.5 times. It is a rare phenomenon and incidence ranges from 1 to 5% in patients undergoing angiography. We report a case of a 58-year-old man with atherosclerotic CAE who experienced ST-elevation myocardial infarction (STEMI) despite prophylactic antiplatelet therapy. He was successfully treated with IV eptifibatide and aspiration thrombectomy. We reviewed the literature of CAE presentation, etiology and treatment and discussed the most appropriate antithrombotic therapy to prevent STEMIs in patients with CAE. While the current literature appears to favour prophylactic antiplatelet and anticoagulant in these patients, more studies are needed to determine the optimal form and duration of antithrombotic therapy. Currently, there is no gold standard treatment for CAE and further prospective and randomized-controlled studies are needed to guide recommendations. Full article
(This article belongs to the Section Cardiology)
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Open AccessReview The Evolving Understanding of the Molecular and Therapeutic Landscape of Pancreatic Ductal Adenocarcinoma
Diseases 2018, 6(4), 103; https://doi.org/10.3390/diseases6040103
Received: 11 October 2018 / Revised: 7 November 2018 / Accepted: 8 November 2018 / Published: 13 November 2018
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Abstract
Pancreatic cancer is the third leading cause of cancer-related deaths, characterised by poor survival, marked molecular heterogeneity and high intrinsic and acquired chemoresistance. Only 10–20% of pancreatic cancer patients present with surgically resectable disease and even then, 80% die within 5 years. Our [...] Read more.
Pancreatic cancer is the third leading cause of cancer-related deaths, characterised by poor survival, marked molecular heterogeneity and high intrinsic and acquired chemoresistance. Only 10–20% of pancreatic cancer patients present with surgically resectable disease and even then, 80% die within 5 years. Our increasing understanding of the genomic heterogeneity of cancer suggests that the failure of definitive clinical trials to demonstrate efficacy in the majority of cases is likely due to the low proportion of responsive molecular subtypes. As a consequence, novel treatment strategies to approach this disease are urgently needed. Significant developments in the field of precision oncology have led to increasing molecular stratification of cancers into subtypes, where individual cancers are selected for optimal therapy depending on their molecular or genomic fingerprint. This review provides an overview of the current status of clinically used and emerging treatment strategies, and discusses the advances in and the potential for the implementation of precision medicine in this highly lethal malignancy, for which there are currently no curative systemic therapies. Full article
(This article belongs to the Special Issue Pathogenesis of Pancreatic Cancer)
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Open AccessReview The Role of Statins in the Management of Patients Undergoing Coronary Artery Bypass Grafting
Diseases 2018, 6(4), 102; https://doi.org/10.3390/diseases6040102
Received: 13 October 2018 / Revised: 3 November 2018 / Accepted: 8 November 2018 / Published: 11 November 2018
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Abstract
Each year, a large number of patients undergo coronary artery bypass grafting surgery (CABG) worldwide. Accumulating evidence suggests that the preoperative administration of statins might be useful in preventing adverse events after CABG. In the present review, we discuss the role of statins [...] Read more.
Each year, a large number of patients undergo coronary artery bypass grafting surgery (CABG) worldwide. Accumulating evidence suggests that the preoperative administration of statins might be useful in preventing adverse events after CABG. In the present review, we discuss the role of statins in the perioperative management of patients undergoing CABG. Preoperative administration of statins in these patients substantially reduces the risk of postoperative atrial fibrillation and shortens hospital and intensive care unit (ICU) stay. Atorvastatin appears to be more effective, particularly when administered at high doses. Given these benefits and the safety of statins, their administration should be considered in patients undergoing CABG, even though the statins do not appear to affect the incidence of cardiovascular events and overall mortality perioperatively. Full article
Open AccessArticle Clinical Characteristics of Nursing- and Healthcare-Associated Tuberculosis
Diseases 2018, 6(4), 101; https://doi.org/10.3390/diseases6040101
Received: 11 October 2018 / Revised: 6 November 2018 / Accepted: 7 November 2018 / Published: 11 November 2018
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Abstract
Tuberculosis remains a serious health problem worldwide. Patients with tuberculosis who also require nursing care due to aging and underlying diseases are considered to have a high mortality rate; however, there are few studies describing detailed examinations of such disease conditions. Objective: The [...] Read more.
Tuberculosis remains a serious health problem worldwide. Patients with tuberculosis who also require nursing care due to aging and underlying diseases are considered to have a high mortality rate; however, there are few studies describing detailed examinations of such disease conditions. Objective: The present study was conducted to investigate differences in clinical features of elderly tuberculosis patients according to the levels of nursing and healthcare required. Design: The study participants included 146 elderly (≥65 years) patients diagnosed with active tuberculosis among patients hospitalized with tuberculosis at a single center. The patients were classified into two groups: a nursing- and healthcare-associated tuberculosis group (n = 71) and a community-acquired tuberculosis group (n = 75). Results: The nursing- and healthcare-associated tuberculosis patients were older and had a higher frequency of comorbidities compared with the community-acquired tuberculosis group. Patients in the nursing- and healthcare-associated tuberculosis group had markedly lower levels of serum albumin and hemoglobin, and higher levels of C-reactive protein. The rate of in-hospital death was significantly higher in the nursing- and healthcare-associated tuberculosis group. This was attributed to malnutrition and comorbid conditions rather than the severity of tuberculosis. Conclusion: The prognosis was poor in elderly tuberculosis patients receiving nursing and healthcare. Full article
(This article belongs to the Special Issue Chronic Inflammatory and Infectious Diseases)
Open AccessCase Report An Unusual Presentation of Pectoralis Major Pyomyositis Presenting as Septic Arthritis of the Shoulder: A Case Report and Review of the Literature
Diseases 2018, 6(4), 100; https://doi.org/10.3390/diseases6040100
Received: 17 October 2018 / Revised: 6 November 2018 / Accepted: 7 November 2018 / Published: 10 November 2018
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Abstract
Pyomyositis is a relatively rare condition and often requires a low index of suspicion. We present a case of an otherwise fit and well woman who had pyomyositis of the pectoralis major muscle and presented as an acute septic arthritis of the shoulder. [...] Read more.
Pyomyositis is a relatively rare condition and often requires a low index of suspicion. We present a case of an otherwise fit and well woman who had pyomyositis of the pectoralis major muscle and presented as an acute septic arthritis of the shoulder. We present the conundrums that arose in arriving at this diagnosis, and how we successfully managed this condition through our multidisciplinary approach. We urge all clinicians to bear in mind this potential diagnosis, even in those patients not deemed to be immunocompromised. Full article
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Open AccessFeature PaperReview The Neglect and Fast Spread of Some Arboviruses: A Note for Healthcare Providers in Nigeria
Received: 9 October 2018 / Revised: 29 October 2018 / Accepted: 2 November 2018 / Published: 5 November 2018
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Abstract
Arboviruses are distributed worldwide and constitute significant health burden globally. Outbreaks of arboviruses have been reported in Africa and beyond. In Nigeria, like in many other countries, arbovirus infections are more often than not neglected. As the early clinical features of arbovirus infections [...] Read more.
Arboviruses are distributed worldwide and constitute significant health burden globally. Outbreaks of arboviruses have been reported in Africa and beyond. In Nigeria, like in many other countries, arbovirus infections are more often than not neglected. As the early clinical features of arbovirus infections are generally nonspecific, most healthcare providers mistake them for other diseases. Outbreaks have been reported in Africa and beyond. The consequence of missed diagnosis of diseases cannot be overstated. In this review, some epidemiological data, classical syndromes, and risk factors for five human arboviruses (yellow fever YF, dengue DENV, chikungunya CHIKV, Rift Valley fever RVF, and West Nile virus WNV) found in Nigeria are presented. Health practitioners should ensure in-depth analysis rather than a superficial diagnosis of diseases before declaring a course of treatment. Full article
(This article belongs to the Special Issue Host-pathogen Interactions in Ebola, Chikungunya, and Zika Viruses)
Open AccessArticle HIV/AIDS Knowledge of Undergraduate Students at a Historically Black College and University
Received: 8 September 2018 / Revised: 18 October 2018 / Accepted: 22 October 2018 / Published: 31 October 2018
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Abstract
Objective: This study among 400 undergraduate students enrolled at Jackson State University (JSU) study aimed to assess knowledge about HIV and AIDS among African-American undergraduate students attending a historically black college and university. A cross-sectional survey was conducted. Data were collected using a [...] Read more.
Objective: This study among 400 undergraduate students enrolled at Jackson State University (JSU) study aimed to assess knowledge about HIV and AIDS among African-American undergraduate students attending a historically black college and university. A cross-sectional survey was conducted. Data were collected using a validated, self-administered, and standardized questionnaire on knowledge regarding risks for HIV and AIDS. Three hundred and eighty-six students (96.5%) had good knowledge about HIV and AIDS, although some participants had misconceptions about the modes of HIV infection transmission. There were no significant gender differences for HIV and AIDS knowledge among the participants (χ2 = 3.05; P = 0.08). In general we concluded that JSU undergraduate students had adequate knowledge about HIV transmission modes and AIDS, although some participants had misconceptions about the routes of HIV infection transmission. Hence, this study calls for strengthening HIV and AIDS awareness education among undergraduate students. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology)
Open AccessArticle Blood Pressure and Oxidative Stress among U.S. Adults Exposed to Lead in Military Environments—A Preliminary Study
Received: 27 September 2018 / Revised: 23 October 2018 / Accepted: 24 October 2018 / Published: 27 October 2018
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Abstract
In this cross-sectional study, lead exposure among those with a history in military environments was examined. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) are clinical markers of blood pressure, while gamma-glutamyl transferase (GGT) is a marker of oxidative stress. These markers [...] Read more.
In this cross-sectional study, lead exposure among those with a history in military environments was examined. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) are clinical markers of blood pressure, while gamma-glutamyl transferase (GGT) is a marker of oxidative stress. These markers and their effects on those exposed to military environments were explored using National Health and Nutrition Examination Survey (NHANES) data from 2009 to 2016. Mean SBP and GGT were significantly elevated in those exposed to military environments, with a moderately significant association existing between blood lead levels (BLLs) and SBP. More attention must be given to lead exposure in military environments to mitigate the risk of exposure. Full article
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Open AccessReview Congenital Nasolacrimal Duct Obstruction (CNLDO): A Review
Received: 30 August 2018 / Revised: 16 October 2018 / Accepted: 17 October 2018 / Published: 22 October 2018
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Abstract
Congenital nasolacrimal duct obstruction (CNLDO) is a common condition causing excessive tearing or mucoid discharge from the eyes, due to blockage of the nasolacrimal duct system. Nasolacrimal duct obstruction affects as many as 20% children aged <1 year worldwide and is often resolved [...] Read more.
Congenital nasolacrimal duct obstruction (CNLDO) is a common condition causing excessive tearing or mucoid discharge from the eyes, due to blockage of the nasolacrimal duct system. Nasolacrimal duct obstruction affects as many as 20% children aged <1 year worldwide and is often resolved without surgery. Available treatment options are conservative therapy, including observation, lacrimal sac massage and antibiotics, and invasive therapy. Observation, combined with conservative options, seems to be the best option in infants aged <1 year. Meanwhile, in children aged >1 year, nasolacrimal probing successfully addresses most obstructions. However, the most favorable timing for probing remains controversial. To alleviate persistent epiphora and mucous drainage that is refractory to probing, repeat probing, silicone tube intubation, balloon catheter dilation or dacryocystorhinostomy can be considered as available treatment options. Our review aims to provide an update to CNDO management protocols. Full article
(This article belongs to the Special Issue Pediatric Diseases)
Open AccessFeature PaperArticle The Cytokine Profile in Acute Chikungunya Infection is Predictive of Chronic Arthritis 20 Months Post Infection
Received: 19 September 2018 / Revised: 15 October 2018 / Accepted: 17 October 2018 / Published: 20 October 2018
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Abstract
The cytokine profile during acute chikungunya infection that predicts future chronic arthritis has not yet been investigated. We conducted a nested case-control study comparing serum cytokine concentrations during acute chikungunya infection in cases (n = 121) that reported the presence of chronic [...] Read more.
The cytokine profile during acute chikungunya infection that predicts future chronic arthritis has not yet been investigated. We conducted a nested case-control study comparing serum cytokine concentrations during acute chikungunya infection in cases (n = 121) that reported the presence of chronic joint pain versus age- and gender-matched controls (n = 121) who reported recovery at 20 months post infection. We observed that a robust cytokine response during acute infection was correlated with a decreased incidence of chronic joint pain and that low TNFα, IL-13, IL-2, and IL-4 during acute infection was predictive of chronic joint pain. These data suggest that a robust cytokine response is necessary for viral clearance and cytokines that are related to immune tolerance during acute infection may be protective for chronic arthritis pathogenesis. Full article
(This article belongs to the Special Issue Host-pathogen Interactions in Ebola, Chikungunya, and Zika Viruses)
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Open AccessInteresting Images Carbapenemase-Producing Raoultella Planticola: A Rare Cause of Pneumonia and Bacteremia
Received: 23 September 2018 / Revised: 9 October 2018 / Accepted: 17 October 2018 / Published: 17 October 2018
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Abstract
Raoultella planticola is a gram-negative bacterium of the Enterobacteriaceae family that is usually found in soil, plant and aquatic environments. It is an uncommon human pathogen and has been associated with cases of bacteremia, pneumonia, urinary tract infections, among others. Here, we present [...] Read more.
Raoultella planticola is a gram-negative bacterium of the Enterobacteriaceae family that is usually found in soil, plant and aquatic environments. It is an uncommon human pathogen and has been associated with cases of bacteremia, pneumonia, urinary tract infections, among others. Here, we present the case of an 85-year-old female that developed nosocomial pneumonia and bacteremia caused by Raoultella planticola. Pertinent microbiological studies detected carbapenemase production codified by the blaKPC gene. The patient was successfully treated with ceftazidime/avibactam and polymyxin. Our case illustrates the pathogenic potential of this organism and highlights the importance of phenotypic and genotypic assays for the appropriate identification of carbapenemase production. Full article
(This article belongs to the Section Infectious Disease)
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Open AccessFeature PaperReview Anti-Diabetic Medications for the Pharmacologic Management of NAFLD
Received: 9 August 2018 / Revised: 5 September 2018 / Accepted: 28 September 2018 / Published: 3 October 2018
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Abstract
As a chronic disease encompassing a wide spectrum of liver-related histologic damage, nonalcoholic fatty liver disease (NAFLD) is becoming a global epidemic with significant impacts on all-cause morbidity and mortality. Insulin resistance and type 2 diabetes mellitus predispose individuals to NAFLD and related [...] Read more.
As a chronic disease encompassing a wide spectrum of liver-related histologic damage, nonalcoholic fatty liver disease (NAFLD) is becoming a global epidemic with significant impacts on all-cause morbidity and mortality. Insulin resistance and type 2 diabetes mellitus predispose individuals to NAFLD and related complications. Therefore, timely intervention with anti-diabetic medications may prevent and delay the development of NAFLD or have a therapeutic implication. The focus of this review is to evaluate the evidence supporting the efficacy of anti-diabetic medications in the treatment of NAFLD. While many of these anti-diabetic agents have shown to improve biochemical parameters, their effect on hepatic histology is limited. Among anti-diabetic medications, only thiazolidinediones and glucagon-like peptide-1 receptor agonists demonstrate significant improvement in hepatic histology. Full article
Open AccessReview Prevention of Progression in Myopia: A Systematic Review
Received: 30 August 2018 / Revised: 7 September 2018 / Accepted: 13 September 2018 / Published: 30 September 2018
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Abstract
The prevalence of myopia has increased worldwide in recent decades and now is endemic over the entire industrial world. This increase is mainly caused by changes in lifestyle and behavior. In particular, the amount of outdoor activities and near work would display an [...] Read more.
The prevalence of myopia has increased worldwide in recent decades and now is endemic over the entire industrial world. This increase is mainly caused by changes in lifestyle and behavior. In particular, the amount of outdoor activities and near work would display an important role in the pathogenesis of the disease. Several strategies have been reported as effective. Spectacles and contact lenses have shown only slight results in the prevention of myopia and similarly ortokerathology should not be considered as a first-line strategy, given the high risk of infectious keratitis and the relatively low compliance for the patients. Thus, to date, atropine ophthalmic drops seem to be the most effective treatment for slowing the progression of myopia, although the exact mechanism of the effect of treatment is still uncertain. In particular, low-dose atropine (0.01%) was proven to be an effective and safe treatment in the long term due to the lowest rebound effect with negligible side effects. Full article
(This article belongs to the Special Issue Pediatric Diseases)
Open AccessFeature PaperReview When to Initiate Weight Loss Medications in the NAFLD Population
Received: 9 August 2018 / Revised: 18 September 2018 / Accepted: 26 September 2018 / Published: 30 September 2018
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by histological evidence of hepatic steatosis, lobular inflammation, ballooning degeneration and hepatic fibrosis in the absence of significant alcohol use and other known causes of chronic liver diseases. NAFLD is subdivided into nonalcoholic fatty liver (NAFL) [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is characterized by histological evidence of hepatic steatosis, lobular inflammation, ballooning degeneration and hepatic fibrosis in the absence of significant alcohol use and other known causes of chronic liver diseases. NAFLD is subdivided into nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). NAFL is generally benign but can progress to NASH, which carries a higher risk of adverse outcomes including cirrhosis, end-stage liver disease, hepatocellular carcinoma and death if liver transplantation is not pursued in a timely fashion. Currently, lifestyle modifications including healthy diet and increased physical activity/exercise culminating in weight loss of 5% to >10% is the cornerstone of treatment intervention for patients with NAFLD. Patients with NAFLD who fail to obtain this goal despite the help of dietitians and regimented exercise programs are left in a purgatory state and remain at risk of developing NASH-related advance fibrosis. For such patients with NAFLD who are overweight and obese, healthcare providers should consider a trial of FDA-approved anti-obesity medications as adjunct therapy to provide further preventative and therapeutic options as an effort to reduce the risk of NAFLD-related disease progression. Full article
Open AccessFeature PaperArticle Association between eNOS Gene Polymorphism (T786C and VNTR) and Sickle Cell Disease Patients in Ghana
Received: 5 September 2018 / Revised: 21 September 2018 / Accepted: 27 September 2018 / Published: 29 September 2018
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Abstract
Endothelial nitric oxide synthase (eNOS) variants have been found to be associated with several vascular disorders as well as the pathogenesis of sickle cell disease (SCD) complications such as vaso-occlusive crises (VOC). Studies on eNOS gene variants among SCD patients are rare in [...] Read more.
Endothelial nitric oxide synthase (eNOS) variants have been found to be associated with several vascular disorders as well as the pathogenesis of sickle cell disease (SCD) complications such as vaso-occlusive crises (VOC). Studies on eNOS gene variants among SCD patients are rare in Ghana and several other African countries. The current study aimed to determine a possible association between variants of the eNOS gene (variable number of tandem repeats in intron 4 and T786C) in SCD complications among Ghanaian patients. This was a cross-sectional study involving 89 HbSS patients with complications and 46 HbSS patients without complications. Genomic DNA was extracted from leukocytes in the buffy coat and separated from collected whole blood samples of the study participants. PCR amplification, followed by restriction fragment length polymorphism (RFLP) was used to genotype T786C (rs2070744) variants. Variable number of tandem repeats (VNTR) in intron 4 was genotyped by PCR and direct electrophoresis. There was a significant difference in the genotype frequency of the T786C variant between HbSS patients with complications and those without complications (p = 0.0165). However, there was no significant difference in the VNTR intron 4 variant of the eNOS gene between patients with complications and those without complications (p > 0.05). The study shows an association between the eNOS gene variant (T786C) and complications in SCD. Full article
Open AccessFeature PaperArticle A Magnetoencephalographic/Encephalographic (MEG/EEG) Brain-Computer Interface Driver for Interactive iOS Mobile Videogame Applications Utilizing the Hadoop Ecosystem, MongoDB, and Cassandra NoSQL Databases
Received: 3 June 2018 / Revised: 8 August 2018 / Accepted: 21 August 2018 / Published: 28 September 2018
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Abstract
In Phase I, we collected data on five subjects yielding over 90% positive performance in Magnetoencephalographic (MEG) mid-and post-movement activity. In addition, a driver was developed that substituted the actions of the Brain Computer Interface (BCI) as mouse button presses for real-time use [...] Read more.
In Phase I, we collected data on five subjects yielding over 90% positive performance in Magnetoencephalographic (MEG) mid-and post-movement activity. In addition, a driver was developed that substituted the actions of the Brain Computer Interface (BCI) as mouse button presses for real-time use in visual simulations. The process was interfaced to a flight visualization demonstration utilizing left or right brainwave thought movement, the user experiences, the aircraft turning in the chosen direction, or on iOS Mobile Warfighter Videogame application. The BCI’s data analytics of a subject’s MEG brain waves and flight visualization performance videogame analytics were stored and analyzed using the Hadoop Ecosystem as a quick retrieval data warehouse. In Phase II portion of the project involves the Emotiv Encephalographic (EEG) Wireless Brain–Computer interfaces (BCIs) allow for people to establish a novel communication channel between the human brain and a machine, in this case, an iOS Mobile Application(s). The EEG BCI utilizes advanced and novel machine learning algorithms, as well as the Spark Directed Acyclic Graph (DAG), Cassandra NoSQL database environment, and also the competitor NoSQL MongoDB database for housing BCI analytics of subject’s response and users’ intent illustrated for both MEG/EEG brainwave signal acquisition. The wireless EEG signals that were acquired from the OpenVibe and the Emotiv EPOC headset can be connected via Bluetooth to an iPhone utilizing a thin Client architecture. The use of NoSQL databases were chosen because of its schema-less architecture and Map Reduce computational paradigm algorithm for housing a user’s brain signals from each referencing sensor. Thus, in the near future, if multiple users are playing on an online network connection and an MEG/EEG sensor fails, or if the connection is lost from the smartphone and the webserver due to low battery power or failed data transmission, it will not nullify the NoSQL document-oriented (MongoDB) or column-oriented Cassandra databases. Additionally, NoSQL databases have fast querying and indexing methodologies, which are perfect for online game analytics and technology. In Phase II, we collected data on five MEG subjects, yielding over 90% positive performance on iOS Mobile Applications with Objective-C and C++, however on EEG signals utilized on three subjects with the Emotiv wireless headsets and (n < 10) subjects from the OpenVibe EEG database the Variational Bayesian Factor Analysis Algorithm (VBFA) yielded below 60% performance and we are currently pursuing extending the VBFA algorithm to work in the time-frequency domain referred to as VBFA-TF to enhance EEG performance in the near future. The novel usage of NoSQL databases, Cassandra and MongoDB, were the primary main enhancements of the BCI Phase II MEG/EEG brain signal data acquisition, queries, and rapid analytics, with MapReduce and Spark DAG demonstrating future implications for next generation biometric MEG/EEG NoSQL databases. Full article
(This article belongs to the Section Neuro-psychiatric Disorders)
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Open AccessArticle The Predictive Value of Plasma Brain Natriuretic Peptide and Galectin-3 in Elderly Patients Admitted for Heart Failure
Received: 29 July 2018 / Revised: 11 September 2018 / Accepted: 21 September 2018 / Published: 27 September 2018
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Abstract
Galectin-3 is demonstrated to be a robust independent marker of cardiovascular mid-term (18-month) outcomes in heart failure (HF) patients. The aim of this study was to analyze the value of a pre-discharged determination of galectin-3 alone and with brain natriuretic peptide (BNP) in [...] Read more.
Galectin-3 is demonstrated to be a robust independent marker of cardiovascular mid-term (18-month) outcomes in heart failure (HF) patients. The aim of this study was to analyze the value of a pre-discharged determination of galectin-3 alone and with brain natriuretic peptide (BNP) in predicting mid-term outcomes in elderly patients (>70 years old) discharged after an acute decompensated HF (ADHF) episode. Methods: all elderly (≥70 years old) HF subjects discharged alive after an ADHF were enrolled. All patients underwent a determination of BNP and galectin-3, a 6-min walking test (6MWT), and an echocardiogram within 48 h of hospital discharge. Cardiac death, cardiac transplantation, and worsening heart failure requiring readmission to hospital were considered cardiovascular events. Results: 84 patients (63 males (75%), age 77.5 ± 5.9 years old) were analyzed (mean follow-up: 16.2 ± 12.3 months). During the follow-up, 45 events (53.6%) were scheduled (18 cardiac deaths, 27 re-hospitalizations for ADHF). HF patients who suffered an event demonstrated more impaired ventricular function (p = 0.04), higher value of BNP (p = 0.02), and Gal-3 at a pre-discharge evaluation (p = 0.05). By choosing adequate cut-off points (BNP ≥ 500 pg/mL and Gal-3 ≥ 17.6 ng/mL), the Kaplan–Meier curves depicted a powerful stratification using Galectin-3 > 17.6 ng/mL alone (log-rank 13.22; p = 0.0003), and by adding BNP + Gal-3, an even better result was obtained (log-rank 17.96; p < 0.00001). Conclusion: in an elderly population, by adding Gal-3 to BNP, a single pre-discharge strategy testing seemed to obtain a satisfactorily predictive value in alive HF patients discharged after an ADHF episode. Full article
(This article belongs to the Section Cardiology)
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Open AccessReview Judicious Use of Lipid Lowering Agents in the Management of NAFLD
Received: 9 August 2018 / Revised: 15 September 2018 / Accepted: 16 September 2018 / Published: 24 September 2018
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world. NAFLD encompasses a spectrum of histological features, including steatosis, steatohepatitis with balloon degeneration, and hepatic fibrosis leading to cirrhosis. In patients with advanced liver damage, [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world. NAFLD encompasses a spectrum of histological features, including steatosis, steatohepatitis with balloon degeneration, and hepatic fibrosis leading to cirrhosis. In patients with advanced liver damage, NAFLD is associated with an increased risk of hepatocellular carcinoma. Diabetes mellitus, hypertension, and dyslipidemia are components of metabolic syndrome and are commonly associated with NAFLD. Cardiovascular disease is the leading cause of mortality in patients with NAFLD. Therefore, it is important to pre-emptively identify and proactively treat conditions like hyperlipidemia in an effort to favorably modify the risk factors associated with cardiovascular events in patients with NAFLD. The management of hyperlipidemia has been shown to reduce cardiovascular mortality and improve histological damage/biochemical abnormalities associated with non-alcoholic steatohepatitis (NASH), a subset of NAFLD with advance liver damage. There are no formal guidelines available regarding the use of anti-hyperlipidemic drugs, as prospective data are lacking. The focus of this article is to discuss the utility of lipid-lowering drugs in patients with NAFLD. Full article
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Open AccessReview The Role of Vitamin E in the Treatment of NAFLD
Received: 9 August 2018 / Revised: 17 September 2018 / Accepted: 19 September 2018 / Published: 24 September 2018
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Abstract
There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching [...] Read more.
There has been a growing interest in the role of vitamin E supplementation in the treatment and/or prevention of nonalcoholic fatty liver (NAFLD). We performed a systematic review of the medical literature from inception through 15 June 2018 by utilizing PubMed and searching for key terms such as NAFLD, vitamin E, alpha-tocopherol, and nonalcoholic steatohepatitis (NASH). Data from studies and medical literature focusing on the role of vitamin E therapy in patients with NAFLD and nonalcoholic steatohepatitis (NASH) were reviewed. Most studies assessing the impact of vitamin E in NAFLD were designed to evaluate patients with NASH with documented biochemical and histological abnormalities. These studies demonstrated improvement in biochemical profiles, with a decline in or normalization of liver enzymes. Furthermore, histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only. However, some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis. In conclusion, the antioxidant, anti-inflammatory, and anti-apoptotic properties of vitamin E accompanied by ease-of-use and exceptional tolerability have made vitamin E a pragmatic therapeutic choice in non-diabetic patients with histologic evidence of NASH. Future clinical trials with study design to assess vitamin E in combination with other anti-fibrotic agents may yield an additive or synergistic therapeutic effect. Full article
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Open AccessReview Cell-Based Methods for Determination of Efficacy for Candidate Therapeutics in the Clinical Management of Cancer
Received: 20 August 2018 / Revised: 12 September 2018 / Accepted: 20 September 2018 / Published: 22 September 2018
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Abstract
Determination of therapeutic efficacy is a major challenge in developing treatment options for cancer. Prior to in vivo studies, candidate therapeutics are evaluated using cell-based in vitro methods to assess their anti-cancer potential. This review describes the utility and limitations of evaluating therapeutic [...] Read more.
Determination of therapeutic efficacy is a major challenge in developing treatment options for cancer. Prior to in vivo studies, candidate therapeutics are evaluated using cell-based in vitro methods to assess their anti-cancer potential. This review describes the utility and limitations of evaluating therapeutic efficacy using human tumor-derived cell lines. Indicators for therapeutic efficacy using tumor-derived cell lines include cell viability, cell proliferation, colony formation, cytotoxicity, cytostasis, induction of apoptosis, and cell cycle arrest. Cell panel screens, 3D tumor spheroid models, drug-drug/drug-radiation combinatorial analysis, and invasion/migration assays reveal analogous in vitro information. In animal models, cellular assays can assess tumor micro-environment and therapeutic delivery. The utility of tumor-derived cell lines for efficacy determination is manifest in numerous commercially approved drugs that have been applied in clinical management of cancer. Studies reveal most tumor-derived cell lines preserve the genomic signature of the primary tumor source and cell line-based data is highly predictive of subsequent clinical studies. However, cell-based data often disregards natural system components, resulting in cell autonomous outcomes. While 3D cell culture platforms can counter such limitations, they require additional time and cost. Despite the limitations, cell-based methods remain essential in early stages of anti-cancer drug development. Full article
(This article belongs to the Section Oncology)
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Open AccessCase Report Polymyalgia Rheumatica (PMR) with Normal Values of Both Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) Concentration at the Time of Diagnosis in a Centenarian Man: A Case Report
Received: 10 August 2018 / Revised: 14 September 2018 / Accepted: 19 September 2018 / Published: 20 September 2018
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Abstract
The possibility that polymyalgia rheumatica (PMR) can be diagnosed when both ESR and CRP are normal at the time of diagnosis and before therapy with glucocorticoids, has been often discussed in the literature. We present a case report of a 100-year-old Caucasian man [...] Read more.
The possibility that polymyalgia rheumatica (PMR) can be diagnosed when both ESR and CRP are normal at the time of diagnosis and before therapy with glucocorticoids, has been often discussed in the literature. We present a case report of a 100-year-old Caucasian man referred to our outpatient clinic, complaining of chronic pain in the shoulder and hip girdle associated with normal values of both ESR (21 mm/1st hour) and CRP (4 mg/dL). In the previous four months, several anti-inflammatory drugs and painkillers associated with physiotherapy treatments gave no significant improvement in pain and self-care. After an ultrasound (US) and an 18-fluorodeoxyglucose positron emission tomography associated with total body computed tomography (18-FDG PET/CT) examination, PMR was diagnosed and he started therapy with 17.5 mg prednisone, obtaining a fast improvement in pain and self-care. After 10 months of tapering, he stopped prednisone without relapse. During a 3-year follow-up, no alternative diagnosis was done. When a patient complains of chronic bilateral shoulder and hip girdle pain associated with normal inflammatory indices, it is reasonable to think in the first instance that this person is not suffering from PMR. Moreover, the possibility that PMR may onset in a centenarian person, is exceptional. In our patient, when we piece the puzzle together, the diagnosis of PMR was the most possible one. Full article
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