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J. Clin. Med., Volume 6, Issue 12 (December 2017) – 11 articles

Cover Story (view full-size image): The cover image summarizes how mucin production is altered between health and fatal asthma. MUC5AC and MUC5B are the principal components of airway mucus. Recent evidence has begun to unveil their contribution to health and asthma. We review our current understanding of the role of MUC5AC and MUC5B in asthma. We discuss how MUC5AC and MUC5B share sequence and structure similarity, but their glycosylation, localization and function differ. We summarize how MUC5AC and MUC5B production is altered in asthma, discuss changes in goblet cell number and how these changes contribute to mucus plugging through MUC5AC tethering. We also discuss how commonly used asthma therapies and cytokine-specific antibodies may serve in part as mucoregulators. View the paper
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2285 KiB  
Review
Hypertrophic Cardiomyopathy—Past, Present and Future
by Alphonsus C. Liew, Vassilios S. Vassiliou, Robert Cooper and Claire E. Raphael
J. Clin. Med. 2017, 6(12), 118; https://doi.org/10.3390/jcm6120118 - 12 Dec 2017
Cited by 37 | Viewed by 12436
Abstract
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy with a prevalence of 1 in 500 in the general population. Since the first pathological case series at post mortem in 1957, we have come a long way in its understanding, diagnosis and management. [...] Read more.
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy with a prevalence of 1 in 500 in the general population. Since the first pathological case series at post mortem in 1957, we have come a long way in its understanding, diagnosis and management. Here, we will describe the history of our understanding of HCM including the initial disease findings, diagnostic methods and treatment options. We will review the current guidelines for the diagnosis and management of HCM, current gaps in the evidence base and discuss the new and promising developments in this field. Full article
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Case Report
Acute Encephalitis in an Adult with Diffuse Large B-Cell Lymphoma with Secondary Involvement of the Central Nervous System: Infectious or Non-Infectious Etiology?
by Surinder S. Moonga, Kenneth Liang and Burke A. Cunha
J. Clin. Med. 2017, 6(12), 117; https://doi.org/10.3390/jcm6120117 - 7 Dec 2017
Cited by 1 | Viewed by 9531
Abstract
Both infectious and non-infectious etiologies of acute encephalitis have been described, as well as their specific presentations, diagnostic tests, and therapies. Classic findings of acute encephalitis include altered mental status, fever, and new lesions on neuroimaging or electroencephalogram (EEG). We report an interesting [...] Read more.
Both infectious and non-infectious etiologies of acute encephalitis have been described, as well as their specific presentations, diagnostic tests, and therapies. Classic findings of acute encephalitis include altered mental status, fever, and new lesions on neuroimaging or electroencephalogram (EEG). We report an interesting case of a 61-year-old male with a history of diffuse large B-cell lymphoma with secondary involvement of the central nervous system (SCNS-DLBCL). He presented with acute encephalitis: altered mental status, fever, leukocytosis, neuropsychiatric symptoms, multiple unchanged brain lesions on computed tomography scan of the head, and EEG showed mild to moderate diffuse slowing with low-moderate polymorphic delta and theta activity. With such a wide range of symptoms, the differential diagnosis included paraneoplastic and autoimmune encephalitis. Infectious and autoimmune/paraneoplastic encephalitis in patients with SCNS-DLBCL are not well documented in the literature, hence diagnosis and therapy becomes challenging. This case report describes the patient’s unique presentation of acute encephalitis. Full article
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4262 KiB  
Review
Imaging Characteristics of Malignant Sinonasal Tumors
by Masaya Kawaguchi, Hiroki Kato, Hiroyuki Tomita, Keisuke Mizuta, Mitsuhiro Aoki, Akira Hara and Masayuki Matsuo
J. Clin. Med. 2017, 6(12), 116; https://doi.org/10.3390/jcm6120116 - 6 Dec 2017
Cited by 80 | Viewed by 18953
Abstract
Malignancies of the nasal cavity and paranasal sinuses account for 1% of all malignancies and 3% of malignancies of the upper aerodigestive tract. In the sinonasal tract, nearly half of all malignancies arise in the nasal cavity, whereas most of the remaining malignancies [...] Read more.
Malignancies of the nasal cavity and paranasal sinuses account for 1% of all malignancies and 3% of malignancies of the upper aerodigestive tract. In the sinonasal tract, nearly half of all malignancies arise in the nasal cavity, whereas most of the remaining malignancies arise in the maxillary or ethmoid sinus. Squamous cell carcinoma is the most common histological subtype of malignant tumors occurring in this area, followed by other epithelial carcinomas, lymphomas, and malignant soft tissue tumors. Although many of these tumors present with nonspecific symptoms, each tumor exhibits characteristic imaging features. Although complex anatomy and various normal variants of the sinonasal tract cause difficulty in identifying the origin and extension of large sinonasal tumors, the invasion of vital structures such as the brain, optic nerves, and internal carotid artery affects patients’ prognosis. Thus, diagnostic imaging plays a key role in predicting the histological subtype and in evaluating a tumor extension into adjacent structures. This article describes the computed tomography and magnetic resonance imaging findings for malignant sinonasal tumors. Full article
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Article
Adipose Derived Stem Cells for Corneal Wound Healing after Laser Induced Corneal Lesions in Mice
by Marco Zeppieri, Maria Letizia Salvetat, Antonio Beltrami, Daniela Cesselli, Rossella Russo, Ignacio Alcalde, Jesús Merayo-Lloves, Paolo Brusini and Pier Camillo Parodi
J. Clin. Med. 2017, 6(12), 115; https://doi.org/10.3390/jcm6120115 - 5 Dec 2017
Cited by 31 | Viewed by 5817
Abstract
The aim of our study was to assess the clinical effectiveness of topical adipose derived stem cell (ADSC) treatment in laser induced corneal wounds in mice by comparing epithelial repair, inflammation, and histological analysis between treatment arms. Corneal lesions were performed on both [...] Read more.
The aim of our study was to assess the clinical effectiveness of topical adipose derived stem cell (ADSC) treatment in laser induced corneal wounds in mice by comparing epithelial repair, inflammation, and histological analysis between treatment arms. Corneal lesions were performed on both eyes of 40 mice by laser induced photorefractive keratectomy. All eyes were treated with topical azythromycin bid for three days. Mice were divided in three treatment groups (n = 20), which included: control, stem cells and basic serum; which received topical treatment three times daily for five consecutive days. Biomicroscope assessments and digital imaging were performed by two masked graders at 30, 54, 78, 100, and 172 h to analyze extent of fluorescein positive epithelial defect, corneal inflammation, etc. Immunohistochemical techniques were used in fixed eyes to assess corneal repair markers Ki67, α Smooth Muscle Actin (α-SMA) and E-Cadherin. The fluorescein positive corneal lesion areas were significantly smaller in the stem cells group on days 1 (p < 0.05), 2 (p < 0.02) and 3. The stem cell treated group had slightly better and faster re-epithelization than the serum treated group in the initial phases. Comparative histological data showed signs of earlier and better corneal repair in epithelium and stromal layers in stem cell treated eyes, which showed more epithelial layers and enhanced wound healing performance of Ki67, E-Cadherin, and α-SMA. Our study shows the potential clinical and histological advantages in the topical ADSC treatment for corneal lesions in mice. Full article
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451 KiB  
Review
Neurological and Sleep Disturbances in Bronchiectasis
by Chun Seng Phua, Tissa Wijeratne, Conroy Wong and Lata Jayaram
J. Clin. Med. 2017, 6(12), 114; https://doi.org/10.3390/jcm6120114 - 30 Nov 2017
Cited by 5 | Viewed by 4643
Abstract
Bronchiectasis unrelated to cystic fibrosis is a chronic lung disease that is increasingly recognised worldwide. While other common chronic lung conditions such as chronic obstructive lung disease have been associated with cardiovascular disease, there is a paucity of data on the relationship between [...] Read more.
Bronchiectasis unrelated to cystic fibrosis is a chronic lung disease that is increasingly recognised worldwide. While other common chronic lung conditions such as chronic obstructive lung disease have been associated with cardiovascular disease, there is a paucity of data on the relationship between bronchiectasis and cardiovascular risks such as stroke and sleep disturbance. Furthermore, it is unclear whether other neuropsychological aspects are affected, such as cognition, cerebral infection, anxiety and depression. In this review, we aim to highlight neurological and sleep issues in relation to bronchiectasis and their importance to patient care. Full article
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Perspective
Ethnic Similarities and Differences in the Relationship between Beta Cell Mass and Diabetes
by Jun Inaishi and Yoshifumi Saisho
J. Clin. Med. 2017, 6(12), 113; https://doi.org/10.3390/jcm6120113 - 30 Nov 2017
Cited by 27 | Viewed by 4598
Abstract
Recent evidence has revealed that a change of functional beta cell mass is an essential factor of the pathophysiology of type 2 diabetes (T2DM). Since beta cell dysfunction is not only present in T2DM but also progressively worsens with disease duration, to preserve [...] Read more.
Recent evidence has revealed that a change of functional beta cell mass is an essential factor of the pathophysiology of type 2 diabetes (T2DM). Since beta cell dysfunction is not only present in T2DM but also progressively worsens with disease duration, to preserve or recover functional beta cell mass is important in both prevention of the development of T2DM and therapeutic strategies for T2DM. Furthermore, ethnic difference in functional beta cell mass may also need to be taken into account. Recent evidences suggest that Asians have less beta cell functional capacity compared with Caucasians. Preservation or recovery of functional beta cell mass seems to be further emphasized for Asians because of the limited capacity of beta cell. This review summarizes the current knowledge on beta cell dysfunction in T2DM and discusses the similarities and differences in functional beta cell mass between ethnicities in the face of obesity and T2DM. Full article
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Review
Airway Mucus and Asthma: The Role of MUC5AC and MUC5B
by Luke R. Bonser and David J. Erle
J. Clin. Med. 2017, 6(12), 112; https://doi.org/10.3390/jcm6120112 - 29 Nov 2017
Cited by 233 | Viewed by 19422
Abstract
Asthma is characterized by mucus abnormalities. Airway epithelial hyperplasia and metaplasia result in changes in stored and secreted mucin and the production of a pathologic mucus gel. Mucus transport is impaired, culminating in mucus plugging and airway obstruction—a major cause of morbidity in [...] Read more.
Asthma is characterized by mucus abnormalities. Airway epithelial hyperplasia and metaplasia result in changes in stored and secreted mucin and the production of a pathologic mucus gel. Mucus transport is impaired, culminating in mucus plugging and airway obstruction—a major cause of morbidity in asthma. The polymeric mucins MUC5AC and MUC5B are integral components of airway mucus. MUC5AC and MUC5B gene expression is altered in asthma, and recent work sheds light on their contribution to asthma pathogenesis. Herein, we review our current understanding of the role of MUC5AC and MUC5B in mucus dysfunction in asthma. Full article
(This article belongs to the Special Issue Role of Respiratory Mucins in Health and Disease)
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6835 KiB  
Review
Viral Oncology: Molecular Biology and Pathogenesis
by Uyen Ngoc Mui, Christopher T. Haley and Stephen K. Tyring
J. Clin. Med. 2017, 6(12), 111; https://doi.org/10.3390/jcm6120111 - 29 Nov 2017
Cited by 133 | Viewed by 17069
Abstract
Oncoviruses are implicated in approximately 12% of all human cancers. A large number of the world’s population harbors at least one of these oncoviruses, but only a small proportion of these individuals go on to develop cancer. The interplay between host and viral [...] Read more.
Oncoviruses are implicated in approximately 12% of all human cancers. A large number of the world’s population harbors at least one of these oncoviruses, but only a small proportion of these individuals go on to develop cancer. The interplay between host and viral factors is a complex process that works together to create a microenvironment conducive to oncogenesis. In this review, the molecular biology and oncogenic pathways of established human oncoviruses will be discussed. Currently, there are seven recognized human oncoviruses, which include Epstein-Barr Virus (EBV), Human Papillomavirus (HPV), Hepatitis B and C viruses (HBV and HCV), Human T-cell lymphotropic virus-1 (HTLV-1), Human Herpesvirus-8 (HHV-8), and Merkel Cell Polyomavirus (MCPyV). Available and emerging therapies for these oncoviruses will be mentioned. Full article
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Review
MUC1: The First Respiratory Mucin with an Anti-Inflammatory Function
by Kosuke Kato, Erik P. Lillehoj, Wenju Lu and Kwang Chul Kim
J. Clin. Med. 2017, 6(12), 110; https://doi.org/10.3390/jcm6120110 - 29 Nov 2017
Cited by 52 | Viewed by 9328
Abstract
MUC1 is a membrane-bound mucin expressed on the apical surfaces of most mucosal epithelial cells. In normal lung epithelia, MUC1 is a binding site for Pseudomonas aeruginosa, an opportunistic human pathogen of great clinical importance. It has now been established that MUC1 [...] Read more.
MUC1 is a membrane-bound mucin expressed on the apical surfaces of most mucosal epithelial cells. In normal lung epithelia, MUC1 is a binding site for Pseudomonas aeruginosa, an opportunistic human pathogen of great clinical importance. It has now been established that MUC1 also serves an anti-inflammatory role in the airways that is initiated late in the course of a bacterial infection and is mediated through inhibition of Toll-like receptor (TLR) signaling. MUC1 expression was initially shown to interfere with TLR5 signaling in response to P. aeruginosa flagellin, but has since been extended to other TLRs. These new findings point to an immunomodulatory role for MUC1 during P. aeruginosa lung infection, particularly during the resolution phase of inflammation. This review briefly summarizes the recent characterization of MUC1’s anti-inflammatory properties in both the respiratory tract and extrapulmonary tissues. Full article
(This article belongs to the Special Issue Role of Respiratory Mucins in Health and Disease)
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Article
Implementing a Psychotherapy Service for Medically Unexplained Symptoms in a Primary Care Setting
by Angela Cooper, Allan Abbass, Joanna Zed, Lisa Bedford, Tara Sampalli and Joel Town
J. Clin. Med. 2017, 6(12), 109; https://doi.org/10.3390/jcm6120109 - 29 Nov 2017
Cited by 13 | Viewed by 13860 | Correction
Abstract
Medically unexplained symptoms (MUS) are known to be costly, complex to manage and inadequately addressed in primary care settings. In many cases, there are unresolved psychological and emotional processes underlying these symptoms, leaving traditional medical approaches insufficient. This paper details the implementation of [...] Read more.
Medically unexplained symptoms (MUS) are known to be costly, complex to manage and inadequately addressed in primary care settings. In many cases, there are unresolved psychological and emotional processes underlying these symptoms, leaving traditional medical approaches insufficient. This paper details the implementation of an evidence-based, emotion-focused psychotherapy service for MUS across two family medicine clinics. The theory and evidence-base for using Intensive Short-Term Dynamic Psychotherapy (ISTDP) with MUS is presented along with the key service components of assessment, treatment, education and research. Preliminary outcome indicators showed diverse benefits. Patients reported significantly decreased somatic symptoms in the Patient Health Questionnaire-15 (d = 0.4). A statistically significant (23%) decrease in family physicians’ visits was found in the 6 months after attending the MUS service compared to the 6 months prior. Both patients and primary care clinicians reported a high degree of satisfaction with the service. Whilst further research is needed, these findings suggest that a direct psychology service maintained within the family practice clinic may assist patient and clinician function while reducing healthcare utilization. Challenges and further service developments are discussed, including the potential benefits of re-branding the service to become a ‘Primary Care Psychological Consultation and Treatment Service’. Full article
(This article belongs to the Special Issue Psychosocial Interaction between Physicians and Patients)
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1083 KiB  
Communication
The Impact of the Brain-Derived Neurotrophic Factor Gene on Trauma and Spatial Processing
by Jessica K. Miller, Siné McDougall, Sarah Thomas and Jan Wiener
J. Clin. Med. 2017, 6(12), 108; https://doi.org/10.3390/jcm6120108 - 27 Nov 2017
Cited by 13 | Viewed by 6671
Abstract
The influence of genes and the environment on the development of Post-Traumatic Stress Disorder (PTSD) continues to motivate neuropsychological research, with one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF) gene, given its impact on the integrity of the hippocampal memory system. Research [...] Read more.
The influence of genes and the environment on the development of Post-Traumatic Stress Disorder (PTSD) continues to motivate neuropsychological research, with one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF) gene, given its impact on the integrity of the hippocampal memory system. Research into human navigation also considers the BDNF gene in relation to hippocampal dependent spatial processing. This speculative paper brings together trauma and spatial processing for the first time and presents exploratory research into their interactions with BDNF. We propose that quantifying the impact of BDNF on trauma and spatial processing is critical and may well explain individual differences in clinical trauma treatment outcomes and in navigation performance. Research has already shown that the BDNF gene influences PTSD severity and prevalence as well as navigation behaviour. However, more data are required to demonstrate the precise hippocampal dependent processing mechanisms behind these influences in different populations and environmental conditions. This paper provides insight from recent studies and calls for further research into the relationship between allocentric processing, trauma processing and BDNF. We argue that research into these neural mechanisms could transform PTSD clinical practice and professional support for individuals in trauma-exposing occupations such as emergency response, law enforcement and the military. Full article
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