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Diseases, Volume 6, Issue 2 (June 2018)

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Cover Story (view full-size image) Aspergillosis of the central nervous system is an uncommon complication following neurosurgical [...] Read more.
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Open AccessFeature PaperReview Renal Impairment in Chronic Hepatitis B: A Review
Received: 15 May 2018 / Revised: 4 June 2018 / Accepted: 4 June 2018 / Published: 19 June 2018
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Abstract
The liver plays a key role in the metabolism of proteins. Liver dysfunction affects many organs because it communicates with the spleen and all digestive organs through the portal vein. Additionally, the kidney is an organ that is closely related to the liver
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The liver plays a key role in the metabolism of proteins. Liver dysfunction affects many organs because it communicates with the spleen and all digestive organs through the portal vein. Additionally, the kidney is an organ that is closely related to the liver and is involved in liver diseases. Glomerulonephritis is an important extrahepatic manifestation of chronic hepatitis B virus (HBV) infection. Nucleos(t)ide analog (NA) therapy effectively suppresses HBV replication by inhibiting HBV polymerase, thus decreasing the levels of serum HBV-DNA and delaying the progression of cirrhosis. Although NA therapy is recommended for all patients with chronic HBV infection, regardless of the level of renal dysfunction, there is limited information on NA use in patients with chronic kidney disease. In addition, in patients with end-stage liver cirrhosis, hepatorenal syndrome can be fatal. Hence, we should take into account the stage of impaired renal function in patients with cirrhosis. The aims of this article are to review the epidemiology, clinical presentation, treatment, and prevention of HBV-associated nephropathy. Full article
(This article belongs to the Special Issue Hepatitis and Treatment)
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Open AccessCommunication Adverse Effects of Direct Acting Antivirals in HIV/HCV Coinfected Patients: A 4-Year Experience in Miami, Florida
Received: 24 May 2018 / Revised: 16 June 2018 / Accepted: 18 June 2018 / Published: 19 June 2018
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Abstract
Introduction: The new direct acting antivirals (DAA) have demonstrated low rates of adverse effects in controlled studies. However, real world-studies have disclosed emerging toxicities and drug-drug interactions in special populations. Methods: We conducted a retrospective review of HIV/HCV coinfected patients who were treated
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Introduction: The new direct acting antivirals (DAA) have demonstrated low rates of adverse effects in controlled studies. However, real world-studies have disclosed emerging toxicities and drug-drug interactions in special populations. Methods: We conducted a retrospective review of HIV/HCV coinfected patients who were treated with DAA at Jackson Memorial Hospital from 2014 to 2017. Our aim was to determine the adverse effects (AE) and factors that are associated with AE in HIV/HCV individuals who are treated with DAA. Results: There were 78 coinfected patients treated with DAA. AE that were secondary to DAA were reported by 21 (26.9%) patients. The most common AE were fatigue (47.6%), gastrointestinal symptoms (38.1%), anemia (14.3%), and headache (14.3%). In comparison with the rest of the study cohort, the patients who developed AE were more often Caucasian (33.3% vs. 10.5%, p = 0.017) and were more frequently treated with PrOD/Ribavirin (9.5% vs. 0%, p = 0.018). In terms of antiretroviral therapy (ART), there was a trend towards a more frequent use of TDF/FTC + NNRTI (33.3% vs. 14%, p = 0.055). Conclusions: These findings demonstrated good tolerability of DAAs in HIV/HCV coinfected patients. More real-world studies are needed to explore the variables that are associated with AE. Full article
(This article belongs to the Special Issue Hepatitis and Treatment)
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Open AccessReview Pancreatic Cystic Lesions: Pathogenesis and Malignant Potential
Received: 15 May 2018 / Revised: 6 June 2018 / Accepted: 7 June 2018 / Published: 13 June 2018
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Abstract
Pancreatic cancer remains one of the most lethal cancers despite extensive research. Further understanding of precursor lesions may enhance the ability to treat and prevent pancreatic cancer. Pancreatic cystic lesions (PCLs) with malignant potential include: mucinous PCLs (intraductal papillary mucinous neoplasms and mucinous
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Pancreatic cancer remains one of the most lethal cancers despite extensive research. Further understanding of precursor lesions may enhance the ability to treat and prevent pancreatic cancer. Pancreatic cystic lesions (PCLs) with malignant potential include: mucinous PCLs (intraductal papillary mucinous neoplasms and mucinous cystic neoplasm), solid pseudopapillary tumors and cystic neuroendocrine tumors. This review summarizes the latest literature describing what is known about the pathogenesis and malignant potential of these PCLs, including unique epidemiological, radiological, histological, genetic and molecular characteristics. Full article
(This article belongs to the Special Issue Pathogenesis of Pancreatic Cancer)
Open AccessArticle Prevalence and Determinants of Antibiotic Self-Medication among Adult Patients with Respiratory Tract Infections in the Mboppi Baptist Hospital, Douala, Cameroon: A Cross-Sectional Study
Received: 30 April 2018 / Revised: 4 June 2018 / Accepted: 7 June 2018 / Published: 8 June 2018
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Abstract
Antibiotic self-medication in patients with respiratory tract infections (RTI) is increasing globally and has been reported to be one of the prime contributors to antimicrobial resistance (AMR). Our study aims to provide data on the prevalence of antibiotic self-medication and identify the factors
[...] Read more.
Antibiotic self-medication in patients with respiratory tract infections (RTI) is increasing globally and has been reported to be one of the prime contributors to antimicrobial resistance (AMR). Our study aims to provide data on the prevalence of antibiotic self-medication and identify the factors contributing to self-medication in adult patients with respiratory tract infection in an urban setting in Cameroon. This was cross-sectional study carried out at Mboppi Baptist Hospital, Douala, Cameroon. A validated structured questionnaire was administered to 308 consenting participants with diagnosed RTIs, to collect data on socio-demographic characteristics and history of antibiotic self-medication. Significance was set at a p-value < 0.05. The prevalence of antibiotic self-medication amongst individuals with RTIs was 41.9% (95% CI 36.5% to 47.5%). Patients with a history of pulmonary tuberculosis (TB) were significantly less likely to self-medicate with antibiotics (p-value = 0.043). The most common source of antibiotic self-medication was pharmacies (62%) and Cotrimoxazole and Amoxicillin were the most commonly used antibiotics (38.8% (50), 26.4% (34), respectively). Self-medication with antibiotics in adult patients with RTIs is common in Cameroon. Control of the use of antibiotics, organisation of medication stewardship programs, and education of the general population on the adverse consequences of antibiotic self-medication are required. Full article
(This article belongs to the Section Infectious Disease)
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Open AccessReview Treatment of Major Depressive Disorder in Pediatric Populations
Received: 30 April 2018 / Revised: 28 May 2018 / Accepted: 31 May 2018 / Published: 4 June 2018
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Abstract
Major depressive disorder (MDD) is a severe illness that afflicts about 16.6% of people over their lifetime. MDD is highly correlated with suicidality, and often first presents in adolescence. Unfortunately, many pediatric patients suffering from MDD go undiagnosed, and current evidence-based treatment options
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Major depressive disorder (MDD) is a severe illness that afflicts about 16.6% of people over their lifetime. MDD is highly correlated with suicidality, and often first presents in adolescence. Unfortunately, many pediatric patients suffering from MDD go undiagnosed, and current evidence-based treatment options in the U.S. are limited to psychotherapy and two selective serotonin reuptake inhibitors approved by the United States Food and Drug Administration. Molecular mechanisms have been shown to play a role in MDD pathogenesis, progression, and response to medication, yet few studies have explored the role of these pathways in pediatric MDD. In this review, we outline the gravity and importance of MDD in pediatric patients, some challenges in diagnosis and treatment, current treatments available for pediatric patients, and research to investigate differences between pediatric and adult MDD. We hope that this review will provide an outline of the current understanding and treatment of MDD in pediatric patients, and provide thoughtful insights for future work that could advance our understanding of MDD in pediatric populations, and also identify new therapeutic strategies. Full article
(This article belongs to the Special Issue Pediatric Diseases)
Open AccessFeature PaperReview Psoriasis and Microbiota: A Systematic Review
Received: 5 May 2018 / Revised: 29 May 2018 / Accepted: 1 June 2018 / Published: 2 June 2018
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Abstract
Background: Recent advances have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases as well as its impact on the efficacy of therapeutic agents. Psoriasis is a chronic, multifactorial inflammatory skin disorder, which has a microbiota distinct from healthy,
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Background: Recent advances have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases as well as its impact on the efficacy of therapeutic agents. Psoriasis is a chronic, multifactorial inflammatory skin disorder, which has a microbiota distinct from healthy, unaffected skin. Aim: Through an extensive review of the literature, we aim to discuss the skin and gut microbiota and redefine their role in the pathogenesis of psoriasis. Conclusions: Unfortunately, the direct link between the skin microbiota and the pathogenesis of psoriasis remains to be clearly established. Apart from improving the course of psoriasis, selective modulation of the microbiota may increase the efficacy of medical treatments as well as attenuate their side effects. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
Open AccessCase Report Central Nervous System Aspergillosis: An Unexpected Complication following Neurosurgery
Received: 19 May 2018 / Revised: 29 May 2018 / Accepted: 30 May 2018 / Published: 31 May 2018
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Abstract
Post-surgical aspergillosis is an uncommon complication that carries a high mortality rate in affected patients. The diagnosis is challenging given the lack of highly sensitive methods to isolate Aspergillus from surgical sites. Here, we present a case of post-surgical aspergillosis that occurred after
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Post-surgical aspergillosis is an uncommon complication that carries a high mortality rate in affected patients. The diagnosis is challenging given the lack of highly sensitive methods to isolate Aspergillus from surgical sites. Here, we present a case of post-surgical aspergillosis that occurred after the resection of acoustic neuroma in an immunocompetent patient. Imaging revealed leptomeningeal enhancement and a cerebellar extra-axial fluid collection adjacent to the right retrosigmoid craniotomy. The patient was taken to the operating room for debridement, where purulent fluid was obtained from subdural space. The diagnosis was achieved by histopathology and polymerase chain reaction (PCR) in brain tissue. Appropriate investigations failed to detect contamination in the operating room. The patient was successfully treated with 3 months of voriconazole. We highlight the importance of recognizing this uncommon complication and advocate for the use of molecular techniques to improve the diagnostic yield in central nervous system aspergillosis. Full article
(This article belongs to the Section Infectious Disease)
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Open AccessReview CVD Risk Stratification in the PCSK9 Era: Is There a Role for LDL Subfractions?
Received: 4 May 2018 / Revised: 23 May 2018 / Accepted: 24 May 2018 / Published: 27 May 2018
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Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce the risk of cardiovascular events and all-cause mortality in patients at high risk of cardiovascular disease (CVD). Due to high costs and unknown long-term adverse effects, critical evaluation of patients considered for PCSK9 inhibitors is
[...] Read more.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce the risk of cardiovascular events and all-cause mortality in patients at high risk of cardiovascular disease (CVD). Due to high costs and unknown long-term adverse effects, critical evaluation of patients considered for PCSK9 inhibitors is important. It has been proposed that measuring low-density lipoprotein (LDL) subfractions, or LDL particle numbers (LDL-P), could be of value in CVD risk assessment and may identify patients at high risk of CVD. This review evaluates the evidence for the use of LDL subfractions, or LDL-P, when assessing CVD risk in patients for whom PCSK9 inhibitors are considered as a lipid-lowering therapy. Numerous methods for measuring LDL subfractions and LDL-P are available, but several factors limit their availability. A lack of standardization makes comparison between the different methods challenging. Longitudinal population-based studies have found an independent association between different LDL subfractions, LDL-P, and an increased risk of cardiovascular events, but definitive evidence that these measurements add predictive value to the standard risk markers is lacking. No studies have proven that these measurements improve clinical outcomes. PCSK9 inhibitors seem to be effective at lowering all LDL subfractions and LDL-P, but any evidence that measuring LDL subfractions and LDL-P yield clinically useful information is lacking. Such analyses are currently not recommended when considering whether to initiate PCKS9 inhibitors in patients at risk of CVD. Full article
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Open AccessFeature PaperReview Management of Dyslipidemia in Type 2 Diabetes: Recent Advances in Nonstatin Treatment
Received: 3 May 2018 / Revised: 22 May 2018 / Accepted: 22 May 2018 / Published: 24 May 2018
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Abstract
Dyslipidemia is a major risk factor for cardiovascular disease (CVD), which is the leading cause of morbidity and mortality in type 2 diabetes (T2DM). Statins have played a crucial role in its management, but residual risk remains since many patients cannot achieve their
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Dyslipidemia is a major risk factor for cardiovascular disease (CVD), which is the leading cause of morbidity and mortality in type 2 diabetes (T2DM). Statins have played a crucial role in its management, but residual risk remains since many patients cannot achieve their desired low-density lipoprotein cholesterol (LDL-C) level and up to 20% of patients are statin-intolerant, experiencing adverse events perceived to be caused by statins, most commonly muscle symptoms. Recently, great advances have been made in nonstatin treatment with ezetimibe, a cholesterol absorption inhibitor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs), all showing a proven benefit with an excellent safety profile in cardiovascular outcome trials. This review summarizes the key aspects and the evolving role of these agents in the management of dyslipidemia in patients with T2DM, along with a brief introduction of novel drugs currently in development. Full article
Open AccessReview Zebrafish Models of Rare Hereditary Pediatric Diseases
Received: 27 April 2018 / Revised: 17 May 2018 / Accepted: 19 May 2018 / Published: 22 May 2018
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Abstract
Recent advances in sequencing technologies have made it significantly easier to find the genetic roots of rare hereditary pediatric diseases. These novel methods are not panaceas, however, and they often give ambiguous results, highlighting multiple possible causative mutations in affected patients. Furthermore, even
[...] Read more.
Recent advances in sequencing technologies have made it significantly easier to find the genetic roots of rare hereditary pediatric diseases. These novel methods are not panaceas, however, and they often give ambiguous results, highlighting multiple possible causative mutations in affected patients. Furthermore, even when the mapping results are unambiguous, the affected gene might be of unknown function. In these cases, understanding how a particular genotype can result in a phenotype also needs carefully designed experimental work. Model organism genetics can offer a straightforward experimental setup for hypothesis testing. Containing orthologs for over 80% of the genes involved in human diseases, zebrafish (Danio rerio) has emerged as one of the top disease models over the past decade. A plethora of genetic tools makes it easy to create mutations in almost any gene of the zebrafish genome and these mutant strains can be used in high-throughput preclinical screens for active molecules. As this small vertebrate species offers several other advantages as well, its popularity in biomedical research is bound to increase, with “aquarium to bedside” drug development pipelines taking a more prevalent role in the near future. Full article
(This article belongs to the Special Issue Pediatric Diseases)
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Open AccessFeature PaperReview Viral Vectors in Gene Therapy
Received: 30 April 2018 / Revised: 15 May 2018 / Accepted: 16 May 2018 / Published: 21 May 2018
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Abstract
Applications of viral vectors have found an encouraging new beginning in gene therapy in recent years. Significant improvements in vector engineering, delivery, and safety have placed viral vector-based therapy at the forefront of modern medicine. Viral vectors have been employed for the treatment
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Applications of viral vectors have found an encouraging new beginning in gene therapy in recent years. Significant improvements in vector engineering, delivery, and safety have placed viral vector-based therapy at the forefront of modern medicine. Viral vectors have been employed for the treatment of various diseases such as metabolic, cardiovascular, muscular, hematologic, ophthalmologic, and infectious diseases and different types of cancer. Recent development in the area of immunotherapy has provided both preventive and therapeutic approaches. Furthermore, gene silencing generating a reversible effect has become an interesting alternative, and is well-suited for delivery by viral vectors. A number of preclinical studies have demonstrated therapeutic and prophylactic efficacy in animal models and furthermore in clinical trials. Several viral vector-based drugs have also been globally approved. Full article
(This article belongs to the Special Issue Gene Therapy)
Open AccessReview Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review
Received: 29 April 2018 / Revised: 17 May 2018 / Accepted: 18 May 2018 / Published: 19 May 2018
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Abstract
Pediatric acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer diagnosis, with numbers rising gradually every year. This paper proposes a novel therapeutic agent for pediatric ALL on the basis of a failed clinical drug trial in 2006. TGN1412 was a promising
[...] Read more.
Pediatric acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer diagnosis, with numbers rising gradually every year. This paper proposes a novel therapeutic agent for pediatric ALL on the basis of a failed clinical drug trial in 2006. TGN1412 was a promising therapeutic agent that yielded outstanding results in both in vitro studies and animal trials. It is a CD28 superagonist monoclonal antibody that activates T regulatory (TReg) cells in the absence of costimulation of the T cell receptor (TCR) by an antigen-presenting cell. This drug was intended as a solution to T cell deficient diseases such as B cell leukemia and autoimmune diseases such as rheumatoid arthritis. When phase I clinical trials were conducted, all volunteers that received the drug experienced severe cytokine release syndrome (CRS) and faced multiple-organ failure within hours. TGN1412 was reassessed and re-entered clinical trials as a therapeutic for rheumatoid arthritis. A new assay was developed to better quantify T cell response, and volunteers in this trial experienced no pro-inflammatory cytokine release. This essay analyzes how misinformation contributed to the failure of TGN1412 in clinical trials and how revisiting this therapeutic could yield a novel treatment for pediatric B cell leukemia. Full article
(This article belongs to the Special Issue Pediatric Diseases)
Open AccessCase Report Case Report of Isoniazid-Related Acute Liver Failure Requiring Liver Transplantation
Received: 2 May 2018 / Revised: 17 May 2018 / Accepted: 17 May 2018 / Published: 19 May 2018
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Abstract
The prevalence of latent tuberculosis infection (LTBI) in the United States in 2011 and 2012 was estimated at 4.4–4.8%. As of 2015, 12.4 million people still possessed LTBI. Isoniazid, or isonicotinic acid hydrazine (INH), is the most commonly used medication among varying regimens
[...] Read more.
The prevalence of latent tuberculosis infection (LTBI) in the United States in 2011 and 2012 was estimated at 4.4–4.8%. As of 2015, 12.4 million people still possessed LTBI. Isoniazid, or isonicotinic acid hydrazine (INH), is the most commonly used medication among varying regimens that exist in the treatment of tuberculosis and LTBI. INH-related hepatotoxicity is a well-known adverse effect of its use, often causing asymptomatic elevations in serum aminotransferase levels. These elevations are typically transient and reversible, but can cause acute, clinically-significant liver injury in rare cases. We report a case of a 67-year old male who developed subacute hepatic injury secondary to INH treatment for LTBI, and ultimately underwent liver transplantation due to the progression to hepatic decompensation, despite withdrawal of the medication. Because symptoms of INH hepatotoxicity are nonspecific and prognosis can be variable, clinicians must maintain a high index of suspicion for this adverse effect. As exemplified by this case, early recognition may be life-saving. Full article
(This article belongs to the Section Gastroenterology)
Open AccessCommentary Heat Shock Gene Inactivation and Protein Aggregation with Links to Chronic Diseases
Received: 10 April 2018 / Revised: 14 May 2018 / Accepted: 16 May 2018 / Published: 18 May 2018
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Abstract
The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and
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The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and autoimmunity. Overnutrition, temperature dysregulation, and stress repress the heat shock gene Sirtuin 1 with the induction of HSP regulated amyloid beta aggregation involved in the autoimmune response. Defective circadian rhythm alterations are connected to inactivation of the peripheral sink amyloid beta clearance pathway and related to insulin resistance, protein aggregation, and autoimmune disease in non-alcoholic fatty liver disease (NAFLD) and various neurodegenerative diseases such as Alzheimer’s disease. Nutritional therapy is critical to prevent immunosenescence, and plasma Sirtuin 1 levels should be determined to reverse, stabilize, and prevent protein aggregation with relevance to mitochondrial apoptosis and programmed cell death in chronic diseases. Full article
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Open AccessFeature PaperReview Pulmonary Arterial Hypertension: Pathophysiology and Treatment
Received: 27 April 2018 / Revised: 12 May 2018 / Accepted: 12 May 2018 / Published: 16 May 2018
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Abstract
Pulmonary arterial hypertension (PAH), the first category of pulmonary hypertension, is a chronic and progressive disorder characterised by angioproliferative vasculopathy in the pulmonary arterioles, leading to endothelial and smooth muscle proliferation and dysfunction, inflammation and thrombosis. These changes increase pulmonary vascular resistance and
[...] Read more.
Pulmonary arterial hypertension (PAH), the first category of pulmonary hypertension, is a chronic and progressive disorder characterised by angioproliferative vasculopathy in the pulmonary arterioles, leading to endothelial and smooth muscle proliferation and dysfunction, inflammation and thrombosis. These changes increase pulmonary vascular resistance and subsequent pulmonary arterial pressure, causing right ventricular failure which leads to eventual death if untreated. The management of PAH has advanced rapidly in recent years due to improved understanding of the condition’s pathophysiology, specifically the nitric oxide, prostacyclin-thromboxane and endothelin-1 pathways. Five classes of drugs targeting these pathways are now available: phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, prostacyclin analogues, prostacyclin receptor agonists and endothelin receptor antagonists. These developments have led to substantial improvements in mortality rate in recent decades. Recently, long-term studies have demonstrated sustained progression-free survival and have created a new paradigm of initial combination therapy. Despite these targeted therapies, PAH is still associated with significant morbidity and mortality. As such, further research into broadening our understanding of PAH pathophysiology is underway with potential of increasing the repertoire of drugs available. Full article
(This article belongs to the Section Cardiology)
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Open AccessFeature PaperArticle Zika Virus and the Risk for Renter Households
Received: 8 March 2018 / Revised: 10 May 2018 / Accepted: 11 May 2018 / Published: 15 May 2018
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Abstract
Recent research on family income indicates that a lack of economic stability can affect healthy housing. Those with limited resources experience higher rates of inadequate and unstable housing many times forcing them to live in undesirable communities in which there can be several
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Recent research on family income indicates that a lack of economic stability can affect healthy housing. Those with limited resources experience higher rates of inadequate and unstable housing many times forcing them to live in undesirable communities in which there can be several community-level health-related issues. One community-level health-related factor of concern has been the reemergence of Zika virus. Some research has indicated that a higher risk of catching Zika virus may exist in neighborhoods and areas with unhealthy housing. Therefore, this study sought to explore the existence of a relationship between rental housing and the Zika virus. Our findings indicated a significant correlation existed between renter occupied household units and the presence of Zika virus. This finding is notable as it indicates that renters have a higher chance of contracting Zika virus than non-renters. Future research should further examine the demographic and housing situation in other communities reporting cases of the Zika virus. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology)
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Open AccessFeature PaperCase Report Proctitis Caused by Mycobacterium avium-intracellulare in an HIV-Infected Patient
Received: 20 April 2018 / Revised: 2 May 2018 / Accepted: 5 May 2018 / Published: 8 May 2018
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Abstract
Infectious proctitis is usually associated with sexually transmitted diseases, especially in HIV-infected individuals. Limited information is found about the role of Mycobacterium avium-intracellulare as a causative agent for this condition. Here, we report the case of an HIV-infected patient with a CD4 count
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Infectious proctitis is usually associated with sexually transmitted diseases, especially in HIV-infected individuals. Limited information is found about the role of Mycobacterium avium-intracellulare as a causative agent for this condition. Here, we report the case of an HIV-infected patient with a CD4 count of 304 cells/uL and undetectable HIV viral load, who presented with constipation and painful defecation. Endoscopic evaluation was significant for shallow rectal ulcerations. Histopathology revealed poorly formed granulomas. Stool culture grew Mycobacterium sp. that was further identified as Mycobacterium avium-intracellulare by DNA probe. He was successfully treated with a 3-drug regimen that included azithromycin, ethambutol and rifabutin. We advocate the use of AFB stool culture in cases of proctitis in which initial investigations for sexually transmitted diseases are unrevealing. Full article
(This article belongs to the Section Infectious Disease)
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Open AccessFeature PaperArticle Survival and Prognostic Factors in Mixed Cryoglobulinemia: Data from 246 Cases
Received: 31 March 2018 / Revised: 24 April 2018 / Accepted: 27 April 2018 / Published: 3 May 2018
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Abstract
Introduction: The clinical and therapeutic management of mixed cryoglobulinemia (MC) remains a subject of controversy. In addition, most studies have not recorded the long-term follow-up and the outcome of these cases. Material and Methods: We enrolled 246 patients affected by MC who were
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Introduction: The clinical and therapeutic management of mixed cryoglobulinemia (MC) remains a subject of controversy. In addition, most studies have not recorded the long-term follow-up and the outcome of these cases. Material and Methods: We enrolled 246 patients affected by MC who were consecutively admitted to our Department from January 1993 to February 2013. Clinical and biological data had been recorded until June 2014. Results: The median age (at diagnosis) was 60 years (range 26–83). The aetiology was HCV in 95% of patients, HBV in 3% and “essential” in 2%. HCV genotype was 1b in 57%, genotypes 2–3 in 43%. MC was Type II in 203 of the cases (87%) and Type III in 52 (13%). The most frequent clinical manifestations were purpura (72%), chronic liver disease (70%), glomerulonephritis (35%), arthralgias (58%), peripheral neuropathy (21%), non-Hodgkin lymphoma (15%) and cutaneous ulcers (3%). Purpura, arthralgias, peripheral neuropathy, glomerulonephritis and non-Hodgkin lymphoma were more frequently observed in Type II than in Type III MC (p < 0.05). Treatments were interferon (IFN) or Pegilated-IFN (PEG-IFN) alone or plus Ribavirin (RIBA) in 101 cases, steroids with or without alkylating agents in 33 cases, Rituximab in 8 patients. The complete clinical, virological and immunological responses were associated with PEG-IFN plus RIBA. Severe infections were associated with renal failure. At 10 years, the overall survival rate was 71% in Type II MC and 84% in Type III (p < 0.053). Conclusions: From our data, antiviral therapy is the first-line therapy in HCV-related MC, whereas steroids, alkylating agents and Rituximab should be considered as a second-line therapy. Given the heterogeneity of the disease, the role of these different therapeutic strategies should be checked in randomized controlled trials. Full article
(This article belongs to the Special Issue Hepatitis and Treatment)
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Open AccessFeature PaperPerspective Epigenetic Regulation of ATP-Binding Cassette Protein A1 (ABCA1) Gene Expression: A New Era to Alleviate Atherosclerotic Cardiovascular Disease
Received: 16 April 2018 / Revised: 27 April 2018 / Accepted: 2 May 2018 / Published: 3 May 2018
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Abstract
The most important function of high density lipoprotein (HDL) is its ability to remove cholesterol from cells and tissues involved in the early stages of atherosclerosis back to the liver for excretion. The ATP-binding cassette transporters ABCA1 and ABCG1 are responsible for the
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The most important function of high density lipoprotein (HDL) is its ability to remove cholesterol from cells and tissues involved in the early stages of atherosclerosis back to the liver for excretion. The ATP-binding cassette transporters ABCA1 and ABCG1 are responsible for the major part of cholesterol efflux to HDL in macrophage foam cells. Thus, promoting the process of reverse cholesterol transport (RCT) by upregulating mainly ABCA1 remains one of the potential targets for the development of new therapeutic agents against atherosclerosis. Growing evidence suggests that posttranscriptional regulation of HDL biogenesis as well as modulation of ABCA1 expression are under the control of several genetic and epigenetic factors such as transcription factor (TFs), microRNAs (miRNAs) and RNA-binding proteins (RBPs).These factors may act either individually or in combination to orchestrate ABCA1 expression. Complementary to our recent work, we propose an exploratory model for the potential molecular mechanism(s) underlying epigenetic signature of ABCA1 gene regulation. Such a model may hopefully provide the basic framework for understanding the epigenetic regulation of RCT and contribute to the development of novel therapeutic strategies to alleviate the burden of cardiovascular diseases (CVD). Full article
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Open AccessFeature PaperArticle Comparison of Brain Natriuretic Peptide Levels to Simultaneously Obtained Right Heart Hemodynamics in Stable Outpatients with Pulmonary Arterial Hypertension
Received: 17 March 2018 / Revised: 21 April 2018 / Accepted: 27 April 2018 / Published: 1 May 2018
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Abstract
Pulmonary arterial hypertension (PAH) is a progressive disease that requires validated biomarkers of disease severity. While PAH is defined hemodynamically by right heart catheterization (RHC), brain natriuretic peptide (BNP) is recommended by guidelines to assess disease status. Retrospectively collected data in 138 group
[...] Read more.
Pulmonary arterial hypertension (PAH) is a progressive disease that requires validated biomarkers of disease severity. While PAH is defined hemodynamically by right heart catheterization (RHC), brain natriuretic peptide (BNP) is recommended by guidelines to assess disease status. Retrospectively collected data in 138 group 1 PAH patients were examined for the correlation of BNP levels to simultaneously obtained right heart catheterization (RHC). Patients were mostly Caucasian women, with functional class III symptoms, mean BNP of 406 ± 443 pg/mL, and an average right atrial pressure (RAP) of 9.9 ± 5.7 mm Hg and mean pulmonary artery pressure (mPAP) of 47.3 ± 14.7 mm Hg. Significant correlation was demonstrated between BNP and RAP (p = 0.021) and mPAP (p = 0.003). Additional correlation was seen with right heart size on echocardiography: right atrial (RAE; p = 0.04) and right ventricular enlargement (p = 0.03). An increased BNP level was an independent predictor of mortality (p < 0.0001), along with RAP (p = 0.039) and RAE (p = 0.018). Simultaneous collection of BNP at the time of RHC confirmed the correlation of BNP with right heart hemodynamics. The current results reinforce the use of BNP level as a continuous variable to assess disease severity in group 1 PAH. Full article
(This article belongs to the Section Cardiology)
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Open AccessArticle Self-Medication with Antibiotics, Attitude and Knowledge of Antibiotic Resistance among Community Residents and Undergraduate Students in Northwest Nigeria
Received: 28 March 2018 / Revised: 24 April 2018 / Accepted: 24 April 2018 / Published: 27 April 2018
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Abstract
This study set out to evaluate self-medicated antibiotics and knowledge of antibiotic resistance among undergraduate students and community members in northern Nigeria. Antibiotic consumption pattern, source of prescription, illnesses commonly treated, attitude towards antibiotics, and knowledge of antibiotic resistance were explored using a
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This study set out to evaluate self-medicated antibiotics and knowledge of antibiotic resistance among undergraduate students and community members in northern Nigeria. Antibiotic consumption pattern, source of prescription, illnesses commonly treated, attitude towards antibiotics, and knowledge of antibiotic resistance were explored using a structured questionnaire. Responses were analyzed and summarized using descriptive statistics. Of the 1230 respondents from undergraduate students and community members, prescription of antibiotics by a physician was 33% and 57%, respectively, amongst undergraduate students and community members. We tested the respondents’ knowledge of antibiotic resistance (ABR) and found that undergraduate students displayed less knowledge that self-medication could lead to ABR (32.6% and 42.2% respectively). Self-medication with antibiotics is highly prevalent in Northwest Nigeria, with most medicines being purchased from un-licensed stores without prescription from a physician. We also observed a significant gap in respondents’ knowledge of ABR. There is an urgent need for public health authorities in Nigeria to enforce existing laws on antibiotics sales and enlighten the people on the dangers of ABR. Full article
(This article belongs to the Section Infectious Disease)
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Open AccessFeature PaperCommunication Hepatitis C in Pregnancy
Received: 27 March 2018 / Revised: 20 April 2018 / Accepted: 23 April 2018 / Published: 27 April 2018
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Abstract
The prevalence of hepatitis C in pregnancy is as high as 3.6% in large cohorts. The prevalence of hepatitis C acquired by vertical transmission is 0.2% to 0.4% in the United States and Europe. Although screening is not recommended in the absence of
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The prevalence of hepatitis C in pregnancy is as high as 3.6% in large cohorts. The prevalence of hepatitis C acquired by vertical transmission is 0.2% to 0.4% in the United States and Europe. Although screening is not recommended in the absence of certain risk factors, the importance of understanding hepatitis C in pregnancy lies in its association with adverse maternal and neonatal outcomes. There is potential for those infants infected by vertical transmission to develop chronic hepatitis C, cirrhosis or hepatocellular carcinoma. The risk of vertical transmission is increased when mothers are co-infected with Human Immunodeficiency Virus (HIV) or possess a high viral load. There is no clear data supporting that mode of delivery increases or reduces risk. Breastfeeding is not associated with increased risk of transmission. Premature rupture of membranes, invasive procedures (such as amniocentesis), intrapartum events, or fetal scalp monitoring may increase risk of transmission. In pregnant patients, hepatitis C is diagnosed with a positive ELISA-3 and detectable Hepatitis C Virus (HCV) RNA viral load. Infants born to HCV-infected mothers should be tested for either HCV RNA on at least two separate occasions. Although prevention is not possible, there may be a role for newer direct acting anti-viral medications in the future. Full article
(This article belongs to the Special Issue Hepatitis and Treatment)
Open AccessFeature PaperCase Report Use of Leukocyte Platelet (L-PRF) Rich Fibrin in Diabetic Foot Ulcer with Osteomyelitis (Three Clinical Cases Report)
Received: 21 March 2018 / Revised: 18 April 2018 / Accepted: 21 April 2018 / Published: 24 April 2018
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Abstract
In this study, the use of fibrin rich in leukocytes and platelets (L-PRF) was explored to heal osteomyelitis ulcers in a diabetic foot. The goal was to standardize the utilization of L-PRF in patients with osteomyelitis to direct it for healing. L-PRF was
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In this study, the use of fibrin rich in leukocytes and platelets (L-PRF) was explored to heal osteomyelitis ulcers in a diabetic foot. The goal was to standardize the utilization of L-PRF in patients with osteomyelitis to direct it for healing. L-PRF was obtained autologously from the peripheral blood of the diabetic patients (n = 3) having osteomyelitis and skin lesions for at least six months. The L-PRF and supernatant serum were inserted into the skin lesion to the bone after a surgical debridement. The evolution of lesions over time was analyzed. All three patients showed positivity to the Probe-to-Bone test and Nuclear Magnetic Resonance detected cortico-periosteal thickening and/or outbreaks of spongy cortical osteolysis in adjacency of the ulcer. The infections were caused by Cocci Gram-positive bacteria, such as S. Aureus, S. β-hemolytic, S. Viridans and Bacilli; and Gram-negative such as Pseudomonas, Proteus, Enterobacter; and yeast, Candida. The blood count did not show any significant alterations. To date, all three patients have healed skin lesions (in a patient for about two years) with no evidence of infection. These preliminary results showed that L-PRF membranes could be a new method of therapy in such problematic diseases. Overall, the L-PRF treatment in osteomyelitis of a diabetic foot seems to be easy and cost-effective by regenerative therapy of chronic skin lesions. In addition, it will improve our understanding of wound healing. Full article
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Open AccessArticle Levels of Soluble Endothelium Adhesion Molecules and Complications among Sickle Cell Disease Patients in Ghana
Received: 27 February 2018 / Revised: 16 April 2018 / Accepted: 17 April 2018 / Published: 21 April 2018
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Abstract
Background: Soluble adhesion molecules are involved in the gathering and joining of inflammatory cells to vascular endothelium. Therefore, they serve as potential markers of endothelial dysfunction in vascular diseases including sickle cell disease (SCD). In Ghana, there are scarcely any report on the
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Background: Soluble adhesion molecules are involved in the gathering and joining of inflammatory cells to vascular endothelium. Therefore, they serve as potential markers of endothelial dysfunction in vascular diseases including sickle cell disease (SCD). In Ghana, there are scarcely any report on the levels of adhesion molecules among SCD patients. The current study aimed to determine plasma levels of ICAM-1, VCAM-1 and E-Selectin as markers of endothelial dysfunction in SCD patients in steady state, complications and controls. Methodology: This was a cross-sectional study involving 60 HbAA controls, 46 HbSS steady state, 57 HbSS VOC, 18 HbSC VOC, 21 HbSS with leg ulcer and 11 HbSS with priapism. Blood samples were collected from all the study subjects (n = 213) and processed into plasma. The plasma levels of VCAM-1, ICAM-1 and E-Selectin concentrations of SCD patients and controls were measured using a double sandwich ELISA technique. Demographic information was also collected from the study subjects. Results: Levels of all soluble proteins (ICAM-1, VCAM-1 and E-Selectin) were significantly higher in HbSS steady-state patients compared to non-SCD controls (p < 0.001). Generally, SCD patients with complications had relatively higher levels of the soluble proteins compared to those in the steady-state. Of the SCD patients with complications, those with vaso-occlusion crisis (HbSS VOC) had relatively higher levels of ICAM-1, VCAM-1 and E-Selectin at (62.42 ng/mL ± 26.09), (634.99 ng/mL ± 324.31) and (236.77 ng/mL ± 114.40) respectively; Conclusion: Although levels of adhesion molecules were high in all the SCD patients with complications, those with vaso-occlusive crisis had higher levels. This might reflect an ongoing endothelial dysfunction in these patients. SCD patients with vaso-occlusive crisis presents with a more severe pathophysiology condition. Full article
Open AccessFeature PaperReview Implications of PI3K/AKT/PTEN Signaling on Superoxide Dismutases Expression and in the Pathogenesis of Alzheimer’s Disease
Received: 27 February 2018 / Revised: 15 April 2018 / Accepted: 18 April 2018 / Published: 20 April 2018
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Abstract
Alzheimer’s disease is a neurodegenerative sickness, where the speed of personal disease progression differs prominently due to genetic and environmental factors such as life style. Alzheimer’s disease is described by the construction of neuronal plaques and neurofibrillary tangles composed of phosphorylated tau protein.
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Alzheimer’s disease is a neurodegenerative sickness, where the speed of personal disease progression differs prominently due to genetic and environmental factors such as life style. Alzheimer’s disease is described by the construction of neuronal plaques and neurofibrillary tangles composed of phosphorylated tau protein. Mitochondrial dysfunction may be a noticeable feature of Alzheimer’s disease and increased production of reactive oxygen species has long been described. Superoxide dismutases (SODs) protect from excess reactive oxygen species to form less reactive hydrogen peroxide. It is suggested that SODs can play a protective role in neurodegeneration. In addition, PI3K/AKT pathway has been shown to play a critical role on the neuroprotection and inhibiting apoptosis via the enhancing expression of the SODs. This pathway appears to be crucial in Alzheimer’s disease because it is related to the tau protein hyper-phosphorylation. Dietary supplementation of several ordinary compounds may provide a novel therapeutic approach to brain disorders by modulating the function of the PI3K/AKT pathway. Understanding these systems may offer a better efficacy of new therapeutic approaches. In this review, we summarize recent progresses on the involvement of the SODs and PI3K/AKT pathway in neuroprotective signaling against Alzheimer’s disease. Full article
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Open AccessFeature PaperReview Update Treatment for HBV Infection and Persistent Risk for Hepatocellular Carcinoma: Prospect for an HBV Cure
Received: 20 March 2018 / Revised: 13 April 2018 / Accepted: 16 April 2018 / Published: 20 April 2018
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Abstract
Since the discovery of the hepatitis B virus (HBV) by Blumberg et al. in 1965, its genome, sequence, epidemiology, and hepatocarcinogenesis have been elucidated. Globally, hepatitis B virus (HBV) is still responsible for the majority of hepatocellular carcinoma (HCC). HCC is the sixth-most
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Since the discovery of the hepatitis B virus (HBV) by Blumberg et al. in 1965, its genome, sequence, epidemiology, and hepatocarcinogenesis have been elucidated. Globally, hepatitis B virus (HBV) is still responsible for the majority of hepatocellular carcinoma (HCC). HCC is the sixth-most common cancer in the world and the second-most common cancer death. The ultimate goal of treating HBV infection is the prevention of HCC. Fortunately, anti-HBV treatment with nucleos(t)ide analogues (NAs), which began with lamivudine in 1998, has resulted in remarkable improvements in the survival of patients with chronic hepatitis B and a reduced incidence of HCC. These results were documented with lamivudine, entecavir, and tenofovir. Nonetheless, as the duration of antiviral treatment increases, the risk for HCC still remains despite undetectable HBV DNA in serum, as reported by different investigators with observation up to 4–5 years. In our own experience, we are witnessing the development of HCC in patients who have received antiviral treatment. Some have enjoyed negative serum HBV DNA for over 12 years before developing HCC. Current treatment with NAs can effectively suppress the replication of the virus but cannot eradicate the covalently closed circular DNA (cccDNA) that is within the nucleus of hepatocytes. There still remains a great need for a cure for HBV. Fortunately, several compounds have been identified that have the potential to eradicate HBV, and there are ongoing clinical trials in progress in their early stages. Full article
(This article belongs to the Special Issue Hepatitis and Treatment)
Open AccessArticle The Voice of the Heart: Vowel-Like Sound in Pulmonary Artery Hypertension
Received: 2 March 2018 / Revised: 5 April 2018 / Accepted: 10 April 2018 / Published: 13 April 2018
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Abstract
Increased blood pressure in the pulmonary artery is referred to as pulmonary hypertension and often is linked to loud pulmonic valve closures. For the purpose of this paper, it was hypothesized that pulmonary circulation vibrations will create sounds similar to sounds created by
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Increased blood pressure in the pulmonary artery is referred to as pulmonary hypertension and often is linked to loud pulmonic valve closures. For the purpose of this paper, it was hypothesized that pulmonary circulation vibrations will create sounds similar to sounds created by vocal cords during speech and that subjects with pulmonary artery hypertension (PAH) could have unique sound signatures across four auscultatory sites. Using a digital stethoscope, heart sounds were recorded at the cardiac apex, 2nd left intercostal space (2LICS), 2nd right intercostal space (2RICS), and 4th left intercostal space (4LICS) undergoing simultaneous cardiac catheterization. From the collected heart sounds, relative power of the frequency band, energy of the sinusoid formants, and entropy were extracted. PAH subjects were differentiated by applying the linear discriminant analysis with leave-one-out cross-validation. The entropy of the first sinusoid formant decreased significantly in subjects with a mean pulmonary artery pressure (mPAp) ≥ 25 mmHg versus subjects with a mPAp < 25 mmHg with a sensitivity of 84% and specificity of 88.57%, within a 10-s optimized window length for heart sounds recorded at the 2LICS. First sinusoid formant entropy reduction of heart sounds in PAH subjects suggests the existence of a vowel-like pattern. Pattern analysis revealed a unique sound signature, which could be used in non-invasive screening tools. Full article
(This article belongs to the Special Issue Non-invasive Diagnostics for Cardiovascular Diseases)
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Open AccessCase Report ERBB1- and ERBB2-Positive Medullary Thyroid Carcinoma: A Case Report
Received: 22 March 2018 / Revised: 5 April 2018 / Accepted: 9 April 2018 / Published: 10 April 2018
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Abstract
Medullary thyroid carcinomas (MTCs) are rare thyroid tumors occurring in both sporadic and hereditary forms, whose pathogenesis is related to RET proto-oncogene alterations. MTCs originate from parafollicular cells, which produce calcitonin that represents the biochemical activity of MTC. Total thyroidectomy is the main
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Medullary thyroid carcinomas (MTCs) are rare thyroid tumors occurring in both sporadic and hereditary forms, whose pathogenesis is related to RET proto-oncogene alterations. MTCs originate from parafollicular cells, which produce calcitonin that represents the biochemical activity of MTC. Total thyroidectomy is the main treatment for MTC and often cures patients with confined diseases. In the presence of metastasis, the therapeutic approach depends on the rate of disease progression. We report a case of a 54-year-old female with a single, incidentally discovered, thyroid nodule of 1 cm, classified as suspicious MTC after a stimulation test with intravenous (iv) calcium. After surgery, we examined the nodule using immunohistochemistry, immunofluorescence, and electron microscopy. In addition to calcitonin, we found that it expressed intracellular positivity for the tyrosine kinase RTK receptors ERBB1 and ERBB2. Consistently with MTC features, the ultrastructural examination of the tumor displayed heterogeneous spindle-shaped cells containing two groups of secretory granules. Because of the significant correlation found between high ERBB1/ERBB2 levels in MTCs and extrathyroidal growth, the detection of ERBB1 and ERBB2 expression suggests that the two oncoproteins may be involved in the tumor proliferative responses and/or in the differentiation of parafollicular C-cells. The biological, prognostic, and therapeutic significance of these patterns would merit further investigations. Full article
(This article belongs to the Section Oncology)
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Open AccessArticle Genomic Influence in the Prevention of Cardiovascular Diseases with a Sterol-Based Treatment
Received: 31 January 2018 / Revised: 26 March 2018 / Accepted: 28 March 2018 / Published: 3 April 2018
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Abstract
Raised serum cholesterol concentration is a well-established risk factor in cardiovascular disease. In addition, genetic load may have an indirect influence on cardiovascular risk. Plant-based sterol-supplemented foods are recommended to help reduce the serum low-density lipoprotein cholesterol level. The objective was to analyse
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Raised serum cholesterol concentration is a well-established risk factor in cardiovascular disease. In addition, genetic load may have an indirect influence on cardiovascular risk. Plant-based sterol-supplemented foods are recommended to help reduce the serum low-density lipoprotein cholesterol level. The objective was to analyse the influence of different polymorphisms in hypercholesterolemia patients following a dietary treatment with plant sterols. A randomised double-blind cross-over controlled clinical trial was carried out in 45 people (25 women). Commercial milk, containing 2.24 g of sterols, was ingested daily during a 3-week period, and then the same amount of skim milk, without sterols, was consumed daily during the 3-week placebo phase. Both phases were separated by a washout period of 2 weeks. At the beginning and end of each phase, blood draws were performed. Genes LIPC C-514T and APOA5 C56G are Ser19Trp carriers and greatly benefit from sterol intake in the diet. LIPC C-514T TT homozygous carriers had lower low-density lipoprotein cholesterol (LDL-c) levels than CC homozygote and CT heterozygote carriers after the ingestion of plant sterols (p = 0.001). These two genes also showed statistically significant changes in total cholesterol levels (p = 0.025; p = 0.005), and no significant changes in high-density lipoprotein (HDL) cholesterol levels (p = 0.032; p = 0.003), respectively. No statistically significant differences were observed for other genes. Further studies are needed to establish which genotype combinations would be the most protective against hypercholesterolemia. Full article
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Open AccessCommentary The Brain–Intestinal Mucosa–Appendix– Microbiome–Brain Loop
Received: 5 February 2018 / Revised: 28 February 2018 / Accepted: 29 March 2018 / Published: 1 April 2018
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Abstract
The brain and the gut are connected from early fetal life. The mother’s exposure to microbial molecules is thought to exert in utero developmental effects on the fetus. These effects could importantly underpin the groundwork for subsequent pathophysiological mechanisms for achieving immunological tolerance
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The brain and the gut are connected from early fetal life. The mother’s exposure to microbial molecules is thought to exert in utero developmental effects on the fetus. These effects could importantly underpin the groundwork for subsequent pathophysiological mechanisms for achieving immunological tolerance and metabolic equilibrium post birth, events that continue through to 3–4 years of age. Furthermore, it is understood that the microbiome promotes cues that instruct the neonate’s mucosal tissues and skin in the language of molecular and cellular biology. Post birth mucosal lymphoid tissue formation and maturation (most probably including the vermiform appendix) is microbiota-encouraged co-establishing the intestinal microbiome with a developing immune system. Intestinal mucosal tissue maturation loops the brain-gut-brain and is postulated to influence mood dispositions via shifts in the intestinal microbiome phyla. A plausible appreciation is that dysregulated pro-inflammatory signals from intestinal resident macrophages could breach the loop by providing adverse mood signals via vagus nerve afferents to the brain. In this commentary, we further suggest that the intestinal resident macrophages act as an upstream traffic controller of translocated microbes and metabolites in order to maintain local neuro-endocrine-immunological equilibrium. When macrophages are overwhelmed through intestinal microbiome and intestinal epithelial cell dysbiosis, pro-inflammatory signals are sustained, which may then lead to mood disorders. The administration of probiotics as an adjunctive medicine co-administered with antidepressant medications in improving depressed mood may have biological and clinical standing. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
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