Open AccessArticle
Competitive Promoter-Associated Matrix Attachment Region Binding of the Arid3a and Cux1 Transcription Factors
Diseases 2017, 5(4), 34; doi:10.3390/diseases5040034 (registering DOI) -
Abstract
Arid3a/Bright/Dril1 is a B cell-specific transactivator that regulates immunoglobulin heavy chain (IgH) gene transcription by binding promoter and enhancer-associated matrix attachment regions (MARs) within the IgH gene locus. Promoter MAR-mediated Arid3a transactivation is antagonized by direct competition of MAR binding by Cux1/CDP—a ubiquitously
[...] Read more.
Arid3a/Bright/Dril1 is a B cell-specific transactivator that regulates immunoglobulin heavy chain (IgH) gene transcription by binding promoter and enhancer-associated matrix attachment regions (MARs) within the IgH gene locus. Promoter MAR-mediated Arid3a transactivation is antagonized by direct competition of MAR binding by Cux1/CDP—a ubiquitously expressed repressor originally termed NF-μNR. We report that the NF-μNR complex includes Arid3a in B cells but not in non-B cells through mobility shift assays. The binding activity of NF-μNR and Arid3a in B cells is reciprocally altered during the cell division cycle and by the B cell mitogen lipopolysaccharide LPS. LPS treatment had no effect on Arid3a localization but increased its total abundance within the nucleus and cytoplasm. We show that this increased level of Arid3a is capable of displacing Cux from the MARs to facilitate IgH gene transcription. Finally, we showed that the MARs (termed Bf150 and Tx125) associated with the VH1 rearranged variable region expressed in the S107 murine plasmacytoma, can repress reporter gene transcription in non-B cells and that they can relieve the repression mediated by Eμ enhancer in B cells. These results have significant implications for early human development and demonstrate that MARs in IgH locus, NF-µNR and Arid3a regulate IgH gene expression in a concerted fashion. This paves the way for future studies examining the misregulation of this pathway in pediatric disease. Full article
Figures

Figure 1

Open AccessFeature PaperCase Report
Histoplasma and Cytomegalovirus Coinfection of the Gastrointestinal Tract in a Patient with AIDS: A Case Report and Review of the Literature
Diseases 2017, 5(4), 30; doi:10.3390/diseases5040030 -
Abstract
Opportunistic infections of the gastrointestinal tract are well-documented complications of patients with acquired immunodeficiency syndrome (AIDS). However, concomitant infection by Histoplasma and cytomegalovirus has been described rarely. We present the case of an HIV patient with a CD4 count of 20 cells/uL who
[...] Read more.
Opportunistic infections of the gastrointestinal tract are well-documented complications of patients with acquired immunodeficiency syndrome (AIDS). However, concomitant infection by Histoplasma and cytomegalovirus has been described rarely. We present the case of an HIV patient with a CD4 count of 20 cells/uL who was admitted with odynophagia and weight loss. Endoscopic evaluation revealed ulcerations in the esophagus and colon, and a mass formation in cecum. Histology revealed budding yeasts in the cecum and a transverse colon consistent with Histoplasma. Urine Histoplasma antigen was positive. Esophageal tissue disclosed viral cytopathic changes. Immunostaining was positive for cytomegalovirus in the esophagus and transverse colon. The patient was started on appropriate antifungal and antiviral treatment with complete resolution of his symptoms. To our knowledge, this is the fifth case of Histoplasma and cytomegalovirus co-infection of the gastrointestinal tract in a patient with AIDS. We also review the literature for similar cases in regards to clinical presentation and the type of gastrointestinal involvement. Full article
Figures

Figure 1

Open AccessFeature PaperReview
Familial Screening for Left-Sided Congenital Heart Disease: What Is the Evidence? What Is the Cost?
Diseases 2017, 5(4), 29; doi:10.3390/diseases5040029 -
Abstract
Since the American Heart Association’s recommendation for familial screening of adults with congenital heart disease for bicuspid aortic valve, similar recommendations for other left-sided heart defects, such as hypoplastic left heart syndrome (HLHS), have been proposed. However, defining at-risk populations for these heart
[...] Read more.
Since the American Heart Association’s recommendation for familial screening of adults with congenital heart disease for bicuspid aortic valve, similar recommendations for other left-sided heart defects, such as hypoplastic left heart syndrome (HLHS), have been proposed. However, defining at-risk populations for these heart defects based on genetics is less straightforward due to the wide variability of inheritance patterns and non-genetic influences such as environmental and lifestyle factors. We discuss whether there is sufficient evidence to standardize echocardiographic screening for first-degree relatives of children diagnosed with HLHS. Due to variations in the inclusion of cardiac anomalies linked to HLHS and the identification of asymptomatic individuals with cardiac malformations, published studies are open to interpretation. We conclude that familial aggregation of obstructive left-sided congenital heart lesions in families with history of HLHS is not supported and recommend that additional screening should adopt a more conservative definition of what truly constitutes this heart defect. More thorough consideration is needed before embracing familial screening recommendations of families of patients with HLHS, since this could inflict serious costs on healthcare infrastructure and further burden affected families both emotionally and financially. Full article
Open AccessFeature PaperArticle
Progression of Renal Insufficiency in Patients with Essential Hypertension Treated with Renin Angiotensin Aldosterone System Blockers: An Electrocardiographic Correlation
Diseases 2017, 5(4), 33; doi:10.3390/diseases5040033 -
Abstract
Background: There is a frequent association between renal insufficiency and cardiovascular disease in patients with essential hypertension (HTN). The aim of this study was to analyze the relationship between ECG parameters and the progress of renal damage in patients with treated HTN. Methods:
[...] Read more.
Background: There is a frequent association between renal insufficiency and cardiovascular disease in patients with essential hypertension (HTN). The aim of this study was to analyze the relationship between ECG parameters and the progress of renal damage in patients with treated HTN. Methods: 109 patients with HTN had their microalbuminuria monitored over a 3-year time frame. During the last 3 months of follow-up, an ECG was recorded. Patients were divided into 3 groups according to the deterioration of their renal function: normoalbuminuria during the study period (normo–normo; n = 51); normoalbuminuria developing microalbuminuria (normo–micro; n = 29); and microalbuminuria at baseline (micro–micro; n = 29). Results: There were no differences in presence of left ventricular hypertrophy between the 3 groups. RV6/RV5 >1 was observed more frequently as renal function declined (p = 0.025). The 12-lead QRS-complex voltage-duration product was significantly increased in patients without microalbuminuria at baseline who went on to develop microalbuminuria (p = 0.006). Patients who developed microalbuminuria during follow-up, with positive Cornell voltage criteria, showed a lesser degree of progression of microalbuminuria when compared with the rest of the subgroups (p = 0.044). Furthermore, patients with microalbuminuria at baseline treated with angiotensin receptor blockers and diuretics, and positive Cornell voltage criteria, showed a higher degree of microalbuminuria compared to those with negative Cornell voltage criteria (p = 0.016). Conclusions: In patients with HTN, we identified some ECG parameters, which predict renal disease progression in patients with HTN, which may permit the identification of patients who are at risk of renal disease progression, despite optimal antihypertensive pharmacotherapy. Full article
Open AccessFeature PaperArticle
Relation between the Disability of the Arm, Shoulder and Hand Score and Muscle Strength in Post-Cardiac Surgery Patients
Diseases 2017, 5(4), 31; doi:10.3390/diseases5040031 -
Abstract
Background: The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire is a valid and reliable patient-reported outcome measure. DASH can be assessed by self-reported upper extremity disability and symptoms. We aimed to examine the relationship between the physiological outcome of muscle strength
[...] Read more.
Background: The Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire is a valid and reliable patient-reported outcome measure. DASH can be assessed by self-reported upper extremity disability and symptoms. We aimed to examine the relationship between the physiological outcome of muscle strength and the DASH score after cardiac surgery. Methods: This cross-sectional study assessed 50 consecutive cardiac patients that were undergoing cardiac surgery. Physiological outcomes of handgrip strength and knee extensor muscle strength and the DASH score were measured at one month after cardiac surgery and were assessed. Results were analyzed using Spearman correlation coefficients. Results: The final analysis comprised 43 patients (men: 32, women: 11; age: 62.1 ± 9.1 years; body mass index: 22.1 ± 4.7 kg/m2; left ventricular ejection fraction: 53.5 ± 13.7%). Respective handgrip strength, knee extensor muscle strength, and DASH score were 27.4 ± 8.3 kgf, 1.6 ± 0.4 Nm/kg, and 13.3 ± 12.3, respectively. The DASH score correlated negatively with handgrip strength (r = −0.38, p = 0.01) and with knee extensor muscle strength (r = −0.32, p = 0.04). Conclusion: Physiological outcomes of both handgrip strength and knee extensor muscle strength correlated negatively with the DASH score. The DASH score appears to be a valuable tool with which to assess cardiac patients with poor physiological outcomes, particularly handgrip strength as a measure of upper extremity function, which is probably easier to follow over time than lower extremity function after patients complete cardiac rehabilitation. Full article
Figures

Figure 1

Open AccessArticle
The Contribution of New Areas to the Total Hirsutism Scores in Basrah Hirsute Women
Diseases 2017, 5(4), 32; doi:10.3390/diseases5040032 -
Abstract
Background: Hirsutism is the presence of excessive growth of terminal hair in a female in the male-like pattern. It is the most common indicator of hyperandrogenism. The primary objective of this study was to evaluate the clinical impact of new androgens sensitive
[...] Read more.
Background: Hirsutism is the presence of excessive growth of terminal hair in a female in the male-like pattern. It is the most common indicator of hyperandrogenism. The primary objective of this study was to evaluate the clinical impact of new androgens sensitive skin area to total body hirsutism score. Methods: This was cross-sectional study. Most of the patients in this study group (n = 300) were women of reproductive age group (20–39 years) with a mean age of 26.6 ± 7.1 years. They were recruited in Faiha Specialized Diabetes, Endocrine, and Metabolism Center (FDEMC) during the period from August 2016 to the end of August 2017. All complained from hirsutism and were assessed by using modified Ferriman-Gallwey (m-FG) score system by a single examiner. Each patient underwent detailed clinical assessment in addition to transabdominal or transvaginal ultrasonography of the pelvis with endocrinological investigations. Results: Comparison of the mean score at different body areas revealed that new androgens sensitive skin areas (sideburn, lower jaw/neck, buttocks/perineum) were comparable to others area of original m-FG score system or higher than at least three area used in the score. The sideburn area was observed to have the highest score among the new androgens sensitive skin areas. Conclusion: Evaluating the terminal hair growth in the new three androgen-sensitive skin areas (sideburn, lower jaw/neck, and buttocks/perineum) were clinically useful in assessing hirsutism score with high impact on total score. Full article
Figures

Figure 1

Open AccessFeature PaperComment
Risk Evaluation Requires an Independent Mind
Diseases 2017, 5(4), 28; doi:10.3390/diseases5040028 -
Abstract
Biomedical research pertaining to pathologies observed in adolescents can involve areas where patients can expect no immediate benefits. Here, Congress stipulates that local review boards are restricted to approving procedures posing no greater than minimal risk (45 CFR 46.404). An evaluation of risk
[...] Read more.
Biomedical research pertaining to pathologies observed in adolescents can involve areas where patients can expect no immediate benefits. Here, Congress stipulates that local review boards are restricted to approving procedures posing no greater than minimal risk (45 CFR 46.404). An evaluation of risk embraces the current state of the art with regard to the safety and efficacy of procedures. A tendency of biomedical scholars to cite highly cited documents can introduce a bias in an argumentation in favor or against a given recommendation in the context that bias in citations can be correlated with an imprudent use of funds for research. We use choice examples to highlight the necessity of approaching any scholarly task with an independent mind. Full article
Open AccessFeature PaperArticle
Development of Evidence-Based Disease Education Literature for Pakistani Rheumatoid Arthritis Patients
Diseases 2017, 5(4), 27; doi:10.3390/diseases5040027 -
Abstract
Rheumatoid arthritis affects 0.5% to 1% of the population globally and is one of the most common causes of disability. Patient education plays a key role in improving treatment outcomes. The purpose of this study was to discuss the process involved in designing
[...] Read more.
Rheumatoid arthritis affects 0.5% to 1% of the population globally and is one of the most common causes of disability. Patient education plays a key role in improving treatment outcomes. The purpose of this study was to discuss the process involved in designing an evidence-based disease education literature for rheumatoid arthritis patients of Pakistan in Urdu language with culturally relevant illustrations. A study was conducted to develop disease education literature using Delphi consensus, content validity, and patient feedback. A panel of experts comprised of university professors and health care experts, including health practitioners and pharmacists as well as a social scientist, was set up to assess the need. Eight patients were randomly selected and were asked to give their feedback. Their feedback was incorporated in the development process. The entire process was carried out in eight steps. A disease education literature for patients of rheumatoid arthritis was developed and edited in the form of a booklet. The booklet contained evidence-based information that must be provided to patients in both Urdu and English languages with culturally relevant illustrations. The availability of such literature is significant, as it enables the patients to seek knowledge at home at their convenience. This home-based knowledge support is as helpful as any other means of medical care. The developed literature is planned to be used in further studies which will evaluate its impact in improving knowledge of RA patients. Full article
Figures

Figure 1

Open AccessFeature PaperCase Report
Pyogenic Brain Abscess Caused by Peptostreptococcus in a Patient with HIV-1 Infection
Diseases 2017, 5(4), 26; doi:10.3390/diseases5040026 -
Abstract
In the setting of HIV, cerebral lesions are usually secondary to lymphoma and opportunistic infections; however, in patients with CD4 counts above 200 cells/uL, other pathologies such as pyogenic brain abscess could gain importance. The microbiology of pyogenic brain abscess has Staphylococcus and
[...] Read more.
In the setting of HIV, cerebral lesions are usually secondary to lymphoma and opportunistic infections; however, in patients with CD4 counts above 200 cells/uL, other pathologies such as pyogenic brain abscess could gain importance. The microbiology of pyogenic brain abscess has Staphylococcus and Streptococcus as the leading etiologic pathogens in immunocompetent individuals. Peptostreptococcus is also recognized as a common cause of brain abscess in this patient population. In HIV-infected individuals, there have been sporadic reports of Peptostreptococcus infections but none of brain abscess. We describe the case of a 43-years-old HIV-infected patient with a CD4 count of 350 cells/uL that developed a Peptostreptococcus brain abscess presumably from hematogenous spread of an odontogenic source. Treatment with stereotactic needle aspiration in two opportunities and four weeks of intravenous antibiotics led to a complete resolution of this infection. This case highlights the importance of a multidisciplinary approach for an effective treatment of pyogenic brain abscess in HIV-1 patients. Full article
Figures

Figure 1

Open AccessFeature PaperArticle
The Vascular Factor Plays the Main Role in the Cause of Pain in Men with Chronic Prostatitis and Chronic Pelvic Pain Syndrome: The Results of Clinical Trial on Thermobalancing Therapy
Diseases 2017, 5(4), 25; doi:10.3390/diseases5040025 -
Abstract
Chronic pain in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), NIH category III is difficult to treat without understanding its cause. The main symptom of chronic prostatitis is pain. In this study, we would like to explain the origin of pain in
[...] Read more.
Chronic pain in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), NIH category III is difficult to treat without understanding its cause. The main symptom of chronic prostatitis is pain. In this study, we would like to explain the origin of pain in men with CP/CPPS and its therapy. Forty-five patients with CP/CPPS have received thermobalancing therapy (TT) enabled by Dr Allen’s therapeutic device (DATD) for six months as mono-therapy. The control group comprised 45 men with CP/CPPS did not receive TT. Before and after six months the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores, prostatic volume (PV) by ultrasound measurement and uroflowmetry (Qmax) were compared between the groups. Baseline characteristics have shown no difference. After TT, significant improvements in pain score (p < 0.001), quality of life index (QoL) (p < 0.001), decrease of PV (p < 0.001), and increase Qmax (p < 0.001) were determined. There were not noteworthy changes in the control group. Chronic pain due to CP/CPPS happens as a consequence and challenges at the capillary level, namely pathological capillary activity. In response to initial triggers—such as inflammation, cold, psychological and other factors—constriction and spontaneous expansion of capillaries follows, creating a continuous secondary trigger—i.e., the micro-focus of hypothermia—which in turn provokes expansion of capillaries. The additional tissue due to vascular changes into the prostate increases pressure on nociceptors causing pain. TT relieves chronic pelvic pain by eliminating the lasting focus of hypothermia in the affected prostate tissue. Full article
Figures

Figure 1

Open AccessArticle
Relationship between Bone Health Biomarkers and Cardiovascular Risk in a General Adult Population
Diseases 2017, 5(4), 24; doi:10.3390/diseases5040024 -
Abstract
Purpose/Introduction: Osteoporosis (OP) and cardiovascular (CV) disease emerge as closely related conditions, showing common risk factors and/or pathophysiological mechanisms. The aim of this study was to evaluate the association between bone health markers (BHM) and individual CV risk factors and overall CV risk
[...] Read more.
Purpose/Introduction: Osteoporosis (OP) and cardiovascular (CV) disease emerge as closely related conditions, showing common risk factors and/or pathophysiological mechanisms. The aim of this study was to evaluate the association between bone health markers (BHM) and individual CV risk factors and overall CV risk (FRAMINGHAM-FRS, and PROCAM scores) in a general adult population. Methods: In 103 subjects (21 males; age: 56 ± 12 years), vitamin D (25(OH)D), osteocalcin (OC), bone alkaline phospatase (BALP), procollagen I aminoterminal propeptide (P1NP), CTx-telopeptide, as well clinical history and life style were evaluated. Results: Aging (p <0.001) and glycemia (p <0.05) emerged as independent 25(OH)D predictors. Aging (p <0.001), male sex (p <0.05), and obesity (p <0.05) represented independent OC determinants. Aging (p <0.05) was the only independent BALP determinant. After multivariate adjustment, low 25(OH)D (<20 ng/mL) (Odds ratio OR (95% confidence intervals CI)) (5 (1.4–18) p <0.05) and elevated OC (>75th percentile-16.6 ng/mL) (6.7 (1.9–23.8) p <0.01) were found to be significant FRS predictors, while subjects with elevated OC and/or BALP (>75th percentile-9.8 μg/L) showed a higher CV risk as estimated by PROCAM (3.6 (1.2–10.7) p <0.05). CTx and P1NP did not significantly correlate with CV risk factors or scores. Conclusion: As we go further into bone and CV physiology, it is evident that a close relationship exists between these diseases. Further studies are needed to investigate mechanisms by which bone turnover markers are related to metabolic risk and could modulate CV risk. This knowledge may help to develop possible multiple-purpose strategies for both CV disease and OP prevention and treatment. Full article
Figures

Figure 1

Open AccessReview
An Overview of Dietary Interventions and Strategies to Optimize the Management of Non-Alcoholic Fatty Liver Disease
Diseases 2017, 5(4), 23; doi:10.3390/diseases5040023 -
Abstract
Aim: To investigate the efficacy of lifestyle adjustment strategies as a preventive measure and/or treatment of obesity-related non-alcoholic fatty liver disease in adults. Method: A systematic review of literature through 1 July 2017 on the PubMed Database was performed. A comprehensive
[...] Read more.
Aim: To investigate the efficacy of lifestyle adjustment strategies as a preventive measure and/or treatment of obesity-related non-alcoholic fatty liver disease in adults. Method: A systematic review of literature through 1 July 2017 on the PubMed Database was performed. A comprehensive search was conducted using key terms, such as non-alcoholic fatty liver disease (NAFLD), combined with lifestyle intervention, diet, and exercise. All of the articles and studies obtained from the search were reviewed. Redundant literature was excluded. Results: Several types of dietary compositions and exercise techniques were identified. Most studies concluded and recommended reduction in the intake of saturated and trans fatty acids, carbohydrates, and animal-based protein, and increased intake of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), plant-based proteins, antioxidants, and other nutrients was recommended. The Mediterranean and Paleo diet both seem to be promising schemes for NAFLD patients to follow. Exercise was also encouraged, but the type of exercise did not affect its efficacy as a NAFLD treatment when the duration is consistent. Conclusions: Although these different dietary strategies and exercise regimens can be adopted to treat NAFLD, current literature on the topic is limited in scope. Further research should be conducted to truly elucidate which lifestyle adjustments individually, and in combination, may facilitate patients with obesity-related NAFLD. Full article
Figures

Figure 1

Open AccessFeature PaperEssay
The Heart Club: How Cyanotic Heart Disease Was Reframed
Diseases 2017, 5(4), 22; doi:10.3390/diseases5040022 -
Abstract
In April 1948, the thoracic surgeon, Russell Brock, convened a meeting at Guy’s Hospital [...] Full article
Figures

Figure 1

Open AccessReview
Anacetrapib, a New CETP Inhibitor: The New Tool for the Management of Dyslipidemias?
Diseases 2017, 5(4), 21; doi:10.3390/diseases5040021 -
Abstract
Cholesteryl ester transfer protein (CETP) inhibitors significantly increase serum high-density lipoprotein cholesterol (HDL) cholesterol levels and decrease low-density lipoprotein cholesterol (LDL) cholesterol concentration. However, three drugs of this class failed to show a decrease of cardiovascular events in high-risk patients. A new CETP
[...] Read more.
Cholesteryl ester transfer protein (CETP) inhibitors significantly increase serum high-density lipoprotein cholesterol (HDL) cholesterol levels and decrease low-density lipoprotein cholesterol (LDL) cholesterol concentration. However, three drugs of this class failed to show a decrease of cardiovascular events in high-risk patients. A new CETP inhibitor, anacetrapib, substantially increases HDL cholesterol and apolipoprotein (Apo) AI levels with a profound increase of large HDL2 particles, but also pre-β HDL particles, decreases LDL cholesterol levels mainly due to increased catabolism of LDL particles through LDL receptors, decreases lipoprotein a (Lp(a)) levels owing to a decreased Apo (a) production and, finally, decreases modestly triglyceride (TRG) levels due to increased lipolysis and increased receptor-mediated catabolism of TRG-rich particles. Interestingly, anacetrapib may be associated with a beneficial effect on carbohydrate homeostasis. Furthermore, the Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) trial showed that anacetrapib administration on top of statin treatment significantly reduces cardiovascular events in patients with atherosclerotic vascular disease without any significant increase of adverse events despite its long half-life. Thus, anacetrapib could be useful for the effective management of dyslipidemias in high-risk patients that do not attain their LDL cholesterol target or are statin intolerable, while its role in patients with increased Lp(a) levels remains to be established. Full article
Figures

Figure 1

Open AccessFeature PaperArticle
Rising Rates of Hepatocellular Carcinoma Leading to Liver Transplantation in Baby Boomer Generation with Chronic Hepatitis C, Alcohol Liver Disease, and Nonalcoholic Steatohepatitis-Related Liver Disease
Diseases 2017, 5(4), 20; doi:10.3390/diseases5040020 -
Abstract
We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945–1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a
[...] Read more.
We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945–1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a retrospective analysis using the United Network for Organ Sharing (UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare HCC-related liver transplant surgery trends between two cohorts—the BB and non-BB—with a secondary diagnosis of HCV, ALD, or NASH. From 2003–2014, there were a total of 8313 liver transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658 (80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%) during the study period. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and NASH suggests the need for increased awareness and improved preventative screening/surveillance measures within NASH and ALD cohorts as well. Full article
Figures

Figure 1

Open AccessFeature PaperPerspective
Flavonoids and Their Metabolites: Prevention in Cardiovascular Diseases and Diabetes
Diseases 2017, 5(3), 19; doi:10.3390/diseases5030019 -
Abstract
The occurrence of atherosclerosis and diabetes is expanding rapidly worldwide. These two metabolic disorders often co-occur, and are part of what is often referred to as the metabolic syndrome. In order to determine future therapies, we propose that molecular mechanisms should be investigated.
[...] Read more.
The occurrence of atherosclerosis and diabetes is expanding rapidly worldwide. These two metabolic disorders often co-occur, and are part of what is often referred to as the metabolic syndrome. In order to determine future therapies, we propose that molecular mechanisms should be investigated. Once the aetiology of the metabolic syndrome is clear, a nutritional intervention should be assessed. Here we focus on the protective effects of some dietary flavonoids, and their metabolites. Further studies may also pave the way for development of novel drug candidates. Full article
Figures

Figure 1a

Open AccessCommentary
The Evolution of Pediatric Disease—A Moving Target in Public Health
Diseases 2017, 5(3), 18; doi:10.3390/diseases5030018 -
Abstract
There is a growing threat in the re-emergence of diseases that impact pediatric demographics. While major strides have been made in the field of childhood cancers, there are still more questions than answers. In addition, public resistance to recommended practices related to childhood
[...] Read more.
There is a growing threat in the re-emergence of diseases that impact pediatric demographics. While major strides have been made in the field of childhood cancers, there are still more questions than answers. In addition, public resistance to recommended practices related to childhood vaccinations fueled by misinformation has allowed infectious diseases to resurface in developed nations. Meanwhile, climate change and other destabilizing factors are shifting vector populations and driving the emergence of new diseases. Herein we call upon the community of human health researchers to confront the evolving specter of pediatric disease. Full article
Figures

Figure 1

Open AccessCase Report
A Case of Systemic Infection Caused by Streptococcus pyogenes Oral Infection in an Edentulous Patient
Diseases 2017, 5(3), 17; doi:10.3390/diseases5030017 -
Abstract
Background: Infections in the oral and maxillofacial region can sometimes extend beyond the oral cavity, with serious consequences. Most oral infections are odontogenic, occurring through the root apex of the tooth or the periodontal pocket. It thus makes sense that edentulous patients have
[...] Read more.
Background: Infections in the oral and maxillofacial region can sometimes extend beyond the oral cavity, with serious consequences. Most oral infections are odontogenic, occurring through the root apex of the tooth or the periodontal pocket. It thus makes sense that edentulous patients have a much lower risk of oral bacterial infection. For this reason, while there are many reports on systemic infections caused by oral infections, few of these describe such infections in edentulous patients. Case presentation: We present a case of oral and maxillofacial cellulitis followed by sepsis due to Streptococcus pyogenes infection in an 89-year-old Japanese edentulous woman. S. pyogenes was detected in the wound of left maxilla and the blood sample. S. pyogenes has been reported to be one of the most common and influential aerobic bacteria associated with deep neck infection and subsequent systemic infection. Left maxillary sinusitis was observed, and this could be the origin of the S. pyogenes infection. S. pyogenes derived from the sinusitis and leaked to the oral cavity might have caused systemic infection through wounding of the oral mucosa. Fortunately, intensive antibiotic therapy was effective, and the patient recovered without any surgical procedures. Conclusions: We experienced a rare case of oral and maxillofacial cellulitis followed by sepsis due to a Streptococcus pyogenes infection in an old edentulous woman. This result indicated that, while edentulous patients are considered to have no risk of odontogenic infection, they still carry a risk of bacterial infection. Full article
Figures

Figure 1

Open AccessReview
Epigenetic Mechanisms of Tamoxifen Resistance in Luminal Breast Cancer
Diseases 2017, 5(3), 16; doi:10.3390/diseases5030016 -
Abstract
Breast cancer is one of the most common cancers and the second leading cause of cancer death in the United States. Estrogen receptor (ER)-positive cancer is the most frequent subtype representing more than 70% of breast cancers. These tumors respond to endocrine therapy
[...] Read more.
Breast cancer is one of the most common cancers and the second leading cause of cancer death in the United States. Estrogen receptor (ER)-positive cancer is the most frequent subtype representing more than 70% of breast cancers. These tumors respond to endocrine therapy targeting the ER pathway including selective ER modulators (SERMs), selective ER downregulators (SERDs) and aromatase inhibitors (AIs). However, resistance to endocrine therapy associated with disease progression remains a significant therapeutic challenge. The precise mechanisms of endocrine resistance remain unclear. This is partly due to the complexity of the signaling pathways that influence the estrogen-mediated regulation in breast cancer. Mechanisms include ER modifications, alteration of coregulatory function and modification of growth factor signaling pathways. In this review, we provide an overview of epigenetic mechanisms of tamoxifen resistance in ER-positive luminal breast cancer. We highlight the effect of epigenetic changes on some of the key mechanisms involved in tamoxifen resistance, such as tumor-cell heterogeneity, ER signaling pathway and cancer stem cells (CSCs). It became increasingly recognized that CSCs are playing an important role in driving metastasis and tamoxifen resistance. Understanding the mechanism of tamoxifen resistance will provide insight into the design of novel strategies to overcome the resistance and make further improvements in breast cancer therapeutics. Full article
Figures

Figure 1

Open AccessReview
Biomarkers and Imaging Findings of Anderson–Fabry Disease—What We Know Now
Diseases 2017, 5(2), 15; doi:10.3390/diseases5020015 -
Abstract
Anderson–Fabry disease (AFD) is an X-linked lysosomal storage disorder, caused by deficiency or absence of the alpha-galactosidase A activity, with a consequent glycosphingolipid accumulation. Biomarkers and imaging findings may be useful for diagnosis, identification of an organ involvement, therapy monitoring and prognosis. The
[...] Read more.
Anderson–Fabry disease (AFD) is an X-linked lysosomal storage disorder, caused by deficiency or absence of the alpha-galactosidase A activity, with a consequent glycosphingolipid accumulation. Biomarkers and imaging findings may be useful for diagnosis, identification of an organ involvement, therapy monitoring and prognosis. The aim of this article is to review the current available literature on biomarkers and imaging findings of AFD patients.An extensive bibliographic review from PubMed, Medline and Clinical Key databases was performed by a group of experts from nephrology, neurology, genetics, cardiology and internal medicine, aiming for consensus. Lyso-GB3 is a valuable biomarker to establish the diagnosis. Proteinuria and creatinine are the most valuable to detect renal damage. Troponin I and high-sensitivity assays for cardiac troponin T can identify patients with cardiac lesions, but new techniques of cardiac imaging are essential to detect incipient damage. Specific cerebrovascular imaging findings are present in AFD patients. Techniques as metabolomics and proteomics have been developed in order to find an AFD fingerprint. Lyso-GB3 is important for evaluating the pathogenic mutations and monitoring the response to treatment. Many biomarkers can detect renal, cardiac and cerebrovascular involvement, but none of these have proved to be important to monitoring the response to treatment. Imaging features are preferred in order to find cardiac and cerebrovascular compromise in AFD patients. Full article