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J. Clin. Med., Volume 7, Issue 9 (September 2018)

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Cover Story (view full-size image) Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper [...] Read more.
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Open AccessArticle Effects of Progressive Resistance Training on Post-Surgery Incontinence in Men with Prostate Cancer
J. Clin. Med. 2018, 7(9), 292; https://doi.org/10.3390/jcm7090292
Received: 19 August 2018 / Revised: 11 September 2018 / Accepted: 18 September 2018 / Published: 19 September 2018
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Abstract
We evaluated the efficacy of progressive resistance training of the pelvic floor muscle for post-prostatectomy incontinence. In this prospective study, 59 patients who underwent radical prostatectomy were evaluated preoperatively. Continence was sequentially assessed within 2 weeks postoperatively, and an exercise regimen was initiated
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We evaluated the efficacy of progressive resistance training of the pelvic floor muscle for post-prostatectomy incontinence. In this prospective study, 59 patients who underwent radical prostatectomy were evaluated preoperatively. Continence was sequentially assessed within 2 weeks postoperatively, and an exercise regimen was initiated at 6- and 12-weeks. The primary outcome was continent status and the secondary outcome was changes in muscle strength and endurance after the exercise intervention. Continence was defined as no urine loss in a 1h pad test. A total of 59 patients participated in this study. Six patients dropped out of the study because of non-compliance and orthopedic problems. Of the remaining 53 patients, 31 (58.5%) achieved pad-free continence at 12 weeks postoperatively. The patients were divided into two groups based on their continence status, and no statistically significant difference was observed in age, body mass index, prostate volume, prostate-specific antigen, pathological Gleason score sum, and pathological T stage. Meanwhile, preoperative maximal urethral closure pressure and change in hip extensor muscle strength and endurance during the 12-week exercise program were significantly higher in the continent group. In multivariate analysis, change in hip extensor muscle strength was the only significant parameter predicting achievement of continence status (Odds ratio, 1.039; p = 0.045). The changes in hip extensor muscle strength in the current exercise program was an independent predictor of continence status after radical prostatectomy. A large-scale prospective study on the relationship between extensor muscle strength and urinary incontinence should be explored in future. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Prostate Cancer)
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Open AccessReview Dystrophin Cardiomyopathies: Clinical Management, Molecular Pathogenesis and Evolution towards Precision Medicine
J. Clin. Med. 2018, 7(9), 291; https://doi.org/10.3390/jcm7090291
Received: 3 August 2018 / Revised: 2 September 2018 / Accepted: 14 September 2018 / Published: 19 September 2018
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Abstract
Duchenne’s muscular dystrophy is an X-linked neuromuscular disease that manifests as muscle atrophy and cardiomyopathy in young boys. However, a considerable percentage of carrier females are often diagnosed with cardiomyopathy at an advanced stage. Existing therapy is not disease-specific and has limited effect,
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Duchenne’s muscular dystrophy is an X-linked neuromuscular disease that manifests as muscle atrophy and cardiomyopathy in young boys. However, a considerable percentage of carrier females are often diagnosed with cardiomyopathy at an advanced stage. Existing therapy is not disease-specific and has limited effect, thus many patients and symptomatic carrier females prematurely die due to heart failure. Early detection is one of the major challenges that muscular dystrophy patients, carrier females, family members and, research and medical teams face in the complex course of dystrophic cardiomyopathy management. Despite the widespread adoption of advanced imaging modalities such as cardiac magnetic resonance, there is much scope for refining the diagnosis and treatment of dystrophic cardiomyopathy. This comprehensive review will focus on the pertinent clinical aspects of cardiac disease in muscular dystrophy while also providing a detailed consideration of the known and developing concepts in the pathophysiology of muscular dystrophy and forthcoming therapeutic options. Full article
(This article belongs to the Special Issue Hereditary Neuromuscular Diseases)
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Open AccessArticle Estimation of Arterial Carbon Dioxide Based on End-Tidal Gas Pressure and Oxygen Saturation
J. Clin. Med. 2018, 7(9), 290; https://doi.org/10.3390/jcm7090290
Received: 27 June 2018 / Revised: 12 September 2018 / Accepted: 13 September 2018 / Published: 19 September 2018
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Abstract
Arterial blood gas (ABG) analysis is the traditional method for measuring the partial pressure of carbon dioxide. In mechanically ventilated patients a continuous noninvasive monitoring of carbon dioxide would obviously be attractive. In the current study, we present a novel formula for noninvasive
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Arterial blood gas (ABG) analysis is the traditional method for measuring the partial pressure of carbon dioxide. In mechanically ventilated patients a continuous noninvasive monitoring of carbon dioxide would obviously be attractive. In the current study, we present a novel formula for noninvasive estimation of arterial carbon dioxide. Eighty-one datasets were collected from 19 anesthetized and mechanically ventilated pigs. Eleven animals were mechanically ventilated without interventions. In the remaining eight pigs the partial pressure of carbon dioxide was manipulated. The new formula (Formula 1) is PaCO2 = PETCO2 + k(PETO2 − PaO2) where PaO2 was calculated from the oxygen saturation. We tested the agreements of this novel formula and compared it to a traditional method using the baseline PaCO2 − ETCO2 gap added to subsequently measured, end-tidal carbon dioxide levels (Formula 2). The mean difference between PaCO2 and calculated carbon dioxide (Formula 1) was 0.16 kPa (±SE 1.17). The mean difference between PaCO2 and carbon dioxide with Formula 2 was 0.66 kPa (±SE 0.18). With a mixed linear model excluding cases with cardiorespiratory collapse, there was a significant difference between formulae (p < 0.001), as well as significant interaction between formulae and time (p < 0.001). In this preliminary animal study, this novel formula appears to have a reasonable agreement with PaCO2 values measured with ABG analysis, but needs further validation in human patients. Full article
(This article belongs to the Special Issue Cardiovascular and Neurological Emergency)
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Open AccessArticle The Role of Objectively Measured, Altered Physical Activity Patterns for Body Mass Index Change during Inpatient Treatment in Female Patients with Anorexia Nervosa
J. Clin. Med. 2018, 7(9), 289; https://doi.org/10.3390/jcm7090289
Received: 23 August 2018 / Revised: 10 September 2018 / Accepted: 12 September 2018 / Published: 18 September 2018
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Abstract
Increased physical activity (PA) affects outcomes in patients with anorexia nervosa (AN). To objectively assess PA patterns of hospitalized AN patients in comparison with healthy, outpatient controls (HC), and to analyze the effect of PA on Body Mass Index (BMI) change in patients
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Increased physical activity (PA) affects outcomes in patients with anorexia nervosa (AN). To objectively assess PA patterns of hospitalized AN patients in comparison with healthy, outpatient controls (HC), and to analyze the effect of PA on Body Mass Index (BMI) change in patients with AN, we measured PA in 50 female patients with AN (median age = 25 years, range = 18–52 years; mean BMI = 14.4 ± 2.0 kg/m2) at the initiation of inpatient treatment and in 30 female healthy controls (median age = 26 years, range = 19–53 years; mean BMI = 21.3 ± 1.7 kg/m2) using the SenseWear™ armband. Duration of inpatient stay and weight at discharge were abstracted from medical records. Compared with controls, AN patients spent more time in very light-intensity physical activity (VLPA) (median VLPA = 647 vs. 566 min/day, p = 0.004) and light-intensity physical activity (LPA) (median LPA = 126 vs. 84 min/day, p < 0.001) and less time in moderate-intensity physical activity (MPA) (median MPA = 82 vs. 114 min/day, p = 0.022) and vigorous physical activity (VPA) (median VPA = 0 vs. 16 min/day, p < 0.001). PA and BMI increase were not associated in a linear model, and BMI increase was mostly explained by lower admission BMI and longer inpatient stay. In a non-linear model, an influence of PA on BMI increase seemed probable (jack knife validation, r2 = 0.203; p < 0.001). No direct association was observed between physical inactivity and BMI increase in AN. An altered PA pattern exists in AN patients compared to controls, yet the origin and consequences thereof deserve further investigation. Full article
(This article belongs to the Special Issue Anorexia Nervosa)
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Open AccessReview New Molecular Technologies for Minimal Residual Disease Evaluation in B-Cell Lymphoid Malignancies
J. Clin. Med. 2018, 7(9), 288; https://doi.org/10.3390/jcm7090288
Received: 23 August 2018 / Revised: 10 September 2018 / Accepted: 14 September 2018 / Published: 18 September 2018
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Abstract
The clearance of malignant clonal cells significantly correlates with clinical outcomes in many hematologic malignancies. Accurate and high throughput tools for minimal residual disease (MRD) detection are needed to overcome some drawbacks of standard molecular techniques; such novel tools have allowed for higher
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The clearance of malignant clonal cells significantly correlates with clinical outcomes in many hematologic malignancies. Accurate and high throughput tools for minimal residual disease (MRD) detection are needed to overcome some drawbacks of standard molecular techniques; such novel tools have allowed for higher sensitivity analyses and more precise stratification of patients, based on molecular response to therapy. In this review, we depict the recently introduced digital PCR and next-generation sequencing technologies, describing their current application for MRD monitoring in lymphoproliferative disorders. Moreover, we illustrate the feasibility of these new technologies to test less invasive and more patient-friendly tissues sources, such as “liquid biopsy”. Full article
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Open AccessArticle Association of Wnt Inhibitors, Bone Mineral Density and Lifestyle Parameters in Women with Breast Cancer Treated with Anastrozole Therapy
J. Clin. Med. 2018, 7(9), 287; https://doi.org/10.3390/jcm7090287
Received: 7 August 2018 / Revised: 3 September 2018 / Accepted: 11 September 2018 / Published: 17 September 2018
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Abstract
Aim: To determine the levels of Wnt inhibitors in patients treated with aromatase inhibitors (AIs) prior to therapy and to investigate their association with bone mineral density (BMD) and lifestyle parameters. Methods: 137 breast cancer patients were divided into a group treated with
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Aim: To determine the levels of Wnt inhibitors in patients treated with aromatase inhibitors (AIs) prior to therapy and to investigate their association with bone mineral density (BMD) and lifestyle parameters. Methods: 137 breast cancer patients were divided into a group treated with 1 mg of anastrozole and a group w/o anastrozole therapy. Serum concentrations of sclerostin and dickkopf1 (DKK1) were measured by ELISA. BMD was measured by dual-energy X-ray absorptiometry (DXA). Lifestyle factors were investigated by a self-reported questionnaire. Results: Sclerostin was significantly higher in the AI-treated group (31.8 pmol/L vs. 24.1 pmol/L; p < 0.001), whereas DKK1 was significantly lower in the AI-treated group (24.3 pmol/L vs. 26.02 pmol/L; p < 0.001). Total hip and femoral neck BMD were significantly lower in the AI-treated group. Conclusion: AI treatment was associated with increased levels of sclerostin and decreased levels of DKK1. Full article
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Open AccessArticle Pre-Procedural Statin Use Is Associated with Improved Long-Term Survival and Reduced Major Cardiovascular Events in Patients Undergoing Carotid Artery Stenting: A Retrospective Study
J. Clin. Med. 2018, 7(9), 286; https://doi.org/10.3390/jcm7090286
Received: 17 August 2018 / Revised: 9 September 2018 / Accepted: 12 September 2018 / Published: 17 September 2018
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Abstract
Carotid artery stenting (CAS) is a minimal invasive procedure used to resolve carotid occlusion that can be affected by peri-procedural complications. Statin use before CAS has shown to reduce peri-procedural risk and improve survival, though time-dependent cofactors that influence mortality has not been
[...] Read more.
Carotid artery stenting (CAS) is a minimal invasive procedure used to resolve carotid occlusion that can be affected by peri-procedural complications. Statin use before CAS has shown to reduce peri-procedural risk and improve survival, though time-dependent cofactors that influence mortality has not been considered. The aim of this study was to evaluate long-term survival of patients who undergo CAS considering new occurred major adverse cardiovascular event (MACE) as time-dependent cofactor. In this study, 171 high cardiovascular risk patients (age 72 ± 8 years, 125 males) were enrolled after CAS procedure and were followed for a median of 8.4 years. Death occurred in 44% of patients with a mean time to death of 69 ± 39 months and MACE in 34% with a mean time of 35 ± 42 months. In patients who used or not statins at baseline, death occurred in 33% and 65%, respectively (p < 0.001). Survival analysis showed that statin use reduced risk of death (hazard ratio HR 0.36, 95% confidence interval CI 0.23–0.58, p < 0.0001). Including MACE as time-dependent variable did not change beneficial effects of statins. Additionally, statin use was associated with a protective effect on MACE (HR 0.48, 95% CI 0.27–0.85, p = 0.012); particularly, the prevalence of stroke was reduced by 59% (p = 0.018). In multivariate analysis, effects of statins were independent of demographic and anthropometric variables, prevalence of cardiovascular risk factors, renal function, antiplatelet use, and MACE occurrence. In conclusion, use of statins before CAS procedure is associated with increased long-term survival and reduced MACE occurrence. This evidence supports the hypothesis that statin use before CAS might be beneficial in high risk patients. Full article
(This article belongs to the Special Issue Developing Novel Therapies to Prevent Atherosclerosis)
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Open AccessArticle Effects of Statin Use in Advanced Chronic Kidney Disease Patients
J. Clin. Med. 2018, 7(9), 285; https://doi.org/10.3390/jcm7090285
Received: 5 August 2018 / Revised: 6 September 2018 / Accepted: 14 September 2018 / Published: 17 September 2018
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Abstract
Although statin treatment is recommended for patients with chronic kidney disease (CKD) stages I–IV, its potential benefits have not been reported in advanced CKD patients. Non-diabetic patients with advanced CKD (pre-dialysis patients, estimated glomerular filtration rate <15 mL/min/1.73 m2) were enrolled
[...] Read more.
Although statin treatment is recommended for patients with chronic kidney disease (CKD) stages I–IV, its potential benefits have not been reported in advanced CKD patients. Non-diabetic patients with advanced CKD (pre-dialysis patients, estimated glomerular filtration rate <15 mL/min/1.73 m2) were enrolled from a National Health Insurance Research Database with a population of 23 million. Statin users and non-users were matched using propensity scoring and analyzed using Cox proportional hazards models, taking mortality as a competing risk with subsequent end-stage renal disease (ESRD) and statin doses as time-dependent variables. A total of 2551 statin users and 7653 matched statin non-users were identified from a total 14,452 patients with advanced CKD. Taking mortality as a competing risk, statin use did not increase the risk of new-onset diabetes mellitus (NODM) or decrease the risk of de novo major adverse cardiovascular events (MACE), but reduced all-cause mortality (hazard ratio (HR) = 0.59 [95% CI 0.42–0.84], p = 0.004) and sepsis-related mortality (HR = 0.53 [95% CI 0.32–0.87], p = 0.012). For advanced CKD patients, statin was neither associated with increased risks of developing NODM, nor with decreased risk of de novo MACE occurrence, but with a reduced risk of all-cause mortality, mainly septic deaths. Full article
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Open AccessArticle The Effect of Gamification through a Virtual Reality on Preoperative Anxiety in Pediatric Patients Undergoing General Anesthesia: A Prospective, Randomized, and Controlled Trial
J. Clin. Med. 2018, 7(9), 284; https://doi.org/10.3390/jcm7090284
Received: 8 August 2018 / Revised: 13 September 2018 / Accepted: 14 September 2018 / Published: 17 September 2018
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Abstract
The use of gamification in healthcare has been gaining popularity. This prospective, randomized, clinical trial was designed to evaluate whether gamification of the preoperative process—via virtual reality (VR) gaming that provides a vivid, immersive and realistic experience—could reduce preoperative anxiety in children. Seventy
[...] Read more.
The use of gamification in healthcare has been gaining popularity. This prospective, randomized, clinical trial was designed to evaluate whether gamification of the preoperative process—via virtual reality (VR) gaming that provides a vivid, immersive and realistic experience—could reduce preoperative anxiety in children. Seventy children scheduled for elective surgery under general anesthesia were randomly divided into either the control or gamification group. Children in the control group received conventional education regarding the preoperative process, whereas those in the gamification group played a 5 min VR game experiencing the preoperative experience. Preoperative anxiety, induction compliance checklist (ICC), and procedural behavior rating scale (PBRS) were measured. Sixty-nine children were included in the final analysis (control group = 35, gamification = 34). Preoperative anxiety (28.3 [23.3–36.7] vs. 46.7 [31.7–51.7]; p < 0.001) and intraoperative compliance measured using ICC (p = 0.038) were lower in the gamification group than in the control group. However, PBRS (p = 0.092) and parent/guardian satisfaction (p = 0.268) were comparable between the two groups. VR experience of the preoperative process could reduce preoperative anxiety and improve compliance during anesthetic induction in children undergoing elective surgery and general anesthesia. Full article
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Open AccessArticle In Vitro Study of Multi-Therapeutic Properties of Thymus bovei Benth. Essential Oil and Its Main Component for Promoting Their Use in Clinical Practice
J. Clin. Med. 2018, 7(9), 283; https://doi.org/10.3390/jcm7090283
Received: 2 September 2018 / Revised: 11 September 2018 / Accepted: 12 September 2018 / Published: 15 September 2018
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Abstract
Thymus bovei Benth. (TB) is an important plant in the traditional medicine of the Mediterranean region. This study investigates the health-promoting properties of TB essential oil (TB-EO) for its possible use in clinical practice with regards to its cytotoxic, anti-herpes simplex virus type
[...] Read more.
Thymus bovei Benth. (TB) is an important plant in the traditional medicine of the Mediterranean region. This study investigates the health-promoting properties of TB essential oil (TB-EO) for its possible use in clinical practice with regards to its cytotoxic, anti-herpes simplex virus type 2 (HSV-2), and antihypertensive (through inhibition of human angiotensin-converting enzyme; ACE) properties. The phytochemical profile of EO (99.9%) was analyzed by Gas Chromatography with Flame-Ionization Detection (GC-FID) and Gas Chromatography-Mass Spectrometry (GC-MS). In this study, all biological methods were performed at the level of in vitro studies. The results showed that TB-EO exerted remarked cytotoxic properties against human cervical carcinoma cells, colon cancer cells, and lung adenocarcinoma cells with the half-maximal inhibitory concentration (IC50) values of 7.22, 9.30, and 8.62 µg/mL, respectively, in comparison with that of standard anticancer drug cisplatin with IC50 values of 4.24, 5.21, and 5.43 µg/mL, respectively. Fascinatingly, TB-EO showed very weak cytotoxicity on the healthy human fetal lung fibroblast cells with an IC50 value of 118.34 µg/mL compared with that of cisplatin (IC50 = 10.08 µg/mL). TB-EO, its main component geraniol, TB-EO combined with acyclovir (ACV) along with standard ACV, have displayed pronounced inhibitory properties against the replication of HSV-2 with the half-maximal effective concentration (EC50) values of 2.13, 1.92, 0.81 and 1.94 µg/mL, respectively, with corresponding selectivity indices (SI) 98.59, 109.38, 259.26 and 108.25, respectively. TB-EO and geraniol at a concentration of 15 µg/mL showed prominent inhibitory activities against ACE with % of inhibition 95.4% and 92.2%, respectively, compared with that of standard inhibitor captopril (99.8%; 15 µg/mL). Molecular docking studies were performed to unveil the mechanism of action of geraniol as well as structural parameters necessary for anti-HSV-2 activity (through the inhibition of HSV-2 protease) and ACE inhibition. This is the first report on the chemical composition of Egyptian TB-EO along with the above-mentioned biological activities. Our results may be considered as novel findings in the course of a search for new and active anticancer, anti-HSV-2 and antihypertensive agents, and expand the medicinal value of this plant and its phytochemicals in clinical practice. Full article
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Open AccessArticle Association between Cigarette Smoking Status and Composition of Gut Microbiota: Population-Based Cross-Sectional Study
J. Clin. Med. 2018, 7(9), 282; https://doi.org/10.3390/jcm7090282
Received: 6 August 2018 / Revised: 3 September 2018 / Accepted: 13 September 2018 / Published: 14 September 2018
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Abstract
There have been few large-scale studies on the relationship between smoking and gut microbiota. We investigated the relationship between smoking status and the composition of gut microbiota. This was a population-based cross-sectional study using Healthcare Screening Center cohort data. A total of 758
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There have been few large-scale studies on the relationship between smoking and gut microbiota. We investigated the relationship between smoking status and the composition of gut microbiota. This was a population-based cross-sectional study using Healthcare Screening Center cohort data. A total of 758 men were selected and divided into three groups: never (n = 288), former (n = 267), and current smokers (n = 203). Among the three groups, there was no difference in alpha diversity, however, Jaccard-based beta diversity showed significant difference (p = 0.015). Pairwise permutational multivariate analysis of variance (PERMANOVA) tests between never and former smokers did not show a difference; however, there was significant difference between never and current smokers (p = 0.017) and between former and current smokers (p = 0.011). Weighted UniFrac-based beta diversity also showed significant difference among the three groups (p = 0.038), and pairwise PERMANOVA analysis of never and current smokers showed significant difference (p = 0.01). In the analysis of bacterial composition, current smokers had an increased proportion of the phylum Bacteroidetes with decreased Firmicutes and Proteobacteria compared with never smokers, whereas there were no differences between former and never smokers. In conclusion, gut microbiota composition of current smokers was significantly different from that of never smokers. Additionally, there was no difference in gut microbiota composition between never and former smokers. Full article
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Open AccessReview Can the Fact That Myelin Proteins Are Old and Break down Explain the Origin of Multiple Sclerosis in Some People?
J. Clin. Med. 2018, 7(9), 281; https://doi.org/10.3390/jcm7090281
Received: 11 July 2018 / Revised: 11 September 2018 / Accepted: 12 September 2018 / Published: 14 September 2018
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Abstract
Recent discoveries may change the way that multiple sclerosis (MS) is viewed, particularly with regard to the reasons for the untoward immune response. The fact that myelin proteins are long-lived, and that by the time we are adults, they are extensively degraded, alters
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Recent discoveries may change the way that multiple sclerosis (MS) is viewed, particularly with regard to the reasons for the untoward immune response. The fact that myelin proteins are long-lived, and that by the time we are adults, they are extensively degraded, alters our perspective on the reasons for the onset of autoimmunity and the origin of MS. For example, myelin basic protein (MBP) from every human brain past the age of 20 years, is so greatly modified, that it is effectively a different protein from the one that was laid down in childhood. Since only a subset of people with such degraded MBP develop MS, a focus on understanding the mechanism of immune responses to central nervous system (CNS) antigens and cerebral immune tolerance appear to be worthwhile avenues to explore. In accord with this, it will be productive to examine why all people, whose brains contain large quantities of a “foreign antigen”, do not develop MS. Importantly for the potential causation of MS, MBP from MS patients breaks down differently from the MBP in aged controls. If the novel structures formed in these MS-specific regions are particularly antigenic, it could help explain the origin of MS. If verified, these findings could provide an avenue for the rational synthesis of drugs to prevent and treat MS. Full article
(This article belongs to the Special Issue Potential Pathogenic Mechanisms of Multiple Sclerosis)
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Open AccessReview The Diagnosis and Clinical Significance of Paragangliomas in Unusual Locations
J. Clin. Med. 2018, 7(9), 280; https://doi.org/10.3390/jcm7090280
Received: 30 July 2018 / Revised: 6 September 2018 / Accepted: 10 September 2018 / Published: 13 September 2018
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Abstract
Paragangliomas are neuroendocrine neoplasms, derived from paraganglia of the sympathetic and parasympathetic nervous systems. They are most commonly identified in the head and neck, being most frequent in the carotid body, followed by jugulotympanic paraganglia, vagal nerve and ganglion nodosum, as well as
[...] Read more.
Paragangliomas are neuroendocrine neoplasms, derived from paraganglia of the sympathetic and parasympathetic nervous systems. They are most commonly identified in the head and neck, being most frequent in the carotid body, followed by jugulotympanic paraganglia, vagal nerve and ganglion nodosum, as well as laryngeal paraganglia. Abdominal sites include the well-known urinary bladder tumors that originate in the Organ of Zuckerkandl. However, other unusual sites of origin include peri-adrenal, para-aortic, inter-aortocaval, and paracaval retroperitoneal sites, as well as tumors in organs where they may not be expected in the differential diagnosis of neuroendocrine neoplasms, such as thyroid, parathyroid, pituitary, gut, pancreas, liver, mesentery, lung, heart and mediastinum. The distinction of these lesions from epithelial neuroendocrine neoplasms is critical for several reasons. Firstly, the determination of clinical and biochemical features is different from that used for epithelial neuroendocrine tumors. Secondly, the genetic implications are different, since paragangliomas/pheochromocytomas have the highest rate of germline susceptibility at almost 40%. Finally, the characterization of metastatic disease is unique in these highly syndromic lesions. In this review, we summarize updated concepts by outlining the spectrum of anatomic locations of paragangliomas, the importance of morphology in establishing the correct diagnosis, the clinical implications for management, and the impact of genetics on the distinction between multifocal primary tumors compared with malignant disease. Full article
(This article belongs to the Special Issue Pheochromocytoma and Paraganglioma: Research Update)
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Open AccessArticle Dose-Response Relationship between Exercise Duration and Executive Function in Older Adults
J. Clin. Med. 2018, 7(9), 279; https://doi.org/10.3390/jcm7090279
Received: 7 August 2018 / Revised: 3 September 2018 / Accepted: 11 September 2018 / Published: 13 September 2018
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Abstract
This study aimed to determine the dose-response relationship between exercise duration and task switching in older adults. Acute moderate intensity aerobic exercise for 20 min resulted in shorter response times than control and 10-min sessions in the heterogeneous, non-switch, and switch conditions, but
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This study aimed to determine the dose-response relationship between exercise duration and task switching in older adults. Acute moderate intensity aerobic exercise for 20 min resulted in shorter response times than control and 10-min sessions in the heterogeneous, non-switch, and switch conditions, but not in the homogeneous condition. Additionally, linear and cubic trends between exercise duration and global switching performance as well as local switching performance were revealed with faster times being predicted by longer duration exercise; however, the cubic relationship resulted in performance following the 45-min session being not significantly different from the other three sessions. Acute aerobic moderate intensity exercise for 20 min is an effective duration to improve task switching. Although a longer duration of exercise is not optimal for benefiting task switching, it does not harm task switching in older adults and hence may be of value for other health-related reasons. Full article
(This article belongs to the Special Issue The Effects of Exercise on Cognitive Function)
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Open AccessArticle Effects of 462 nm Light-Emitting Diode on the Inactivation of Escherichia coli and a Multidrug-Resistant by Tetracycline Photoreaction
J. Clin. Med. 2018, 7(9), 278; https://doi.org/10.3390/jcm7090278
Received: 13 August 2018 / Revised: 6 September 2018 / Accepted: 10 September 2018 / Published: 12 September 2018
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Abstract
The adaptability of bacterial resistance to antibiotics contributes to its high efficiency during evolution. Tetracycline (TC) is a broad-spectrum antimicrobial agent. Chromatographic analyses and mass spectrometry were used to study the effects of the light illumination of a 462 nm light-emitting diode (LED)
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The adaptability of bacterial resistance to antibiotics contributes to its high efficiency during evolution. Tetracycline (TC) is a broad-spectrum antimicrobial agent. Chromatographic analyses and mass spectrometry were used to study the effects of the light illumination of a 462 nm light-emitting diode (LED) on the conformational changes of TC in a phosphate buffer solution (PBS, pH 7.8). Especially, the inactivation of superoxide anion radicals (O2) and Escherichia coli (E. coli), including that of a multidrug-resistant E. coli (MDR E. coli), were investigated during the photolysis of TC. A photolysis product of TC (PPT) was generated in an alkaline solution after the illumination of a blue light. The mass spectra of PPT had characteristic ion signals in m/z 459, 445, and 249.1 Da. The PPT has the molecular formula of C22H22N2O9, and the exact mass is 458.44 g/mol. The inactivation of MDR E. coli is not significant with TC treatment. The drug-resistant ability of MDR E. coli has a less significant effect on PPT, and the changed conformation of TC retained the inactivation ability of MDR E. coli upon blue light photoreaction. With TC, illuminated by a blue light in a pH 7.8 PBS, O2 was generated from TC photolysis, which enhanced the inactivation of E. coli and MDR E. coli. A 96.6% inactivation rate of MDR E. coli was reached with TC under 2.0 mW/cm2 blue light illumination at 25 ± 3 °C for 120 min, and the effects of the TC-treated photoreaction on MDR E. coli viability repressed the growth of MDR E. coli by 4 to 5 logs. The present study of the blue light photoreaction of TC offers a new approach to the inactivation of MDR E. coli. Full article
(This article belongs to the Special Issue Advances in Antibacterial Drug Discovery and Therapy)
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Open AccessArticle Development of a Prediction Model for Colorectal Cancer among Patients with Type 2 Diabetes Mellitus Using a Deep Neural Network
J. Clin. Med. 2018, 7(9), 277; https://doi.org/10.3390/jcm7090277
Received: 21 August 2018 / Revised: 8 September 2018 / Accepted: 10 September 2018 / Published: 12 September 2018
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Abstract
Objectives: Observational studies suggested that patients with type 2 diabetes mellitus (T2DM) presented a higher risk of developing colorectal cancer (CRC). The current study aims to create a deep neural network (DNN) to predict the onset of CRC for patients with T2DM. Methods:
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Objectives: Observational studies suggested that patients with type 2 diabetes mellitus (T2DM) presented a higher risk of developing colorectal cancer (CRC). The current study aims to create a deep neural network (DNN) to predict the onset of CRC for patients with T2DM. Methods: We employed the national health insurance database of Taiwan to create predictive models for detecting an increased risk of subsequent CRC development in T2DM patients in Taiwan. We identified a total of 1,349,640 patients between 2000 and 2012 with newly diagnosed T2DM. All the available possible risk factors for CRC were also included in the analyses. The data were split into training and test sets with 97.5% of the patients in the training set and 2.5% of the patients in the test set. The deep neural network (DNN) model was optimized using Adam with Nesterov’s accelerated gradient descent. The recall, precision, F1 values, and the area under the receiver operating characteristic (ROC) curve were used to evaluate predictor performance. Results: The F1, precision, and recall values of the DNN model across all data were 0.931, 0.982, and 0.889, respectively. The area under the ROC curve of the DNN model across all data was 0.738, compared to the ideal value of 1. The metrics indicate that the DNN model appropriately predicted CRC. In contrast, a single variable predictor using adapted the Diabetes Complication Severity Index showed poorer performance compared to the DNN model. Conclusions: Our results indicated that the DNN model is an appropriate tool to predict CRC risk in patients with T2DM in Taiwan. Full article
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
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Open AccessArticle Regeneration of Transected Recurrent Laryngeal Nerve Using Hybrid-Transplantation of Skeletal Muscle-Derived Stem Cells and Bioabsorbable Scaffold
J. Clin. Med. 2018, 7(9), 276; https://doi.org/10.3390/jcm7090276
Received: 14 August 2018 / Revised: 5 September 2018 / Accepted: 9 September 2018 / Published: 12 September 2018
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Abstract
Hybrid transplantation of skeletal muscle-derived multipotent stem cells (Sk-MSCs) and bioabsorbable polyglyconate (PGA) felt was studied as a novel regeneration therapy for the transected recurrent laryngeal nerve (RLN). Sk-MSCs were isolated from green fluorescence protein transgenic mice and then expanded and transplanted with
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Hybrid transplantation of skeletal muscle-derived multipotent stem cells (Sk-MSCs) and bioabsorbable polyglyconate (PGA) felt was studied as a novel regeneration therapy for the transected recurrent laryngeal nerve (RLN). Sk-MSCs were isolated from green fluorescence protein transgenic mice and then expanded and transplanted with PGA felt for the hybrid transplantation (HY group) into the RLN transected mouse model. Transplantation of culture medium (M group) and PGA + medium (PGA group) were examined as controls. After eight weeks, trans-oral video laryngoscopy demonstrated 80% recovery of spontaneous vocal-fold movement during breathing in the HY group, whereas the M and PGA groups showed wholly no recoveries. The Sk-MSCs showed active engraftment confined to the damaged RLN portion, representing favorable prevention of cell diffusion on PGA, with an enhanced expression of nerve growth factor mRNAs. Axonal re-connection in the HY group was confirmed by histological serial sections. Immunohistochemical analysis revealed the differentiation of Sk-MSCs into Schwann cells and perineurial/endoneurial cells and axonal growth supportive of perineurium/endoneurium. The number of axons recovered was over 86%. These results showed that the stem cell and cytokine delivery system using hybrid transplantation of Sk-MSCs/PGA-felt is a potentially practical and useful approach for the recovery of transected RLN. Full article
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Open AccessArticle Association of Pre-Eclampsia with Carotid Artery Intima–Media Thickness and Non-Alcoholic Fatty Liver Disease
J. Clin. Med. 2018, 7(9), 275; https://doi.org/10.3390/jcm7090275
Received: 21 July 2018 / Revised: 29 August 2018 / Accepted: 3 September 2018 / Published: 12 September 2018
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Abstract
Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are considered important complications of pre-eclampsia. This study was conducted to determine the association of pre-eclampsia with non-alcoholic fatty liver disease and the association of pre-eclampsia with bilateral intima–media thickness (IMT; right and left), separately. Twenty-one
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Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are considered important complications of pre-eclampsia. This study was conducted to determine the association of pre-eclampsia with non-alcoholic fatty liver disease and the association of pre-eclampsia with bilateral intima–media thickness (IMT; right and left), separately. Twenty-one pregnant women with pre-eclampsia and 21 normal pregnant women were enrolled in the present study. The right and left intima–media thicknesses of carotid arteries were evaluated using Doppler sonography. The diagnosis of NAFLD was based on sonography. Linear and binary logistic regression analyses were performed to evaluate the association between pre-eclampsia and related outcomes. The mean right IMT was determined as 0.60 ± 0.07 mm in women with pre-eclampsia and 0.51 ± 0.08 mm in normal pregnant women (p = 0.001). On the other hand, the mean left IMT was 0.59 ± 0.09 mm in women with pre-eclampsia and 0.50 ± 0.10 mm in normal pregnant women (p = 0.003). The frequencies of NAFLD in women with pre-eclampsia and normal pregnant women were found to be 66.7% and 23.8% respectively (p = 0.006). Multivariate linear regression analysis revealed an association between pre-eclampsia and right (p = 0.014) and left (p = 0.019) IMT, without removing the effects of other confounding variables. Binary regression analysis (multivariate) did not confirm an independent association between pre-eclampsia and NAFLD. Pre-eclampsia exhibited a direct and independent association with right and left IMT. Although the prevalence of NAFLD was significantly higher in women with pre-eclampsia, pre-eclampsia was not an independent predictor for NAFLD. Full article
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Open AccessArticle Norepinephrine Administration Is Associated with Higher Mortality in Dialysis Requiring Acute Kidney Injury Patients with Septic Shock
J. Clin. Med. 2018, 7(9), 274; https://doi.org/10.3390/jcm7090274
Received: 5 August 2018 / Revised: 7 September 2018 / Accepted: 9 September 2018 / Published: 12 September 2018
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Abstract
(1) Background: Norepinephrine (NE) is the first-line vasoactive agent used in septic shock patients; however, the effect of norepinephrine on dialysis-required septic acute kidney injury (AKI-D) patients is uncertain. (2) Methods: To evaluate the impact of NE on 90-day mortality and renal recovery
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(1) Background: Norepinephrine (NE) is the first-line vasoactive agent used in septic shock patients; however, the effect of norepinephrine on dialysis-required septic acute kidney injury (AKI-D) patients is uncertain. (2) Methods: To evaluate the impact of NE on 90-day mortality and renal recovery in septic AKI-D patients, we enrolled patients in intensive care units from 30 hospitals in Taiwan. (3) Results: 372 patients were enrolled and were divided into norepinephrine users and non-users. After adjustment by Inverse probability of treatment weighted (IPTW), there was no significant difference of baseline comorbidities between the two groups. NE users had significantly higher 90-day mortality rate and using NE is a strong predictor of 90-day mortality in the multivariate Cox regression (HR = 1.497, p = 0.027) after adjustment. The generalized additive model disclosed norepinephrine alone exerted a dose–dependent effect on 90-day mortality, while other vasoactive agents were not. (4) Conclusion: Using norepinephrine in septic AKI-D patients is associated with higher 90-day mortality and the effect is dose-dependent. Further study to explore the potential mechanism is needed. Full article
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Open AccessArticle Autoalgometry: An Important Tool for Pressure Pain Threshold Evaluation
J. Clin. Med. 2018, 7(9), 273; https://doi.org/10.3390/jcm7090273
Received: 24 August 2018 / Revised: 7 September 2018 / Accepted: 10 September 2018 / Published: 12 September 2018
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Abstract
The term “pain threshold” refers to the measurement of the intensity of a physical stimulus that evokes pain. To estimate the pain threshold, a mechanical or electrical stimulus with increasing intensity is usually applied until the subject under evaluation refers to a pain
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The term “pain threshold” refers to the measurement of the intensity of a physical stimulus that evokes pain. To estimate the pain threshold, a mechanical or electrical stimulus with increasing intensity is usually applied until the subject under evaluation refers to a pain sensation. This study aims to evaluate the autoalgometric pain threshold as a perfect technique to determine the effects of stimulation rate in relation to both gender and the site of stimulation. In this experimental model, pressure algometry was applied: the subject under evaluation pushed a finger against a small round metal tip, producing and at the same time controlling the intensity of the noxious stimulus. Through autoalgometry, the stimulus intensity was recorded over time, measuring the force change rate applied and studying the subject’s behavior on approaching pain. This test was performed with 50 healthy volunteers on two days, applying a fast or slow rate of stimulation. The results described demonstrate that there is a positive correlation between the pressure increase rate and the pressure threshold evaluation. In light of these findings, autoalgometry can be proposed as an objective measure of pressure pain threshold for clinical and research use. Full article
(This article belongs to the Special Issue Cardiovascular and Neurological Emergency)
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Open AccessArticle Aerobic Capacity Is Not Associated with Most Cognitive Domains in Patients with Multiple Sclerosis—A Cross-Sectional Investigation
J. Clin. Med. 2018, 7(9), 272; https://doi.org/10.3390/jcm7090272
Received: 17 August 2018 / Revised: 5 September 2018 / Accepted: 7 September 2018 / Published: 11 September 2018
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Abstract
(1) Background: Cognitive impairment is highly prevalent in multiple sclerosis (MS). Staying physically fit may be associated with preservation of cognitive performance in persons with MS (pwMS); (2) Objective: To investigate the association between aerobic capacity and the cognitive domains of information processing,
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(1) Background: Cognitive impairment is highly prevalent in multiple sclerosis (MS). Staying physically fit may be associated with preservation of cognitive performance in persons with MS (pwMS); (2) Objective: To investigate the association between aerobic capacity and the cognitive domains of information processing, learning and memory, and verbal fluency as well as single and composite z-scores of the Brief Repeatable Battery of Neuropsychological tests (BRBNT) in pwMS; (3) Methods: All subjects first performed the BRBNT and then a maximal oxygen consumption (VO2-max) test on a bicycle ergometer as a measure of aerobic capacity. Simple and multiple (adjusting for age, sex, and education level) regression analyses were performed to evaluate the relationship between aerobic capacity and cognitive performance in different domains. Published international norms were used to compute z-scores for each individual and composite BRBNT score. Furthermore, cognitive impairment was defined as one or more z-scores ≤−1.5 standard deviation (SD) of healthy controls; (4) Results: Eighty-four subjects were included (44.9 ± 9 years, 16.3 ± 2 education years, Expanded Disability Status Scale (EDSS): 2.6 ± 1.4, MS-type (relapsing-remitting, primary progressive, or secondary progressive): 73/6/5, disease duration: 9.9 ± 7 years, VO2-max: 28.4 ± 7.0 mL O2/min/kg). No significant associations between aerobic capacity and cognitive performance in the individual BRBNT tests were found, except that a weak relationship was found between aerobic capacity and the composite processing speed z-score (R2 = 0.06, p = 0.02). The average global BRBNT z-score (−0.2 ± 0.66) was not associated with aerobic capacity. Comparison of the cognitively impaired group (34.5%) with the nonimpaired group (65.5%) showed lower aerobic capacity in the impaired group (25.9 ± 1 vs. 29.7 ± 1 mLO2/min/kg, p = 0.02); (5) Conclusions: Limited support was found for an association between performance in most cognitive domains and aerobic capacity in the present MS group with a third of patients showing signs of cognitive impairments. Full article
(This article belongs to the Special Issue The Effects of Exercise on Cognitive Function)
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Open AccessArticle Use of Linagliptin for the Management of Medicine Department Inpatients with Type 2 Diabetes in Real-World Clinical Practice (Lina-Real-World Study)
J. Clin. Med. 2018, 7(9), 271; https://doi.org/10.3390/jcm7090271
Received: 23 July 2018 / Revised: 7 September 2018 / Accepted: 8 September 2018 / Published: 11 September 2018
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Abstract
The use of noninsulin antihyperglycaemic drugs in the hospital setting has not yet been fully described. This observational study compared the efficacy and safety of the standard basal-bolus insulin regimen versus a dipeptidyl peptidase-4 inhibitor (linagliptin) plus basal insulin in medicine department inpatients
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The use of noninsulin antihyperglycaemic drugs in the hospital setting has not yet been fully described. This observational study compared the efficacy and safety of the standard basal-bolus insulin regimen versus a dipeptidyl peptidase-4 inhibitor (linagliptin) plus basal insulin in medicine department inpatients in real-world clinical practice. We retrospectively enrolled non-critically ill patients with type 2 diabetes with mild to moderate hyperglycaemia and no injectable treatments at home who were treated with a hospital antihyperglycaemic regimen (basal-bolus insulin, or linagliptin-basal insulin) between January 2016 and December 2017. Propensity score was used to match patients in both treatment groups and a comparative analysis was conducted to test the significance of differences between groups. After matched-pair analysis, 227 patients were included per group. No differences were shown between basal-bolus versus linagliptin-basal regimens for the mean daily blood glucose concentration after admission (standardized difference = 0.011), number of blood glucose readings between 100–140 mg/dL (standardized difference = 0.017) and >200 mg/dL (standardized difference = 0.021), or treatment failures (standardized difference = 0.011). Patients on basal-bolus insulin received higher total insulin doses and a higher daily number of injections (standardized differences = 0.298 and 0.301, respectively). Basal and supplemental rapid-acting insulin doses were similar (standardized differences = 0.003 and 0.012, respectively). There were no differences in hospital stay length (standardized difference = 0.003), hypoglycaemic events (standardized difference = 0.018), or hospital complications (standardized difference = 0.010) between groups. This study shows that in real-world clinical practice, the linagliptin-basal insulin regimen was as effective and safe as the standard basal-bolus regimen in non-critical patients with type 2 diabetes with mild to moderate hyperglycaemia treated at home without injectable therapies. Full article
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Open AccessArticle Body Fatness and Cardiovascular Health in Newborn Infants
J. Clin. Med. 2018, 7(9), 270; https://doi.org/10.3390/jcm7090270
Received: 16 August 2018 / Revised: 4 September 2018 / Accepted: 8 September 2018 / Published: 11 September 2018
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Abstract
Birth weight is associated with cardiovascular disease, with those at both ends of the spectrum at increased risk. However, birth weight is a crude surrogate of fetal growth. Measures of body composition may more accurately identify high risk infants. We aimed to determine
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Birth weight is associated with cardiovascular disease, with those at both ends of the spectrum at increased risk. However, birth weight is a crude surrogate of fetal growth. Measures of body composition may more accurately identify high risk infants. We aimed to determine whether aortic wall thickening, cardiac autonomic control, and cardiac structure/function differ in newborns with high or low body fatness compared to those with average body fatness. 189 healthy singleton term born neonates were recruited and stratified by body fat percentiles (sex and gestation-specific). Infants with low body fat had higher aortic intima-media thickness (43 µm (95% confidence interval (CI) 7, 78), p = 0.02), lower heart rate variability (log total power, −0.5 (95% CI −0.8, −0.1), p = 0.008), and thicker ventricular walls (posterior wall thickness, 3.1 mm (95% CI 1.6, 4.6), p < 0.001) compared to infants with average body fatness. Infants with high body fat showed no differences in aortic intima-media thickness (−2 µm (95% CI −37, 33), p = 0.91) or cardiac structure compared to average body fatness, although stroke volume (−0.3 mL/kg (95% CI −0.6, −0.0), p = 0.003) and heart rate variability were lower (log total power, −0.8 (95% CI −1.1, −0.5), p < 0.001). The non-linear association of body fatness with heart rate variability was independent of birth weight. Infants born with low or high body fat have altered markers of cardiovascular health. Assessment of body fatness alongside birth weight may assist in identifying high risk individuals. Full article
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Open AccessArticle Risk and Predisposing Factors for Suicide Attempts in Patients with Migraine and Status Migrainosus: A Nationwide Population-Based Study
J. Clin. Med. 2018, 7(9), 269; https://doi.org/10.3390/jcm7090269
Received: 16 August 2018 / Accepted: 9 September 2018 / Published: 11 September 2018
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Abstract
Objective: To investigate the risk and risk factors for suicide attempt by patients with regular migraines (RM) and status migrainosus (SM) in Taiwan. Methods: We analyzed a subset of the National Health Insurance Research Database of Taiwan and enrolled patients (≥20 years old)
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Objective: To investigate the risk and risk factors for suicide attempt by patients with regular migraines (RM) and status migrainosus (SM) in Taiwan. Methods: We analyzed a subset of the National Health Insurance Research Database of Taiwan and enrolled patients (≥20 years old) who had ever received a diagnosis of RM or SM between 2000 and 2012 in the RM and SM cohort. The SM cohort included 13,605 patients, the RM cohort had 21,485 patients, and the comparison cohort contained approximately four times that many patients. We calculated the adjusted hazard ratios and 95% confidence intervals (CI) for suicide attempts after adjusting for age, sex, monthly income, urbanization level, occupation, and comorbidities. Results: The SM cohort had a 1.81-fold risk of attempting suicide (95% CI = 1.14–2.89) compared to the comparison cohort. Other factors that predispose patients with SM to attempt suicide include the following: female sex, relatively young age (<50 years old), and low monthly income (<15,000 New Taiwan Dollars, approximately equivalent to 495 US Dollars). Additionally, the risk of attempting suicide only increased in patients who had been diagnosed with SM for longer than five years. Conclusion: SM is associated with a higher risk for suicide attempt in migraineurs in Taiwan. This finding is important to clinicians and government officials seeking to prevent patients from attempting suicide in Taiwan and other similar East Asian countries. Full article
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Open AccessArticle Application and Validation of Activity Monitors’ Epoch Lengths and Placement Sites for Physical Activity Assessment in Exergaming
J. Clin. Med. 2018, 7(9), 268; https://doi.org/10.3390/jcm7090268
Received: 11 August 2018 / Revised: 28 August 2018 / Accepted: 7 September 2018 / Published: 11 September 2018
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Abstract
We assessed the agreement of two ActiGraph activity monitors (wGT3X vs. GT9X) placed at the hip and the wrist and determined an appropriate epoch length for physical activity levels in an exergaming setting. Forty-seven young adults played a 30-min exergame while wearing wGT3X
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We assessed the agreement of two ActiGraph activity monitors (wGT3X vs. GT9X) placed at the hip and the wrist and determined an appropriate epoch length for physical activity levels in an exergaming setting. Forty-seven young adults played a 30-min exergame while wearing wGT3X and GT9X on both hip and wrist placement sites and a heart rate sensor below the chest. Intraclass correlation coefficient indicated that intermonitor agreement in steps and activity counts was excellent on the hip and good on the wrist. Bland-Altman plots indicated good intermonitor agreement in the steps and activity counts on both placement sites but a significant intermonitor difference was detected in steps on the wrist. Time spent in sedentary and physical activity intensity levels varied across six epoch lengths and depended on the placement sites, whereas time spent from a 1-s epoch of the hip-worn monitors most accurately matched the relative exercise intensity by heart rate. Hip placement site was associated with better step-counting accuracy for both activity monitors and more valid estimation of physical activity levels. A 1-s epoch was the most appropriate epoch length to detect short bursts of intense physical activity and may be the best choice for data processing and analysis in exergaming studies examining intermittent physical activities. Full article
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Open AccessArticle Fibrosis Staging Using Direct Serum Biomarkers is Influenced by Hepatitis Activity Grading in Hepatitis C Virus Infection
J. Clin. Med. 2018, 7(9), 267; https://doi.org/10.3390/jcm7090267
Received: 15 August 2018 / Revised: 7 September 2018 / Accepted: 9 September 2018 / Published: 11 September 2018
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Abstract
Background: Chronic liver diseases (CLDs) generally progress from inflammation to fibrosis and finally to carcinogenesis. Staging of liver fibrosis progression is inevitable for the management of CLD patients. The purpose of this study was to compare the diagnostic abilities of Wisteria floribunda agglutinin-positive
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Background: Chronic liver diseases (CLDs) generally progress from inflammation to fibrosis and finally to carcinogenesis. Staging of liver fibrosis progression is inevitable for the management of CLD patients. The purpose of this study was to compare the diagnostic abilities of Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA-M2BP), Enhanced liver fibrosis (ELF) score, Fibrosis-4 index, and AST to platelet ratio index (APRI) based on histopathological analysis of liver biopsy samples, from patients with positive Hepatitis C Virus (HCV) infection. Methods: Japanese patients with HCV infection who underwent liver biopsy examinations were enrolled in this study. WFA-M2BP levels and ELF scores were calculated using preserved serum samples. The fibrosis staging and activity grading were assessed using a modified METAVIR score. Results: A total of 122 patients were enrolled; the cohort included 27 patients with stage 1, 66 with stage 2, 20 with stage 3, and nine with stage 4 fibrosis. All four biomarkers distinguished stage 3 and stage 2 fibrosis. ROC curves revealed that all four fibrosis biomarkers presented AUC values greater than 0.8. Each of the four biomarkers in stage 2 was significantly different between the activity grade 1 and 2 groups. Conclusion: Fib-4 index and APRI were comparable with WFA-M2BP and ELF score in the diagnosis of advanced liver fibrosis in Japanese patients with HCV infection. All four biomarkers of liver fibrosis were influenced by histopathological activity grading, which implies that liver biopsy should be the gold standard to evaluate liver fibrosis staging even though several noninvasive biomarkers have been investigated well. Full article
(This article belongs to the Special Issue Advanced Analytical Methods in Clinical Diagnosis and Therapy)
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Open AccessArticle Translational Medicine in Pulmonary-Renal Crosstalk: Therapeutic Targeting of p-Cresyl Sulfate Triggered Nonspecific ROS and Chemoattractants in Dyspneic Patients with Uremic Lung Injury
J. Clin. Med. 2018, 7(9), 266; https://doi.org/10.3390/jcm7090266
Received: 15 August 2018 / Revised: 31 August 2018 / Accepted: 7 September 2018 / Published: 9 September 2018
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Abstract
Molecular mechanisms and pathological features of p-Cresyl sulfate (PCS)-induced uremic lung injury (ULI) in chronic kidney disease (CKD) remain unclear. We analyzed pleural effusions (PE) from CKD and non-CKD patients for uremic toxins, reactive oxygen species (ROS), and chemotactic cytokines. Correlations between PE
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Molecular mechanisms and pathological features of p-Cresyl sulfate (PCS)-induced uremic lung injury (ULI) in chronic kidney disease (CKD) remain unclear. We analyzed pleural effusions (PE) from CKD and non-CKD patients for uremic toxins, reactive oxygen species (ROS), and chemotactic cytokines. Correlations between PE biomarkers and serum creatinine were also studied. Cell viability and inflammatory signaling pathways were investigated in PCS-treated human alveolar cell model. To mimic human diseases, CKD-ULI mouse model was developed with quantitative comparison of immunostaining and morphometric approach. PE from CKD patients enhance expressions of uremic toxins, hydroxyl radicals, and IL-5/IL-6/IL-8/IL-10/IL-13/ENA-78/GRO α/MDC/thrombopoietin/VEGF. PE concentrations of ENA-78/VEGF/IL-8/MDC/PCS/indoxyl sulphate correlate with serum creatinine concentrations. In vitro, PCS promotes alveolar cell death, cPLA2/COX-2/aquaporin-4 expression, and NADPH oxidase/mitochondria activation-related ROS. Intracellular ROS is abrogated by non-specific ROS scavenger N-acetyl cysteine (NAC), inhibitors of NADPH oxidase and mitochondria-targeted superoxide scavenger. However, only NAC protects against PCS-induced cell death. In vivo, expressions of cPLA2/COX2/8-OHdG, resident alveolar macrophages, recruited leukocytes, alveolar space, interstitial edema and capillary leakage increase in lung tissues of CKD-ULI mice, and NAC pretreatment ameliorates alveolar–capillary injury. PCS causes alveolar–capillary injury through triggering intracellular ROS, downstream prostaglandin pathways, cell death, and activating leukocytes to release multiplex chemoattractants and extracellular ROS. Thus PCS and nonspecific ROS serve as potential therapeutic targets. Full article
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Open AccessArticle Idiopathic Nephrotic Syndrome: Characteristics and Identification of Prognostic Factors
J. Clin. Med. 2018, 7(9), 265; https://doi.org/10.3390/jcm7090265
Received: 16 August 2018 / Revised: 3 September 2018 / Accepted: 7 September 2018 / Published: 9 September 2018
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Abstract
There are various histopathological forms of idiopathic nephrotic syndrome, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Whereas some relapse predictor factors have been identified in renal transplantation, the clinical future of idiopathic nephrotic syndrome in the native kidney remains uncertain.
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There are various histopathological forms of idiopathic nephrotic syndrome, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). Whereas some relapse predictor factors have been identified in renal transplantation, the clinical future of idiopathic nephrotic syndrome in the native kidney remains uncertain. We designed a multicentric retrospective descriptive cohort study including all patients aged 15 years and over whose renal biopsy confirmed MCD or FSGS between January 2007 and December 2014. We studied 165 patients with idiopathic nephrotic syndrome; 97 with MCD and 68 with FSGS. In the MCD cohort, 91.7% of patients were treated with corticosteroids for a median total duration of 13 months. During 45 months of follow-up, 92.8% of patients achieved remission and 45.5% experienced relapse. In this cohort, 5% of patients experienced terminal kidney disease. With respect to FSGS patients, 51.5% were treated with corticosteroids for a median total duration of 15 months. During 66 months of follow-up, 73.5% of patients achieved remission and 20% experienced relapse. In this cohort, 26.5% of patients experienced terminal kidney disease. No statistical association was observed between clinical and biological initial presentation and relapse occurrence. This study describes the characteristics of a cohort of patients with the nephrotic idiopathic syndromes of MCD and FSGS from the time of renal biopsy and throughout follow-up. Full article
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Open AccessArticle Metformin Decreases Risk of Tuberculosis Infection in Type 2 Diabetes Patients
J. Clin. Med. 2018, 7(9), 264; https://doi.org/10.3390/jcm7090264
Received: 31 August 2018 / Revised: 5 September 2018 / Accepted: 7 September 2018 / Published: 9 September 2018
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Abstract
Background: Metformin may show an antibiotic effect, but whether its use can reduce the risk of tuberculosis infection has rarely been investigated in population-based studies. Methods: This is a retrospective cohort analysis of the Taiwan’s National Health Insurance database. New-onset type 2 diabetes
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Background: Metformin may show an antibiotic effect, but whether its use can reduce the risk of tuberculosis infection has rarely been investigated in population-based studies. Methods: This is a retrospective cohort analysis of the Taiwan’s National Health Insurance database. New-onset type 2 diabetes patients, 148,468 ever users and 15,799 never users of metformin, identified during 1999–2005 were followed up until 31 December 2011 for the incidence of tuberculosis infection. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results: A total of 360 never users and 1976 ever users developed a tuberculosis infection with respective incidence of 510.91 and 282.94 per 100,000 person–years. The overall hazard ratio of presenting a tuberculosis infection among metformin ever users in respect to never users was 0.552 (95% confidence interval: 0.493–0.617). The hazard ratios for the first (<27.10 months), second (27.10–58.27 months), and third (>58.27 months) tertile of cumulative duration of metformin therapy were 1.116 (0.989–1.261), 0.543 (0.478–0.618), and 0.200 (0.171–0.233), respectively; and were 1.037 (0.918–1.173), 0.533 (0.469–0.606), and 0.249 (0.215–0.288), respectively, for the first (<817,000 mg), second (817,000–2,047,180 mg), and third (>2,047,180 mg) tertile of cumulative doses of metformin. The findings were consistent when analyses were restricted to pulmonary tuberculosis. Additionally, regular users of metformin tended to have greater benefit than irregular users. Conclusions: Metformin use is associated with a reduced risk of tuberculosis infection in a dose–response pattern in type 2 diabetes patients. Full article
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Open AccessArticle Can Intradetrusor OnabotulinumtoxinA Injections Alter Heart Function in Patients with Cardiac Arrhythmia?
J. Clin. Med. 2018, 7(9), 263; https://doi.org/10.3390/jcm7090263
Received: 21 August 2018 / Revised: 2 September 2018 / Accepted: 7 September 2018 / Published: 9 September 2018
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Abstract
The prevalence of overactive bladder (OAB) increases with age and can be associated with other co-morbidities, such as cardiac arrhythmia. Unfortunately, commonly used anticholinergic drugs for OAB can affect the cardiovascular system, leading to tachycardia. However, there are no data, which consider the
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The prevalence of overactive bladder (OAB) increases with age and can be associated with other co-morbidities, such as cardiac arrhythmia. Unfortunately, commonly used anticholinergic drugs for OAB can affect the cardiovascular system, leading to tachycardia. However, there are no data, which consider the influence of intradetrusor onabotulinumtoxinA injections on heart function in idiopathic OAB patients. The aim of the present study was to evaluate the influence of intradetrusor onabotulinumtoxinA injections on electrocardiogram (ECG) parameters. Additionally, changes in ECG were analyzed in OAB patients without cardiac arrhythmia. Thirty-one patients with cardiac arrhythmia and 31 participants without irregular heart rate (HR) completed the study. ECG measurements were performed in supine positions 2 h before onabotulinumtoxinA injections, 1 h after treatment, and at 2 weeks of follow-up. At week 6, a phone-call survey was conducted to collect data about adverse events. OnabotulinumtoxinA injections were performed with rigid cystoscopy under local anesthesia. We did not observe any clinically significant changes in the analyzed ECG parameters between consecutive measurements. While a slight increase of HR was observed in patients without cardiac arrhythmia, it remained within normal range. Intravesical onabotulinumtoxinA injections are, hence, safe for female patients with cardiac arrhythmia and do not significantly influence changes in ECG. Full article
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