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Purpose: To identify symptoms and their impacts on daily functioning and health-related quality of life (HRQoL) experienced by adult patients with ulcerative colitis (UC) and evaluate patient-reported outcome (PRO) measures for UC clinical studies. Methods: A conceptual model of symptoms and impacts of UC were developed from a literature review. PRO measures were identified from the literature, clinical trials databases, health technology assessment submissions, and regulatory label claims, and were selected for conceptual analysis based on disease specificity and use across information sources. PRO measures covering the most concepts when mapped against the conceptual model were assessed for gaps in psychometric properties using Food and Drug Administration (FDA) guidance and consensus-based standards for the selection of health measurement instruments (COSMIN) criteria. Results: The conceptual model grouped the 52 symptom concepts and 72 proximal and distal impacts into eight, two, and five dimensions, respectively. Of 65 PRO measures identified, eight underwent conceptual analysis. Measures covering the most concepts and assessed for psychometric properties were the Inflammatory Bowel Disease Questionnaire, Symptoms and Impacts Questionnaire for UC, UC-PRO symptoms modules, UC-PRO impact modules, and Crohn's and UC Questionnaire; all had good or excellent support for content validity. The UC-PRO Signs and Symptoms fully met FDA guidance and COSMIN criteria for content validity and most psychometric properties. Conclusion: Existing PRO measures assess concepts relevant to patients with UC, but all PRO measures reviewed require further psychometric evaluation to demonstrate they are fit for purpose. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES In this cohort study, we aimed to assess the 1-year clinical outcomes of using the E-vita Open NEO™ hybrid prosthesis for total arch replacement with frozen elephant trunk (FET) to repair extensive aortic pathologies. METHODS We reviewed individuals who underwent thoracic aortic surgery between April 2021 and March 2023 from the Gangnam Severance Aortic Registry. Exclusion criteria included ascending aortic replacement, 1 or 2 partial arch replacement, descending aortic replacement and total arch replacement without an FET. Finally, all consecutive patients who underwent total arch replacement and FET with E-vita Open NEO for aortic arch pathologies between April 2021 and March 2023 were included in this cohort study. The patients were divided into 3 groups based on their pathology: acute aortic dissection, chronic aortic dissection and thoracic aortic aneurysm. The primary end point was in-hospital mortality. The secondary end points during the postoperative period comprised stroke, spinal cord injury and redo sternotomy for bleeding. Additionally, the secondary end points during the follow-up period included the 1-year survival rate, 1-year freedom from all aortic procedures and 1-year freedom from unplanned aortic interventions. RESULTS The study included 167 patients in total: 92 patients (55.1%) with acute aortic dissection, 20 patients (12.0%) with chronic aortic dissection and 55 patients (32.9%) with thoracic aortic aneurysm. The in-hospital mortality was 1.8% (n  = 3). Strokes occurred in 1.8% (n  = 3) of the patients, spinal cord injury in 1.8% (n  = 3) and redo sternotomy for bleeding was performed in 3.0% (n  = 5). There were no significant differences between the pathological groups. The median follow-up period (quartile 1–quartile 3) was 198 (37–373) days, with 1-year survival rates of 95.9%. At 1 year, the freedom from all aortic procedures and unplanned aortic interventions were 90.3% and 92.0%, respectively. CONCLUSIONS The 1-year clinical outcomes of total arch replacement with FET using the E-vita Open NEO were favourable. Long-term follow-up is required to evaluate the durability of the FET. [ABSTRACT FROM AUTHOR]

In recent years, there have been growing interests on the study of software-oriented computer numerical control (Soft-CNC) system which plays an important role in the field of advanced manufacturing. However, existing Soft-CNC systems have somewhat limitations in that special motion control and I/O card should be inserted into PC or needed to use the servo driver based on digital communication such as SERCOS, EtherCAT, and so on. To get a better universality, in this paper we propose a novel external modular hardware architecture for developing Soft-CNC system on general PC. The external modular hardware architecture consists of seven kinds of partial module units: main module unit, axis module unit, spindle module unit, digital I/O module unit, analog I/O module unit, MPG module unit, and MCP module unit. We present the detailed design and functions of seven kinds of particular module units, and the data communication methods are described. Also the software implementations of Soft-CNC system using the external modular hardware architecture are presented. The proposed system has implemented on three axis machine tool and verified the operating correctness of proposed architecture by experiments on path of 3D butterfly shape. The experimental result shows that the external modular hardware architecture for Soft-CNC system operates correctly. [ABSTRACT FROM AUTHOR]

Not only the water quantity consumed but also the source of drinking water has been considered for their health benefits, but there is limited evidence. We aimed to determine whether the amount and type of drinking water affect physiological and biological functions, including brain function, by confirming how it affects gut microbiota which has an important regulatory role in host physiology. Three-week-old infant mice were subjected to 1) a water restriction experiment (control group, ad libitum consumption of distilled water; dehydration group, time-limited access to distilled water [15 min/day]) and 2) different water source experiment (distilled water, purified water, spring water, and tap water groups). The gut microbiota and cognitive development were analyzed using the 16S ribosomal ribonucleic acid sequencing method and the Barnes maze, respectively. The relative abundance of Firmicutes and Bacteroidetes and the Firmicutes-to-Bacteroidetes ratio (F/B ratio) changed depending on age (juveniles vs. infants). Insufficient water intake reversed these developmental changes, showing that the relative abundances of Bacteroidetes and Firmicutes and the F/B ratio in dehydrated juvenile mice were similar to those in normal infant mice. Additionally, clustering analysis revealed no significant differences in the intestinal flora in the mice from the different drinking water sources; however, dehydration significantly altered the composition of the genera compared to the other water source groups wherein water was provided ad libitum. Moreover, cognitive development was significantly disrupted by insufficient water intake, although the type of drinking water had no significant influence. Cognitive decline, measured by relative latency, was positively associated with the relative abundance of unclassified Erysipelotrichaceae that were in significantly high relative abundance in the dehydration group. These results suggest that the water quantity consumed, rather than the mineral content of drinking water, is imperative for shaping the early gut microbiota associated with cognitive development during infancy. [ABSTRACT FROM AUTHOR]

Spinal cord stimulation is an increasingly used treatment for a number of chronic pain states. Dorsal column stimulation is historically and currently the anatomical target of choice for most chronic pain conditions, including postlaminectomy syndrome and radicular pain. However, early studies suggested that stimulation of an alternative target, the ventral columns that carry pain fibers in the anterior and lateral spinothalamic tracts, may offer comparable or superior pain relief. A patient undergoing standard-of-care spinal cord stimulation trial had an additional lead placed on the right ventrolateral aspect of the spinal cord. After the usual 7-day trial of dorsal column stimulation, the dorsal leads were removed and ventrolateral column stimulation was applied through the retained ventral lead for a period of 3 days. The Brief Pain Index Short Form and Numeric Rating Scale were recorded for both dorsal and ventral stimulation. Ventrolateral spinal cord stimulation provided comparable outcomes compared with dorsal column stimulation using nonparesthesia-based stimulation. The results suggest further investigation into spinal cord stimulation anatomical placement and mechanism of action is warranted. [ABSTRACT FROM AUTHOR]

In this study, we examine how tradition and sustainability were preserved in Hahoe Village over the course of modernization, using the analytic narrative method. Combining historical and ethnographic narratives with game theoretic analysis, we try to understand the distinctive character of Hahoe Village, resulting from systems of norms, beliefs, and checks and balances between traditional, semi-traditional, and modern institutions for managing its tangible and intangible cultural and natural resources. In the game theory analysis, we assume that Hahoe Village's current condition resulted from repeated interactions between two groups of individuals: tradition-oriented agents and market-oriented agents. We formulate the payoff structure underlying responses to the social dilemma of managing Hahoe Village's common resources based on the affordability hypothesis and shared mental model hypothesis. We find that the preservation of Hahoe Village's traditions was closely connected to the successful institutionalization of tradition and sustainability through what can be termed the "tradition game." We specify the characteristics of Hahoe Village's sustainable institutions and argue that their sustainability gradually shifted from embedded sustainability to institutional sustainability. [ABSTRACT FROM AUTHOR]

Background: Achondroplasia (ACH), the most common form of disproportionate short stature, is caused by a pathogenic variant in the fibroblast growth factor receptor 3 gene. Recent advances in drug therapy for ACH have highlighted the importance of elucidating the natural history and socioeconomic burden of this condition. Recognition that there are many potential issues for the patient with ACH is the first step in planning cost-effective interventions in Latin America (LATAM), a vast geographic territory comprising countries with multicultural characteristics and wide socioeconomic differences. We conducted a systematic literature review to characterize the impact of ACH on affected individuals and on healthcare resources in LATAM countries.Methods: Searches of the global medical literature as well as regional and local medical literature up to August 2020. Observational studies on patients with ACH from any LATAM country. Pairs of reviewers independently screened eligible articles, extracted data from included studies, and assessed their risk of bias.Results: Fifty-three unique studies (28 case series and cross-sectional studies and 25 case reports) including data on 1604 patients were eligible. Of these studies, 11 had data available for meta-analysis. Both premature mortality and all-cause mortality in the pooled studies was 15% [95% Confidence Interval (CI) 1.0E-3 to 0.47; I2 = 82.9%, p = 0.0029; three studies, n = 99 patients]. Frequency of cardio-respiratory-metabolic disorders was 17% [95% CI 0.04-0.37; I2 = 90.3%, p < 0.0001; four studies, n = 230 patients]; nervous system disorders was 18% [95% CI 0.07-0.33; I2 = 84.6%, p < 0.0001; six studies, n = 262 patients]; ear, nose, throat and speech disorders was 32% [95% CI 0.18-0.48; I2 = 73.4%, p = 0.0046; five studies, n = 183 patients]; and spinal issues including stenosis, compression and associated pain was 24% [95% CI 0.07-0.47; I2 = 91.3%, p < 0.0001; five studies, n = 235 patients].Conclusions: There is currently evidence of high clinical burden in ACH patients in LATAM countries. Establishing the impact of ACH provides the necessary foundation for planning tailored and effective public health interventions. [ABSTRACT FROM AUTHOR]

This study investigated the effect of high-pressure enzymatic treatment (HPET) on the quality characteristics such as soluble solid content, yield, flavonoid content, and phenolic acid content of mulberry fruits. Of particular note, first, the quality characteristics of the mulberry fruits were most significantly improved under the high-pressure treatment with mixture of Pectinex Be XXL and Ultra color. Second, in the flavonoids, a decrease in rutin content and increases in hyperoside and quercetin contents were confirmed by HPET, which may be the result of the two-step deglycosylation of rutin by pectinase activity. Finally, the extraction yield of mulberry fruits was maintained during HPET 0–36 h, and its bioactive compound profile was variously changed. Therefore, this study provided new clues as to how the HPET may promote changes in the extraction yield and bioactive substance profile of mulberry fruits and suggest the potential for use of natural materials based on mulberry fruit extracts. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop and test personalized predictions for functional recovery after Total Knee Arthroplasty (TKA) surgery, using a novel neighbors-based prediction approach. We used data from 397 patients with TKA to develop the prediction methodology and then tested the predictions in a temporally distinct sample of 202 patients. The Timed Up and Go (TUG) Test was used to assess physical function. Neighbors-based predictions were generated by estimating an index patient's prognosis from the observed recovery data of previous similar patients (a.k.a., the index patient's "matches"). Matches were determined by an adaptation of predictive mean matching. Matching characteristics included preoperative TUG time, age, sex and Body Mass Index. The optimal number of matches was determined to be m = 35, based on low bias (− 0.005 standard deviations), accurate coverage (50% of the realized observations within the 50% prediction interval), and acceptable precision (the average width of the 50% prediction interval was 2.33 s). Predictions were well-calibrated in out-of-sample testing. These predictions have the potential to inform care decisions both prior to and following TKA surgery. [ABSTRACT FROM AUTHOR]

Ventilation and mechanics of breathing are an integral part of respiratory physiology that directly affect aerosol transport and deposition in the lung. Although natural breathing pattern varies widely among individuals, breathing pattern is controllable, and by using an appropriate breathing pattern, aerosol deposition can be substantially modified for desired purposes. Effects of breathing pattern have been investigated under carefully controlled inhalation conditions covering a wide range of tidal volumes (VT) and breathing frequencies (f) or respiratory times (T = 1/f). The studies have shown that lung deposition can increase or decrease as much as two times by changing the breathing pattern. Specific functional relationships have been found between lung deposition and breathing pattern parameters such that lung deposition can be estimated for any given breathing pattern. Both VT and T have shown strong effects on lung deposition, but their influence is variable depending on particle size, particularly, ultrafine vs. micron-sized particles. VT is more influential than T for micron-sized particles whereas VT and T are equally influential for ultrafine particles. Although effects of lung morphology are difficult to study systematically, comparison between normals and patients with obstructive airway disease has shown that lung deposition is closely related with the degree of airways obstruction and can be 2–3 times greater in patients with obstructive airway disease compared to normals. Thus, breathing pattern and the status of airways obstruction should be carefully considered in designing aerosol delivery and estimating deposition dose. [ABSTRACT FROM AUTHOR]

Probiotics have been proposed to ameliorate cognitive impairment and depressive disorder via the gut-brain axis in patients and experimental animal models. However, the beneficial role of probiotics in brain functions of healthy older adults remains unclear. Therefore, a randomized, double-blind, and placebo-controlled multicenter trial was conducted to determine the effects of probiotics on cognition and mood in community-dwelling older adults. Sixty-three healthy elders (≥65 years) consumed either placebo or probiotics containing Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 12 weeks. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Brain functions were measured using the Consortium to Establish a Registry for Alzheimer's disease, Satisfaction with life scale, stress questionnaire, Geriatric depression scale, and Positive affect and negative affect schedule. Blood brain-derived neurotrophic factor (BDNF) was determined using enzyme-linked immunosorbent assay. Relative abundance of inflammation-causing gut bacteria was significantly reduced at Week 12 in the probiotics group (p < .05). The probiotics group showed greater improvement in mental flexibility test and stress score than the placebo group (p < .05). Contrary to placebo, probiotics significantly increased serum BDNF level (p < .05). Notably, the gut microbes significantly shifted by probiotics (Eubacterium and Clostridiales) showed significant negative correlation with serum BDNF level only in the probiotics group (RS = -0.37, RS = -0.39, p < .05). In conclusion, probiotics promote mental flexibility and alleviate stress in healthy older adults, along with causing changes in gut microbiota. These results provide evidence supporting health-promoting properties of probiotics as a part of healthy diet in the older adults. [ABSTRACT FROM AUTHOR]

The LLC resonant converter is one of the most attractive topologies in many applications, due to its simple structure and zero-voltage-switching capability. However, under wide-input-voltage condition, it has large primary conduction and turn-off switching losses because of small magnetizing inductance. Thus, in this article, the LLC resonant converter using three switches is proposed for high-efficiency under wide universal ac input voltage. These three switches can make two operating modes of LLC resonant converter according to low/high line input conditions. As a result, the proposed converter can be designed with larger magnetizing inductance, resulting in high efficiency. The validity of the proposed converter is verified with a 60-W prototype for high efficiency, almost maintaining the system size, compared with the conventional LLC converter. [ABSTRACT FROM AUTHOR]

An LLC resonant converter is a very attractive topology for high efficiency and high power density applications, thanks to zero-voltage switching of primary switches and zero-current switching of secondary rectifiers as well as low-voltage stress of the overall components. Its critical drawback is the unintended increase of output voltage beyond the regulation limit at very light load, in spite of much higher switching frequency for low input-to-output voltage gain. To suppress output voltage within the regulation range at very light load, the external capacitor attached across drain–source of primary switches is investigated and the optimal capacitance is designed in this article. Its validity is verified experimentally with the implemented 240-W prototype for flat-panel display application. [ABSTRACT FROM AUTHOR]

Introduction: Densin‐180 interacts with postsynaptic molecules including calcium/calmodulin‐dependent protein kinase IIα (CaMKIIα) but its function in learning and memory process has been unclear. Methods: To investigate a role of hippocampal densin‐180 in contextual fear conditioning (CFC) learning and memory processes, knockdown (KD) of densin‐180 in hippocampal subareas was applied. Results: First, ventral hippocampal (vHC) densin‐180 KD impaired single‐trial CFC (stCFC) memory one day later. stCFC caused freezing behaviors to reach the peak about one hour later in both control and KD mice, but then freezing was disappeared at 2 hr postshock in KD mice. Second, stCFC caused an immediate and transient reduction of vHC densin‐180 in control mice, which was not observed in KD mice. Third, stCFC caused phosphorylated‐T286 (p‐T286) CaMKIIα to change similarly to densin‐180, but p‐T305 CaMKIIα was increased 1 hr later in control mice. In KD mice, these effects were gone. Moreover, both basal levels of p‐T286 and p‐T305 CaMKIIα were reduced without change in total CaMKIIα in KD mice. Fourth, we found double‐trial CFC (dtCFC) memory acquisition and retrieval kinetics were different from those of stCFC in vHC KD mice. In addition, densin‐180 in dorsal hippocampal area appeared to play its unique role during the very early retrieval period of both CFC memories. Conclusion: This study shows that vHC densin‐180 is necessary for stCFC memory formation and retrieval and suggests that both densin‐180 and p‐T305 CaMKIIα at 1 ~ 2 hr postshock are important for stCFC memory formation. We conclude that roles of hippocampal neuronal densin‐180 in CFC are temporally dynamic and differential depending on the pattern of conditioning stimuli and its location along the dorsoventral axis of hippocampal formation. [ABSTRACT FROM AUTHOR]

The evidence for the beneficial effects of drinking hydrogen-water (HW) is rare. We aimed to investigate the effects of HW consumption on oxidative stress and immune functions in healthy adults using systemic approaches of biochemical, cellular, and molecular nutrition. In a randomized, double-blind, placebo-controlled study, healthy adults (20–59 y) consumed either 1.5 L/d of HW (n = 20) or plain water (PW, n = 18) for 4 weeks. The changes from baseline to the 4th week in serum biological antioxidant potential (BAP), derivatives of reactive oxygen, and 8-Oxo-2′-deoxyguanosine did not differ between groups; however, in those aged ≥ 30 y, BAP increased greater in the HW group than the PW group. Apoptosis of peripheral blood mononuclear cells (PBMCs) was significantly less in the HW group. Flow cytometry analysis of CD4+, CD8+, CD20+, CD14+ and CD11b+ cells showed that the frequency of CD14+ cells decreased in the HW group. RNA-sequencing analysis of PBMCs demonstrated that the transcriptomes of the HW group were clearly distinguished from those of the PW group. Most notably, transcriptional networks of inflammatory responses and NF-κB signaling were significantly down-regulated in the HW group. These finding suggest HW increases antioxidant capacity thereby reducing inflammatory responses in healthy adults. [ABSTRACT FROM AUTHOR]

Background: A pre‐plasma exchange ADAMTS13 measurement differentiates thrombotic thrombocytopenic purpura (TTP) from other forms of thrombotic microangiopathy (TMA). Given that many hospitals do not perform the ADAMTS13 assay in‐house and that the turnaround time (TAT) differs among reference laboratories, we performed an analysis investigating the potential impact of a delay in obtaining the results on the healthcare system. Methods: An economic model was developed to estimate the impact of a delay in obtaining the pretreatment ADAMTS13 results on patients admitted with TMA with cost (US dollars) as the primary outcome. Incremental cost‐effectiveness ratio (ICER) as a composite outcome was calculated from both cost and life days [LDs], an effectiveness surrogate marker. Model parameters were gathered from the medical literature, except for the institutional cost of the ADAMTS13 test. Results: In patients with TMA, during the 6‐day study period, the incremental cost to the healthcare system ranged from approximately $4155 to $5123 for every 1‐day delay in obtaining the pre‐exchange ADAMTS13 results with virtually no change in the effectiveness marker. The ICER composite outcome established the cost‐effectiveness of having a fast TAT for pre‐exchange ADAMTS13 results. Probabilistic sensitivity analyses also confirmed the robustness of the model. Conclusions: In patients with clinical presentations of TMAs, having a rapid TAT for pre‐exchange ADAMTS13 measurement appeared to be cost‐effective. If testing cannot be performed in‐house, then our findings support the necessity of contracting with a reference laboratory that can reliably provide the result, preferably within 1 day of admission. [ABSTRACT FROM AUTHOR]

This article presents a semiresonant half-bridge zeta (HBZ) converter for high-efficiency power supply. Since the proposed converter utilizes a primary inductor and secondary capacitor as a resonant tank, it can make a resonant operation during the on-state of a low-side primary switch. Therefore, the proposed converter can effectively reduce turn-off currents of the low-side primary switch and the secondary diode without any additional component and control scheme, which decreases turn-off switching loss and reverse-recovery loss. Moreover, the proposed converter can maintain advantages of the conventional HBZ converter such as high input/output (I/O) voltage gain and wide zero-voltage-switching (ZVS) range with the proposed design procedure. As a result, the proposed converter can improve its efficiency over the entire load conditions compared to the conventional HBZ converter. A 250 W, 300–400 V input, and 56 V output prototype has been built and tested to verify the effectiveness of the proposed converter. [ABSTRACT FROM AUTHOR]

Background: Acquired haemophilia A (AHA), with potentially high risk of morbidity and mortality, occurs as a result of inhibitors against factor VIII. Bleeding due to AHA can be treated with activated prothrombin complex concentrate (aPCC), recombinant activated factor VII (rFVIIa) or recently, recombinant porcine‐sequence factor VIII (rpFVIII). We extended our previous cost‐effectiveness analysis (CEA) comparing rpFVIII against the available traditional options. Methods: For high‐titred, haemorrhaging AHA patients treated with either aPCC, rFVIIa or rpFVIII, over the course of 6‐days, a Markov simulation was conducted to evaluate the outcomes when these patients transitioned into any of the four following health states: (1) continuous bleeding, (2) thrombosis, (3) stop bleeding and (4) death, with states (2), (3) and (4) modelled as absorbing states. All model parameters were obtained from the medical literature, except the costs of aPCC, rFVIIa and the factor VIII assay, which came from our institutional data. Results: Excluding the cost of the initial treatment on day 0, the total subsequent treatment cost of rFVIIa was substantially more than the costs of aPCC and rpFVIII ($13 925 vs. $1778 vs. $6957, respectively). The average quality‐adjusted life days (QALDs) gained from rpFVIII was lowest (4·89 vs. 4·9 for rFVIIa and 4·91 for aPCC). Overall, aPCC dominated the other two treatments. The model was determined to be robust across the tested ranges for all input variables. Conclusion: Based on this economic model, for AHA patients with high titres who were bleeding, aPCC was the most cost‐effective treatment option and may be considered for use if there is no clinical contraindication. [ABSTRACT FROM AUTHOR]

[Display omitted] • IGF-1 is overexpressed in DG mature neurons of adult mice with AAV. • IGF-1 OX in Ca v 1.3 KO mouse enhances the DG DCX (+) cell number. • IGF-1 OX restores the impaired recent CFC consolidation in Ca v 1.3 KO mouse. Insulin-like growth factor-1 (IGF-1) exogenously supplied in the brain was shown to enhance the survival of hippocampal dentate gyrus (DG) newborn cells and some cognitive functions of mice. This study aims to test whether IGF-1 requires Ca v 1.3 activity critically while enhancing newborn cell survival and cognitive functions. We used Ca v 1.3 KO mice, where both DG newborn cell survival and the recent (1 day) single-trial contextual fear conditioning (CFC) memory consolidation were impaired. To supply IGF-1, we overexpressed (OX) IGF-1 in DG mature neurons by injecting an adeno-associated virus (AAV-IGF-1-mCherry) into the hippocampal areas of Ca v 1.3 KO mice. Our results, first, confirmed the enhanced expression of IGF-1 in the DG granule cell layer by immunohistochemistry. Next, we found this IGF-1 OX resulted in fully restoring both the survival rate of DCX (+) newborn cells and the recent single-trial CFC memory formation in Ca v 1.3 KO mice. Our results show that IGF-1 can enhance the survival of DG immature newborn cells and the recent CFC memory formation in a Ca v 1.3 channel-independent manner in vivo , suggesting activation of complementary pathways including the Ca v 1.2 channel. The result will help the application of adult newborn cell-based therapy improve the cognitive functions of neurological disorders. [ABSTRACT FROM AUTHOR]

A magneto-optical Kerr effect system with a spatial resolution of 2 μm was used to measure the local M-H loops for the free layer of a magnetic tunnel junction with a structure of Ta/Cu/Ta/NiFe/Cu/Mn75Ir25/Co70Fe30/Al2O3/Co70Fe30/Ta to investigate the exchange bias field HE and the coercivity HC for the free layer. The HE and HC measured along the direction of the free layer varied symmetrically with respect to the junction center. The measurements indicate that the enhanced HC correlated with HE, and HE could be reasonably explained by using an “orange-peel-type” coupling based on variations in the thickness of the pinned layer along the direction of the free layer. The variation in HE along the pinned-layer’s direction could be ascribed to that of the free-layer’s thickness, and the increase in HE at the junction edge along the pinned layer was due to a decrease in the thickness of the free layer near the edge. However, the nearly constant HC along the pinned layer indicates that the thickness of the free layer can be excluded from the mechanism for enhancing HC, which is a unique difference in the parameters involved in HE and HC, and in the mechanism for enhancing HC. [ABSTRACT FROM AUTHOR]

Phase-shift full-bridge (PSFB) converter is a widely used topology for high-efficiency and high-power applications, thanks to low voltage/current stress of all components and zero-voltage-switching operation of primary mosfets. The critical drawback of the PSFB converter is hard-switching characteristics of primary mosfets at a very light load, which causes severe thermal explosion and extremely high input power consumption, especially with the latest super-junction mosfet. To minimize the switching loss of the PSFB converter at a very light load, a new optimal dead-time control scheme with burst-mode operation is proposed in this paper and its validity is verified experimentally with the implemented 2.2-kW server power supply unit. [ABSTRACT FROM AUTHOR]

Although an in vivo diagnosis of coronary plaque erosion has become possible by optical coherence tomography (OCT), angiographic characteristics of erosion have not been studied. The aim of this study was to investigate the angiographic features of plaque erosion in patients with non-ST elevation acute coronary syndromes (NSTE-ACS). Patients with NSTE-ACS who underwent OCT of the culprit lesion were collected at 11 institutions from 6 countries. Patients were classified as erosion or non-erosion based on OCT images. Angiographic features of both groups were compared. Among 494 cases with NSTE-ACS, 242 had plaque erosion and 252 had non-erosion. Compared to non-erosion group, erosion patients had less multivessel disease (28.5% vs. 49.6%, p < 0.001), lower Jeopardy score (4.2 vs. 5.0, p < 0.001), lower Gensini score (21.3 vs. 25.6, p = 0.014), and lower Syntax score (8.9 vs. 11.5, p < 0.001). With regard to the culprit lesion morphology, plaque erosion group had smaller reference diameter (2.8 mm vs. 3.0 mm, p = 0.032), less frequent type B2/C lesions (51.2% vs. 71.8%, p < 0.001), and lower prevalence of calcification (4.1% vs. 13.9%, p < 0.001) and thrombus (16.5% vs. 28.2%, p = 0.002). In the mid left anterior descending artery (LAD), erosion was significantly more frequent than non-erosion (30.2% vs. 21.8%, p = 0.034). Patients with NSTE-ACS caused by plaque erosion have less complex angiographic features both at the 3-vessel level and at the culprit lesion level. Plaque erosion was frequently found in the mid LAD. • Plaque erosion is associated with less overall plaque burden in patients with non-ST elevation acute coronary syndromes. • Plaque erosion is associated with less complex culprit lesion on angiogram in non-ST elevation acute coronary syndromes. • Plaque erosion was a frequent pathology in the mid left anterior descending coronary artery. • Different angiographic features between plaque erosion and plaque rupture may reflect different underlying pathobiology. • Using angiography, patients with higher likelihood of plaque erosion can be identified for confimative OCT procedure. [ABSTRACT FROM AUTHOR]

The improved three switch-active clamp forward (3S-ACF) converter is proposed in this paper. The proposed converter has minimized the switching loss on all switches of the conventional 3S-ACF converter by simply changing the gate control method without any additional components. Moreover, the modified gate control enables peak and average currents on the clamp diode to be reduced. Though, all switches of the proposed converter have low-voltage stress similarly to those of the conventional 3S-ACF converter. Consequently, the proposed converter can achieve a high efficiency without any additional components. To confirm the operation, features, and validity of the proposed converter, a 180–288 Vdc input and 12 V/550 W output laboratory prototype is built and tested. [ABSTRACT FROM AUTHOR]

Objective: Prognosis of myocardial infarction tends to be worse when serum C-reactive protein (CRP) level is high. miRNAs are also known to be involved in different pathogeneses of heart diseases such as myocardial infarction. However, how CRP is involved in myocardial infarction has not been fully elucidated. We hypothesized that serum CRP changes the miRNA profile during ischemia-reperfusion injury (IRI) of the myocardium. To confirm this hypothesis, we performed global miRNA expression profiling of myocardium using IRI and CRP infusion rat model. Methods: After ligation of the coronary artery of rat hearts, human serum CRP was intravenously injected, and reperfusion was performed (I/R+CRP group, n = 6). Control group consisted of the sham group (n = 3), IV CRP infusion group (CRP only, n = 3), and the I/R-only group (I/R only, n = 5). We evaluated 423 miRNA expression in non-ischemic areas and areas at risk (AAR) of each group using NanoString nCounter miRNA expression assay. Results: MiR-124 was downregulated in non-ischemic myocardium in CRP-only group. In AAR, 7 miRNAs were commonly upregulated in both I/R-only and I/R+CRP groups. And additional 6 miRNAs were upregulated in the I/R+CRP group (miR-33, miR-409-3p, miR-384-3p, miR-3562, miR-101a, and miR-340-5p). Similarly, in the non-ischemic areas, 6 miRNAs were commonly upregulated in both I/R-only and I/R+CRP groups, and additional 5 miRNAs changed in the I/R+CRP group (upregulation of miR-3559-5p, miR-499, and miR-21 and downregulation of miR-500 and miR-532-3p). Conclusion: We showed that when serum CRP level is high, IRI results in multiple miRNA profile changes not only in ischemic areas but also in non-ischemic myocardium. Our results may provide a strong basis for studying the role of CRP and miRNAs in ischemic heart disease. [ABSTRACT FROM AUTHOR]

Background: Lumbar spinal stenosis (LSS) can lead to compression of neural elements and manifest as low back and leg pain. LSS has traditionally been treated with a variety of conservative (pain medications, physical therapy, epidural spinal injections) and invasive (surgical decompression) options. Recently, several minimally invasive procedures have expanded the treatment options. Methods: The Lumbar Spinal Stenosis Consensus Group convened to evaluate the peer‐reviewed literature as the basis for making minimally invasive spine treatment (MIST) recommendations. Eleven consensus points were clearly defined with evidence strength, recommendation grade, and consensus level using U.S. Preventive Services Task Force criteria. The Consensus Group also created a treatment algorithm. Literature searches yielded 9 studies (2 randomized controlled trials [RCTs]; 7 observational studies, 4 prospective and 3 retrospective) of minimally invasive spine treatments, and 1 RCT for spacers. Results: The LSS treatment choice is dependent on the degree of stenosis; spinal or anatomic level; architecture of the stenosis; severity of the symptoms; failed, past, less invasive treatments; previous fusions or other open surgical approaches; and patient comorbidities. There is Level I evidence for percutaneous image‐guided lumbar decompression as superior to lumbar epidural steroid injection, and 1 RCT supported spacer use in a noninferiority study comparing 2 spacer products currently available. Conclusions: MISTs should be used in a judicious and algorithmic fashion to treat LSS, based on the evidence of efficacy and safety in the peer‐reviewed literature. The MIST Consensus Group recommend that these procedures be used in a multimodal fashion as part of an evidence‐based decision algorithm. [ABSTRACT FROM AUTHOR]

Background: Acquired haemophilia A (AHA) is an autoimmune bleeding disorder with significant morbidity and mortality. Bleeding AHA patients with high titre inhibitors can be treated with either activated prothrombin complex concentrate (aPCC) or recombinant activated factor VII (rFVIIa). Given that both replacement therapies have inherent benefits and limitations, a cost‐effectiveness analysis (CEA) was performed in this population to compare rFVIIa with aPCC. Methods: In high‐titered AHA patients with bleeding treated with either aPCC or rFVIIa, during a 5‐day study period, a Markov model was developed such that these patients were transitioned into four different health states: (1) continuous bleeding, (2) thrombosis, (3) stop bleeding and (4) death, with states (2), (3) and (4) modelled as absorbing states. Model parameters, including probabilities, health utility index and costs, were gathered from the medical literature, except for the costs of aPCC and rFVIIa, which were obtained from our institutional data. Results: During the 5‐day period, the total treatment cost of rFVIIa was substantially more than the cost of aPCC ($13 635 vs. $1741). The average quality‐adjusted life days (QALDs) gained for rFVIIa were slightly lower compared to aPCC (4·08 vs. 4·09). Overall, aPCC prevailed over rFVIIa. Sensitivity analysis confirmed the robustness of the model across tested ranges of all input variables. Conclusion: In high‐titered AHA patients with bleeding, aPCC is a cost‐effective treatment option when compared to rFVIIa. Thus, aPCC may be considered in these patients, if available, and provided there is no clinical contraindication. [ABSTRACT FROM AUTHOR]

Investigates the role and effect of Co[sub2]O[sub3] additive on the upturn characteristics of zinc oxide (ZnO) varistors. Analysis of the capacitance-voltage characteristics; Explanation for the typical V-I characteristics of ZnO varistors; Defect responsible for the n-type semiconductivity of ZnO.

Provides information on a study which investigated the effect of buffer layer on the structural and electrical properties of (BaSr)TiO[sub3] thin films deposited on indium tin oxide-coated glass substrate. Way that the films were deposited; Influence of the buffer layer on the structural and electrical properties; Step taken in order to use thin films of perovskite structural materials for applications in electronic devices.

Presents a study that examined the structural and electrical properties of radio frequency magnetron-sputtered ferroelectric thin films on indium-tin-oxide-coated glass substrate. Analysis of the crystallographic structure and orientations of the samples; Determination of the dielectric constant and dissipation factor; Evaluation of the current-voltage and breakdown characteristics of the samples.

Supplemental digital content is available in the text. Chemotherapy-induced neuropathy has limited treatment options, and conventional medications used to treat neuropathic pain often do not provide adequate pain relief for patients with a history of cancer. Neuromodulation such as dorsal root ganglion stimulation remains a treatment that has been studied for chronic painful conditions such as low back pain, pelvic pain, complex regional pain syndrome, and phantom limb pain. Dorsal root ganglion stimulation has been presented for treatment of chemotherapy-induced neuropathy, but with limited duration of follow-up. We present a case of pain resolution after placement of a dorsal root ganglion stimulation for persistent chemotherapy-induced neuropathy. Our patient developed burning pain and allodynia in both feet 3 mos into her chemotherapy regimen, with worsened symptoms after cessation of chemotherapy. After failure of conservative pharmacotherapies, a 7-day dorsal root ganglion stimulation trial was implanted, resulting in 100% pain relief. A dorsal root ganglion stimulation was then implanted permanently, and our patient reported continued resolution of symptoms at evaluation 3 yrs after placement. To the author's knowledge, this is the first case of sustained relief with dorsal root ganglion stimulation placement for chemotherapy-induced neuropathy and presents a treatment option that warrants further investigation. [ABSTRACT FROM AUTHOR]

Although sclerostin (SOST) and Dickkopf-related protein 1 (DKK1) are major regulators in bone metabolism, their associations with osteoporotic fracture (OF) in Asians are inconclusive. Furthermore, there have been no clinical studies separately considering non-vertebral and vertebral fractures in terms of the blood levels of SOST and DKK1. Among 513 consecutive postmenopausal Korean women, we identified 103 cases defined as subjects with OF (i.e., non-vertebral and/or vertebral fractures). The controls were randomly selected from the remaining 410 subjects and matched 1:1 to cases according to both age and body mass index. Non-vertebral and morphological vertebral fractures were identified by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs, respectively. Bone mineral density (BMD) and plasma levels of SOST and DKK1 were measured. Plasma SOST levels were lower in subjects with OF than in the control group. Each standard deviation decrement of plasma SOST concentration was associated with a multivariable-adjusted odds ratio of 1.77 for any prevalent OF type. The odds for OF was 2.97-fold higher in subjects in the lowest SOST tertile compared with subjects in the highest SOST tertile. These associations remained significant when the non-vertebral and vertebral fractures were analyzed separately. However, prevalent OF was not associated with plasma DKK1 levels, regardless of the type of fracture and the adjustment model employed. Consistently, plasma SOST levels were positively related with BMD values at all measured skeletal sites, although this was not observed for DKK1. Circulating SOST but not DKK1 may be a potential biomarker for predicting bone health in Asians. [ABSTRACT FROM AUTHOR]

The phase-shifted full-bridge (PSFB) converter with synchronous rectifier (SR) is one of the most attractive dc–dc converters for the server power supply due to its high power capability and small secondary ripple current with the output inductor. Moreover, it can more reduce the secondary conduction loss by using parallel-connected mosfets in SR. However, due to large input capacitance of the parallel-connected mosfets in SR, the PSFB converter has large SR gate driving loss, which particularly degrades the light load efficiency. Thus, in this paper, one additional resistor is added to the conventional SR gate driving circuit to recycle the gate driving energy. As a result, the proposed circuit can improve the light load efficiency of the PSFB converter without operation mode change, additional controls, and complex circuits. The most advantage of the proposed circuit is that it is very simple and available to any other SR gate driver IC. The validity of the proposed circuit is confirmed by experimental results from a prototype with 340–400 V input and 12 V/66.66 A output. [ABSTRACT FROM AUTHOR]

In this paper, a new single-stage half-bridge (HB) resonant $LLC$ converter additionally employing one resonant capacitor and two relays with one package is proposed, compared with a single-stage HB $LLC$ converter. Moreover, a center-tapped transformer is replaced with a coupled transformer. Since the proposed converter changes the turns ratio of the coupled transformer using a relay according to low- or high-input-voltage range, it can decrease the range of its needed voltage gain. It means that the proposed converter can be designed with large transformer magnetizing inductance compared with the conventional single-stage HB $LLC$ converter. As a result, the primary conduction and turn-off losses are reduced. Moreover, in low input voltage range, it has smaller total primary wire resistance of the transformer due to parallel connection of the coupled transformer, which decreases its conduction loss. In addition, additionally employed small-sized components can be inserted to the conventional system. To confirm the operation, features, and validity of the proposed converter, universal input with low line and high line and 16.5 V/60 W output laboratory prototype targeting laptop adapters with wide-input-voltage range is built and tested. [ABSTRACT FROM AUTHOR]

Abstract: The effects of different setting times (15–120 min) on the rheological properties of cold thickened protein‐based beverage (PBB) samples prepared with different xanthan gum (XG)‐based food thickeners were examined. In this study, four commercial XG‐based food thickeners (coded A–D) and three commercial PBB products (whole milk, skim milk, and soybean milk) were used to prepare thickened PBB samples at a 3% thickener concentration. The fastest increases in ηa,50 values of thickened PBB samples were observed at 15 min, and at longer time periods their ηa,50 values gradually increased or remained constant with an increase in setting time (15–120 min). The magnitudes of the rheological parameters (ηa,50, K, G′, and G″) of thickened PBB samples with thickener A were significantly higher compared with those with other thickeners (coded B, C, and D). The flow and dynamic rheological properties of thickened PBB samples prepared with different XG‐based thickeners were significantly different (p < .05), demonstrating that their rheological properties were greatly affected by the type of PBB and thickener as well as the setting time. Practical statements: Food thickeners have been commonly used in the preparation of various thickened fluids with desirable rheological properties for dysphagic patients to elicit an optimal swallow response. However, among various thickened fluids, there is limited rheological information on cold thickened protein‐based beverage (PBB) (e.g., whole milk, skim milk, and soybean milk) prepared with various xanthan gum (XG)‐based thickeners. Our flow and dynamic rheological results showed that the flow and viscoelastic properties of the thickened PBB samples prepared with different food thickeners were dependent on the PBB type, thickener type, and setting time. These rheological results presented in this study will provide both thickener manufacturers and clinicians with valuable information for thickened PBB products with desirable rheological properties for safe and easy swallowing. New knowledge of the different rheological characterizations of thickened PBB can be practically applied to develop the commercial dysphagia thickeners suitable for PBB in food industry. [ABSTRACT FROM AUTHOR]

A computational method for a performance analysis of the switched reluctance motor has been developed. Most of the papers present static characteristics, such as static torque based on a finite element method analysis. However, this method is based on a Fourier series expansion with step-by-step, current-dependent, adjustable coefficients. Analytical expression for the calculation of instantaneous phase inductance, flux linkage, co-energy, and electromagnetic torque as a function of rotor position and winding current are derived. Finally, the strategy to represent the winding inductance variation with position is made by approximating the actual inductance profile. [ABSTRACT FROM AUTHOR]

Background: The ADAMTS13 test distinguishes thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies (TMAs). The PLASMIC score helps determine the pretest probability of ADAMTS13 deficiency. Due to inherent limitations of both tests, and potential adverse effects and cost of unnecessary treatments, we performed a cost-effectiveness analysis (CEA) investigating the benefits of incorporating an in-hospital ADAMTS13 test and/or PLASMIC score into our clinical practice.Study Design and Methods: A CEA model was created to compare four scenarios for patients with TMAs, utilizing either an in-house or a send-out ADAMTS13 assay with or without prior risk stratification using PLASMIC scoring. Model variables, including probabilities and costs, were gathered from the medical literature, except for the ADAMTS13 send-out and in-house tests, which were obtained from our institutional data.Results: If only the cost is considered, in-house ADAMTS13 test for patients with intermediate- to high-risk PLASMIC score is the least expensive option ($4,732/patient). If effectiveness is assessed as measured by the number of averted deaths, send-out ADAMTS13 test is the most effective. Considering the cost/effectiveness ratio, the in-house ADAMTS13 test in patients with intermediate- to high-risk PLASMIC score is the best option, followed by the in-house ADAMTS13 test without the PLASMIC score.Conclusions: In patients with clinical presentations of TMAs, having an in-hospital ADAMTS13 test to promptly establish the diagnosis of TTP appears to be cost-effective. Utilizing the PLASMIC score further increases the cost-effectiveness of the in-house ADAMTS13 test. Our findings indicate the benefit of having a rapid and reliable in-house ADAMTS13 test, especially in the tertiary medical center. [ABSTRACT FROM AUTHOR]

Purpose Intensive blood pressure (BP) lowering is important for the treatment of hypertension; however, it has been a challenge to achieve target BP in many patients. The purpose of this study was to explore the optimal dosage of a fixed-dose combination of candesartan cilexetil (CAN) and amlodipine besylate (AML), by examining the tolerability and efficacy of CAN/AML combination therapy compared with those of monotherapy with either drug in patients with essential hypertension. Methods This Phase II multicenter, randomized, double-blind clinical trial enrolled patients aged 19 years or older with essential hypertension, defined as a mean sitting diastolic BP (msDBP) between 95 and 115 mm Hg, and a mean sitting systolic BP (msSBP) of <200 mm Hg after a 2-week placebo run-in period. A total of 635 patients were screened, of whom 439 were randomized to receive treatment; 425 patients were included in the full analysis set (combination therapy, 212; monotherapy, 213). Participants were randomly assigned to receive 1 of 8 treatments: CAN (8 or 16 mg), AML (5 or 10 mg), CAN/AML (8 mg/5 mg, 8 mg/10 mg, 16 mg/5 mg, or 16 mg/10 mg), once daily for 8 weeks. Findings After 8 weeks of treatment, changes in msDBP were significantly greater in the groups receiving CAN/AML combination therapies compared with monotherapies at matched doses, with the exception of CAN 8 mg/AML 10 mg versus AML 10 mg. The response to treatment and the achievement of target BP (both msSBP and msDBP) at week 8 were significantly greater overall in the groups that received combination therapy versus monotherapy. All medications were relatively well tolerated in each group. Implications Eight-week administration of CAN/AML (8 mg/5 mg, 16 mg/5 mg, and 16 mg/10 mg) resulted in a significantly greater BP reduction than that with CAN or AML monotherapy, and was determined to be well tolerated. ClinicalTrials.gov identifier: NCT02944734. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), an endocrine disrupter, is widely used to make chemicals for polycarbonate, plastics, beverage containers, epoxy resins, and cash register receipts. BPA is one of the known xenoestrogens, which have weak estrogenic activity and cause obesity, diabetes, breast cancer, and reproductive disorders. Even though the concentration level of metabolomes in hair is usually lower than that in urine and blood, there are several reasons why we chose to use hair samples. First, the sampling procedure of hairs is simple. Second, it is also easy to preserve the sample for long term and track the drug-exposure record of a given sample. Third, deformation and contamination of samples rarely occur. In this study, an improved analytical method to determine the levels of BPA and estrogens in hair samples was developed by liquid chromatography-electrospray tandem mass spectrometry (LC-ESI/MS/MS). Hair samples were extracted by an Oasis HLB extraction cartridge after incubation with 1 N HCl and derivatized with dansyl chloride to increase sensitivity. BPA and estrogens (estrone, 17β-estradiol, and estriol) were separated using Shiseido CAPCELL PAK C 18 column (2.0 × 100 mm, 3 μm) and a mobile phase consisting of 10 mM ammonium acetate in water and acetonitrile with a gradient program at a flow rate of 0.3 mL/min and were monitored with electrospray tandem mass spectrometry (ESI–MS/MS). The linearity of this method was over 0.995. The limits of detection (LOD) at a signal-to-noise (S/N) ratio of 3 were 0.25–6.0 ng/g. The alteration of estrogens levels induced by BPA may play important role to understanding probable endocrine disruptive exposure, and the described methods could be used to evaluate and monitor exposure of endocrine disruptor. [ABSTRACT FROM AUTHOR]

RATIONALE: Volatile organic compounds (VOCs) are ubiquitous environmental pollutants that have a high vapor pressure at room temperature. Some VOCs have been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC), because they can bind to DNA and cause cell mutations. Therefore, monitoring of VOCs in human urine is very important to evaluate the correlation between exposure to VOCs and human disease. METHODS:We have developed an improved analyticalmethod for the simultaneous determination of VOCswith awide range of polarities in human urine samples by headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography/mass spectrometry (GC/MS). In the improved method, a bi-polar carboxen-polydimethylsiloxane (CAR/PDMS) fiber was used for the optimized extraction of 15 VOCs with a wide range of polarities, including benzene, toluene, ethylbenzene, xylenes (BTEX), alkylbenzenes, cresols, and naphthalene, in human urine samples. Extracted VOCs from the human urine were effectively separated by GC using a mid-polarity column (DB-35, 35% phenylmethylpolysiloxane) and monitored by MS using extracted ion monitoring (EIM) mode. RESULTS: Under the optimized method, the linearity of the calibration curves was greater than 0.993. The limits of detection (LODs) at a signal-to-noise (S/N) ratio of 3 were 0.3-0.6 ng/mL. The coefficients of variation were in the range of 0.1-9.7% for within-day variation and 0.2-14.2% for day-to-day variation. CONCLUSIONS: Themethod was shown to be rapid and simple for the simultaneous determination of VOCswith awide range of polarities in human urine and it could be applied to monitoring and to biomedical investigations to check exposure to VOCs. [ABSTRACT FROM AUTHOR]

Recently, the full-bridge (FB) LLC resonant converter is getting more attention due to its zero-voltage switching of the primary switches, zero-current switching of rectifier diodes, and high power capability. However, the conversion efficiency is degraded under light-load conditions due to the core loss in magnetic components and the switching loss in semiconductor devices. In this paper, a new control method is proposed for the FB LLC resonant converter. In the proposed method, the frequency control is basically used to regulate the output voltage over entire load conditions. Moreover, the proposed method utilizes phase-shifted gate signals between switch legs, based on predetermined optimal duty ratio under light-load conditions. At this point, the optimal duty ratio is determined to get minimum power loss under each light-load condition through the loss analysis of all components. Therefore, the proposed method makes high efficiency under light-load conditions. To confirm the validity of this paper, the prototype of the network power supply with 320–385 V dc input and 48 V/720 W dc output is tested. [ABSTRACT FROM AUTHOR]

Background: This study was to evaluate the efficacy and safety of triple fixed-dose combination (FDC) therapy with olmesartan medoxomil (OM) 20 mg, amlodipine (AML) 5 mg, and hydrochlorothiazide (HCTZ) 12.5 mg (OM/AML/HCTZ 20/5/12.5) in Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5). Methods: In this multicenter, randomized, double-blind, parallel-group study, Korean patients aged 20 to 75 years with stage 2 hypertension who had a mean seated diastolic blood pressure (msDBP) ≥100 mmHg were enrolled when their BP was uncontrolled [mean seated systolic BP (msSBP)/msDBP >140/90 mmHg or msSBP/msDBP >130/80 mmHg with diabetes or chronic kidney disease] with 4-week dual FDC therapy (OM/HCTZ 20/12.5). The patients were randomized to receive either OM/AML/HCTZ 20/5/12.5 or OM/HCTZ 20/12.5 once daily for 8 weeks. At the end of 8 weeks, patients with uncontrolled BP were assigned to receive either OM/AML/HCTZ 40/5/12.5 or OM/AML/HCTZ 20/5/12.5 in an additional 8-week open-label extension period. Results: A total of 623 patients received a 4-week run-in treatment with OM/HCTZ, 341 patients were randomized, and finally, 167 patients in the OM/AML/HCTZ group and 171 patients in the OM/HCTZ group were analyzed for the full analysis set. Non-responders after the 8 weeks of double-blind treatment continued the 8-week open-label treatment with OM/AML/HCTZ 40/5/12.5 mg ( n = 32) or OM/AML/HCTZ 20/5/12.5 mg ( n = 71). After 8 weeks of double-blind treatment, the changes in msDBP were −9.50 (8.46) mmHg in the OM/AML/HCTZ group and −4.23 (7.41) mmHg in the OM/HCTZ group (both p < 0.0001 vs. baseline; p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 8 were 65.27 % in the OM/AML/HCTZ group and 37.43 % in the OM/HCTZ group ( p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 16 after open-label treatment were 18.75 % in the OM/AML/HCTZ 40/5/12.5 group and 46.48 % in the OM/AML/HCTZ 20/5/12.5 group ( p = 0.0073 between groups). All medications were well tolerated. Conclusion: In Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5) as first-line therapy, switching to triple FDC therapy (OM/AML/HCTZ 20/5/12.5) was associated with significant BP reductions and greater achievement of BP goals, and was well tolerated (ClinicalTrials.gov Identifier: NCT01838850). [ABSTRACT FROM AUTHOR]

• PLCβ1 expression in DG granule cells in vivo and neurosphere cells. • Comparable increase of NSPC proliferation in vivo and neurospheres of PLCβ1 KO mice. • Occlusion of high KCl-induced increase of neurosphere proliferation in PLCβ1 KO mice. • Increase of DG granule cell excitability in PLCβ1 KO mice. PLCβ1 null mouse, a model for epilepsy/schizophrenia, shows enhanced moving activity, seizures, and excessive neurogenesis in the DG of the hippocampus. Since physical or epileptic activity increases neurogenesis, we asked whether the increase of neurogenesis in PLCβ1 null mice was mainly due to the loss of PLCβ1 in stem cells or from in vivo effects of the enhanced movement or seizures of null mice. To avoid in vivo effects, we did neurosphere cultures from the DG of the adult hippocampus and quantified the cell proliferation. We found an increase in the number and size of neurospheres in KO mice cultures, which was similar to the enhancement of in vivo proliferation of DG newborn cells in KO mice. Moreover, the positive effect of high KCl treatment on the proliferation of neurosphere culture was occluded in KO mice. Further DG neurons of PLCβ1 KO mice display increased excitability, consistent with a model for epilepsy. In conclusion, these results suggest cell-autonomous inhibitory roles of PLCβ1 in the proliferation of adult neural stem/progenitor cells in vivo and the excitability of DG granule cells. [ABSTRACT FROM AUTHOR]

GLO:8DU/01sep21:cge14013-toc-0001.jpg PHOTO (COLOR): . gl DExH-Box Helicase 30 ( I DHX30 i ) (NM 138615.3) mutations cause autosomal dominant neurodevelopmental disorder with severe motor impairment and absent language (OMIM #617804). Further accumulation of patients and longitudinal follow-up are needed to understand the full spectrum of the I DHX30 i -related phenotype. De novo missense mutations in DHX30 impair global translation and cause a neurodevelopmental disorder. [Extracted from the article]

The square-planar complex [Ni(L3)]Cl 2 ·2H 2 O ( 1 ) (L1 = 3,14-diethyl-2,6,13,17-tetraazatricyclo[14,4,0 1.18 ,0 7.12 ]docosane) with inorganic salts KNO 3 and NaN 3 yields the octahedral nickel(II) complexes [Ni(L3)(NO 3 ) 2 ] ( 2 ) and [Ni(L3)(N 3 ) 2 ] ( 3 ). The structures were characterized by X-ray crystallography, spectroscopic, thermogravimetry and cyclic voltammetry. The crystal structures of compounds 2 and 3 show that each nickel(II) centre has an elongated distorted octahedral geometry with the axial ligands. Electronic spectra and redox potentials of the complexes 2 and 3 reveal a high-spin octahedral environment, which is reflected by the nature of the axial ligands. The TGA behaviors of two compounds 2 and 3 are also significantly affected by the nature of the axial ligands. [ABSTRACT FROM AUTHOR]

Background.Cancer of unknown primary origin (CUP) is defined by the presence of pathologically identified metastatic disease without clinical or radiological evidence of a primary tumour. Our objective was to identify incident cases of CUP in Ontario, Canada, and determine the influence of histology and sites of metastases on overall survival (OS). Material and methods.We used the Ontario Cancer Registry (OCR) and the Same-Day Surgery and Discharge Abstract Database (SDS/DAD) to identify patients diagnosed with CUP in Ontario between 1 January 2000, and 31 December 2005. Patient diagnostic information, including histology and survival data, was obtained from the OCR. We cross-validated CUP diagnosis and obtained additional information about metastasis through data linkage with the SDS/DAD database. OS was assessed using Cox regression models adjusting for histology and sites of metastases. Results.We identified 3564 patients diagnosed with CUP. Patients without histologically confirmed disease (n = 1821) had a one-year OS of 10.9%, whereas patients with confirmed histology (n = 1743) had a one-year OS of 15.6%. The most common metastatic sites were in the respiratory or digestive systems (n = 1603), and the most common histology was adenocarcinoma (n = 939). Three-year survival rates were 3.5%, 5.3%, 41.6% and 3.6% among adenocarcinoma, unspecified carcinoma, squamous cell carcinoma and undifferentiated histology, respectively. Three-year survival rates were 40%, 2.4%, 8.0% and 4.6% among patients with metastases localised to lymph nodes, the respiratory or digestive systems, other specified sites, and unspecified sites, respectively. Conclusion.CUP patients in Ontario have a poor prognosis. Some subgroups may have better survival rates, such as patients with metastases localised to lymph nodes and patients with squamous cell histology. [ABSTRACT FROM PUBLISHER]

The molecular mechanism of temporal lobe epilepsy has not been clearly identified. T-type calcium channels play a role in burst firing in neurons and have been implicated in several seizure models. In this study, the role of Ca v 3.1 T-type (α1G) calcium channel has been investigated in the kainic acid (KA)-induced temporal lobe epilepsy model (TLE) by using conventional α1G knock-out (ko) mice. After intraperitoneal (i.p.) administration or intrahippocampal injection of KA, depth hippocampal and cortical electroencephalogram (EEG) and behavioral monitoring were recorded, and timm and Nissl staining of brain sections were made later. Seizure was mainly identified by EEG signals, rather than behaviorally, with analytic criteria. During the acute status epilepticus (SE) period, both the duration and the frequency of hippocampal seizures were significantly reduced and increased, respectively, in αlG ko mice compared to those of wild type mice. Epileptogenicity, the total period of seizures (hr −1 ), was also significantly reduced in α1G ko mice. However, the latency of seizure occurrence was not significantly different between wild type and ko mice. These differential effects were not observed in cortical seizures. Furthermore, the injection of KA caused a strong increase in δ rhythm power spectrum density (PSD) of EEG in αlG ko mice compared to that in wild type mice. The results with conventional ko mice indicate that α1G T-type calcium channel plays a modulatory role in the duration and frequency of hippocampal seizures as well as the epileptogenicity of KA-induced TLE in mice, mostly during acute periods. [ABSTRACT FROM AUTHOR]

The homeostatic regulation of neuronal activity in glutamatergic and GABAergic synapses is critical for neural circuit development and synaptic plasticity. The induced expression of the transcription factor early growth response 1 (Egr-1) in neurons is tightly associated with many forms of neuronal activity, but the underlying target genes in the brain remained to be elucidated. This study uses a quantitative real-time PCR approach, in combination with in vivo chromatin immunoprecipitation, and reveals that GABAA receptor subunit, GABRA2 (α2), GABRA4 (α4), and GABRQ (θ) genes, are transcriptional targets of Egr-1. Transfection of a construct that over-expresses Egr-1 in neuroblastoma (Neuro2A) cells up-regulates the α2, α4, and θ subunits. Given that Egr-1 knockout mice display less GABRA2, GABRA4, and GRBRQ mRNA in the hippocampus, and that Egr-1 directly binds to their promoters and induces mRNA expression, the present findings support a role for Egr-1 as a major regulator for altered GABAA receptor composition in homeostatic plasticity, in a glutamatergic activity-dependent manner. [ABSTRACT FROM AUTHOR]

Objective: Acute funisitis is a histologic hallmark of the fetal inflammatory response syndrome. This study was conducted to examine the hematologic profiles of preterm newborns with funisitis. Methods: The hematologic profiles of umbilical cord blood obtained at birth were compared according to the presence or absence of acute funisitis in 197 preterm neonates (gestational age before 34 weeks) born to mothers with preterm labor with intact membranes or premature rupture of membranes. Results: (1) Funisitis was identified in 22.3% (44/197) of patients; (2) newborns with funisitis had higher median leukocyte, neutrophil, monocyte counts ( p < 0.005 for each), higher rate of neutrophilia ( p < 0.05), higher proportion of neutrophils among leukocytes and lower proportion of lymphocytes among leukocytes than those without funisitis ( p < 0.01 for each); (3) newborns with funisitis had a significantly lower median RBC count, hemoglobin concentration and hematocrit than those without funisitis ( p < 0.05 for each); (4) there was no significant difference in the median lymphocyte, eosinophil, basophil, NRBC and platelet counts between the two groups ( p > 0.1 for each). Conclusions: The hematologic profiles of preterm newborns with funisitis are characterized by increased total white blood cell, neutrophil, and monocyte counts and decreased RBC count and hemoglobin concentration. [ABSTRACT FROM AUTHOR]

Clinicopathological features in six cases of focal fibrocartilaginous dysplasia (FFCD) which involved either the tibia (n = 4) or the femur (n = 2) were reviewed. All cases presented clinical and radiological characteristic features, and histopathological findings were analyzed in five of the six cases. The subject group comprised three boys and three girls, ages ranged from 12 to 18 months. Histologically, the individual lesions showed regional variation in cellularity, amount of fibrous and cartilaginous components. Paucicellular areas were mainly composed of dense fibrous tissue while more cellular areas contained foci of fibrocartilaginous element. The chondrocytes and stellate cells around cartilaginous area were positive for S-100 protein. One case contained both hyaline and fibrocartilage, and architecturally mimicked normal tendinous insertion. One case, which involved proximal tibia, was purely composed of fibrous tissue without fibrocartilage. All cases formed undulating and irregular borders against underlying cortical bone. Histopathologically variable spectrum suggests a strong possibility of undergoing transition from initial cellular and cartilagnous to late paucicellular, fibrous phase. Although any evidence that can explain basic pathogenesis or prognostic histological parameter is lacking, we believe that the term FFCD is not relevant because the presence of fibrocartilage is not an essential feature, and it can cause confusion with other pathological processes. We propose the term ‘subperiosteal fibrocartilaginous pseudotumor of long bone’ for this unique clinicopathological entity with which heterologous cartilaginous element can be associated. [ABSTRACT FROM AUTHOR]

Signed directed graphs contain both sign and direction information on their edges, providing richer information about real-world phenomena compared to unsigned or undirected graphs. However, analyzing such graphs is more challenging due to their complexity, and the limited availability of existing methods. Consequently, despite their potential uses, signed directed graphs have received less research attention. In this paper, we propose a novel spectral graph convolution model that effectively captures the underlying patterns in signed directed graphs. To this end, we introduce a complex Hermitian adjacency matrix that can represent both sign and direction of edges using complex numbers. We then define a magnetic Laplacian matrix based on the adjacency matrix, which we use to perform spectral convolution. We demonstrate that the magnetic Laplacian matrix is positive semi-definite (PSD), which guarantees its applicability to spectral methods. Compared to traditional Laplacians, the magnetic Laplacian captures additional edge information, which makes it a more informative tool for graph analysis. By leveraging the information of signed directed edges, our method generates embeddings that are more representative of the underlying graph structure. Furthermore, we showed that the proposed method has wide applicability for various graph types and is the most generalized Laplacian form. We evaluate the effectiveness of the proposed model through extensive experiments on several real-world datasets. The results demonstrate that our method outperforms state-of-the-art techniques in signed directed graph embedding. • This paper introduces a novel complex Hermitian adjacency matrix that encodes signed directed graphs using complex numbers. • It proposes a magnetic Laplacian matrix via the Hermitian and proves its positive semi-definite property. • With the magnetic Laplacian, this paper define a spectral graph convolution operation. • The proposed convolution enjoys wide applicability for several graph types from vanilla to signed directed. • SD-GCN shows superior performance in several datasets compare to other SOTAs. [ABSTRACT FROM AUTHOR]