A process of making a new type of silicon depth-probe microelectrode array is described using a combination of plasma and wet etch. The plasma etch, which is done using a low temperature oxide (LTO) ...mask, enables probe thickness to be controlled over a range from 5 to 90 /spl mu/. Bending tests show that the probe's mechanical strength depends largely on shank thickness. More force can he applied to thicker shanks while thinner shanks are more flexible. One can then choose a thickness and corresponding mechanical strength using the process developed. The entire probe shaping process is performed only at low temperature, and thus is consistent with the standard CMOS fabrication. Using the probe in recording from rat's somatosensory cortex, the authors obtained four channel simultaneous recordings which showed clear independence among channels with a signal-to-noise ratio performance comparable with that obtained using other devices.
Abstract Background The optimal statin treatment strategy that is balanced for both efficacy and safety has not been clearly determined in older adults with coronary artery disease (CAD). Methods In ...the post hoc analysis of the LODESTAR (low-density lipoprotein cholesterol-targeting statin therapy versus intensity-based statin therapy in patients with coronary artery disease) trial, the impact between a treat-to-target strategy versus a high-intensity statin therapy strategy was compared in older adults (aged 75 years or older). The goal of treat-to-target low-density lipoprotein cholesterol (LDL-C) level was 50–70 mg/dl. The primary endpoint comprised the three-year composite of all-cause death, myocardial infarction, stroke or coronary revascularisation. Results Among 4,400 patients with CAD enrolled in the LODESTAR trial, 822 (18.7%) were aged 75 years or older. Poor clinical outcomes and risk factors for atherosclerosis were more frequently observed in older adults than in younger population (<75 years old). Among these older adults with CAD, the prescription rate of high-intensity statin was significantly lower in the treat-to-target strategy group throughout the study period (P < 0.001). The mean LDL-C level for three years was 65 ± 16 mg/dl in the treat-to-target strategy group and 64 ± 18 mg/dl in the high-intensity statin group (P = 0.34). The incidence of primary endpoint occurrence was 10.9% in the treat-to-target strategy group and 12.0% in the high-intensity statin group (hazard ratio 0.92, 95% confidence interval 0.61–1.38, P = 0.69). Conclusions High-intensity statin therapy is theoretically more necessary in older adults because of worse clinical outcomes and greater number of risk factors for atherosclerosis. However, the primary endpoint occurrence with a treat-to-target strategy with an LDL-C goal of 50–70 mg/dl was comparable to that of high-intensity statin therapy and reduced utilisation of a high-intensity statin. Taking efficacy as well as safety into account, adopting a tailored approach may be considered for this high-risk population. Trial Registration ClinicalTrials.gov, NCT02579499.
A 12-year-old intact female poodle was presented with a history of an acute episode of tenesmus and passage of ribbon-shaped stools. Anaemia, leucocytosis, hypoalbuminaemia, hyperglycaemia, and ...elevated ALP were found. Faecal floatation and wet mount preparation were negative for parasites. Anaerobic faecal culture resulted in a heavy growth of Clostridium. Survey abdominal radiographs revealed extensive intramural emphysema of colon and rectum. Ultrasonography of the abdomen revealed bright echoes within the layers of the colon wall, confirming the accumulation of intramural gas. Abdominal computed tomography revealed extraluminal gas tracking along the colon and the rectum. Based on the radiographic, ultrasonographic, and computed tomographic findings, the present case was diagnosed as pneumatosis coli with an underlying cause of bacterial overgrowth. The patient was treated with antibiotics for seventeen days. Clinical signs were resolved after three days of treatment. Decreased intramural gas accumulation was evident during radiography of the abdomen performed at fourteen days after the initial evaluation. Therefore, pneumatosis coli should be considered when a dog is presented with clinical signs of colitis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Summary
Purpose: We assessed the efficacy and safety of solifenacin compared with tolterodine for treatment of overactive bladder (OAB) in Korean patients.
Materials and methods: The study was ...randomised, double‐blind, tolterodine‐controlled trial in Korea. Patients had average frequency of ≥ 8 voids per 24 h and episodes of urgency or urgency incontinence ≥ 3 during 3‐day voiding diary period. Patients were randomised to 12‐week double‐blind treatment with either tolterodine immediate release (IR) 2 mg twice daily (TOL4) or solifenacin 5 mg (SOL5) or 10 mg (SOL10) once daily. The outcome measure was mean change in daily micturition frequency, volume, daily frequency of urgency incontinence, urgency and nocturia from baseline to week 12. Quality of life was assessed using the King’s Health Questionnaire.
Results: A total of 357 were randomised and 329 were evaluated for efficacy. All voiding parameters recorded in micturition diary improved after treatment in all three groups. Mean changes in volume voided were 19.30 ml (26.69%) in TOL4, 30.37 ml (25.89%) in SOL5 and 37.12 ml (33.36%) in SOL10 group (p = 0.03). Speed of onset of SOL10 efficacy on urgency incontinence was faster than that of SOL5 and TOL4. Quality of life improved in all three groups. Dry mouth was the most common adverse event; its incidence was the lowest in SOL5 group (7.63%, compared with 19.49% and 18.64% in SOL10 and TOL4 groups respectively).
Conclusions: Solifenacin succinate 5 and 10 mg once daily improve OAB symptoms with acceptable tolerability levels compared with tolterodine IR 4 mg. Solifenacin 5 mg is a recommended starting dose in Korean patients with OAB.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
ForestGEO is a network of scientists and long-term forest dynamics plots (FDPs) spanning the Earth's major forest types. ForestGEO's mission is to advance understanding of the diversity and dynamics ...of forests and to strengthen global capacity for forest science research. ForestGEO is unique among forest plot networks in its large-scale plot dimensions, censusing of all stems ≥1 cm in diameter, inclusion of tropical, temperate and boreal forests, and investigation of additional biotic (e.g., arthropods) and abiotic (e.g., soils) drivers, which together provide a holistic view of forest functioning. The 71 FDPs in 27 countries include approximately 7.33 million living trees and about 12,000 species, representing 20% of the world's known tree diversity. With >1300 published papers, ForestGEO researchers have made significant contributions in two fundamental areas: species coexistence and diversity, and ecosystem functioning. Specifically, defining the major biotic and abiotic controls on the distribution and coexistence of species and functional types and on variation in species' demography has led to improved understanding of how the multiple dimensions of forest diversity are structured across space and time and how this diversity relates to the processes controlling the role of forests in the Earth system. Nevertheless, knowledge gaps remain that impede our ability to predict how forest diversity and function will respond to climate change and other stressors. Meeting these global research challenges requires major advances in standardizing taxonomy of tropical species, resolving the main drivers of forest dynamics, and integrating plot-based ground and remote sensing observations to scale up estimates of forest diversity and function, coupled with improved predictive models. However, they cannot be met without greater financial commitment to sustain the long-term research of ForestGEO and other forest plot networks, greatly expanded scientific capacity across the world's forested nations, and increased collaboration and integration among research networks and disciplines addressing forest science.
•ForestGEO - a global network of large long-term forest dynamics plots•71 plots, 27 countries, 7.3 million trees include 20% of tree species diversity•sampling more than trees is needed to capture drivers of forest diversity & change•knowledge gaps constrain predictions on future forest change•funding, training and collaborations are needed to sustain long-term forest research
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A global health concern has emerged as a response to the recent SARS-CoV-2 pandemic. The identification and inhibition of drug targets of SARS-CoV-2 is a decisive obligation of scientists. In ...addition to the cell entry mechanism, SARS-CoV-2 expresses a complicated replication mechanism that provides excellent drug targets. Papain-like protease (PLsup.pro ) and 3-chymotrypsin-like protease (3CLsup.pro ) play a vital role in polyprotein processing, producing functional non-structural proteins essential for viral replication and survival in the host cell. Moreover, PLsup.pro is employed by SARS-CoV-2 for reversing host immune responses. Therefore, if some particular compound has the potential to interfere with the proteolytic activities of 3CLsup.pro and PLsup.pro of SARS-CoV-2, it may be effective as a treatment or prophylaxis for COVID-19, reducing viral load, and reinstating innate immune responses. Thus, the present study aims to inhibit SARS-CoV-2 through 3CLsup.pro and PLsup.pro using marine natural products isolated from marine algae that contain numerous beneficial biological activities. Molecular docking analysis was utilized in the present study for the initial screening of selected natural products depending on their 3CLsup.pro and PLsup.pro structures. Based on this approach, Ishophloroglucin A (IPA), Dieckol, Eckmaxol, and Diphlorethohydroxycarmalol (DPHC) were isolated and used to perform in vitro evaluations. IPA presented remarkable inhibitory activity against interesting drug targets. Moreover, Dieckol, Eckmaxol, and DPHC also expressed significant potential as inhibitors. Finally, the results of the present study confirm the potential of IPA, Dieckol, Eckmaxol, and DPHC as inhibitors of SARS-CoV-2. To the best of our knowledge, this is the first study that assesses the use of marine natural products as a multifactorial approach against 3CLsup.pro and PLsup.pro of SARS-CoV-2.
Summary
Enterotoxin produced by enterotoxigenic Bacteroides fragilis (BFT) has been associated with mucosal inflammation and diarrhoeal diseases. In this study, the anti‐inflammatory molecular ...mechanism of 5,7‐dihydroxy‐3,4,6‐trimethoxyflavone (eupatilin) was characterized in an HT‐29 intestinal epithelial cell line stimulated with BFT. Pre‐treatment of HT‐29 cells with eupatilin decreased the production significantly of both interleukin (IL)‐8 and prostaglandin E2 induced by BFT in a dose‐dependent manner. BFT‐activated nuclear factor‐kappaB (NF‐κB) signals in HT‐29 cells and pretreatment with eupatilin suppressed NF‐κB activation that resulted in the significant inhibition of IL‐8 and cyclo‐oxygenase‐2 expression. BFT‐induced phosphorylation of both IκBα and IκB kinase (IKK) signals was prevented in eupatilin‐pretreated HT‐29 cells. Transfection of siRNA for IKK‐α and IKK‐β decreased the production of IL‐8 and prostaglandin E2; however, the transfection of IKK‐β siRNA showed a more significant reduction of BFT‐induced IκBα phosphorylation compared with that of IKK‐α siRNA. In addition, herbimycin A, a specific inhibitor of heat shock protein 90 (Hsp90), decreased the BFT‐induced activation of IKK and NF‐κB, suggesting that Hsp90 is associated with a pathway of IKK‐NF‐κB‐IL‐8/cyclo‐oxygenase‐2 gene signalling. Furthermore, eupatilin dissociated the complex between Hsp90 and IKK‐γ in BFT‐stimulated HT‐29 cells. These results suggest that eupatilin can suppress the NF‐κB signalling pathway by targeting the Hsp90‐IKK‐γ complex in intestinal epithelial cells and may attenuate BFT‐induced inflammatory responses.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Claudin-1 (CLDN1), a major component of tight junction complexes in the epithelium, maintains cellular polarity, and plays a critical role in cell-to-cell communication as well as epithelial cell ...homeostasis. Although the role of CLDN1 has been widely studied in cancer, its role in the progression and the exact regulatory mechanisms, remain controversial. Using next-generation sequencing, we first analyzed the expression profiles of tumor/non-tumor paired tissue in patients with head and neck squamous cell carcinoma (HNSC) from public and local cohorts and found out that CLDN1 is upregulated in tumors compared to normal tissues. Next, its correlation with lymph node metastasis and poor prognosis was validated in the retrospective cohort, which collectively suggests CLDN1 as an oncogene in HNSC. As expected, the knockdown of CLDN1 inhibited invasive phenotypes by downregulating epithelial-to-mesenchymal transition (EMT) in vitro. To ascertain the regulatory mechanism of CLDN1 in HNSC analysis of GO term enrichment, KEGG pathways, and curated gene sets were used. As a result, CLDN1 was negatively associated with AMP-activated protein kinase (AMPK) and positively associated with transforming growth factor-β (TGF-β) signaling. In vitro mechanistic assay showed that CLDN1 inhibited AMPK phosphorylation by regulating AMPK upstream phosphatases, which led to inhibition of Smad2 activity. Intriguingly, the invasive phenotype of cancer cells increased by CLDN1 overexpression was rescued by AMPK activation, indicating a role of the CLDN1/AMPK/TGF-β/EMT cascade in HNSC. Consistently in vivo, CLDN1 suppression significantly inhibited the tumor growth, with elevated AMPK expression, suggesting the novel observation of oncogenic CLDN1-AMPK signaling in HNSC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Understanding how animals are exposed to the large repository of metal pollutants in aquatic sediments is complicated and is important in regulatory decisions. Experiments with four types of ...invertebrates showed that feeding behavior and dietary uptake control bioaccumulation of cadmium, silver, nickel and zinc. Metal concentrations in animal tissue correlated with metal concentrations extracted from sediments, but not with metal in porewater, across a range of reactive sulfide concentrations, from 0.5 to 30 micromoles per gram. These results contradict the notion that metal bioavailability in sediments is controlled by geochemical equilibration of metals between porewater and reactive sulfides, a proposed basis for regulatory criteria for metals.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
To demonstrate temporal lobe necrosis (TLN) rate and clinical/dose-volume factors associated with TLN in radiation-naïve patients with head and neck cancer treated with proton therapy where the field ...of radiation involved the skull base.
Medical records and dosimetric data for radiation-naïve patients with head and neck cancer receiving proton therapy to the skull base were retrospectively reviewed. Patients with <3 months of follow-up, receiving <45 GyRBE or nonconventional fractionation, and/or no follow-up magnetic resonance imaging (MRI) were excluded. TLN was determined using MRI and graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Clinical (gender, age, comorbidities, concurrent chemotherapy, smoking, radiation techniques) and dose-volume parameters were analyzed for TLN correlation. The receiver operating characteristic curve and area under the curve (AUC) were performed to determine the cutoff points of significant dose-volume parameters.
Between 2013 and 2019, 234 patients were included. The median follow-up time was 22.5 months (range = 3.2-69.3). Overall TLN rates of any grade, ≥ grade 2, and ≥ grade 3 were 5.6% (N = 13), 2.1%, and 0.9%, respectively. The estimated 2-year TLN rate was 4.6%, and the 2-year rate of any brain necrosis was 6.8%. The median time to TLN was 20.9 months from proton completion. Absolute volume receiving 40, 50, 60, and 70 GyRBE (absolute volume aV); mean and maximum dose received by the temporal lobe; and dose to the 0.5, 1, and 2 cm
volume receiving the maximum dose (D0.5cm
, D1cm
, and D2cm
, respectively) of the temporal lobe were associated with greater TLN risk while clinical parameters showed no correlation. Among volume parameters, aV50 gave maximum AUC (0.921), and D2cm
gave the highest AUC (0.935) among dose parameters. The 11-cm
cutoff value for aV50 and 62 GyRBE for D2cm
showed maximum specificity and sensitivity.
The estimated 2-year TLN rate was 4.6% with a low rate of toxicities ≥grade 3; aV50 ≤11 cm
, D2cm
≤62 GyRBE and other cutoff values are suggested as constraints in proton therapy planning to minimize the risk of any grade TLN. Patients whose temporal lobe(s) unavoidably receive higher doses than these thresholds should be carefully followed with MRI after proton therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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