Κυριακή 8 Νοεμβρίου 2020

DEVELOPMENT OF OPTICALLY STIMULATED LUMINESCENCE BADGE READER SYSTEM FOR INDIVIDUAL MONITORING OF RADIATION WORKERS

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Abstract
A new Optically Stimulated Luminescence Badge Reader (OSBARE-1) system has been designed and developed for application in the individual monitoring dosimetry. This badge reader system utilizes the 470-nm light of a blue LED for CW-OSL readout with the help of PMT photon counting module. The developed reader system can process four element 24 OSLD cards within 25 min. These four-element OSLD card consists of the Teflon embedded indigenously developed dosimetric grade α-Al2O3:C phosphor. The minimum measurable dose (MMD) was found to be ~26 μGy for these OSLD cards with reproducibility of ~1.12%. The various operational parameters such as variation in the dark counts, OSL scattering background counts and reproducibility have been studied in detailed for this reader system. The dosimetric studies performed on this developed reader system found to have a great potential for the OSLD-based large-scale personnel monitoring progr am for the radiation workers.
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COEFFICIENTS FOR ESTIMATING PRENATAL DOSE IN PREGNANT WORKERS FROM ACUTE INTAKES

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Abstract
Inhalation and ingestion dose coefficients for the embryo and fetus from intakes of radionuclides by the mother are provided in the International Commission on Radiological Protection (ICRP) Publication 88 for intake of each of 74 radionuclides. To address the many other possible radionuclides to which workers may be exposed, effective dose coefficients were developed for the embryo/fetus for all additional radionuclides addressed in ICRP Publication 107 with half-life of 10 min or more. The general approach was to use the estimated dose to the mother's uterus during pregnancy as a scalable proxy for the dose to the embryo/fetus. The set of scaling factors used in the study was derived from analyses of the relationships of the dose to the mother's uterus and the effective dose to the embryo/fetus for the ~400 cases (considering two intake modes and multiple forms of many of the radionuclides) addressed in Publication 88.
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Pancreas ultrasound two-dimensional shear wave elastography in healthy children

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Abstract

Background

Pancreas shear wave speed might be a biomarker of pancreatic disease in children.

Objective

This study aimed to measure pancreas shear wave speed by two-dimensional (2-D) ultrasound shear wave elastography (SWE) in a balanced cohort of presumed healthy children.

Materials and methods

This was a prospective study of 120 children (<18 years of age) without a known history of pancreatic disease, who underwent ultrasound 2-D SWE of the pancreas. Five shear wave speed measurements in the pancreas body and/or tail were obtained for each participant using a Canon Aplio i800 system, i8CX1 transducer. The Mann-Whitney U test or Kruskal-Wallis test were used to compare continuous distributions. Spearman's correlation was used to assess univariate relationships between continuous variables. Multivariable regression with stepwise selection was used to evaluate independent predictors of pancreas shear wave speed.

Results

The median age for the study population was 5.0 years (range: 7 days to 17.8 years) and 61 (50.8%) of the participants were female. The median depth of shear wave speed measurement was 4.7 cm (interquartile range [IQR]: 4.2–5.3). The median pancreas shear wave speed was 1.31 m/s (IQR: 1.21–1.40). On multivariable analysis, female biological sex (P=0.051), the number of hours nil per os (P=0.097), the median depth of measurement (P=0.001) and the median liver shear wave speed (P=0.020) were positively associated with pancreas shear wave speed.

Conclusion

We report pancreas shear wave speed in a large, balanced cohort of children without a known history of pancreatic disease, providing reference values for normal.

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Sex- and age-related variations in the three-dimensional orientations and curvatures of the articular surfaces of the human talus

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Abstract

The high prevalence of foot pathologies in women and the elderly could be associated with gender and age difference in the morphology of the foot, particularly the morphology of the keystone of the foot, the talus. The present study investigated the orientation and curvature of the three articular surfaces of the talus in relation to sex and age based on computer tomography (CT), to identify possible morphological factors of the higher prevalence of foot disorders in women and elderly. Fifty-six participants were included in this study. The orientations of the talocrural, subtalar, and talonavicular joints were quantified three-dimensionally by calculating normal and principal axes of the articular surfaces defined by planar approximation. The curvature radii of the articular surfaces were quantified by cylindrical and spherical approximations. The talonavicular surface was significantly more twisted in the frontal plane and less adducted in the transverse plane in females than in males. With aging, the subtalar articular surface was significantly facing more posteriorly. Moreover, it was found that the curvature radii of the trochlea and navicular articular surfaces significantly increased with aging, indicating a flattening of these surfaces. The identified changes in the talar morphology with aging could potentially lead to a higher prevalence of foot disorders in the elderly.

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Efficacy and Safety of Acupuncture at Tianshu (ST25) for Functional Constipation: Evidence from 10 Randomized Controlled Trials

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Objective. To evaluate the evidence for the efficacy and safety of acupuncture at Tianshu (ST25) for functional constipation (FC). Methods. We systematically searched seven databases to identify randomized controlled trials of acupuncture at ST25 alone or in combination with conventional therapy in the treatment of FC. Risk ratios (RRs) and mean differences (MDs) were calculated using RevMan 5.3 with 95% confidence interval (CI). Results. The study included ten trials with 1568 participants. Meta-analysis showed that the Cleveland Constipation Score (CCS) for deep needling was significantly lower than that for lactulose (deep needling with low-frequency dilatational wave: MD −0.58, 95% CI −0.94 to −0.22; deep needling with sparse wave: MD −3.67, 95% CI −6.40 to −0.94; deep needling with high-fr equency dilatational wave: MD −3.42, 95% CI −5.03 to −1.81). Furthermore, CCS for shallow needling with high-frequency dilatational wave was lower than that for lactulose (MD −1.77, 95% CI −3.40 to −0.14). In addition, when deep needling was combined with high-frequency dilatational wave, the weekly frequency of spontaneous defecation (FSD) was significantly higher than that for lactulose (MD 1.57, 95% CI 0.93 to 2.21). Colonic Transit Time (CTT) scores were significantly higher when deep needling was combined with sparse wave (MD −14.36, 95% CI −18.31 to −10.41) or high-frequency dilatational wave (MD −11.53, 95% CI −19.25 to −3.81). The time of first defecation after treatment (TFD) of the shallow needling therapy was significantly longer than that of the lactulose (MD 13.67, 95% CI 5.66 to 21.67). The CCS 6 months after treatment (CCS6m) for deep needling was significantly lower than that for lactulose (MD −4.90, 95% CI −5.97 to −3.84). Moreover, the FSD 6 months after treatment (FSD6m) for shallow needling was significantly higher than that for lactulose (MD 0.49, 95% CI 0.02 to 0.97). The adverse event (AE) rate for lactulose was significantly higher than that achieved with the needling treatments, and this held true for both deep needling therapy (RR 0.41, 95% CI 0.23 to 0.72) and shallow needling therapy (RR 0.33, 95% CI 0.15 to 0.77). Conclusions. The meta-analysis demonstrates that acupuncture at ST25 appears to be more effective than lactulose in the treatment of functional constipation. This was found to be especially true for deep needling with high-frequency dilatational wave, which had a greater impact on improving CCS, FSD, CTT, and CCS6m. Additionally, acupuncture at ST25 was shown to be safer than conventional treatment, with the rate of AE being significantly lower for both deep needling and shallow needling. The trial is registered with https://www.crd.york.ac.uk/prospero/(CRD42019141017)).
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Sipjeondaebo-Tang (Shi-Quan-Da-Bu-Tang) for Chronic Fatigue Syndrome: Study Protocol for a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

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Background. Sipjeondaebo-tang (SDT), also known as Shi-Quan-Da-Bu-Tang, is a treatment for both qi and blood deficiency syndromes in traditional Korean medicine. It is also used to treat chronic fatigue syndrome (CFS) in Korea. Herein, we present the protocol for a study to assess the efficacy and safety of SDT for treating CFS. Methods. This will be a multicenter, randomized, double-blind, controlled trial with two parallel-treatment arms: an SDT group and a placebo group. Ninety-six patients with CFS aged between 19 and 65 years will be recruited from two hospitals in Korea. Participants will be randomly allocated at a ratio of 1 : 1 between the two groups. Participants will receive 3 g doses of SDT or placebo thrice daily for 8 weeks. Follow-up evaluations will be performed for 4–6 weeks after t he drug administration period. The primary outcome will be the rating of participants' fatigue symptoms using the Checklist Individual Strength questionnaire. Outcomes will be assessed at baseline, week 4, and week 8, as well as during follow-up. An efficacy evaluation and safety assessment will be performed. This study will be based on the Consolidated Standards of Reporting Trials (CONSORT) guidelines and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement. This protocol and informed consent guidelines were reviewed and approved by the institutional review board of Kyung Hee University Korean Medicine Hospital at Gangdong in the Republic of Korea (KHNMCOH 2017-06-004-001). The protocol was registered with the Clinical Research Information Service. Written informed consent will be obtained from all study participants prior to enrollment in the study. Results will be published in a peer-reviewed journal and presented at a scientific confe rence. Discussion. This study is expected to provide novel, accurate information regarding the 38 efficacy and safety of SDT for CFS in adults. Trial Registration. This trial is registered with https://cris.nih.go.kr; CRIS identifier (KCT0002684) registered on February 9, 2018.
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Renoprotective Effects of Origanum majorana Methanolic L and Carvacrol on Ischemia/Reperfusion-Induced Kidney Injury in Male Rats

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Background. The most important cause of acute renal failure in normal kidneys is ischemia-reperfusion (I/R) injury. The aim of the current study was to investigate the protective effects of Origanum majorana (OM) methanolic extract, carvacrol, and vitamin E on I/R-induced kidney injury in male rats. Material and Method. Thirty Wistar male rats were randomly allocated into 5 groups; sham, I/R, I/R + OM (300 mg/kg), I/R + carvacrol (75 mg/kg), and I/R + vitamin E (100 mg/kg). Renal function markers, oxidant-antioxidant parameters, and histopathological examination were evaluated. Results. It was exhibited that the urea, creatinine, protein carbonyl, glomerular filtration rate, total thiol, ferric reducing antioxidant power, and histopathological changes markedly reversed in the treatment gr oups with OM or carvacrol in comparison to the I/R merely group. Conclusion. We conclude that OM extract or its ingredient, carvacrol, exerts renoprotective impacts in I/R-induced kidney injury possibly by scavenging free radicals and increasing antioxidant power.
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Acupoint Catgut Embedding for Insomnia: A Meta-Analysis of Randomized Controlled Trials

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Objectives. A Meta-analysis was carried out to evaluate the efficacy and safety of acupoint catgut embedding (ACE), a procedure of embedding sutures made of absorbable materials into the skin tissue of acupoints, on insomnia. Methods. Relevant clinical randomized controlled trials (RCTs) were comprehensively searched from eleven electronic databases (up to 1 March 2020). Two authors independently screened literature, extracted data, and assessed the risk of bias of included studies. Stata 12 and RevMan 5.3.0 software were used for meta-analysis. PyCharm 2019 and Gephi software (version 0.9.2) were used for complex network analysis. Results. Thirty-four RCTs involving 2,655 patients were included. The meta-analysis suggested that ACE induced a better clinical efficacy compared with that in the estazolam tab lets (EZ) group (RR = 1.22, 95% CI: 1.13, 1.31) or in the acupuncture (ACU) group (RR = 1.21, 95% CI: 1.14, 1.28) and could significantly reduce the score of Pittsburgh Sleep Quality Index (). ACE resulted in better long-term efficacy compared to that in the EZ group (RR = 1.87, 95% CI: 1.58, 2.22) and ACU group (RR = 1.30, 95% CI: 1.14, 1.48). ACE could significantly reduce the incidence of adverse events (RR = 0.30, 95% CI: 0.15, 0.60) compared with that in the EZ group. Complex network analysis indicated that acupoints of BL23, SP6, PC6, BL15, BL20, BL18, and HT7 were the core acupoints selected in ACE for insomnia. Conclusion. The clinical efficacy of ACE for insomnia is better than that of other interventions (EZ and ACU) in both short-term and long-term observations. Considering the efficacy and reduced visits to the clinic by ACE, the present study provides a practical and convenient complementary and alternative therapy for insomnia. This trial is registe red with PROSPERO CRD 42020169866.
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Ligustrazine in the Treatment of Idiopathic Pulmonary Fibrosis

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Objective. To systematically review the efficacy and safety of Ligustrazine in the treatment of idiopathic pulmonary fibrosis (IPF). Methods. The electronic literature databases (PubMed, EMbase, CNKI, WanFang database, and VIP) were retrieved through a computer to find out the randomized controlled trials (RCT) of Ligustrazine in the treatment of IPF according to the inclusion/exclusion criteria screening test. Cochrane's bias risk table was also used to evaluate the quality of the study and to extract effective data. RevMan 5.3 was used for statistical analysis. Results. A total of 7 RCTs (a total of 366 patients, including 196 in experimental and 170 in control group). Compared with the control group, Ligustrazine could improve the clinical symptoms ([OR] = 2.20, 95% CI [1.40, 3.46], ), lung functi on (VC % [MD] = 3.92, 95% CI [0.68, 7.17], ), (TLC% [MD] = 4.94, 95% CI [0.37, 9.52], ), the pulmonary diffusion function (DLCO % [MD] = 9.12, 95% CI [5.70, 12.55], ), and arterial blood gas analysis (PaO2 [MD] = 7.11, 95% CI [1.96, 12.25], ) (PaCO2 [MD] = −2.42, 95% CI [−4.36, −0.49], ) of IPF patients, respectively. However, FEV1/FVC % ([MD] = 9.37, 95% CI [−1.23, 19.97], ) and adverse reactions ([MD] = 0.35, 95% CI [0.02, 5.36], ) were not significantly improved. Conclusion. Ligustrazine has certain clinical efficacy in the treatment of IPF, but the safety of applying it and the adverse reactions need to be further analyzed and determined. It can be considered as a new alternative and complementary medicine to be promoted and recommended for use in medical units in various countries in the world and it solved the difficult problem of conventional drug treatment of IPF; therefore, more research strength can be put in the treatment of the patholo gical mechanism of IPF for further exploration. The study was registered under registration number CRD42020193626.
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Inhibition of G protein-coupled receptor kinase 2 promotes unbiased downregulation of IGF-1 receptor and restrains malignant cell growth

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The ability of a receptor to preferentially activate only a subset of available downstream signal cascades is termed biased signaling. While comprehensively recognized for the G protein-coupled receptors (GPCR), this process is scarcely explored downstream of receptor tyrosine kinases (RTK), including the cancer-relevant insulin-like growth factor-1 receptor (IGF-1R). Successful IGF-1R targeting requires receptor downregulation, yet therapy-mediated removal from the cell surface activates cancer-protective β-arrestin-biased signaling (β-arr-BS). As these overlapping processes are initiated by the β-arr/IGF-1R interaction and controlled by GPCR-kinases (GRK), we explored GRKs as potential anti-cancer therapeutic targets to disconnect IGF-1R downregulation and β-arr-BS. Transgenic modulation demonstrated that GRK2-inhibition or GRK6-overexpression enhanced degradation of IGF-1R, but both scenarios sustained IGF-1-induced β-arr-BS. Pharmacological inhibition of GRK2 by the cl inically approved antidepressant, serotonin reuptake inhibitor paroxetine (PX), recapitulated the effects of GRK2-silencing with dose- and time-dependent IGF-1R downregulation without associated β-arr-BS. In vivo, PX-treatment caused substantial downregulation of IGF-1R, suppressing the growth of Ewing's sarcoma xenografts. Functional studies reveal that PX exploits the antagonism between β-arrestin isoforms: in low ligand conditions, PX favored β-arrestin1/Mdm2-mediated ubiquitination/degradation of IGF-1R, a scenario usually exclusive to ligand abundancy, making PX more effective than antibody-mediated IGF-1R downregulation. This study provides the rationale, molecular mechanism, and validation of a clinically feasible concept for 'system bias' targeting of the IGF-1R to uncouple downregulation from signaling. Demonstrating system bias as an effective anti-cancer approach, our study reveals a novel strategy for the rational design or repurposing of therapeutics to selectively c ross-target the IGF-1R or other RTK.
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Loss of ARID1A promotes epithelial-mesenchymal transition and sensitizes pancreatic tumors to proteotoxic stress

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Cellular de-differentiation is a key mechanism driving cancer progression. Acquisition of mesenchymal features has been associated with drug resistance, poor prognosis, and disease relapse in many tumor types. Therefore, successful targeting of tumors harboring these characteristics is a priority in oncology practice. The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex has also emerged as a critical player in tumor progression, leading to the identification of several SWI/SNF complex genes as potential disease biomarkers and targets of anti-cancer therapies. AT-rich interaction domain-containing protein 1A (ARID1A) is a component of SWI/SNF, and mutations in ARID1A represent one of the most frequent molecular alterations in human cancers. ARID1A mutations occur in ~10% of pancreatic ductal adenocarcinomas (PDAC), but whether these mutations confer a therapeutic opportunity remains unclear. Here we demonstrate that loss of ARID1A promotes an epithelial-mese nchymal transition (EMT) phenotype and sensitizes PDAC cells to a clinical inhibitor of HSP90, NVP-AUY922, both in vitro and in vivo. While loss of ARID1A alone did not significantly affect proliferative potential or rate of apoptosis, ARID1A-deficient cells were sensitized to HSP90 inhibition, potentially by promoting the degradation of intermediate filaments driving EMT, resulting in cell death. Our results describe a mechanistic link between ARID1A defects and a quasi-mesenchymal phenotype, suggesting that deleterious mutations in ARID1A associated with protein loss exhibits potential as a biomarker for PDAC patients who may benefit by HSP90-targeting drugs treatment.
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