Non-destructive testing techniques for the observation of healing effects in cementitious materials: an introduction

To develop an appropriate method of self-healing for cementitious materials including the right composition and amount of suitable healing agents it is required to investigate the healing efficiency for certain material mixtures. While some researchers evaluate the regain in compressive strength by means of destructive load tests, this method is obviously second best in particular for field applications. In a large EU project the best candidates among the non-destructive testing methods are investigated to be applied in small and large laboratory experiments as well as at real structures in-situ. The paper is giving an introduction to these techniques and addresses also issues of structural health monitoring used for example to monitor the healing effects on a long term basis and to assess the condition of the structure, where self-healing techniques are applied

User's guide for the Nimbus 7 Scanning Multichannel Microwave Radiometer (SMMR) CELL-ALL tape

The SMMR instrument onboard the Nimbus-7 satellite has been in operation since October 1978. It provided global coverage of passive microwave observations at 6.6, 10.7, 18, 21, and 37 GHz. The oberved brightness temperature can be used to retrieve geophysical parameters, principally sea surface temperature, atmospheric water vapor and liquid water content over oceans, sea ice concentration, and snow cover over land. The SMME CELL-ALL Tape contains earth-located calibrated brightness temperature data which have been appropriately binned into cells of various grid sizes, allowing intercomparisons of observations made at different frequencies (with corresponding different footprint sizes). This user's guide describes the operation of the instrument, the flow of the data processing the calibration procedure, and the characteristics of the calibrated brightness temperatures and how they are binned. Detailed tape specifications and lists of available data are also provided

THE PATENTED DRUGS UTILIZATION: A STUDY AT NGUYEN DINH CHIEU HOSPITAL IN BEN TRE PROVINCE FROM 2011 TO 2017

Objective: With their new and efficacious active ingredients, patented drugs have important roles in offering high-quality healthcare. However, huge cost-related barriers in accessing patented drugs along with the availability of low-cost bioequivalent generics have great impact on drugs policy in Vietnam. To understand situation of patented drugs utilization at hospitals for a certain period, this pilot study was conducted at Nguyen-Dinh-Chieu Hospital in Ben-Tre Province. Methods: The cross-sectional descriptive study was conducted on the retrospective data of all patented drugs used at Nguyen-Dinh-Chieu Hospital in Ben-Tre Province from 2011-2017. Characteristics of drugs utilization were described by frequency and percentage of drugs quantities and costs. Criteria for the description were as follows: active ingredient, route of administration, therapeutic class and manufacturing country. Data were extracted from the hospital information system and were processed by R software. Results: From 2011 to 2017, there were 212 patented drugs used which related to 145 active ingredients and 20 therapeutic classes. 88% were single active ingredient drugs and 49% were oral drugs. Antimicrobial and cardiovascular drugs represented the largest number of drugs and the highest cost. 79% of patented drugs were manufactured by companies in Europe and the majority came from France and Germany. Conclusion: This study provided initial information about the utilization of patented drugs during a long period of time at a Vietnamese hospital. The understanding gained will aid medical managers in assessment and adjustment of the drugs list, thus, optimizing the hospital budget and the equity in access to drugs within communities

Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies

Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11–34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7–16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9–25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14–29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15–23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17–48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20–41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20–34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20–33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21–46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18

Small molecule inhibition of CBP/catenin interactions eliminates drug resistant clones in acute lymphoblastic leukemia

Drug resistance in acute lymphoblastic leukemia (ALL) remains a major problem warranting new treatment strategies. Wnt/catenin signaling is critical for the self-renewal of normal hematopoietic progenitor cells. Deregulated Wnt signaling is evident in chronic and acute myeloid leukemia, however little is known about ALL. Differential interaction of catenin with either the Kat3 coactivator CREBBP (CBP) or the highly homologous EP300 (p300) is critical to determine divergent cellular responses and provides a rationale for the regulation of both proliferation and differentiation by the Wnt signaling pathway. Usage of the coactivator CBP by catenin leads to transcriptional activation of cassettes of genes that are involved in maintenance of progenitor cell self-renewal. However, the use of the coactivator p300, leads to activation of genes involved in the initiation of differentiation. ICG-001 is a novel small molecule modulator of Wnt/catenin signaling, which specifically binds to the N-terminus of CBP and not p300, within amino acids 1–110, thereby disrupting the interaction between CBP and catenin. Here, we report that selective disruption of the CBP/β- and γ-catenin interactions using ICG-001 leads to differentiation of pre-B ALL cells and loss of self-renewal capacity. Survivin, an inhibitor-of-apoptosis protein, was also downregulated in primary ALL after treatment with ICG-001. Using ChIP assay, we demonstrate occupancy by CBP of the survivin promoter, which is decreased by ICG-001 in primary ALL. CBP-mutations have been recently identified in a significant percentage of ALL patients, however, almost all of the identified mutations reported occur C-terminal to the binding site for ICG-001. Importantly, ICG-001, regardless of CBP mutational status and chromosomal aberration, leads to eradication of drug-resistant primary leukemia in combination with conventional therapy in vitro and significantly prolongs the survival of NOD/SCID mice engrafted with primary ALL. Therefore, specifically inhibiting CBP/catenin transcription represents a novel approach to overcome relapse in ALL

Elucidating the role of metal ions in carbonic anhydrase catalysis

Why metalloenzymes often show dramatic changes in their catalytic activity when subjected to chemically similar but non-native metal substitutions is a long-standing puzzle. Here, we report on the catalytic roles of metal ions in a model metalloenzyme system, human carbonic anhydrase II (CA II). Through a comparative study on the intermediate states of the zinc-bound native CA II and non-native metal-substituted CA IIs, we demonstrate that the characteristic metal ion coordination geometries (tetrahedral for Zn2+, tetrahedral to octahedral conversion for Co2+, octahedral for Ni2+, and trigonal bipyramidal for Cu2+) directly modulate the catalytic efficacy. In addition, we reveal that the metal ions have a long-range (~10 ??) electrostatic effect on restructuring water network in the active site. Our study provides evidence that the metal ions in metalloenzymes have a crucial impact on the catalytic mechanism beyond their primary chemical properties. ?? 2020, The Author(s)

Growth performance, meat quality, and blood characteristics of finisher crossbred pigs fed diets supplemented with different levels of green tea (Camellia sinensis) by-products.

peer reviewed[en] BACKGROUND AND AIM: Dietary supplementation with green tea by-product shows special effects on animal parameters. This study aimed to assess the effects of green tea by-products (GTBP) in the diet on some blood parameters, growth performance, and carcass characteristics of finishing pigs and on meat quality, and nutritional composition of pork. MATERIALS AND METHODS: One hundred and sixty crossbred pigs with an initial body weight of 65.15 ± 0.38 kg, were distributed into four dietary treatments, with four replicates of 10 pigs each. The dietary treatments were a basal diet (control diet, CON), and three experimental diets (GTBP8, GTBP16, and GTBP24) based on the CON diet supplemented with GTBP at 8, 16, and 24 g/kg of feed. The studied parameters were examined during the experimental period of 10 weeks. RESULTS: No statistical differences in average daily feed intake, average daily gain, and feed conversion ratio were observed between the diet treatments (p > 0.05). Backfat thickness decreased (linear, p 0.05). However, pigs fed with GTBP had a decrease in cholesterol content and an increase in crude protein and total omega-3 content of pork compared to the CON diet (p < 0.05). Moreover, dietary supplementation with GTBP significantly decreased plasma cholesterol (p < 0.05), and trends for the decrease in low-density lipoprotein cholesterol and urea nitrogen were observed (linear, p = 0.08). CONCLUSION: Up to 24 g/kg GTBP in the diet for finishing pigs does not impair animal performance and makes carcass leaner with softer meat as well as positive effects on cholesterol and fatty acid metabolism. Further experiments are needed to determine the optimal levels of GTBP addition in finishing pig diet to produce higher meat quality

Diagnostic performance of contrast enhanced CT and 18F-FDG PET/CT in suspicious recurrence of biliary tract cancer after curative resection

<p>Abstract</p> <p>Background</p> <p>Because of the late clinical presentation of biliary tract cancer (BTC), only 10% of patients are eligible for curative surgery. Even among those patients who have undergone curative surgery, most patients develop recurrent cancer. This study is to determine the clinical role of ¹⁸F-FDG PET/CT during post-operative surveillance of suspected recurrent BTC based on symptoms, laboratory findings and contrast-enhanced CT (ceCT) findings.</p> <p>Methods</p> <p>We consecutively enrolled 50 patients with BTC who underwent curative surgery. An ¹⁸F-FDG PET/CT was obtained for assessment of recurrence based on clinical suspicion during post-operative surveillance. The final confirmation of recurrence was determined pathologically or clinically. When a pathologic confirmation was impossible or inconclusive, a clinical confirmation was used by radiologic correlation with subsequent follow-up ceCT at a minimum of 3-month intervals. Diagnostic efficacy was evaluated by comparing the results of ceCT and ¹⁸F-FDG PET/CT with the final diagnosis.</p> <p>Results</p> <p>Among the 50 patients, 34(68%) were confirmed to have a recurrence. PET/CT showed higher sensitivity (88% <it>vs</it>. 76%, <it>p </it>= 0.16) and accuracy (82% <it>vs</it>. 66%, <it>p </it>= 0.11) for recurrence compared to ceCT, even though the difference was not significant. The positive (86% <it>vs</it>. 74%, <it>p </it>= 0.72) and negative predictive values for recurrence (73% <it>vs</it>. 47%, <it>p </it>= 0.55) were not significantly different between PET/CT and ceCT. However, an additional PET/CT on ceCT significantly improved the sensitivity than did a ceCT alone (94% [32/34] for PET/CT on ceCT <it>vs</it>. 76% [26/34] for ceCT alone, <it>p </it>= 0.03) without increasing the specificity, positive predictive value, and negative predictive value.</p> <p>Conclusions</p> <p>¹⁸F-FDG PET/CT alone is not more sensitive or specific than ceCT in the detection of recurrent BTC after curative surgery. These results do not reach statistical significance, probably due to the low number of patients. However, an additional ¹⁸F-FDG PET/CT on ceCT significantly improves the sensitivity of detecting recurrences.</p

Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences

Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them using genomic-phenotypic data from 792 strains. A rapid online ‘TB-Profiler’ tool was developed to report DR and strain-type profiles directly from raw sequences. Using our DR mutation library, in silico diagnostic accuracy was superior to some commercial diagnostics and alternative databases. The library will facilitate sequence-based drug-susceptibility testing

The duck hepatitis virus 5'-UTR possesses HCV-like IRES activity that is independent of eIF4F complex and modulated by downstream coding sequences

Duck hepatitis virus (DHV-1) is a worldwide distributed picornavirus that causes acute and fatal disease in young ducklings. Recently, the complete genome of DHV-1 has been determined and comparative sequence analysis has shown that possesses the typical picornavirus organization but exhibits several unique features. For the first time, we provide evidence that the 626-nucleotide-long 5'-UTR of the DHV-1 genome contains an internal ribosome entry site (IRES) element that functions efficiently both in vitro and in mammalian cells. The prediction of the secondary structure of the DHV-1 IRES shows significant similarity to the hepatitis C virus (HCV) IRES. Moreover, similarly to HCV IRES, DHV-1 IRES can direct translation initiation in the absence of a functional eIF4F complex. We also demonstrate that the activity of the DHV-1 IRES is modulated by a viral coding sequence located downstream of the DHV-1 5'-UTR, which enhances DHV-1 IRES activity both in vitro and in vivo. Furthermore, mutational analysis of the predicted pseudo-knot structures at the 3'-end of the putative DHV-1 IRES supported the presence of conserved domains II and III and, as it has been previously described for other picornaviruses, these structures are essential for keeping the normal internal initiation of translation of DHV-1