Characterization of fatty acid compositions in longissimus thoracis muscle and identification of candidate gene and SNPs related to polyunsaturated fatty acid in Hu sheep.
Fatty acid (FA) composition contributes greatly to the quality and nutritional value of lamb meat. In the present study, FA was measured in longissimus thoracis (LT) muscles of 1,085 Hu sheep using gas chromatography. Comparative transcriptomic analysis was conducted in LT muscles to identify differentially expressed genes (DEGs) between six individuals with high polyunsaturated fatty acids (H-PUFA, 15.27% ± 0.42%) and six with low PUFA (L-PUFA, 5.22% ± 0.25%). Subsequently, the single nucleotide polymorphisms (SNPs) in a candidate gene PLIN2 were correlated with FA traits. The results showed a total of 29 FA compositions and 8 FA groups were identified, with the highest content of monounsaturated fatty acids (MUFA, 46.54%, mainly C18:1n9c), followed by saturated fatty acids (SFA, 44.32%, mainly C16:0), and PUFA (8.72%, mainly C18:2n6c), and significant correlations were observed among the most of FA traits. Transcriptomic analyses identified 110 upregulated and 302 downregulated DEGs between H-PUFA and L-PUFA groups. The functional enrichment analysis revealed three significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 17 gene ontology (GO) terms, in which regulation of lipolysis in adipocytes, the AMPK signaling pathway, and the PPAR signaling pathway may play important roles in FA metabolism and biosynthesis. In addition, weighted gene co-expression network analysis (WGCNA) identified 37 module genes associated with PUFA-related traits. In general, PLIN1, LIPE, FABP4, LEP, ACACA, ADIPOQ, SCD, PCK2, FASN, PLIN2, LPL, FABP3, THRSP, and ACADVL may have a great impact on PUFA metabolism and lipid deposition. Four SNPs within PLIN2 were significantly associated with FA. Of those, SNP1 (g.287 G>A) was significantly associated with C18:1n9c and MUFA, and SNP4 (g.7807 T>C) was significantly correlated with PUFA (C18:3n3). In addition, the combined genotype of SNP1 (g.287 G>A), SNP3 (g.7664 T>C), and SNP4 (g.7807 T>C) were significantly correlated with C16:1, C17:0, C18:1C6, PUFA (C18:3n3, C22:6n3), and n-6/n-3 PUFA. These results contribute to the knowledge of the biological mechanisms and genetic markers involved in the composition of FA in Hu sheep.


Inhibition of osteoclasts does not prevent joint ankylosis in a mouse model of spondyloarthritis.
The relationship between inflammation, destruction and new tissue formation leading to ankylosis, determines the severity and prognosis of patients with SpA. Recent data in mice and men suggest that new cartilage and bone formation and subsequent ankylosis are uncoupled from chronic inflammation. These data challenge the hypothesis that inflammation and tissue damage trigger an excessive repair response in SpA. We tested whether inhibition of bone erosion by targeting osteoclasts, would prevent or influence joint ankylosis in a mouse model. Male DBA/1 mice from different litters were caged together at the age of 8 weeks. Treatment with zoledronic acid (ZA) (100 ng/g) or placebo was started at the age of 10 weeks and administered every 2 weeks. Clinical incidence and severity of arthritis were evaluated twice a week until the age of 26 weeks. At this point, bone density measurements were performed, mice were sacrificed and severity of arthritis was evaluated by histology. Treatment with ZA did not affect incidence or clinical severity of arthritis in male DBA/1 mice. ZA treatment significantly increased bone mineral density and content as demonstrated by dual X-ray densitometry and peripheral quantitative CT. However, the treatment did not affect histomorphological appearance of arthritis or ankylosis. These data suggest that bone erosion at the enthesis does not necessarily precede entheseal ankylosis. Therefore, these observations further support the concept that inflammation and new tissue formation in SpA are at least partially uncoupled events and may be different therapeutic targets.


Genome engineering of disease susceptibility genes for enhancing resistance in plants.
Introgression of disease resistance genes (R-genes) to fight against an array of phytopathogens takes several years using conventional breeding approaches. Pathogens develop mechanism(s) to escape plants immune system by evolving new strains/races, thus making them susceptible to disease. Conversely, disruption of host susceptibility factors (or S-genes) provides opportunities for resistance breeding in crops. S-genes are often exploited by phytopathogens to promote their growth and infection. Therefore, identification and targeting of disease susceptibility genes (S-genes) are gaining more attention for the acquisition of resistance in plants. Genome engineering of S-genes results in targeted, transgene-free gene modification through CRISPR-Cas-mediated technology and has been reported in several agriculturally important crops. In this review, we discuss the defense mechanism in plants against phytopathogens, tug of war between R-genes and S-genes, in silico techniques for identification of host-target (S-) genes and pathogen effector molecule(s), CRISPR-Cas-mediated S-gene engineering, its applications, challenges, and future prospects.


Case Report: Suspected Hyperacute Rejection During Living Kidney Transplantation.
We report a case of suspected hyperacute rejection during living kidney transplantation. A 61-year-old man underwent kidney transplantation in November 2019. Before the transplantation, immunologic tests revealed the presence of anti-HLA antibodies but not donor-specific HLA antibodies. The patient was intravenously administered 500 mg of methylprednisolone (MP) and basiliximab before perioperative blood flow reperfusion. After blood flow restoration, the transplanted kidney turned bright red and then blue. Hyperacute rejection was suspected. After the intravenous administration of 500 mg of MP and 30 g of intravenous immunoglobulin, the transplanted kidney gradually changed from blue to bright red. The initial postoperative urine output was good. On the 22nd day after the renal transplantation, the patient was discharged with a serum creatinine level of 2.38 mg/dL, and the function of the transplanted kidney gradually improved. In this study, non-HLA antibodies may have been a cause of the hyperacute rejection, which was managed with additional perioperative therapies.


The impact of overweight and obesity on unemployment duration among young American workers.
Obesity has a profound effect on the working careers of Americans. Prior studies pertaining to workers in other countries report that obese women experienced longer spells of unemployment than normal weight peers. However, the effect of obesity on unemployment duration has not been studied for American workers. To address this gap in the literature, we report estimates of the effects of overweight and obesity from a proportional hazards model of unemployment duration that controls for unobserved individual characteristics. Using a data sample of young workers drawn from the National Longitudinal Survey of Youth (1997), our findings indicate that, on average, overweight and obese job seekers experienced significantly longer spells of unemployment. The effects differed by race, sex, and ethnicity: Overweight and obese White and Black women experienced significantly longer spells than White women with normal body mass index (BMI) levels. Although overweight White and Black men had longer unemployment spells compared to White men with normal BMI levels, the magnitudes were smaller than those for White and Black women. In contrast, overweight Hispanic women had shorter duration of unemployment spells compared to White women with normal BMI levels.


Wanted: An endothelial cell targeting atlas for nanotherapeutic delivery in allograft organs.
Despite the profound shortage of organs available for transplant in the U.S., over 5,000 donated organs were declined for use in 2020. Many of these organs were declined due to donor comorbidities or preservation injuries that predispose grafts to rejection and loss. The risks of these poor outcomes can potentially be reduced by pre-transplant application of normothermic machine perfusion (NMP). To date, the clinical use of NMP has focused on extending preservation and improving organ assessment, but the opportunity for ex situ therapeutic delivery may be the most transformative aspect of this technology. In this Personal Viewpoint, we argue that the endothelial cells (ECs) that line the graft vasculature are an accessible, under-exploited, and attractive target for transplant therapeutics delivered during NMP. We further contend that molecularly targeted nanoparticles (NPs) represent a promising therapeutic vehicle particularly well-suited to NMP. However, to achieve this potential, we need to answer the following three key questions: (1) What EC sub-populations exist within an organ? (2) How can these cells be accessed? (3) And most important, how can preferential retention of NPs by the cells of interest be maximized? Here we argue for creating an EC-targeting atlas as a body of knowledge that answers these questions.


Carbon dioxide embolism during minimally invasive vein harvesting.
Gas embolism is a known complication of minimal access procedures in which carbon dioxide insufflation is used. We report a case of significant venous and right heart gas embolization, which occurred during performance of routine minimally invasive vein harvesting. This was manifest by hemodynamic deterioration secondary to transmission by a patent foramen ovale into the left heart and coronary circulation. Techniques to predict, diagnose, and prevent this rare but potentially fatal complication of minimally invasive vein harvesting are suggested.


Synaptic protein degradation by the ubiquitin proteasome system.
Synaptic plasticity -- the modulation of synaptic strength between a presynaptic terminal and a postsynaptic dendrite -- is thought to be a mechanism that underlies learning and memory. It has become increasingly clear that regulated protein synthesis is an important mechanism used to regulate the protein content of synapses that results in changes in synaptic strength. Recent experiments have highlighted a role for the opposing process, that is, regulated protein degradation via the ubiquitin-proteasome system, in synaptic plasticity. These recent findings raise exciting questions as to how proteasomal activity can regulate synapses over different temporal and spatial scales.


Improvement of the print-capture polymerase chain reaction procedure for efficient amplification of DNA virus genomes from plants and insect vectors.
A rapid and simple procedure is described to amplify efficiently geminivirus DNA genomes by improving the print-capture polymerase chain reaction (PCR) procedure reported recently for RNA viruses. This method, termed print-PCR (P-PCR), allows direct amplification of DNA from infected plant or whitefly tissues printed directly on Whatman 3MM paper, without the need of any grinding, incubation, or washing steps previous to the amplification reaction. P-PCR reduces sample manipulation and avoids previous extraction of nucleic acids, thereby diminishing the possibilities of cross-contamination between samples. P-PCR has been successfully applied to whiteflies and various plant species infected by two different tomato yellow leaf curl viruses, TYLCV-Sr and TYLCV-Is, and for the amplification of the full-length genome of TYLCV-Is from infected plants.


Assessment of prokaryotic communities in Southwestern Atlantic deep-sea sediments reveals prevalent methanol-oxidising Methylomirabilales.
Continental slopes can play a significant contribution to marine productivity and carbon cycling. These regions can harbour distinct geological features, such as salt diapirs and pockmarks, in which their depressions may serve as natural sediment traps where different compounds can accumulate. We investigated the prokaryotic communities in surface (0-2 cm) and subsurface (18-20 or 22-24 cm) sediments from a salt diapir and pockmark field in Santos Basin, Southwest Atlantic Ocean. Metabarcoding of 16 samples revealed that surface sediments were dominated by the archaeal class Nitrososphaeria, while the bacterial class Dehalococcoidia was the most prevalent in subsurface samples. Sediment strata were found to be a significant factor explaining 27% of the variability in community composition. However, no significant difference was observed among geomorphological features. We also performed a metagenomic analysis of three surface samples and analysed the highest quality metagenome-assembled genome retrieved, which belonged to the family CSP1-5, phylum Methylomirabilota. This non-methanotrophic methylotroph contains genes encoding for methanol oxidation and Calvin Cycle pathways, along with diverse functions that may contribute to its adaptation to deep-sea habitats and to oscillating environmental conditions. By integrating metabarcoding and metagenomic approaches, we reported that CSP1-5 is prevalent in the sediment samples from Santos Basin slope, indicating the potential importance of methanol metabolism in this region. Finally, using a phylogenetic approach integrating 16S rRNA sequences assigned to Methylomirabilota in this study with those from a public database, we argued that CSP1-5 public sequences might be misclassified as Methylomirabilaceae (the methanotrophic clade) and, therefore, the role of these organisms and the methanol cycling could also be neglected in other environments.


Brain amyloid and the transition to dementia in Down syndrome.
Down syndrome (DS) is associated with elevated risk for Alzheimer's disease (AD) due to amyloid beta (Aβ) lifelong accumulation. We hypothesized that the spatial distribution of brain Aβ predicts future dementia conversion in individuals with DS. We acquired 18F-florbetapir positron emission tomography scans from 19 nondemented individuals with DS at baseline and monitored them for 4 years, with five individuals transitioning to dementia. Machine learning classification using an independent test set determined features on 18F-florbetapir standardized uptake value ratio maps that predicted transition. In addition to "AD signature" regions including the inferior parietal cortex, temporal lobes, and the cingulum, we found that Aβ cortical binding in the prefrontal and superior frontal cortices distinguished subjects who transitioned to dementia. Classification did well in predicting transitioners. Our study suggests that specific regional profiles of brain amyloid in older adults with DS may predict cognitive decline and are informative in evaluating the risk for dementia.


Analysis of gender differences with traditional posterior stabilized versus kinematic designs in total knee arthroplasty.
Total knee arthroplasty (TKA) is a good treatment for end-stage knee osteoarthritis (KOA). Approximately 60% of the patients are females, and 40% are males. This study analyzed pre- and postoperative angle differences in the range of motion (ROM), and the occurrence of complications with traditional posterior stabilization versus kinematic TKA in relation to gender. Data from 434 patients with primary cemented total knee arthroplasty from 2018 to 2021 were collected. Alpha and beta angles were determined pre- and postsurgery. The ROM was collected pre- and postoperatively and during follow-up. Additionally, perioperative complications, revision rate, and blood transfusion management were investigated. The pre- and postoperative alpha-angle between men and women was significantly different, as was the level of alpha-angle correction between men and women (p = 0.001; p = 0.003). Same-gender differences in pre- to postoperative alpha-angles between traditional and kinematic TKA were shown (women (w): p = 0.001; men (m); p = 0.042). High postoperative alpha angles led to less ROM in traditional TKA for women (p = 0.008). No significant gender differences in ROM, perioperative complications, or revision surgery and transfusion rates were found. Despite high gender differences in pre- and postoperative angles, only female patients with traditional arthroplasty and high postoperative alpha angles showed less ROM in the follow-up. This leads to the assumption that gender-related pre- and postoperative angle differences, and the degree of angle correction, do not influence the ROM or perioperative occurrence of complications. Both designs present safe procedures for both genders with a wide spectrum of axis deformities.


A simplified method for estimating 5-phosphoribosyl 1-pyrophosphate in mouse liver and spleen.
A simplified method for the estimation of 5-phosphoribosyl 1-pyrophosphate (PRPP) in mouse liver and spleen is described. The method uses the enzymic conversion of [8-14C] hypoxanthine to [8-14C] inosine 5'-monophosphate in the presence of PRPP and has the advantage over previously published methods in that the enzyme used in this assay, hypoxanthine-guanine phosphoribosyltransferase (HG-PRTase), is present in the tissue being analyzed and does not require preparation. In addition, each assay uses as its internal standard PRPP, thus overcoming the problem of the chemical instability inherent in this molecule. The two-minute heat treatment used in the method was found to destroy most interfering enzymes and resulted in average recovery of PRPP of 56% and 85% for the liver and spleen, respectively. The counts obtained in the assay were about ten-fold above background (80 c.p.m) and allowed accurate measurement of the phosphoribose sugar. The levels of PRPP (+/- standard deviation) found for liver and spleen in twelve (12) separate Balb/C male mice were 6.3 +/- 1.8 and 10.8 +/- 5.0 nmoles/g wet weight tissue, respectively, and agree with the tissue concentrations already reported for this metabolite. A further advantage of this assay is that it gives an index of the HG-PRTase activity in the tissues.


Escaping the correction for body surface area when calculating glomerular filtration rate in children.
(51)Cr ethylene diamine tetraacetic acid ((51)Cr EDTA) clearance is nowadays considered as an accurate and reproducible method for measuring glomerular filtration rate (GFR) in children. Normal values in function of age, corrected for body surface area, have been recently updated. However, much criticism has been expressed about the validity of body surface area correction. The aim of the present paper was to present the normal GFR values, not corrected for body surface area, with the associated percentile curves. For that purpose, the same patients as in the previous paper were selected, namely those with no recent urinary tract infection, having a normal left to right (99m)Tc MAG3 uptake ratio and a normal kidney morphology on the early parenchymal images. A single blood sample method was used for (51)Cr EDTA clearance measurement. Clearance values, not corrected for body surface area, increased progressively up to the adolescence. The percentile curves were determined and allow, for a single patient, to estimate accurately the level of non-corrected clearance and the evolution with time, whatever the age.


A mutual titer-enhancing relationship and similar localization patterns between Citrus exocortis viroid and Hop stunt viroid co-infecting two citrus cultivars.
Citrus exocortis viroid (CEVd) and Hop stunt viroid (HSVd) are commonly found simultaneously infecting different citrus cultivars in Taiwan. A crucial question to be addressed is how accumulations of these two viroids affect each other in an infected plant. In this study, we investigated the relationship between the two viroids at macroscopic and microscopic levels. CEVd and HSVd titers were examined by real-time RT-PCR in 17 plants of two citrus cultivars (blood orange and Murcott mandarin) every 3 months (spring, summer, fall and winter) from 2011 to 2013. Three nonparametric tests (Spearman's rank correlation coefficient, Kendall's tau rank correlation coefficient and Hoeffding's inequality) were performed to test the correlation between CEVd and HSVd. Cellular and subcellular localizations of the two viroids were detected by digoxigenin- and colloidal gold-labeled in situ hybridization using light and transmission electron microscopy. The two viroids were unevenly distributed in four different types of citrus tissues (rootstock bark, roots, twig bark and leaves). Compared with blood orange, Murcott mandarin was generally more susceptible to CEVd and HSVd infection. Both viroids replicated and preferentially accumulated in the underground tissues of the two citrus cultivars. Except for blood orange at high temperatures, significant positive correlations were observed between the two viroids in specific tissues of both cultivars. Relative to concentrations under single-infection conditions, the CEVd population significantly increased under double infection during half of the 12 monitored seasons; in contrast, the population of HSVd significantly increased under double infection during only one season. At cellular/subcellular levels, the two viroids showed similar localization patterns in four tissues and the cells of these tissues in the two citrus cultivars. Our findings of titer enhancement, localization similarity, and lack of symptom aggravation under CEVd and HSVd double infection suggest that the two viroids have a positive relationship in citrus. The combination of molecular and cellular techniques used in this study provided evidence of titer correlation and localization of co-infecting viroids in the host. These methods may thus be useful tools for exploring viroid-viroid and viroid-host interactions.


Evaluating the Impact of Functional Genetic Variation on HIV-1 Control.
Previous genetic association studies of human immunodeficiency virus-1 (HIV-1) progression have focused on common human genetic variation ascertained through genome-wide genotyping. We sought to systematically assess the full spectrum of functional variation in protein coding gene regions on HIV-1 progression through exome sequencing of 1327 individuals. Genetic variants were tested individually and in aggregate across genes and gene sets for an influence on HIV-1 viral load. Multiple single variants within the major histocompatibility complex (MHC) region were observed to be strongly associated with HIV-1 outcome, consistent with the known impact of classical HLA alleles. However, no single variant or gene located outside of the MHC region was significantly associated with HIV progression. Set-based association testing focusing on genes identified as being essential for HIV replication in genome-wide small interfering RNA (siRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) studies did not reveal any novel associations. These results suggest that exonic variants with large effect sizes are unlikely to have a major contribution to host control of HIV infection.


Effect of sodium selenite on chosen anti- and pro-oxidative parameters in rats treated with lithium: A pilot study.
Selenium is an essential element of antioxidant properties. Lithium is widely used in medicine but its administration can cause numerous side effects including oxidative stress. The present study aimed at evaluating if sodium selenite could influence chosen anti- and pro-oxidant parameters in rats treated with lithium. The experiment was performed on four groups of Wistar rats: I (control) - treated with saline; II (Li) - treated with lithium (2.7 mgLi/kg b.w. as Li2CO3), III (Se) - treated with selenium (0.5 mgSe/kg b.w. as Na2SeO3), IV (Li+Se) - treated with Li2CO3 and Na2SeO3 together at the same doses as in group II and III, respectively. All treatments were performed by stomach tube for three weeks in form of water solutions. The following anti- and pro-oxidant parameters: total antioxidant status (TAS) value, catalase (CAT) activity, concentrations of ascorbic acid (AA) and malonyldialdehyde (MDA) in plasma as well as whole blood superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured. Selenium given alone markedly enhanced whole blood GPx and diminished plasma CAT vs. Lithium significantly decreased plasma CAT and slightly increased AA vs. Selenium co-administration restored these parameters to the values observed in control animals. Furthermore, selenium co-administration significantly increased GPx in Li-treated rats. All other parameters (TAS, SOD and MDA) were not affected by lithium and/or selenium. Further research seems to be warranted to decide if application of selenium as an adjuvant in lithium therapy is worth considering.


Preclinical Study of Locoregional Therapy of Hepatocellular Carcinoma by Bioelectric Ablation with Microsecond Pulsed Electric Fields (μsPEFs).
Unresectable hepatocellular carcinoma (HCC) needs locoregional ablation as a curative or downstage therapy. Microsecond Pulsed Electric Fields (μsPEFs) is an option. A xenograft tumor model was set up on 48 nude mice by injecting human hepatocellular carcinoma Hep3B cells subcutaneously. The tumor-bearing mice were randomly divided into 3 groups: μsPEFs treated, sham and control group. μsPEFs group was treated by μsPEFs twice in 5 days. Tumor volume, survival, pathology, mitochondria function and cytokines were followed up. μsPEFs was also conducted on 3 swine to determine impact on organ functions. The tumors treated by μsPEFs were completely eradicated while tumors in control and sham groups grew up to 2 cm(3) in 3 weeks. The μsPEFs-treated group indicated mitochondrial damage and tumor necrosis as shown in JC-1 test, flow cytometry, H&E staining and TEM. μsPEFs activates CD56+ and CD68+ cells and inhibits tumor proliferating cell nuclear antigen. μsPEFs inhibits HCC growth in the nude mice by causing mitochondria damage, tumor necrosis and non-specific inflammation. μsPEFs treats porcine livers without damaging vital organs. μsPEFs is a feasible minimally invasive locoregional ablation option.


Isolation and characterization of a new simian foamy virus serotype from lymphocytes of a Papio cynocephalus baboon.
A new type of syncytium-forming (foamy) virus was isolated from peripheral lymphocytes of a Papio cynocephalus baboon after cocultivation with a rhesus monkey cell line. The isolate was characterized by cytopathogenic effect, host range, electron microscopy, reverse transcriptase activity and physical and chemical properties. Seroneutralization tests indicate that the new isolate is antigenically distinct from the other nine known simian foamy virus serotypes.


Electrolytic ablation as an adjunct to liver resection: experimental studies of predictability and safety.
Combined liver resection and local ablation may offer the only chance of cure to patients with liver metastases who are presently deemed unresectable because of a single awkwardly placed metastasis. By definition, such a metastasis is often close to a major vein. An ablative technique is needed that is both predictable and safe in such a circumstance. Electrolytic liver lesions were created in 21 pigs using platinum electrodes, connected to a direct current generator. Both electrolytic 'dose' and electrode separation were varied to produce different sized lesions. The 'dose' was correlated with the volume of necrosis and any vascular damage was determined histologically. There was a significant (P < 0.001) correlation between the electrolytic 'dose' and the volume of liver necrosis. For a given 'dose' the volume of necrosis was less when the electrodes were together, rather than separated. Liver enzymes were only transiently deranged. There were no significant vascular injuries. Predictable and reproducible necrosis is produced by electrolysis in the pig liver. The treatment appears to cause little or no damage to immediately adjacent liver or major vascular structures and, when combined with resection, may offer the chance of a cure to many patients who are currently unresectable.


Restorative dentistry in the young cleft patient.
This clinical paper outlines the role of the restorative consultant in the treatment of young cleft lip and palate patients up to the end of their cleft package of care on their 22nd birthday. The multidisciplinary nature of the care is highlighted, including the role of the general dental practitioner in caring for cleft patients in primary care. The various clinical treatment modalities used in this patient group are described with an emphasis on minimally invasive and adhesive approaches. The role of dental implants and removable prostheses are described. Considerations for long-term maintenance, much of which will take place in primary care, are also included.


[A personal system of automated planning of microprocessor printing plates for radio-electronic medical equipment].
Personal CAD/CAM for graphic projection and manufacture of microprocessor PCB masks, input information-carrying medium and numeric controlled lathes has been designed. CAD/CAM instrument-software could be interfaced to an APRICOT type PC and to the USSR-manufactured equipment. Personal CAD/CAM is considered as a person-machine system and works in the automatic and semi-automatic modes. The convertor program, which is included into the software allows one to use the present CAD/CAM system with the alternative USSR and foreign manufactured systems.


Specificity of relations between adolescents' cognitive emotion regulation strategies and Internalizing and Externalizing psychopathology.
Of the study was to examine the extent to which cognitive emotion regulation strategies were 'common determinants' of Internalizing and Externalizing problems and/or 'specific determinants' distinguishing one problem category from the other. The sample comprised 271 12- to 18-year-old secondary school students. Internalizing and Externalizing problems were measured by the Youth Self-Report (YSR) and Cognitive Emotion Regulation Strategies were measured by the Cognitive Emotion Regulation Questionnaire (CERQ), in a cross-sectional design. First, adolescents with Internalizing problems, Externalizing problems, comorbid Internalizing and Externalizing problems and a control group were compared on their specific cognitive emotion regulation strategies. Results showed that adolescents with Internalizing problems (both pure and comorbid) scored significantly higher on the cognitive emotion regulation strategies of self-blame and rumination than those with Externalizing (pure) problems or the control group. Unique relationships between the separate cognitive strategies and Internalizing and Externalizing problems were tested by means of Multiple Regression Analyses. Specific relationships were found between Internalizing problems and self-blame, rumination and positive reappraisal and between Externalizing problems and positive refocusing. No 'common' correlates were found. Theoretical models designed for the prediction of Internalizing problems might not simply be used for the prediction of Externalizing problems. Different (cognitive) intervention strategies should be used for adolescents with Internalizing problems and Externalizing problems.


Paracentric inversion in a female with multiple miscarriages (7inv)(q2.13;q3.13).
A phenotypically normal woman with a history of multiple miscarriages was found to have a paracentric inversion in the long arm of chromosome, which may be the reason for the miscarriages.


[Controlled observation of efficacy on herb-partitioned moxibustion and western medicine in the treatment of persistent and chronic diarrhea of children].
To evaluate clinical efficacy of herb-partitioned moxibustion with spontaneous heating bag in the treatment of persistent and chronic diarrheal disease (PCDD) of children, and to explore the new treatment protocols for pediatric PCDD. One hundred and twenty cases of PCDD were randomly divided into a herb-partitioned moxibustion group (group M) and a western medicine group (group C), 60 cases in each one. The herb-partitioned moxibustion with spontaneous heating bags was given in the group M, which was placed on the herbal cake at Shenque (CV 8) and Guanyuan (CV 4) for 12 hours, once a day. The group C was orally administrated with smectite powder and live combined bifidobacterium and lactobacillus tablets. Plasma motilin (MOT) level and T cell subset CD4+/CD8+ ratio were observed after 10 days of the treatment, also the clinical efficacy was evaluated. The cured rate was 53.3% (32/60) in the group M, which was superior to 40.0% (24/60) in the group C (P < 0.05). After the treatment, MOT levels were both decreased (both P < 0.01) while CD4+/CD8+ ratios were both increased (both P < 0.01) in the two groups. The level of MOT in the group M was lower than that in the group C (P < 0.05). The herb-partitioned moxibustion with spontaneous hea-ting bag has better therapeutic effect than routine western medicine on pediatric PCDD, and it has the advantage of easy manipulation, safety and good compliance of children.


A multidisciplinary perspective on the complex interactions between sleep, circadian, and metabolic disruption in cancer patients.
Sleep is a basic need that is frequently set aside in modern societies. This leads to profound but complex physiological maladaptations in the body commonly referred to as circadian disruption, which recently has been characterized as a carcinogenic factor and reason for poor treatment outcomes, shortened survival, and reduced quality of life in cancer patients. As sleep and circadian physiology in cancer patients spans several disciplines including nursing science, neurology, oncology, molecular biology and medical technology, there is a lack of comprehensive and integrated approaches to deal with this serious and growing issue and at best a fractionated understanding of only part of the problem among researchers within each of these segments. Here, we take a multidisciplinary approach to comprehensively review the diagnosis and impact of sleep and circadian disruption in cancer patients. We discuss recent discoveries on molecular regulation of the circadian clock in healthy and malignant cells, the neurological and endocrine pathways controlling sleep and circadian rhythmicity, and their inputs to and outputs from the organism. The benefits and drawbacks of the various technologies, devices, and instruments used to assess sleep and circadian function, as well as the known consequences of sleep disruption and how sleep can be corrected in cancer patients, will be analyzed. We will throughout the review highlight the extensive crosstalk between sleep, circadian rhythms, and metabolic pathways involved in malignancy and identify current knowledge gaps and barriers for addressing the issue of sleep and circadian disruption in cancer patients. By addressing these issues, we hope to provide a foundation for further research as well as better and more effective care for the patients in the future.


The buzz-lag effect.
In the flash-lag illusion, a brief visual flash and a moving object presented at the same location appear to be offset with the flash trailing the moving object. A considerable amount of studies investigated the visual flash-lag effect, and flash-lag-like effects have also been observed in audition, and cross-modally between vision and audition. In the present study, we investigate whether a similar effect can also be observed when using only haptic stimuli. A fast vibration (or buzz, lasting less than 20 ms) was applied to the moving finger of the observers and employed as a "haptic flash." Participants performed a two-alternative forced-choice (2AFC) task where they had to judge whether the moving finger was located to the right or to the left of the stationary finger at the time of the buzz. We used two different movement velocities (Slow and Fast conditions). We found that the moving finger was systematically misperceived to be ahead of the stationary finger when the two were physically aligned. This result can be interpreted as a purely haptic analogue of the flash-lag effect, which we refer to as "buzz-lag effect." The buzz-lag effect can be well accounted for by the temporal-sampling explanation of flash-lag-like effects.


Acceptability of the dengue vaccination among parents in urban poor communities of Quezon City, Philippines before and after vaccine suspension.
The study aims to illustrate the acceptability of the dengue vaccine before and after the dengue vaccination suspension in urban poor communities in Quezon City, Philippines. There were 12 interviews conducted in November 2017 and 5 focus group discussions in January 2018, a month after vaccine program suspension with 41 participants. All participants were selected through purposive criterion sampling. Thematic analysis showed acceptability of the dengue vaccine was associated with parental experience with vaccination and dengue, trust in public health institutions and communication received by parents. Post-dengue vaccination suspension triangulation indicated that the parents regretted the experience, trust to public institutions was eroded and the communication strategy was deemed inadequate. This led to low vaccine acceptability post-vaccine suspension.


Chimeric antigen receptor T-cell therapy in hematologic malignancies: Successes, challenges, and opportunities.
The success of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies has realized a longstanding effort toward harnessing the immune system to fight cancer in a truly personalized fashion. Second generation chimeric antigen receptors (CAR) incorporating co-stimulatory molecules like 4-1BB or CD28 were able to overcome some of the hindrances with initial CAR constructs resulting in efficacious products. Many second-generation CAR-T products have been approved in the treatment of relapsed/refractory hematologic malignancies including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia. However, challenges remain in optimizing the manufacturing, timely access, limiting the toxicity from CAR-T infusions and improving sustainability of responses derived with CAR-T therapy. Here, we summarize the clinical trial data leading to approval CAR-T therapies in MM and NHL, discuss the limitations with current CAR-T therapy strategies and review emerging strategies for overcoming these limitations.


An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia.
Xenotransplantation of patient-derived AML (acute myeloid leukemia) cells in NOD-scid Il2rγ null (NSG) mice is the method of choice for evaluating this human hematologic malignancy. However, existing models constructed using intravenous injection in adult or newborn NSG mice have inferior engraftment efficiency, poor peripheral blood engraftment, or are difficult to construct. Here, we describe an improved AML xenograft model where primary human AML cells were injected into NSG newborn pups intrahepatically. Introduction of primary cells from AML patients resulted in high levels of engraftment in peripheral blood, spleen, and bone marrow (BM) of recipient mice. The phenotype of engrafted AML cells remained unaltered during serial transplantation. The mice developed features that are consistent with human AML including spleen enlargement and infiltration of AML cells into multiple organs. Importantly, we demonstrated that although leukemic stem cell activity is enriched and mediated by CD34+CD117+ subpopulation, CD34+CD117- subpopulation can acquire CD34+CD117+ phenotype through de-differentiation. Lastly, we evaluated the therapeutic potential of Sorafenib and Regorafenib in this AML model and found that periphery and spleen AML cells are sensitive to these treatments, whereas BM provides a protective environment to AML. Collectively, our improved model is robust, easy-to-construct, and reliable for pre-clinical AML studies.


Site of temperature monitoring and prediction of afterdrop after open heart surgery.
To determine which of the commonly used "core" temperature sites, remote from the brain, best indicates total body rewarming, the temperatures in the rectum (RT), urinary bladder (UBT) and the pulmonary artery (PAT) at the termination of cardiopulmonary bypass (CPB) were correlated with the decrease in nasopharyngeal temperature (NPT) after CPB (afterdrop) in 29 patients. The amount of afterdrop is inversely related to the adequacy of total body rewarming, smaller values indicating better rewarming. All patients had uncomplicated cardiac surgery and received high pump flows during rewarming on CPB. The UBT showed the best correlation with afterdrop (p less than 0.001) compared with the other temperature sites, the durations of CPB and rewarming during CPB, and the time that the NPT was greater than 37 degrees C during rewarming. The urinary bladder is a simple, non-invasive monitoring site when a urinary catheter is required and our results indicated that the UBT is a better monitor of the adequacy of total body rewarming on CPB than NPT alone. The study also suggested that rewarming to a UBT in excess of 36.2 degrees C prior to the termination of CPB is unlikely to further reduce afterdrop.


Racial and ethnic disparities in physical abuse reporting and child protective services interventions in the United States.
Minorities are more prevalent than the general population in the child protection system; however, racial/ ethnic disparities in physical abuse and child protective services interventions are not understood. Bivariate and multivariate analyses evaluated racial/ethnic differences in reported and substantiated physical abuse, physical abuse deaths, and interventions provided in all reported maltreatment from the 2006 National Child Abuse and Neglect Data System. In bivariate analyses, African American (25%), Asian/ Pacific Islander (21%), and multiracial children (21%) have a higher prevalence of substantiated physical abuse than whites (20%). Native Americans (0.21%), African Americans (0.15%), Asians/Pacific Islanders (0.12%), and Latinos (0.11%) are more likely to die from physical abuse than whites (0.09%). African Americans have higher odds than whites of reported (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.11-1.14) and substantiated (OR, 1.27; 95% CI, 1.23-1.31) physical abuse. Latinos have higher odds of reported physical abuse (OR, 1.18; 95% CI, 1.16-1.20) and lower odds of substantiated physical abuse (OR, 0.93; 95% CI, 0.90-0.96). Native Americans have lower odds (OR, 0.53; 95% CI, 0.49-0.56) and Asian/Pacific Islanders higher odds (OR, 1.34; 95% CI, 1.26-1.44) of reported physical abuse vs whites. Latinos have significantly lower odds than whites of receiving support services. Compared with whites, African Americans are at increased risk. Latino, Asian/Pacific Islander, and multiracial children have greater odds of reports, and Native Americans have lower odds of reports for physical abuse. Significant disparities exist in interventions provided to minority families. Understanding these disparities has the potential to improve reporting, prevention, and interventions.


The pediatric "Spine at Risk" program: 9-year review of a novel safety screening tool.
We implemented an EMR-based "Spine at Risk" (SAR) alert program in 2011 to identify pediatric patients at risk for intraoperative spinal cord injury (SCI) and prompt an evaluation for peri-operative recommendations prior to anesthetic. SAR alerts were activated upon documentation of a qualifying ICD-9/10 diagnosis or manually entered by providers. We aimed to determine the frequency of recommended precautions for those auto-flagged by diagnosis versus by provider, the frequency of precautions, and whether the program prevented SCIs during non-spinal surgery. We performed a retrospective chart review of patients from 2011 to 19 with an SAR alert. We recorded how the chart was flagged, recommended precautions, and reviewed data for SCIs at our institution during non-spinal operations. Of the 3453 patients with an SAR alert over the 9-year study period, 1963 were auto-flagged by diagnosis and 1490 by manual entry. Only 38.7% and 24.3% of the patients in these respective groups were assigned precaution recommendations, making the auto-flag 62.8% better than providers at identifying patients needing precautions. Cervical spine positioning precautions were needed most frequently (86.7% of diagnosis-flagged; 30.0% of provider-flagged), followed by intraoperative neuromonitoring (IONM) (25.2%; 6.1%), thoracolumbar positioning restrictions (16.1%; 7.9%), and fiberoptic intubation (13.9%; 5.7%). There were no SCIs in non-spinal procedures during the study. EMR-based alerts requiring evaluation by a Neurosurgeon or Orthopaedic surgeon prior to anesthesia can prevent SCIs during non-spinal procedures. The majority of identified patients are not found to be at risk, and will not require special precautions. III.


Age-related decrease in physical activity and functional fitness among elderly men and women.
To determine differences in physical activity level and functional fitness between young elderly (60-69 years) and old elderly (70-80 years) people with the hypothesis that an age-related decline would be found. A total of 1288 participants' level of physical activity was evaluated using the International Physical Activity Questionnaire: 594 were male (mean ± standard deviation: body height 175.62 ± 9.78 cm; body weight 82.26 ± 31.33 kg) and 694 female (mean ± standard deviation: body height 165.17 ± 23.12 cm; body weight 69.74 ± 12.44 kg). Functional fitness was also estimated using the Senior Fitness Test: back scratch, chair sit and reach, 8-foot up and go, chair stand up for 30 seconds, arm curl, and 2-minute step test. Significant differences (P < 0.05) were found for all Senior Fitness tests between young elderly (60-69 years) and old elderly (70-80) men. Similar results were found for the women, except no significant differences were found for the chair sit and reach and the 2-minute step test. From the viewpoint of energy consumption estimated by the International Physical Activity Questionnaire, moderate physical activity is dominant. In addition, with aging, among men and women older than 60 years, the value of the Metabolic Equivalent of Task in total physical activity significantly reduces (P < 0.05). This study found that the reduction in physical activity level and functional fitness was equal for both men and women and was due to the aging process. These differences between young and old elderly people were due to the reduction of muscle strength in both upper and lower limbs and changes in body-fat percentage, flexibility, agility, and endurance.


An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.
To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.


Pregnancies and births achieved from in vitro matured oocytes retrieved from poor responders undergoing stimulation in in vitro fertilization cycles.
To describe pregnancies that resulted from in vitro matured oocytes derived from stimulated IVF cycles before cancellation owing to poor response of gonadotropins. Case report. University hospital. Eight patients who underwent in vitro maturation.Immature oocyte retrieval, in vitro maturation of immature oocytes, fertilization, and ET. Luteal support with progesterone and plvyeron was given. Pregnancy and live birth. Three pregnancies (two live births and another ongoing) were achieved after immature oocyte retrieval, in vitro maturation, fertilization with ICSI, and ET. Immature oocyte retrieval from poor responders during stimulation, followed by in vitro maturation, may be an alternative before the cycle is canceled.


The free energy of mechanically unstable phases.
Phase diagrams provide 'roadmaps' to the possible states of matter. Their determination traditionally rests on the assumption that all phases, even unstable ones, have well-defined free energies under all conditions. However, this assumption is commonly violated in condensed phases due to mechanical instabilities. This long-standing problem impedes thermodynamic database development, as pragmatic attempts at solving this problem involve delicate extrapolations that are highly nonunique and that lack an underlying theoretical justification. Here we propose an efficient computational solution to this problem that has a simple interpretation, both as a topological partitioning of atomic configuration space and as a minimally constrained physical system. Our natural scheme smoothly extends the free energy of stable phases, without relying on extrapolation, thus enabling a formal assessment of widely used extrapolation schemes.


Fecal calprotectin in healthy children aged 4-16 years.
Reference values of fecal calprotectin (fCP) have not been convincingly established in children. We aimed to investigate fCP concentrations in a larger population of healthy children aged 4-16 years to analyze more in depth the behavior of fCP in this age range and to determine if cut-off levels could be conclusively recommended. A prospective study was conducted to investigate fCP concentrations of healthy children aged 4-16 years. In 212 healthy children, the median and 95th percentile for fCP were 18.8 mg/kg and 104.5 mg/kg, respectively. We found a statistically significant association between the 95th percentile of fCP concentrations and age (p < 0.001). We propose a nomogram to facilitate the interpretation of fCP results in children aged 4-16 years. Further studies are required to validate the proposed values in clinical practice.


Vasonatrin peptide, a synthetic natriuretic peptide, attenuates myocardial injury and oxidative stress in isoprenaline-induced cardiomyocyte hypertrophy.
Isoprenaline-induced cardiac hypertrophy can deteriorate to heart failure, which is a leading cause of mortality. Endogenous vasonatrin peptide (VNP) has been reported to be cardioprotective against myocardial ischemia/reperfusion injury in diabetic rats. However, little is known about the effect of exogenous VNP on cardiac hypertrophy. We further explored whether VNP attenuated isoprenaline-induced cardiomyocyte hypertrophy by examining the levels and activities of cGMP and PKG. In this study, we found that VNP significantly attenuated isoprenaline-induced myocardial hypertrophy and cardiac fibroblast activation in vivo. Moreover, VNP effectively halted the activation of apoptosis and oxidative stress in the isoprenaline-treated myocardium. VNP promoted superoxide dismutase (SOD) activity. Further study revealed that the protective effects of VNP might be mediated by the activity of the cGMP-PKG signaling pathway in vivo or in vitro, while the use of agonists and antagonists confirmed these results. Therefore, we demonstrated that the antiapoptosis and antioxidative stress effects of VNP depends on elevated cGMP-PKG signaling activity both in vivo and in vitro. These results suggest that VNP may be used in the treatment of myocardial hypertrophy.


Study of coordinative gene expression at the biological process level.
Cellular processes are not isolated groups of events. Nevertheless, in most microarray analyses, they tend to be treated as standalone units. To shed light on how various parts of the interlocked biological processes are coordinated at the transcription level, there is a need to study the between-unit expressional relationship directly. We approach this issue by constructing an index of correlation function to convey the global pattern of coexpression between genes from one process and genes from the entire genome. Processes with similar signatures are then identified and projected to a process-to-process association graph. This top-down method allows for detailed gene-level analysis between linked processes to follow up. Using the cell-cycle gene-expression profiles for Saccharomyces cerevisiae, we report well-organized networks of biological processes that would be difficult to find otherwise. Using another dataset, we report a sharply different network structure featuring cellular responses under environmental stress. http://kiefer.stat.ucla.edu/lap2/download/KL_supplement.pdf.


Titanium dioxide nanoparticle-induced testicular damage, spermatogenesis suppression, and gene expression alterations in male mice.
Although titanium dioxide nanoparticles (TiO2 NPs) have been demonstrated to accumulate in organs resulting in toxicity, there is currently only limited data regarding male reproductive toxicity by TiO2 NPs. In this study, testicular damage and alterations in gene expression profiles in male mice induced by intragastric administration of 2.5, 5, and 10mg/kg body weight of TiO2 NPs for 90 consecutive days were examined. Our findings showed that TiO2 NPs can cross the blood-testis barrier to reach the testis and accumulate therein, which, in turn, results in testicular lesions, sperm malformations, and alterations in serum sex hormone levels. Furthermore, microarray analysis showed that 70 genes with known functions were up-regulated, while 72 were down-regulated in TiO2 NPs-exposed testes. Of the altered gene expressions, Ly6e, Adam3, Tdrd6, Spata19, Tnp2, and Prm1 are involved in spermatogenesis, whereas Sc4mol, Psmc3ip, Mvd, Srd5a2, Lep, and Cyp2e1 are associated with steroid and hormone metabolism. Hence, the production and application of TiO2 NPs should be carried out cautiously, especially by humans of reproductive age.


Traumatic cranial defects reconstructed with the HTR-PMI cranioplastic implant.
Titanium mesh, polymethyl methacrylate application, and autogenous bone grafting have been used to reconstruct traumatic cranial defects, with varying success. A more recent technique utilizing hard tissue replacement-patient matched implants (HTR-PMIs) involves the production of a cranioplastic implant using three-dimensional computed tomography imaging. It has proven less time-consuming and provides an excellent cosmetic result for the patient. The authors present two case reports using this technique to correct traumatic cranial defects. Both patients exhibited satisfactory results and no postoperative complications. The authors believe this relatively new technique represents an advance in the management of large cranial defects.


Asymmetric shoe height induces reactive changes in gait kinematics but not kinetics in healthy young adults.
Footwear interventions are a potential avenue to correct walking asymmetry in neurologic populations, such as stroke. However, the motor learning mechanisms that underlie the changes in walking imposed by asymmetric footwear are unclear. The objectives of this study were to examine symmetry changes during and after an asymmetric shoe height intervention in (1) vertical impulse and (2) spatiotemporal gait parameters and (3) joint kinematics, in healthy young adults METHODS: Eleven healthy young adults (3 males, 8 females; 21.2 ± 3.1 years old) participated in this study. Participants walked on an instrumented treadmill at 1.3 m/s for four conditions: (1) a 5-minute familiarization with equal shoe height, (2) a 5-minute baseline with equal shoe height, (3) a 10-minute intervention, where participants walked with asymmetric shoe height with a 10 mm shoe insert in one shoe, and (4) a 10-minute post-intervention, where participants walked with equal shoe height. Asymmetry in kinetics and kinematics were used to identify changes during intervention and aftereffects, a hallmark of feedforward adaptation RESULTS: Participants did not alter vertical impulse asymmetry (p = 0.667) nor stance time asymmetry (p = 0.228). During the intervention, step time asymmetry (p = 0.003) and double support asymmetry (p < 0.001) were greater compared to baseline. Leg joint asymmetry during stance (Ankle plantarflexion: p < 0.001; Knee flexion: p < 0.001; Hip extension: p = 0.011) was greater during the intervention compared to baseline. However, changes in spatiotemporal gait variables and joint mechanics did not demonstrate aftereffects. Our results show that healthy human adults change gait kinematics, but not weight-bearing symmetry with asymmetrical footwear. This suggests that healthy humans prioritize maintaining vertical impulse by changing their kinematics. Further, the changes in gait kinematics are short-lived, suggesting feedback-based control, and a lack of feedforward motor adaptations.


Reductions in abundances of intracellular and extracellular antibiotic resistance genes by SiO2 nanoparticles during composting driven by mobile genetic elements.
Applying exogenous additives during the aerobic composting of livestock manure is effective for slowing down the spread of antibiotic resistance genes (ARGs) in the environment. Nanomaterials have received much attention because only low amounts need to be added and they have a high capacity for adsorbing pollutants. Intracellular ARGs (i-ARGs) and extracellular ARGs (e-ARGs) comprise the resistome in livestock manure but the effects of nanomaterials on the fates of these different fractions during composting are still unclear. Thus, we investigated the effects of adding SiO2 nanoparticles (SiO2NPs) at four levels (0 (CK), 0.5 (L), 1 (M), and 2 g/kg (H)) on i-ARGs, e-ARGs, and the bacterial community during composting. The results showed that i-ARGs represented the main fraction of ARGs during aerobic composting of swine manure, and their abundance was lowest under M. Compared with CK, M increased the removal rates of i-ARGs and e-ARGs by 17.9% and 100%, respectively. SiO2NPs enhanced the competition between ARGs hosts and non-hosts. M optimized the bacterial community by reducing the abundances of co-hosts (Clostridium_sensu_stricto_1, Terrisporobacter, and Turicibacter) of i-ARGs and e-ARGs (by 96.0% and 99.3%, respectively) and killing 49.9% of antibiotic-resistant bacteria. Horizontal gene transfer dominated by mobile genetic elements (MGEs) played a key role in the changes in the abundances of ARGs. i-intI1 and e-Tn916/1545 were key MGEs related closely to ARGs, and the maximum decreases of 52.8% and 100%, respectively, occurred under M, which mainly explained the decreased abundances of i-ARGs and e-ARGs. Our findings provide new insights into the distribution and main drivers of i-ARGs and e-ARGs, as well as demonstrating the possibility of adding 1 g/kg SiO2NPs to reduce the propagation of ARGs.


Relationship between risk markers for cardiovascular disease and peri-implant diseases.
The aim of this paper is to explore the serum biochemical parameters also known as risk markers for cardiovascular system, in individuals who have received dental implant treatment, and to reveal risk factors for peri-implant diseases. The study included 58 subjects with peri-implantitis, 49 subjects with peri-implant mucositis, and 49 healthy subjects. All the subjects were assessed in terms of both peri-implant clinical parameters-probing depth (PD), bleeding on probing (BOP), the type of prosthesis, gingival index (GI), keratinized mucosa width (KMW), and plaque index (PI)-and serum biochemical parameters (e.g., LDL cholesterol, HDL cholesterol, triglyceride, total cholesterol, vitamin D, uric acid, white blood cell (WBC), neutrophil, hemoglobin (Hb), and platelet counts). KMW was the lowest in the peri-implantitis group. Compared with the other groups, the peri-implantitis group showed significantly higher levels of triglyceride, uric acid, and WBC. The peri-implantitis group had the lowest level of vitamin D. Triglyceride and uric acid levels had positive correlations with peri-implant clinical parameters. High levels of triglyceride and uric acid may pose a risk for both peri-implant diseases and cardiovascular diseases. Prior to dental implant surgery, patients' serum biochemical parameters should be checked.


Two-dimensional gel electrophoresis pattern (pH 6-11) and identification of water-soluble barley seed and malt proteins by mass spectrometry.
A protocol was established for two-dimensional gel electrophoresis (2-DE) of barley seed and malt proteins in the pH range of 6-11. Proteins extracted from flour in a low-salt buffer were focused after cup-loading onto IPG strips. Successful separation in the second dimension was achieved using gradient gels in a horizontal SDS-PAGE system. Silver staining of gels visualized around 380 (seed) and 500 (malt) spots. Thirty-seven different proteins from seeds were identified in 60 spots, among these 46 were visualized also in the malt 2-D pattern. Proteins were identified by peptide mass fingerprinting and by tandem MS sequencing after in-gel digestion by trypsin. In addition, the N-terminal sequence of 10 different proteins from 11 spots was determined after electroblotting to a polyvinylidene difluoride (PVDF) membrane. Five identified proteins (in 9 spots) are involved in glycolysis, 12 in defence against pathogens (21 spots), 4 in storage, folding, and synthesis of proteins, and in nitrogen metabolism (5 spots), 6 in carbohydrate metabolism (11 spots), and 4 in stress and detoxification (9 spots). Six proteins (7 spots) were not grouped in these categories, and 3 were not ascribed a function. The presented 2-D patterns and identifications will be used to describe proteome differences between cultivars and changes during malting.


Neural correlates of feigned memory impairment are distinguishable from answering randomly and answering incorrectly: an fMRI and behavioral study.
Previous functional magnetic resonance imaging (fMRI) studies have identified activation in the prefrontal-parietal-sub-cortical circuit during feigned memory impairment when comparing with truthful telling. Here, we used fMRI to determine whether neural activity can differentiate between answering correctly, answering randomly, answering incorrectly, and feigned memory impairment. In this study, 12 healthy subjects underwent block-design fMRI while they performed digit task of forced-choice format under four conditions: answering correctly, answering randomly, answering incorrectly, and simulated feigned memory impairment. There were three main results. First, six areas, including the left prefrontal cortex, the left superior temporal lobe, the right postcentral gyrus, the right superior parietal cortex, the right superior occipital cortex, and the right putamen, were significantly modulated by condition type. Second, for some areas, including the right superior parietal cortex, the right postcentral gyrus, the right superior occipital cortex, and the right putamen, brain activity was significantly greater in feigned memory impairment than answering randomly. Third, for the areas including the left prefrontal cortex and the right putamen, brain activity was significantly greater in feigned memory impairment than answering incorrectly. In contrast, for the left superior temporal lobe, brain activity was significantly greater in answering incorrectly than feigned memory impairment. The results suggest that neural correlates of feigned memory impairment are distinguishable from answering randomly and answering incorrectly in healthy subjects.


Progression of diabetic macular edema: correlation with blood retinal barrier permeability, retinal thickness, and retinal vessel diameter.
To study the progression of diabetic macular edema (DME) in relation to baseline retinal thickness, retinal vascular leakage, and retinal trunk vessel diameters. In this single-center study, 45 patients were enrolled with 62 eligible eyes defined as having DME of a grade less than clinically significant macular edema (CSME). From the start, the patients were included in a multicenter study exploring the effect of ruboxistaurin versus placebo for 3.4 years. Subsequently, the patients were followed up for a mean of 5.7 years by optical coherence tomography, fundus photography, and vitreous fluorometry. Baseline values in eyes that progressed to photocoagulation treatment were compared with values from eyes that did not reach this endpoint. In the 22 eyes of 18 patients in which CSME was diagnosed and treated, mean retinal vascular leakage at baseline was 5.6 (95% CI 4.2-7.6) nm/s, whereas eyes that did not progress to photocoagulation had a significantly lower mean leakage at baseline of 3.4 (95% CI 2.7-4.3) nm/s. No significant difference was found for measures of baseline retinal thickness or summarized retinal trunk vessel diameters. Eyes that progressed to photocoagulation treatment (mean delay to treatment, 3.6 years) had significantly higher foveal thicknesses than did nonprogressing eyes, from 18 months after study initiation. Progression to photocoagulation treatment for CSME was associated with higher retinal vascular leakage at baseline, whereas baseline retinal vessel diameters and retinal thickness were comparable in progressing and nonprogressing eyes. Baseline leakage was the strongest predictor of progression from non-CSME to photocoagulation for CSME.


Analysis of tetracycline residues in bovine milk by CE-MS with field-amplified sample stacking.
A rapid, sensitive, and robust CE-MS method has been developed for the determination of tetracycline, oxytetracycline, and chlortetracycline in milk. Field-amplified sample stacking with electromigration injection (FASS-EMI) was used for the online concentration of tetracyclines. The conditions of separation, MS detection, and stacking were systematically optimized. The optimum buffer composition was 35 mM Tris, 1.1% formic acid, 5% methanol, and 15% ACN. By using the online concentration method of field-enhanced sample stacking (FESI)-EMI stacking, the sensitivity was increased six- to seven-fold. The RSDs (n=6) of the relative migration time of tetracyclines were 1.1-1.4% for intraday and 2.4-2.9% for interday. The RSDs (n=6) of the relative peak area of tetracyclines were 3.2-4.6% for intraday and 4.7-6.1% for interday. The LODs (S/N=3) were 7.14 ng/mL for tetracycline, 11.4 ng/mL for oxytetracycline, and 14.9 ng/mL for chlortetracycline. The method has been successfully used to analyze tetracyclines residues in bovine milk.


Evaluation of impotence. Monitoring periodic penile erections during sleep.
The monitoring of periodic penile erections during sleep has helped alter the understanding and treatment of impotent patients. The reasons why this has occurred, the procedures used in monitoring sleep erections, and the validation of the procedures are reviewed.


HIV/AIDS, declining family resources and the community safety net.
Families play central roles in the HIV/AIDS pandemic, caring for both orphaned children and the ill. This extra caregiving depletes two family resources essential for supporting children: time and money. We use recent data from published studies in sub-Saharan Africa to illustrate deficits and document community responses. In Botswana, parents caring for the chronically ill had less time for their preschool children (74 versus 96 hours per month) and were almost twice as likely to leave children home alone (53% versus 27%); these children experienced greater health and academic problems. Caregiving often prevented adults from working full time or earning their previous level of income; 47% of orphan caregivers and 64% of HIV/AIDS caregivers reported financial difficulties due to caregiving. Communities can play an important role in helping families provide adequate childcare and financial support. Unfortunately, while communities commonly offer informal assistance, the value of such support is not adequate to match the magnitude of need: 75% of children's families in Malawi received assistance from their social network, but averaging only US$81 annually. We suggest communities can strengthen the capacity of families by implementing affordable quality childcare for 0-6 year olds, after-school programming for older children and youth, supportive care for ill children and parents, microlending to enhance earnings, training to increase access to quality jobs, decent working conditions, social insurance for the informal sector, and income and food transfers when families are unable to make ends meet.


Aflatoxin M1 in yoghurts in Portugal.
Aflatoxin M1 (AFM1) may occur in milk and milk products, resulting from the ingestion of aflatoxin B1 in feedstuffs by dairy cow. Ninety-six samples of commercial yoghurts (48 natural yoghurts and 48 yoghurt with pieces of strawberries) that are produced in Portugal were analyzed for the presence of AFM1 by immunoaffinity column extraction and high-performance liquid chromatography (HPLC). The limit of detection was 10 ng/kg. The recoveries of AFM1 from the samples spiked at levels of 10.0, 50.0, 100.0 and 150.0 ng/kg were 88.0%, 91.0%, 93.0% and 99.0%, respectively. AFM1 was detected in 18 (18.8%) of yogurt samples ranging from 19 to 98 ng/kg, and 78 samples (81.2%) did not reveal the presence of the toxin. Of the 48 natural yoghurts tested, only two (4.2%) were contaminated with 43 and 45 ng/kg of AFM1. Of the 48 yoghurts with pieces of strawberries tested, 16 samples (33.3%) contained levels ranging from 19 to 98 ng/kg; six samples (12.5%) were contaminated with low levels ranging from 19 to 35 ng/kg; four samples (8.3%) were contaminated with levels ranging from 36 to 50 ng/kg, two samples (4.2%) with levels of 51 and 65 ng/kg and four samples (8.3%) presented high contamination levels, from 90 to 98 ng/kg. This paper reports the data of the first survey on the presence of AFM1 in yoghurt in Portugal.


[Allergology and public health].
The authors are reviewing epidemiologic data about the link between the increasing prevalence of allergic diseases and recent changes in way of life all around the world: urbanization, new modes of dwelling, new vegetations, change in environment, parasitosis and infections.


The effects of prolonged single night session of videogaming on sleep and declarative memory.
Use of electronic media is widespread among adolescents. Many male adolescents spend a major part of their evenings playing video games. The increased exposure to artificial light as well as the exciting nature of this pastime is under suspicion to impair sleep. Sleep is considered to be important for memory consolidation, so there is also a potential risk for memory impairment due to video gaming. As learning and gaining knowledge is a very important part of adolescence, we decided to study the effects of prolonged video gaming on sleep and memory. The study was structured in a repeated measures design. Eighteen male participants played either the violent video game "Counter Strike: Global Offensive" or the board game "Monopoly" for five hours each on two Saturday nights. The game evenings were followed by sleep studies. Memory testing and vigilance evaluation was performed the next morning. During the course of the study, saliva samples were taken to determine melatonin and cortisol levels. The results of this crossover study showed slightly reduced sleep efficiency after "Counter Strike: Global Offensive" (-3.5%, p = .017) and impaired declarative memory recall (p = .005) compared to "Monopoly". Melatonin levels at bedtime were lower after "Counter Strike: Global Offensive" (p = .005), cortisol levels were elevated while playing the video game (p = .031). Negative effects on sleep were not strong but consistent with more wake after sleep onset (+12 min) and a higher arousal index after "Counter Strike: Global Offensive". We conclude that excessive video gaming in the evening can contribute to worsened sleep and impaired memory in male adolescents.


Establishment and characterization of cell lines from human adenovirus type 12-induced murine tumors producing endogenous virus particles.
Two cell lines designated IC-KMS and D-KMS were established from human adenovirus type 12-induced tumors of C3Hf/OK mouse. The cell lines retained the characteristics of the original tumor i.e., production of numerous C-type and intracisternal A-type particles, integration of Ad12 E1 region DNA and amplification of the myc gene family. Chromosomal analysis revealed chromosome aberrations in both IC-KMS and D-KMS cells. The modal chromosome number of IC-KMS cells was 54 and that of D-KMS cells was 48. Metacentric chromosomes and minichromosomes were found. Trisomy of chromosome 3, 7 and 12 was seen frequently in D-KMS cells. Although DNA aneuploidy was revealed by flow cytometry, the DNA indices of these cells showed no relation to the copy number of integrated Ad12 DNA. These cells have been propagated by serial culture during the past 17 months. Production of endogenous virus particles is a unique characteristic of IC-KMS and D-KMS cells. These cell lines would be useful materials for examining the contribution of Ad12 carcinogenesis to activation of endogenous virus particles, and also the correlation between Ad12 carcinogenesis and cancer-related genes.


Controllability, antiproliferative activity, Ag+ release, and flow behavior of silver nanoparticles deposited onto cellulose nanocrystals.
Silver nanoparticles (AgNPs)/carboxylated cellulose nanocrystals (Ag-cCNC) from Eucalyptus pulp were prepared using a three-step process. The cCNC were synthesized by oxidation of CNC from Eucalyptus pulp with ammonium persulfate, followed by a hydrothermal reaction to form Ag-cCNC. The Ag-cCNC was then characterized with respect to Ag+ release, flow behavior, and anticancer activity for potential applications in biomedicine and drug delivery. AgNPs with particle sizes in the range of 16.25 ± 7.83 to 21.84 ± 7.21 nm were uniformly embedded on the surface of the cCNC. The Ag-cCNC exhibited a slow and controllable release of Ag+ at a rate of 0.02 % per day for 28 days. Ag+ release was best described by the Korsmeyer-Peppas model based on non-Fickian diffusion. The Ag-cCNC at 200 μg/mL exerted antiproliferative activity in MCF-7 human breast cancer cells with 1.01 % ± 0.35 % cell viability and was non-toxic against normal Vero cells with 90 % viability. In contrast, the chemotherapeutic drug melphalan exhibited cytotoxic effects against both MCF-7 and Vero cells. The Ag-cCNC samples showed shear thinning properties with a pseudoplastic fluid behavior, indicating that Ag-cCNCs are suitable for drug delivery by injection.


Exploring and reducing stress in young restaurant workers: results of a randomized field trial.
Young adult restaurant workers face the dual stressors of work adjustment and managing personal responsibilities. We assessed a new psychosocial/health promotion training designed to reduce these stressors in the context of restaurant work. DESIGN . A cluster-randomized trial of a training program, with surveys administered approximately 2 weeks before training and both 6 and 12 months after training. A national restaurant chain. A total of 947 restaurant workers in 28 restaurants. Personal stress, exposure to problem coworkers, and personal and job characteristics. Team Resilience (TR) is an interactive program for stress management, teamwork, and work-life balance. TR focuses on "five Cs" of resilience: compassion, commitment, centering, community, and confidence. ANALYSIS . Mixed-model (multilevel) analysis of covariances. Compared with workers in control stores, workers in TR-trained stores showed significant reductions over time in exposure to problem coworkers (F[2, 80.60] = 4.48; p = .01) and in personal stress (F[2, 75.28] = 6.12; p = .003). The TR program may help young workers who face the challenges of emerging adulthood and work-life balance.


Intermediate-term prognostic value of reversible perfusion deficit diagnosed by adenosine CMR: a prospective follow-up study in a consecutive patient population.
The aim of this study was to assess the hypothesis that cardiac magnetic resonance (CMR) myocardial perfusion imaging can provide incremental prognostic value over other risk factors regarding the prediction of major cardiovascular events in a large, consecutive, and thereby unselected population of patients presenting with stable angina pectoris. Recently, it has been shown that CMR provides good short-term prognosis in patients with stable coronary heart disease. Reversible myocardial ischemia can be assessed using a combination of perfusion and late gadolinium enhancement imaging. Data concerning intermediate-term prognostic information, especially on major clinical endpoints such as cardiac death or myocardial infarction, are limited. From 2003 to 2007, consecutive patients with stable angina pectoris who underwent adenosine perfusion CMR were enrolled unless they met the predefined exclusion criteria. Myocardial perfusion imaging by adenosine stress and late gadolinium enhancement was assessed using a 1.5-T whole-body CMR scanner. Follow-up information concerning the combined endpoint of cardiac death, nonfatal myocardial infarction, and stroke was obtained from patients, general practitioners, or treating hospitals, respectively. In our study, 1,229 consecutive patients were enrolled. The mean follow-up period was 4.2 ± 2.1 years. During this time, 88 primary endpoints occurred. In patients with reversible perfusion deficits, significantly more cardiac deaths (p < 0.0001) and nonfatal myocardial infarctions (p = 0.001) were observed than in the control group. On multivariate analysis, reversible perfusion deficit was the strongest independent predictor for an event, with a 3-fold increased risk. Moreover, the absence of a perfusion deficit was shown to exhibit high negative predictive value. Adenosine perfusion CMR provides excellent risk stratification and intermediate-term prognostic value in patients with stable coronary artery disease. The presence of a myocardial perfusion deficit is an incremental prognostic risk factor over other risk factors.


[The long-term monotherapy with preparations from the 4 basic groups of antihypertensive agents of patients with mild and moderate arterial hypertension. The Multicenter Captopril and the Quality of Life Study. The working group of the Multicenter Captopril and the Quality of Life Study].
A multicenter randomized controlled trial was performed to compare antihypertensive effects and tolerance of captopril monotherapy with those of reference drugs from three other main groups of antihypertensive drugs: propranolol, hydrochlorothiazide, nifedipine. The trial included 345 males with essential hypertension stage I-II by WHO criteria. Evaluable patients after 8 months of treatment comprised 85.8%. 8-month monotherapy with captopril, nifedipine, hydrochlorothiazide and propranolol was completed by 53.49%, 75.28%, 45.78% of patients, respectively. An antihypertensive effect was reached in 57.97% of patients on monotherapy. Normalization of arterial pressure took place in 51.3%. The 4 drugs in the given doses produced a significant and similar effect in relation to the action on arterial pressure (absolute value). As for individual effects (complete and partial), captopril and propranolol were equal, nifedipine was more beneficial than hydrochlorothiazide. Side effects in captopril monotherapy arose 1.5-2 times less frequently than in response to propranolol or nifedipine and were similar to those of hydrochlorothiazide.


Anatomic viral detection is automated: the application of a robotic molecular pathology system for the detection of DNA viruses in anatomic pathology substrates, using immunocytochemical and nucleic acid hybridization techniques.
This paper presents the first automated system for simultaneously detecting human papilloma, herpes simplex, adenovirus, or cytomegalovirus viral antigens and gene sequences in standard formalin-fixed, paraffin-embedded tissue substrates and tissue culture. These viruses can be detected by colorimetric in situ nucleic acid hybridization, using biotinylated DNA probes, or by indirect immunoperoxidase techniques, using polyclonal or monoclonal antibodies, in a 2.0-hour assay performed at a single automated robotic workstation.


Expanding horizons in complement drug discovery: challenges and emerging strategies.
The complement system is best known for its role in innate immunity, providing a first line of defence against infection, maintaining tissue homeostasis by flagging apoptotic cells and debris for removal, and orchestrating crosstalk between adaptive and innate immunity. In a growing number of diseases, complement is known to drive pathogenesis or to contribute as an inflammatory amplifier of a disease trigger. Association of complement with common and devastating diseases has driven an upsurge in complement drug discovery, but despite a wealth of knowledge in the complexities of the cascade, and many decades of effort, very few drugs have progressed to late-stage clinical studies. The reasons for this are becoming clear with difficulties including high target concentration and turnover, lack of clarity around disease mechanism and unwanted side effects. Lessons learnt from drugs which are either approved, or are currently in late-stage development, or have failed and dropped off the drug development landscape, have been invaluable to drive a new generation of innovative drugs which are progressing through clinical development. In this review, the challenges associated with complement drug discovery are discussed and the current drug development landscape is reviewed. The latest approaches to improve drug characteristics are explored and those agents which employ these technologies to improve accessibility to patients are highlighted.


Molecular Docking and Interaction Studies of Identified Abscisic Acid Receptors in Oryza sativa: An In-Silico Perspective on Comprehending Stress Tolerance Mechanisms.
Abiotic stresses affect plants in several ways and as such, phytohormones such as abscisic acid (ABA) play an important role in conferring tolerance towards these stresses. Hence, to comprehend the role of ABA and its interaction with receptors of the plants, a thorough investigation is essential. The current study aimed to identify the ABA receptors in Oryza sativa, to find the receptor that binds best with ABA and to examine the mutations present to help predict better binding of the receptors with ABA. Protein sequences of twelve PYL (Pyrabactin resistance 1) and seven PP2C (type 2C protein phosphatase) receptors were retrieved from the Rice Annotation Project database and their 3D structures were predicted using RaptorX. Protein-ligand molecular docking studies between PYL and ABA were performed using AutoDock 1.5.6, followed by 100ns molecular dynamic simulation studies using Desmond to determine the acceptable conformational changes after docking via root mean square deviation RMSD plot analysis. Protein-protein docking was then carried out in three sets: PYL-PP2Cs, PYL-ABA-PP2C and PYL(mut)-ABA-PP2C to scrutinize changes in structural conformations and binding energies between complexes. The amino acids of interest were mapped at their respective genomic coordinates using SNP-seek database to ascertain if there were any naturally occurring single nucleotide polymorphisms (SNPs) responsible for triggering rice PYLs mutations. Initial protein-ligand docking studies revealed good binding between the complexes, wherein PYL6-ABA complex showed the best energy of -8.15 kcal/mol. The 100ns simulation studies revealed changes in the RMSD values after docking, indicating acceptable conformational changes. Furthermore, mutagenesis study performed at specific PYL-ABA interacting residues followed by downstream PYL(mut)-ABA-PP2C protein-protein docking results after induction of mutations demonstrated binding energy of -8.17 kcal/mol for PP2C79-PYL11-ABA complex. No naturally occurring SNPs that were responsible for triggering rice PYL mutations were identified when specific amino acid coordinates were mapped at respective genomic coordinates. Thus, the present study provides valuable insights on the interactions of ABA receptors in rice and induced mutations in PYL11 that can enhance the downstream interaction with PP2C.


A diffusion strategy for robust distributed estimation based on streaming graph signals.
The problem of robust distributed estimation over dynamic and streaming graph signals is investigated in this paper. Existing works related to distributed estimation over dynamic and streaming graph signals are mainly derived from the Mean-Square-Error criterion, and they are vulnerable to non-Gaussian noise. Therefore, a new kind of diffusion Mixture correntropy (d-MC) algorithm is developed to deal with the disadvantage in this paper. Incorporating the diffusion strategy and a novel cost function, the proposed algorithm could accurately estimate the graph filter parameter with the dynamic and streaming graph signals, and achieve desirable performance under both Gaussian and impulsive noise environment. Besides, the theoretical analysis results of mean and mean-square stability are derived. Simulations on various case studies indicate the desirable performance of proposed d-MC algorithm by comparing it to other benchmarks.


A simple reproducible method of preventing lobar torsion.
Torsion of remaining lobes after pulmonary resection is a potentially serious complication with high reported morbidity and mortality. A range of additional procedures has been described, we have used a simple, effective, quick and easy to reproduce minor procedure to prevents torsion.


Phosphatidylinositol phosphate 5-kinase Ibeta recruits AP-2 to the plasma membrane and regulates rates of constitutive endocytosis.
Overexpression of phosphatidylinositol phosphate 5-kinase (PIP5KI) isoforms alpha, beta, or gamma in CV-1 cells increased phosphatidylinositol 4,5-bisphosphate (PIP2) levels by 35, 180, and 0%, respectively. Endocytosis of transferrin receptors, association of AP-2 proteins with membranes, and the number of clathrin-coated pits at the plasma membrane increased when PIP2 increased. When expression of PIP5KIbeta was inhibited with small interference RNA in HeLa cells, expression of PIP5KIalpha was also reduced slightly, but PIP5KIgamma expression was increased. PIP2 levels and internalization of transferrin receptors dropped 50% in these cells; thus, PIP5KIgamma could not compensate for loss of PIP5KIbeta. When expression of PIP5KIalpha was reduced, expression of both PIP5KIbeta and PIP5KIgamma increased and PIP2 levels did not change. A similar increase of PIP5KIalpha and PIP5KIbeta occurred when PIP5KIgamma was inhibited. These results indicate that constitutive endocytosis in CV-1 and HeLa cells requires (and may be regulated by) PIP2 produced primarily by PIP5KIbeta.


An enzyme-linked lectin-binding assay on cells (CELLBA) for the comparison of lectin receptor expression on cell surfaces.
Lectins can be used to specifically detect some cell surface glycans. Their expression on different cells or on cells of a given lineage throughout differentiation or following treatment with drugs can be compared using lectins labelled with radioactive, fluorescent or enzymatic probes. We describe a new method which, by analogy with CELISA (ELISA on cells), is called CELLBA (or ELLBA on cells) for cellular, enzyme-linked lectin-binding assay. It permits the comparison of the expression of specific glycans in a large number of different cell samples. As an example, it was able to detect alterations of cell surface glycan expression caused by inhibitors of N-linked oligosaccharide trimming.


The use of in vitro diagnostic kits in hospital laboratories in Canada.
1. A survey conducted among hospital laboratories has yielded data from 640 institutions concerning the use of diagnostic kits and reagents in Canada. 2. Kits designed to test for chemical constituents were most frequently used in hospitals of 51 to 600 bed capacity whereas the ones for enzymes were most extensively used in 201 to 700 bed-size institutions. Kits based on the CPB principles were generally used in hospitals of more than 200 beds whereas those based on RIA were only in frequent use where the bed capacity was 351 or more. 3. The following tests were most often performed by kits: aminotransferases, amylase, urea, LDH, phosphatases, glucose, CPK, bilirubin, calcium, uric acid, T-4, T-3, digoxin and vitamin B12. 4. The survey reflects a continuing and increasing usage of in vitro diagnostic kits and associated blood analyzer systems. It also indicates a significant adoption of assay kits which utilize RIA and CPB principles.


CNN-based ranking for biomedical entity normalization.
Most state-of-the-art biomedical entity normalization systems, such as rule-based systems, merely rely on morphological information of entity mentions, but rarely consider their semantic information. In this paper, we introduce a novel convolutional neural network (CNN) architecture that regards biomedical entity normalization as a ranking problem and benefits from semantic information of biomedical entities. The CNN-based ranking method first generates candidates using handcrafted rules, and then ranks the candidates according to their semantic information modeled by CNN as well as their morphological information. Experiments on two benchmark datasets for biomedical entity normalization show that our proposed CNN-based ranking method outperforms traditional rule-based method with state-of-the-art performance. We propose a CNN architecture that regards biomedical entity normalization as a ranking problem. Comparison results show that semantic information is beneficial to biomedical entity normalization and can be well combined with morphological information in our CNN architecture for further improvement.


A Systematic Survey of Reversibly Covalent Dipeptidyl Inhibitors of the SARS-CoV-2 Main Protease.
SARS-CoV-2, the COVID-19 pathogen, relies on its main protease (MPro) for replication and pathogenesis. MPro is a demonstrated target for the development of antivirals for SARS-CoV-2. Past studies have systematically explored tripeptidyl inhibitors such as nirmatrelvir as MPro inhibitors. However, dipeptidyl inhibitors especially those with a spiro residue at their P2 position have not been systematically investigated. In this work, we synthesized about 30 dipeptidyl MPro inhibitors and characterized them on enzymatic inhibition potency, structures of their complexes with MPro, cellular MPro inhibition potency, antiviral potency, cytotoxicity, and in vitro metabolic stability. Our results indicated that MPro has a flexible S2 pocket to accommodate inhibitors with a large P2 residue and revealed that dipeptidyl inhibitors with a large P2 spiro residue such as (S)-2-azaspiro [4,4]nonane-3-carboxylate and (S)-2-azaspiro[4,5]decane-3-carboxylate have favorable characteristics. One compound, MPI60, containing a P2 (S)-2-azaspiro[4,4]nonane-3-carboxylate displayed high antiviral potency, low cellular cytotoxicity, and high in vitro metabolic stability.


Unaltered dopamine transporter availability in adult attention deficit hyperactivity disorder.
The authors examined whether patients with attention deficit hyperactivity disorder (ADHD) have altered striatal dopamine transporter levels, which may explain psychostimulant effects in this disorder. Single photon emission computed tomography and [(123)I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT) were used to assess dopamine transporter availability in nine adult patients with ADHD (eight of whom were stimulant naive) and nine age- and gender-matched healthy comparison subjects. Striatal [(123)I]beta-CIT binding did not differ significantly between the ADHD and comparison subjects. The findings suggest that a hypothesized dysregulation of dopamine function in ADHD does not entail altered dopamine transporter levels.


Early loss of fixation after surgical treatment of distal radius fractures: Does the number of screws matter?
Fixation methods in distal radius fractures has been studied biomechanically, but studies evaluating clinical correlation of that data are lacking. We hypothesize that the use of unthreaded pegs and decreased screw number would correlate with an early failure of fixation. There were 50 operatively treated distal radius fractures with initial post-operative radiographs that demonstrated loss of fixation. An age, BMI, and fracture-type matched cohort of 50 non-failed distal radius fractures was used for comparison. The average number of distal screws in the failed fixation group was 5.3 compared to 4.8 in the group with no loss of fixation (p = 0.07). The average number of proximal shaft screws used in the failed fixation group was 3.2 compared to 3.2 in the control group (p = 0.60). There was no difference between the use of pegs in either group. There was a significant difference between distal screw number between constructs that failed from distal screw pullout as compared to the control group, 5.6 vs. 4.8 (p = 0.0001). In conclusion, there was no difference in the number of proximal screws used in distal radius fractures that demonstrated loss of early fixation. Additionally, having more than five screws in the distal fragment had a higher rate of failure from distal screw pullout, however this was likely confounded by the more severe intra-articular fractures that had additional fixation applied in an attempt to increase stability. Finally, using smooth pegs or screws in the distal fragment made no difference in loss of fixation.


New insights into the effect of fermentation temperature and duration on catechins conversion and formation of tea pigments and theasinensins in black tea.
The phenol oxidative pathway during fermentation remains unclear. To elucidate the effect of fermentation on phenol conversion, we investigated the effects of fermentation temperature and duration on the conversion of catechins and the formation of theasinensins (TSs), theaflavins (TFs), thearubigins (TRs), and theabrownins (TBs). During fermentation, TSs formation increased initially and then decreased. Long fermentation durations were unfavorable for liquor brightness (LB) and resulted in the production of large amounts of TRs and TBs. Low fermentation temperatures (20 °C and 25 °C) favored the maintenance of polyphenol oxidase activity and the continuous formation of TFs, TSs, and TRSI (a TRs fraction), resulting in better LB and liquor color. Higher temperatures (30 °C, 35 °C, and 40 °C) resulted in higher peroxidase activity, higher oxidative depletion rates of catechins, and excessive production of TRSII (a TRs fraction) and TBs. Analysis of the conversion pathway of polyphenolic compounds during fermentation showed that, during early fermentation, large amounts of catechins were oxidized and converted to TFs and theasinensin B. As fermentation progressed, considerable amounts of theaflavin-3'-gallate, theasinensin A, theaflavin-3-gallate, theaflavin-3,3'-digallate, and theasinensin C were produced and then converted to TRSI; in the final stage, TRSII and TBs were converted continuously. Different fermentation temperature and duration combinations directly affected the type and composition of phenolic compounds. The key conditions for controlling phenolic compound conversion and fermentation direction were 60 or 90 min and 25 or 30 °C. Our study provides insights into the regulation of phenolic compound conversion during black tea fermentation. © 2021 Society of Chemical Industry.


Use of adhesive tissue for repair in experimental vesico-vaginal fistulas in dogs.
Experimental vesico-vaginal fistulas were successfully treated using the transvaginal approach and strengthening the bladder sutures with adhesive tissue. Despite inflammation of the surrounding tissues good results were obtained, without cystotomy, permanent catheterization and antibiotics.


Quantitative structure-toxicity relationship models for predication of toxicity of ionic liquids toward leukemia rat cell line IPC-81 based on index of ideality of correlation.
The application of ionic liquids (ILs) as green solvents has attracted the attention of the scientific community. However, ILs may play the role of toxins. Even though ionic liquids may assist to minimize air pollution, but their discharge into aquatic ecosystems might result in significant water pollution due to their potential toxicity and inaccessibility to biodegradation. Recently, more attention has been paid to the toxicity of ILs on plants, bacteria, and humans. Here, a quantitative structure-toxicity relationship study (QSTR) based on the Monte Carlo method of CORAL software has been applied to estimate the logarithm of the half-maximal effective concentration of toxicity of ILs against leukemia rat cell line IPC-81 (logEC50). A hybrid optimal descriptor is used to build QSTR models for a large set of 304 diverse ILs including ammonium, imidazolium, morpholinium, phosphonium, piperidinium, pyridinium, pyrrolidinium, quinolinium, sulfonium, and protic ILs. The SMILES notations of ILs are utilized to compute the descriptor correlation weight (DCW). Four splits are made from the whole dataset and each split is randomly divided into four sets (training subsets and validation set). The index of ideality of correlation (IIC) is applied to evaluate the authenticity and robustness of the QSTR models. A QSTR model with statistical parameters R2 = 0.85, CCC = 0.92, Q2 = 0.84, and MAE = 0.25 for the validation set of the best split is considered as a prime model. The outliers and promoters of increase/decrease of logEC50 are extracted and the mechanistic interpretation of effective descriptors for the model is also offered.HighlightsGlobal SMILES-based QSAR model was developed to predict the toxicity of ILs.The CORAL software is used to model the ILs toxicity on IPC-81 leukemia rat cell line.IIC is tested as a criterion of predictive potential.The toxicological effects of ILs are discussed based on the proposed model.