IDH2, a novel target of OGT, facilitates glucose uptake and cellular bioenergy production via NF-κB signaling to promote colorectal cancer progression.
Although isocitrate dehydrogenase 2 (IDH2) mutations have been the hotspots in recent anticancer studies, the impact of wild-type IDH2 on cancer cell growth and metabolic alterations is still elusive. IDH2 expression in CRC tissues was evaluated by immunohistochemistry, and the correlation between the expression level and the patient's survival rate was analyzed. Cell functional assays included CCK8 and colony formation for cell proliferation in vitro and ectopic xenograft as in vivo experimental model for tumor progression. A targeted metabolomic procedure was performed by liquid chromatography/tandem mass spectrometry to profile the metabolites from glycolysis and tricarboxylic acid (TCA) cycle. Mitochondrial function was assessed by measuring cellular oxygen consumption (OCR) and mitochondrial membrane potential (ΔΨ). Confocal microscope analysis and Western blotting were applied to detect the expression of GLUT1 and NF-κB signaling. O-GlcNAcylation and the interaction of IDH2 with OGT were confirmed by co-immunoprecipitation, followed by Western blotting analysis. IDH2 protein was highly expressed in CRC tissues, and correlated with poor survival of CRC patients. Wild-type IDH2 promoted CRC cell growth in vitro and tumor progression in xenograft mice. Overexpression of wild-type IDH2 significantly increased glycolysis and TCA cycle metabolites, the ratios of NADH/NAD+ and ATP/ADP, OCR and mitochondrial membrane potential (ΔΨ) in CRC cells. Furthermore, α-KG activated NF-κB signaling to promote glucose uptake by upregulating GLUT1. Interesting, O-GlcNAcylation enhanced the protein half-time of IDH2 by inhibiting ubiquitin-mediated proteasome degradation. The O-GlcNAc transferase (OGT)-IDH2 axis promoted CRC progression. Wild-type IDH2 reprogrammed glucose metabolism and bioenergetic production via the NF-κB signaling pathway to promote CRC development and progression. O-GlcNAcylation of IDH2 elevated the stability of IDH2 protein. And the axis of OGT-IDH2 played an essential promotive role in tumor progression, suggesting a novel potential therapeutic strategy in CRC treatment.


Simple drop cast method for enumeration of bacteriophages.
Phage enumeration is a basic prerequisite for application of phages in industrial, medical and other processes. Double layer agar (DLA) plaque assay is the classical method employed for isolation, detection as well as enumeration of phage particles in a solution. However, DLA method is considered cumbersome due to its specific temperature requirements and need for one petriplate with two agar layers for each phage sample. We are proposing a drop cast method for enumeration of phages which is comparatively easier and cost effective than classical DLA method as single layer of agar without any specific temperature condition is required. Added advantage of this method is that 7-10 dilutions of phage suspension can be enumerated on a single agar plate in contrast to one dilution per plate as required in DLA method. Although standard deviation in phage count was higher in the proposed method than DLA method, still drop cast method provided first-approximation phage titer which can be further validated by DLA method for more accuracy. Hence, the present method can be considered reliable, easy and cost effective for determining approximate phage count in an unknown phage suspension.


Acute serotonin 2A receptor activation impairs behavioral flexibility in mice.
Serotonin 2A (5-HT2A) receptors are the primary site of action of hallucinogenic drugs and the target of atypical antipsychotics. 5-HT2A receptors are also implicated in executive function, including behavioral flexibility. Previous studies showed that 5-HT2A receptor blockade improved behavioral flexibility in rodent models related to autism spectrum disorder and schizophrenia. The current study instead was conducted to examine the impact of acute 5-HT2A receptor activation on behavior flexibility in the control C57BL/6 J strain. Because of the therapeutic potential of serotonergic hallucinogens and the unknown impact of many of these compounds on cognition, the present study examined how the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the more selective 5-HT2A agonist 25CN-NBOH impacted behavioral flexibility in C57BL/6 J mice. Male mice were tested on a probabilistic spatial discrimination and reversal learning task after an intraperitoneal injection of vehicle, 2.5 mg/kg DOI, 1.0 mg/kg 25CN-NBOH, 1.0 mg/kg of the 5-HT2C receptor antagonist SER-082 or combined treatment with SER-082 (1.0 mg/kg) and 2.5 mg/kg DOI before testing of probabilistic reversal learning. All groups demonstrated comparable performance on the initial spatial discrimination, i.e. similar trials to criterion. DOI alone did not impair reversal learning, whereas 25CN-NBOH increased the number of trials to criterion during reversal learning. Because 5-HT2A and 5-HT2C receptors have been shown to functionally antagonize each other in several behavioral paradigms, we also tested whether blockade of 5-HT2C receptors would unmask 5-HT2A receptor activation by DOI and impair reversal learning. Mice treated with SER-082 in combination with DOI required significantly more trials to reach criterion. In an additional experiment, a dose response experiment with 25CN-NBOH revealed that the 1.0 mg/kg dose tested in reversal learning did not affect locomotor activity. Together, these findings indicate that activation of 5-HT2A receptors impairs probabilistic reversal learning and that 5-HT2A and 5-HT2C receptors exert opposing effects on behavioral flexibility in male mice.


The S4 voltage sensor packs against the pore domain in the KAT1 voltage-gated potassium channel.
In voltage-gated ion channels, the S4 transmembrane segment responds to changes in membrane potential and controls channel opening. The local environment of S4 is still unknown, even regarding the basic question as to whether S4 is close to the pore domain. Relying on the ability of functional KAT1 channels to rescue potassium (K+) transport-deficient yeast, we have performed an unbiased mutagenesis screen aimed at determining whether S4 packs against S5 of the pore domain. Starting with semilethal mutations of surface-exposed S5 residues of the KAT1 pore domain, we have screened randomly mutagenized libraries of S4 or S1-S3 for second-site suppressors. Our study identifies two S4 residues that interact in a highly specific manner with two S5 residues in the middle of the membrane-spanning regions, supporting a model in which the S4 voltage sensor packs against the pore domain in the hyperpolarized, or "down," state of S4.


Chronic obstructive pulmonary disease as a risk factor for ventricular arrhythmias independent of left ventricular function.
The association between chronic obstructive pulmonary disease (COPD) and sudden cardiac death has not been fully elucidated. The purpose of this study was to investigate whether decreased left ventricular ejection fraction (LVEF) can explain the increased rate of ventricular tachycardia (VT) in COPD. This retrospective study included consecutive adult patients who underwent pulmonary function testing (PFT), Holter monitoring, and transthoracic echocardiography. COPD was correlated with the frequency of VT in a multivariate analysis that adjusted for known confounders including LVEF. Long-term all-cause mortality of patients with COPD and VT was examined. Of the 6351 patients included in this study (age 66 ± 15 years; 48% woman; 92% Caucasian, LVEF 59% ± 12%), 2800 (44%) had PFT indicative of COPD. VT was nearly twice as likely to occur during Holter monitoring in COPD patients (13% vs 23%; P <.001), and the severity of COPD correlated with the risk of VT (21% vs 28% vs 37% for mild-moderate, severe, and very severe COPD; P <.001). COPD and VT remained independently associated (P <.001) even after adjusting for LVEF, demographics, and comorbidities (age, sex, body mass index, hypertension, chronic kidney disease, coronary artery disease, cancer history, diabetes mellitus). COPD was associated with all-cause mortality independently of LVEF (P <.001). COPD patients are at higher risk for VT and mortality. This may not be fully attributed to the confounding effect of systolic heart failure measured by LVEF. Further studies are needed to explore the mechanistic interactions between VT and COPD in order to determine whether antiarrhythmic strategies would apply especially to patients with severe COPD.


Essential constituents of the 3'-phosphoesterase domain of bacterial DNA ligase D, a nonhomologous end-joining enzyme.
DNA ligase D (LigD) catalyzes end-healing and end-sealing steps during nonhomologous end joining in bacteria. Pseudomonas aeruginosa LigD consists of a central ATP-dependent ligase domain fused to a C-terminal polymerase domain and an N-terminal 3'-phosphoesterase (PE) module. The PE domain catalyzes manganese-dependent phosphodiesterase and phosphomonoesterase reactions at a duplex primer-template with a short 3'-ribonucleotide tract. The phosphodiesterase, which cleaves a 3'-terminal diribonucleotide to yield a primer strand with a ribonucleoside 3'-PO4 terminus, requires the vicinal 2'-OH of the penultimate ribose. The phosphomonoesterase converts the terminal ribonucleoside 3'-PO4 to a 3'-OH. Here we show that the PE domain has a 3'-phosphatase activity on an all-DNA primer-template, signifying that the phosphomonoesterase reaction does not depend on a 2'-OH. The distinctions between the phosphodiesterase and phosphomonoesterase activities are underscored by the results of alanine-scanning, limited proteolysis, and deletion analysis, which show that the two reactions depend on overlapping but nonidentical ensembles of protein functional groups, including: (i) side chains essential for both ribonuclease and phosphatase activity (His-42, His-48, Asp-50, Arg-52, His-84, and Tyr-88); (ii) side chains important for 3'-phosphatase activity but not for 3' ribonucleoside removal (Arg-14, Asp-15, Glu-21, Gln-40, and Glu-82); and (iii) side chains required selectively for the 3'-ribonuclease (Lys-66 and Arg-76). These constellations of critical residues are unique to LigD-like proteins, which we propose comprise a new bifunctional phosphoesterase family.


Entry-level practice: challenges, obligations, and opportunities.
Each of us has a unique and varied set of experiences, ideas, and skills that we bring to dietetic practice. This diversity is the strength of the profession. With a strong commitment to provide nutrition services to the public, entry-level practitioners can successfully meet the challenges, fulfill the obligations, and maximize opportunities in a way that will make the vision of the future a reality for the profession of dietetics.


Urinary histamine in severe atopic dermatitis.
Urinary histamine was studied in 11 patients with severe atopic dermatitis and 17 controls, as well as in seven atopics prior to and 6 months following hyposensitization. No statistically significant differences were found between the groups. Urinary histamine seems to be of no value as an indicator of disease activity in atopic dermatitis.


Transvaginal recovery of oocytes for in vitro fertilization using vaginal ultrasound.
Vaginal recovery of oocytes for in vitro fertilization (IVF) was performed in 75 patients using a vaginal puncture transducer. Follicles were aspirated and flushed four times using a controlled vacuum. Oocytes were collected in 74 patients and an average of 5.1 oocytes was collected per patient. An average of 8.8 follicles was aspirated per procedure, giving an oocyte recovery rate of 58% per follicle. Pregnancy was obtained in seven patients (9.3%). The only complication was bleeding from the vagina of an estimated 40 ml in one case.


Regulation of Notch signaling by dynamic changes in the precision of S3 cleavage of Notch-1.
Intramembrane proteolysis by presenilin-dependent gamma-secretase produces the Notch intracellular cytoplasmic domain (NCID) and Alzheimer disease-associated amyloid-beta. Here, we show that upon Notch signaling the intracellular domain of Notch-1 is cleaved into two distinct types of NICD species due to diversity in the site of S3 cleavage. Consistent with the N-end rule, the S3-V cleavage produces stable NICD with Val at the N terminus, whereas the S3-S/S3-L cleavage generates unstable NICD with Ser/Leu at the N terminus. Moreover, intracellular Notch signal transmission with unstable NICDs is much weaker than that with stable NICD. Importantly, the extent of endocytosis in target cells affects the relative production ratio of the two types of NICD, which changes in parallel with Notch signaling. Surprisingly, substantial amounts of unstable NICD species are generated from the Val-->Gly and the Lys-->Arg mutants, which have been reported to decrease S3 cleavage efficiency in cultured cells. Thus, we suggest that the existence of two distinct types of NICD points to a novel aspect of the intracellular signaling and that changes in the precision of S3 cleavage play an important role in the process of conversion from extracellular to intracellular Notch signaling.


Biomimetic Nanophotosensitizer Amplifies Immunogenic Pyroptosis and Triggers Synergistic Cancer Therapy.
Immunotherapy is considered to be an effective treatment for cancer and has drawn extensive interest. Nevertheless, the insufficient antigenicity and immunosuppressive tumor microenvironment often cause unsatisfactory therapeutic efficacy. Herein, a photo-activated reactive oxygen species (ROS) amplifying system (defined as "M-Cu-T") is developed to induce antitumor immune response by triggering a tumor-specific immunogenic pyroptosis. In M-Cu-T, M1 macrophage membrane-based vesicles are used for drug loading and tumor targeting, photosensitizers (meso-tetra(4-aminophenyl) porphyrin, TAPP) are used as a pyroptosis inducer, copper ions (Cu2+ ) can enhance ROS-induced pyroptosis by consuming antioxidant systems in cells. As expected, the prepared M-Cu-T targets enrichment into tumor cells and cascades the generation of ROS, which further induces pyroptosis through caspase 3-mediated gasdermin E (GSDME) cleavage under laser activation. The pyroptotic cancer cells accompanying secrete related pattern molecules, induce immunogenic cell death, and activate antitumor immunity for immunotherapy. An effective tumor ablation is observed in LLC and CT26 cancer mouse models. This study provides inspiration for boosting the immunogenicity and achieving satisfactory therapeutic effects in cancer therapy.


X-ray diffraction study of cholesterol-phosphatidylserine mixtures.
Phosphatidylserine-cholesterol mixtures at a molar ratio of 2:1 were investigated by X-ray diffraction. Phase separation of cholesterol independent of temperature was detected, indicating limited solubility of cholesterol in phosphatidylserine bilayers. The second phase present, the mixed phospholipid-cholesterol phase, continued to undergo melting as determined by changes with temperature in both the small angle scattering profile and in the acyl chain packing.


Outcome of a polymer-free drug-coated coronary stent in bifurcation lesions-Pilot registry with serial OCT imaging.
Polymer-free and carrier-free drug-coated stents (DCS) represent a novel therapeutic option for the treatment of coronary artery disease. The objective of this pilot registry is to evaluate the safety and efficacy of DCS implantation in bifurcation lesions. Overall, 23 consecutive patients with 24 lesions received a Biolimus A9-coated DCS for coronary bifurcation lesions. Patients were examined with quantitative coronary angiography (QCA) and optical coherence tomography (OCT) at 3-6 months of follow-up. A total of 23 patients with 24 bifurcation lesions were included in this study. Nine (33.3%) lesions of eight patients revealed angiographical target lesion failure due to in-stent restenosis (ISR). In total, 19 patients with 20 bifurcation lesions were suitable for OCT analysis. A total of 2936 struts were analyzed and 14 struts (0.47%) were classified as malapposed. The mean luminal area (mm2) was not different in lesions with ISR vs. lesions with no ISR (5.07 ± 2.0 vs. 5.73 ± 1.34, p = 0.39) at follow-up. Lesions with ISR showed higher mean neointimal burden (27.11 ± 10.59 vs. 13.93 ± 9.16%, respectively; p = 0.009). All of the patients who presented with significant ISR required percutaneous re-intervention. We observed a high rate of DCS ISR in bifurcation lesions, possibly related to increased inflammation and neoatherosclerosis. The small size of the study warrants careful interpretation of our results. Larger trials are necessary to expand knowledge of these findings.


The bio-availability and accumulation of the trace elements in rock-soil-fruit system in carbonatite regions of different stratums: Critical soil factors and transfer models.
For exploring the key factors affecting trace element accumulation in crops in limestone soil derived from limestone area of different stratums, the loquat (Eriobotrya japonica Lindl.) orchard of three limestone units (Middle Devonian, Upper Devonian and Middle Cambrian) in Mengzi city of Yunnan Province, China were investigated. Loquat fruits grown on soil from Middle Devonian limestone exhibited significantly higher bio-enrichment in cadmium. The Middle Devonian (Chemical Index of Alteration [CIA] = 86.07) and Upper Devonian (CIA = 84.84) soils were more weathered than those derived from Middle Cambrian rocks (CIA = 74.42). In the Middle Devonian limestone area, Fe element (for As uptake into fruit), Al element (for Cu and Zn) and metal speciation (for Cd, extracted by diethylene triamine pentaacetic acid) in the soil were the important influencing factors. For the Upper Devonian, soil weathering was found to be the key factors controlling fruit Cu uptake, respectively. For the Middle-Cambrian-derived soils, soil Ca concentration and pH played a critical role in Cd accumulation in fruit. In conclusion, under acidic soil conditions derived from limestone, the Ca concentration and metal fraction in the soil are the pivotal factors affecting Cd accumulation of fruit, whereas the soil Fe element content control the fruit As and Pb uptake. These results are helpful to further understand the migration regularity of trace elements into fruit in different limestone geology types.


Widespread translational control contributes to the regulation of Arabidopsis photomorphogenesis.
Environmental 'light' has a vital role in regulating plant growth and development. Transcriptomic profiling has been widely used to examine how light regulates mRNA levels on a genome-wide scale, but the global role of translational regulation in the response to light is unknown. Through a transcriptomic comparison of steady-state and polysome-bound mRNAs, we reveal a clear impact of translational control on thousands of genes, in addition to transcriptomic changes, during photomorphogenesis. Genes encoding ribosomal protein are preferentially regulated at the translational level, which possibly contributes to the enhanced translation efficiency. We also reveal that mRNAs regulated at the translational level share characteristics of longer half-lives and shorter cDNA length, and that transcripts with a cis-element, TAGGGTTT, in their 5' untranslated region have higher translatability. We report a previously neglected aspect of gene expression regulation during Arabidopsis photomorphogenesis. The identities and molecular signatures associated with mRNAs regulated at the translational level also offer new directions for mechanistic studies of light-triggered translational enhancement in Arabidopsis.


Variety-Specific Transcriptional and Alternative Splicing Regulations Modulate Salt Tolerance in Rice from Early Stage of Stress.
Salt stress poses physiological drought, ionic toxicity and oxidative stress to plants, which causes premature senescence and death of the leaves if the stress sustained. Salt tolerance varied between different rice varieties, but how different rice varieties respond at the early stage of salt stress has been seldom studied comprehensively. By employing third generation sequencing technology, we compared gene expressional changes in leaves of three rice varieties that varied in their level of tolerance after salt stress treatment for 6 h. Commonly up-regulated genes in all rice varieties were related to water shortage response and carbon and amino acids metabolism at the early stage of salt stress, while reactive oxygen species cleavage genes were induced more in salt-tolerant rice. Unexpectedly, genes involved in chloroplast development and photosynthesis were more significantly down-regulated in the two salt tolerant rice varieties 'C34' and 'Nona Bokra'. At the same time, genes coding ribosomal protein were suppressed to a more severe extent in the salt-sensitive rice variety 'IR29'. Interestingly, not only variety-specific gene transcriptional regulation, but also variety-specific mRNA alternative splicing, on both coding and long-noncoding genes, were found at the early stage of salt stress. In summary, differential regulation in gene expression at both transcriptional and post-transcriptional levels, determine and fine-tune the observed response in level of damage in leaves of specific rice genotypes at early stage of salt stress.


Trehalose and maltose metabolism in yeast transformed by a MAL4 regulatory gene cloned from a constitutive donor strain.
A 6.8 kb fragment of DNA containing the regulatory sequence MAL4p has been cloned from a genomic library prepared from Saccharomyces cerevisiae strain 1403-7A which ferments maltose constitutively. The library was prepared by ligation of 5-20 kb Sau3AI restriction fragments of total yeast DNA into the BamH1 restriction site of shuttle vector YEp13. A restriction map of the cloned fragment indicates that it encompasses a 2.6 kb segment which closely resembles the regulatory MAL6 gene previously identified (Needleman et al. 1984). The hybrid plasmid, p(MAL4p)4, could transform maltose-nonfermenting strains which contain cryptic alpha-glucosidase and maltose permease genes (malp MALg), but could not transform strains containing a functional regulatory sequence and a defective maltase-permease region (MAlp malg). A correlated absence of maltase and permease DNA from the cloned fragment was indicated by the restriction map. Although the cloned DNA fragment was derived from a constitutive strain, maltose fermentation and alpha-glucosidase formation by yeast transformed with p(MAL4p)4 was largely inducible by maltose and sensitive to catabolite repression. Moreover, the active trehalose accumulation pattern (TAC(+) phenotype) linked to the complete MAL4 locus in strain 1403-7A and other constitutive MAL strains (Oliveira et al. 1981b) was not found in p(MAL4p)4 transformants. It may be concluded that constitutivity of maltose fermentation and the associated active trehalose accumulation are not merely consequences of a cis-dominant mutation causing constitutive formation of the MALp regulatory product. Moreover, constitutivity may not be caused solely by a mutation within the structural region of the MALp gene.


Reproductive Outcomes Following Uterine Artery Occlusion at the Time of Myomectomy: Systematic Review and Meta-analysis.
This investigation sought systematically to review and meta-analyze evidence on reproductive outcomes following uterine artery occlusion (UAO) at myomectomy. Databases searched included PubMed, EMBASE, Ovid MEDLINE, Web of Science, and ClinicalTrials.gov. Eligible studies included observational and randomized controlled trials in which patients underwent abdominal, laparoscopic, or robotic myomectomy and in which at least one measure of clinical pregnancy rate, live birth rate, or ovarian reserve was reported. The primary outcome was live birth rate. Secondary outcomes included clinical pregnancy rate, miscarriage rate, adverse pregnancy outcomes, and measures of ovarian reserve. Twelve articles involving 689 women were included in the systematic review. The intervention group underwent UAO at laparoscopic or abdominal myomectomy (UAO+M) (n = 470). The control group underwent myomectomy alone (n = 219). Seven articles involving 420 women were included in the meta-analysis (201 underwent UAO+M; 219 underwent myomectomy alone). Live births occurred in 54 of 201 (27%) women in the UAO+M group and in 74 of 219 (34%) women in the control group. Clinical pregnancies occurred in 73 of 201 (36%) women in the UAO+M group and in 102 of 219 (47%) control subjects. There was no difference in live birth rates (odds ratio 0.89; 95% CI 0.56-1.43; P = 0.51; 7 studies, 420 patients) or clinical pregnancy rates (odds ratio 0.81; 95% confidence interval 0.53-1.24; P = 0.33; 7 studies, 420 patients) between the UAO+M and control groups. Data on miscarriage rates, adverse pregnancy outcomes, and measures of ovarian reserve precluded meta-analysis. In conclusion, UAO at myomectomy is not associated with reductions in live birth or clinical pregnancy rates. Before routine use can be recommended in women desiring future fertility, more research is required on reproductive outcomes and effects on ovarian reserve.


Predicting sedimentary bedrock subsurface weathering fronts and weathering rates.
Although bedrock weathering strongly influences water quality and global carbon and nitrogen budgets, the weathering depths and rates within subsurface are not well understood nor predictable. Determination of both porewater chemistry and subsurface water flow are needed in order to develop more complete understanding and obtain weathering rates. In a long-term field study, we applied a multiphase approach along a mountainous watershed hillslope transect underlain by marine shale. Here we report three findings. First, the deepest extent of the water table determines the weathering front, and the range of annually water table oscillations determines the thickness of the weathering zone. Below the lowest water table, permanently water-saturated bedrock remains reducing, preventing deeper pyrite oxidation. Secondly, carbonate minerals and potentially rock organic matter share the same weathering front depth with pyrite, contrary to models where weathering fronts are stratified. Thirdly, the measurements-based weathering rates from subsurface shale are high, amounting to base cation exports of about 70 kmolc ha-1 y-1, yet consistent with weathering of marine shale. Finally, by integrating geochemical and hydrological data we present a new conceptual model that can be applied in other settings to predict weathering and water quality responses to climate change.


Copy number variation in plasma as a tool for lung cancer prediction using Extreme Gradient Boosting (XGBoost) classifier.
The main cause of cancer death is lung cancer (LC) which usually presents at an advanced stage, but its early detection would increase the benefits of treatment. Blood is particularly favored in clinical research given the possibility of using it for relatively noninvasive analyses. Copy number variation (CNV) is a common genetic change in tumor genomes, and many studies have indicated that CNV-derived cell-free DNA (cfDNA) from plasma could be feasible as a biomarker for cancer diagnosis. In this study, we determined the possibility of using chromosomal arm-level CNV from cfDNA as a biomarker for lung cancer diagnosis in a small cohort of 40 patients and 41 healthy controls. Arm-level CNV distributions were analyzed based on z score, and the machine-learning algorithm Extreme Gradient Boosting (XGBoost) was applied for cancer prediction. The results showed that amplifications tended to emerge on chromosomes 3q, 8q, 12p, and 7q. Deletions were frequently detected on chromosomes 22q, 3p, 5q, 16q, 10q, and 15q. Upon applying a trained XGBoost classifier, specificity and sensitivity of 100% were finally achieved in the test group (12 patients and 13 healthy controls). In addition, five-fold cross-validation proved the stability of the model. Finally, our results suggested that the integration of four arm-level CNVs and the concentration of cfDNA into the trained XGBoost classifier provides a potential method for detecting lung cancer. Our results suggested that the integration of four arm-level CNVs and the concentration from of cfDNA integrated withinto the trained XGBoost classifier could become provides a potentially method for detecting lung cancer detection. Significant findings of the study: Healthy individuals have different arm-level CNV profiles from cancer patients. Amplifications tend to emerge on chromosome 3q, 8q, 12p, 7q and deletions tend to emerge on chromosome 22q, 3p, 5q, 16q, 10q, 15q. CfDNA concentration, arm 10q, 3q, 8q, 3p, and 22q are key features for prediction. Trained XGBoost classifier is a potential method for lung cancer detection.


Psychometric properties of the TSK-11: a shortened version of the Tampa Scale for Kinesiophobia.
The Tampa Scale for Kinesiophobia (TSK) is one of the most frequently employed measures for assessing pain-related fear in back pain patients. Despite its widespread use, there is relatively little data to support the psychometric properties of the English version of this scale. This study investigated the psychometric properties of the English version of the TSK in a sample of chronic low back pain patients. Item analysis revealed that four items possessed low item total correlations (4, 8, 12, 16) and four items had response trends that deviated from a pattern of normal distribution (4, 9, 12, 14). Consequently, we tested the psychometric properties of a shorter version of the TSK (TSK-11), having excluded the six psychometrically poor items. The psychometric properties of this measure were compared to those of the original TSK. Both measures demonstrated good internal consistency (TSK: alpha=0.76; TSK-11: alpha=0.79), test-retest reliability (TSK: ICC=0.82, SEM=3.16; TSK-11: ICC=0.81, SEM=2.54), responsiveness (TSK: SRM=-1.19; TSK-11: SRM=-1.11), concurrent validity and predictive validity. In respect of specific cut-off scores, a reduction of at least four points on both measures maximised the likelihood of correctly identifying an important reduction in fear of movement. Overall, the TSK-11 possessed similar psychometric properties to the original TSK and offered the advantage of brevity. Further research is warranted to investigate the utility of the new instrument and the cut-off scores in a wider group of chronic pain patients in different clinical settings.


Point of care echocardiography and lung ultrasound in critically ill patients with COVID-19.
Hundreds of millions got infected, and millions have died worldwide and still the number of cases is rising.Chest radiographs and computed tomography (CT) are useful for imaging the lung but their use in infectious diseases is limited due to hygiene and availability.Lung ultrasound has been shown to be useful in the context of the pandemic, providing clinicians with valuable insights and helping identify complications such as pleural effusion in heart failure or bacterial superinfections. Moreover, lung ultrasound is useful for identifying possible complications of procedures, in particular, pneumothorax.Associations between coronavirus disease 2019 (COVID-19) and cardiac complications, such as acute myocardial infarction and myocarditis, have been reported. As such, point of care echocardiography as well as a comprehensive approach in later stages of the disease provide important information for optimally diagnosing and treating complications of COVID-19.In our experience, lung ultrasound in combination with echocardiography, has a great impact on treatment decisions. In the acute state as well as in the follow-up setting after a severe or critical state of COVID-19, ultrasound can be of great impact to monitor the progression and regression of disease.


Mode of promoter recognition by the Escherichia coli RNA polymerase holoenzyme containing the sigma S subunit: identification of the recognition sequence of the fic promoter.
Transcription of a number of genes during stationary phase in Escherichia coli requires the alternative sigma factor sigma S, encoded by the rpoS gene. No consensus sequence for the promoters recognized by the RNA polymerase holoenzyme containing the sigma S subunit (E sigma S) is known. To identify the E sigma S recognition sequence, we analysed the promoter region of the fic gene, whose expression depends on E sigma S both in vivo and in vitro. By random mutagenesis, we isolated a large number of the fic promoter mutants that had defective promoter activities in an rpoS+ strain. All such mutants contained alterations within the -10 region, TATACT, whereas no mutant was isolated with alterations in the -35 region. Based on further analyses including scanning mutagenesis and DNase I footprinting assays of the fic promoter region, and in vitro transcription assays, we conclude that the -10 hexamer is essential to transcription initiation from the fic promoter by E sigma S.


Stimulatory effect of ginsenosides on DNA, protein and lipid synthesis in rat bone marrow and participation of cyclic nucleotides.
Effects of several kinds of ginsenosides, saponins from Panax ginseng on DNA, RNA, protein and lipid synthesis in bone marrow were investigated. Single i.p. injection of 0.5--1 mg/100 g body weight of ginsenosides Rb2, Rc, Re and Rg1 4 h prior to the sacrifice increased DNA synthesis in bone marrow cells. RNA, protein and lipid synthesis were also increased. The direct addition of ginsenosides Rb1, Rb2 and Rc mixture (GNS) enhanced DNA synthesis. Cyclic AMP levels in bone marrow cells were decreased 20 min after i.p. injection of ginsenosides Rb2, Rc and Rg1 and the direct addition of ginsenosides Rb2, Rc and Rg1 also decreased cyclic AMP levels. While cyclic GMP levels were increased by administration of ginsenosides Rb2, Re and Rg1. Relationship between chemical structure and actions of ginsenosides and the role of cyclic nucleotides in the stimulatory action of ginsenosides on DNA synthesis in bone marrow cells were discussed.


Evaluation of symptom control and functional quality of life in Turkish patients with cancer during chemotherapy.
This study was designed to evaluate the severity of symptoms, functional quality of life, and related factors experienced by Turkish cancer patients receiving chemotherapy. The study was carried out with 430 patients at a medical oncology clinic. The data were collected using a personal and disease-related characteristics questionnaire, the Edmonton Symptom Assessment Scale (ESAS) and the Functional Life Scale-Cancer (FLIC). The three symptoms experienced most by patients were nausea (91.2%), depression (89.1%), and anxiety (87.7%). The mean FLIC total score of patients with cancer was 86.26 ± 23.15. Age, ECOG performance score, pain, nausea, depression, and a decreased sense of well-being independently affected the FLIC score (p < 0.05). There was a negative correlation between ESAS and FLIC scores (p < 0.05). Nausea and psychological symptoms are common in Turkish patients with cancer. The more severe the symptoms, the worse the functional quality of life. Age, ECOG performance score, pain, nausea, depression, and decreased sense of well-being affect Turkish cancer patients' functional quality of life. We conclude that healthcare professionals should evaluate symptoms experienced by their patients and plan appropriate nursing interventions to address the symptoms experienced by Turkish patients with cancer.


Expression of integrins and other adhesion molecules in Epstein-Barr virus-transformed B lymphoblastoid cells and Burkitt's lymphoma cells.
Lymphocytes adhere to cells or extracellular matrices to perform functions relating to cytotoxicity, extravasation and tissue localization, as well as modulation of lymphocyte growth and maturation. This adherence is mainly mediated by 3 families of cell-surface adhesion molecules: integrins, immunoglobulin-related molecules and selectins. Since variations in the degree of adherence may affect the pathophysiology of lymphoproliferative disorders, the expression of a large number of adhesion molecules was analysed on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs), and on EBV-positive or EBV-negative Burkitt's lymphoma (BL) lines, by immunofluorescence flow cytometry and immunoprecipitation with monoclonal antibodies. With regard to the beta 1, beta 2 and beta 3 integrin subfamilies, LCLs strongly expressed CD49d/CD29 (VLA-4), CD11a/CD18 (Leu-CAMa, LFA-1) and CD51/CD61 (vitronectin receptor). These cells also abundantly expressed CD54 (ICAM-1) and CD58 (LFA-3) as well as the "homing receptors" L-selectin (LECAM-1) and CD44. BL lines had considerably lower amounts of VLA-4 than LCLs, and ICAM-1 was expressed only by some of the tumor lines. All other adhesion molecules were absent or minimally expressed in the BL cells.


Concentrations of catecholamines in transplanted hearts after extracorporeal perfusion and cold storage.
Using different perfusion regimes and orthograde implantation, some investigators have found sufficient heart function after extracorporeal perfusion of hearts for 24 and even 72 h. However, we found no significant improvement of perfused hearts compared to cold stored hearts after a 9-h extracorporeal period. A possible explanation for this finding could be the excessive liberation of catecholamines during ischemia, as has been demonstrated in isolated perfused hearts. Therefore, the aim of this study was to investigate whether concentrations of noradrenaline and dihydroxyphenylglycol (DOPEG)--a noradrenaline metabolite-increased pathologically during continuous extracorporeal heart perfusion for 5 h in pigs, in comparison to hearts stored at 4 degrees C. The venoarterial differences in noradrenaline and DOPEG were not significantly different in the two groups. Concentrations of lactate and pyruvate decreased substantially after 3-h hypothermic perfusion. The lactate/pyruvate ratio remained at a value of 25-35. Only after the end of the extracorporeal circulation did this ratio reach a value of 40-65. In our model, these findings demonstrate that the excessive liberation of catecholamines is not a reason for heart failure after cold storage or perfusion.


Inhibition of trypsin and chymotrypsin by thiols. Biphasic kinetics of reactivation and inhibition induced by sodium periodate addition.
Biphasic kinetic data were obtained when trypsin (EC 220.127.116.11) which had previously been complexed with a thiol-containing inhibitor (present in Ehrlich ascites tumour cells) was incubated with incremental additions of periodate. At low concentrations of periodate the trypsin was re-activated whilst at higher concentrations of periodate the trypsin was irreversibly inhibited. This biphasic reactivation followed by inhibition was also demonstrated when trypsin was first inhibited by dithiothreitol and followed by incremental addition of periodate. Similar results were obtained with chymotrypsin (EC 184.108.40.206). Incremental additions of either dithiothreitol or periodate caused inhibition of both these enzymes. The biphasic kinetic data can be explained in terms of reduction and oxidation of a significant disulphide bond in both trypsin and chymotrypsin which can be cleaved by thiols in a disulphide exchange reaction [1]. This bond is thought to maintain the active centres of each of these enzymes in a conformation sterically favourable for enzymic cleavage of specific peptide bonds in the protein substrates (polymeric collagen fibrils and casein) employed in this study.


Are amniotic fluid neutrophils in women with intraamniotic infection and/or inflammation of fetal or maternal origin?
Neutrophils are the most abundant white blood cells found in the amniotic cavity of women with intraamniotic infection and/or inflammation. The current belief is that these neutrophils are of fetal origin. However, abundant neutrophils have been found in the amniotic fluid of women with a severe acute maternal inflammatory response but without a severe fetal inflammatory response in the placenta, suggesting that these innate immune cells can also be of maternal origin or a mixture of both fetal and maternal neutrophils. We sought to investigate the origin of amniotic fluid neutrophils from women with intraamniotic infection and/or inflammation and to correlate these findings with acute histologic maternal and fetal inflammatory responses in the placenta. Amniotic fluid was collected from 15 women with suspected intraamniotic infection and/or inflammation (positive microbiological cultures and/or interleukin-6 concentrations ≥2.6 ng/mL). Amniotic fluid neutrophils were purified by fluorescence-activated cell sorting, DNA was extracted, and DNA fingerprinting was performed. DNA fingerprinting was also performed in the umbilical cord and maternal blood DNA. Fluorescence in situ hybridization was assayed in women with male neonates. Blinded placental histopathological evaluations were conducted. First, DNA fingerprinting revealed that 43% (6/14) of women who underwent a single amniocentesis had mostly fetal neutrophils in the amniotic fluid. Second, DNA fingerprinting showed that 36% (5/14) of the women who underwent a single amniocentesis had predominantly maternal neutrophils in the amniotic fluid. Third, DNA fingerprinting indicated that 21% (3/14) of the women who underwent a single amniocentesis had an evident mixture of fetal and maternal neutrophils in the amniotic fluid. Fourth, DNA fingerprinting revealed that a woman who underwent 2 amniocenteses (patient 15) had fetal neutrophils first, and as infection progressed, abundant maternal neutrophils invaded the amniotic cavity. Fifth, fluorescence in situ hybridization confirmed DNA fingerprinting results by showing that both fetal and maternal neutrophils were present in the amniotic fluid. Sixth, most of the women who had predominantly amniotic fluid neutrophils of fetal origin at the time of collection delivered extremely preterm neonates (71% [5/7]). Seventh, all of the women who had predominantly amniotic fluid neutrophils of maternal origin at the time of collection delivered term or late preterm neonates (100% [6/6]). Eighth, 2 of the women who had an evident mixture of fetal and maternal neutrophils in the amniotic fluid at the time of collection delivered extremely preterm neonates (67% [2/3]), and the third woman delivered a term neonate (33% [1/3]). Finally, most of the women included in this study presented acute maternal and fetal inflammatory responses in the placenta (87% [13/15]). Amniotic fluid neutrophils can be either predominantly of fetal or maternal origin, or a mixture of both fetal and maternal origin, in women with intraamniotic infection and/or inflammation. The findings herein provide evidence that both fetal and maternal neutrophils can invade the amniotic cavity, suggesting that both the fetus and the mother participate in the host defense mechanisms against intraamniotic infection.


Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T cells.
The adoptive transfer of T cells modified to express a chimeric antigen receptor (CAR) comprised of an extracellular single-chain antibody (scFV) fragment specific for a tumor cell surface molecule, and linked to an intracellular signaling module, has activity in advanced malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a tumor-associated molecule expressed in prevalent B-lymphoid and epithelial cancers and is absent on normal mature B cells and vital tissues, making it a candidate for CAR T-cell therapy. We constructed ROR1-CARs from scFVs with different affinities and containing extracellular IgG4-Fc spacer domains of different lengths, and evaluated the ability of T cells expressing each CAR to recognize ROR1(+) hematopoietic and epithelial tumors in vitro, and to eliminate human mantle cell lymphoma (MCL) engrafted into immunodeficient mice. ROR1-CARs containing a short "Hinge-only" extracellular spacer conferred superior lysis of ROR1(+) tumor cells and induction of T-cell effector functions compared with CARs with long "Hinge-CH2-CH3" spacers. CARs derived from a higher affinity scFV conferred maximum T-cell effector function against primary CLL and ROR1(+) epithelial cancer lines in vitro without inducing activation-induced T-cell death. T cells modified with an optimal ROR1-CAR were equivalently effective as CD19-CAR-modified T cells in mediating regression of JeKo-1 MCL in immunodeficient mice. Our results show that customizing spacer design and increasing affinity of ROR1-CARs enhances T-cell effector function and recognition of ROR1(+) tumors. T cells modified with an optimized ROR1-CAR have significant antitumor efficacy in a preclinical model in vivo, suggesting they may be useful to treat ROR1(+) tumors in clinical applications.


Vascularized muscle fibers: etiopathogenesis and clinical significance.
Contrary to common assumption, internal vascularization of muscle fiber occurs independent of muscle fiber splitting. Review of 1091 cases who underwent muscle biopsies demonstrated muscle fibers with internal blood vessels in a wide variety of chronic neuromuscular disease states, predominantly in patients with chronic neurogenic diseases. Many of these cases show evidence of internal disorganization or focal degeneration of muscle fibers, in particular, formation of targets, targetoids or similar structural alterations. Internal vascularization of muscle fiber probably occurs as a "healing" or "reparative process" in such fibers. Myopathic features, especially secondary myopathic changes (as seen in chronic denervation-reinnervation) are common and appear to be a necessary accompaniment of this phenomena. The vascularized muscle fiber is more likely to be seen in a distal lower extremity muscle than in a proximal limb muscle biopsy.


An effective simulation of aqueous micellar aggregates by computational models.
We have computationally studied the interaction modes, localization and orientation of a benzene (Bz) molecule on the surface of micelles formed by cetyltrimethylammonium salts CTAX. Experimental 1H-NMR data on complexation shifts induced by Bz on the polar head hydrogens and on the adjacent methylene hydrogens of CTAX have been interpreted using a computational approach that combines an automatic molecular docking procedure with a calculation module that accounts for NMR complexation shifts due to ring current diamagnetic anisotropy. Three different models were used to reduce the complexity of the micellar system. Computational results, in good agreement with available experimental data, point to a preferential localization of the Bz molecule along the CTAX alkyl tail, about 3.9 angstroms away from the charged nitrogen. The Bz molecular plane is predicted perpendicular to the C-H bonds of the alkyl tail. The good results obtained with the simplest model suggest that it could be used to study more complex systems involving surfactants endowed with molecular recognition or catalytic abilities.


Targeting of autonomous parvoviruses to colon cancer by insertion of Tcf sites in the P4 promoter.
The Wnt signaling pathway is activated by mutations in the adenomatous polyposis coli (APC) or beta-catenin genes in most colon cancers, leading to the transactivation of promoters containing binding sites for the Tcf/LEF family of transcription factors. We have previously shown that it is possible to confer colon cancer specificity on autonomous parvoviruses by inserting Tcf sites into the viral P4 promoter. The mutant Tcf promoters were responsive to activation of the Wnt pathway but the viruses replicated poorly. We show here that reduction of the number of Tcf sites from four to two leads to an increase in the efficiency of replication and toxicity of the viruses in Co115 colon cancer cells, with only a small reduction in selectivity for cells with an active Wnt signaling pathway. Despite this improvement, virus production by most colon cancer cells remained low. Analysis of parental phH1 virus infection of SW480 colon cancer cells showed that the nonstructural and capsid proteins were expressed, but single stranded DNA and progeny virus were not produced. This defect reflects the dependence of autonomous parvoviruses on host functions for many steps in their replication cycle and represents a major limitation to the use of selectively replicating parvoviruses for colon cancer therapy.


Outcomes of Postchemotherapy Retroperitoneal Lymph Node Dissection from a High-volume UK Centre Compared with a National Data Set.
Retroperitoneal lymph node dissection (RPLND) is essential for the treatment of metastatic germ cell tumours of the testis. Recommendations on the referral and management of complex urological cancers in the UK includes centralisation of services to regional centres. To review contemporary PC-RPLND outcomes at a high-volume centre with a complex case-mix, and compare with national registry data. We retrospectively reviewed the medical records of PC-RPLNDs performed for germ cell tumours at our centre between July 2012 and September 2018. Primary outcomes were Clavien 3+ complications, histology, rates of positive margin, relapse, in-field recurrences, and mortality. Secondary outcomes were blood loss, operation time, blood transfusion, adjuvant procedures, length of stay, and lymph node count. Surgical and histological outcomes of all RPLNDs for testicular cancers were compared with national RPLND registry data. For statistical difference, χ2 testing was used. A total of 178 procedures were performed, including 31 (17%) redo RPLNDs. Clavien 3+ complications occurred in 11 (7%). Histological findings in non-redo cases were the following: necrosis 24%, teratoma 62%, viable germ cell tumour 11%, and dedifferentiated cancers 3%. Rates of positive margin, relapse, and in-field recurrence were 11%, 17%, and 2%, respectively. Overall survival was 89% at a median of 36 mo. The median blood loss was 650 ml (350, 1250), with a transfusion rate of 8%. Nephrectomy, vascular reconstruction, and visceral resection was required in 12%, 6%, and 3% respectively. The median inpatient stay was 6 d (5, 8) and the median node count was 35 (20, 37). A comparison of all RPLNDs with national data showed no statistical difference in primary outcomes. Our blood transfusion rate was significantly lower (12% vs 21%, χ2 [1, N = 322] = 4.296, p = 0.038). Centralisation led to high quality of RPLND in UK. Within that, our series (the largest in the UK) demonstrates no significant difference in outcomes despite higher complexity cases. Our blood transfusion rates are in fact lower than national figures. Complex RPLNDs should be performed in high-volume centres where possible. In the UK, retroperitoneal lymph node dissections (RPLND) are centralised to specialist centres and the quality of surgery is high, with low complications and good histological outcomes. When compared to national data, we found no significant difference in the majority of outcomes from our high-volume centre despite our complex case-mix.


Fabrication, characterization and application of pectin degrading Fe3O4-SiO2 nanobiocatalyst.
The covalent binding of pectinase onto amino functionalized silica-coated magnetic nanoparticles (CSMNPs) through glutaraldehyde activation was investigated for nanobiocatalyst fabrication. The average particle size and morphology of the nanoparticles were characterized using transmission electron microscopy (TEM). The statistical analysis for TEM image suggests that the coating and binding process did not cause any significant change in size of MNPs. The morphological and phase change of the magnetic nanoparticles (MNPs) after various coatings and immobilization were characterized by X-ray diffraction (XRD) studies. The various surface modifications and pectinase binding onto nanoparticles were confirmed by Fourier transform infrared (FT-IR) spectroscopy. The maximum activity of immobilized pectinase was obtained at its weight ratio of 19.0×10(-3) mg bound pectinase/mg CSMNPs. The pH, temperature, reusability, storage ability and kinetic studies were established to monitor their improved stability and activity of the fabricated nanobiocatalyst. Furthermore, the application was extended in the clarification of Malus domestica juice.


Left Ventricular Layer-Specific Myocardial Strains in Children with Recovered Primary Dilated Cardiomyopathy: What Lies Beneath the Iceberg?
We aimed to detect residual cardiac dysfunction-if any-in children with recovered primary dilated cardiomyopathy (DCM) by using the left ventricular (LV) layer-specific myocardial strains. Fifty children with recovered primary DCM both clinically and echocardiographically were included as the patient group. Fifty healthy children of matched age and sex served as the control group. Echocardiographic evaluation was performed for all included children in the form of conventional echocardiography, tissue Doppler imaging (TDI), two-dimensional speckle tracking echocardiography (2D-STE), and LV layer-specific myocardial strain. Both LV systolic and diastolic functions measured by conventional echocardiography were similar in children with recovered DCM and the control group. There was a significant reduction in LV systolic and diastolic functions measured by TDI in the patient group. Moreover, there was a significant reduction of LV global longitudinal systolic strain (GLSS) by 2D-STE in children with recovered DCM. Interestingly, there was a significant reduction of LV layer-specific myocardial strain from endocardium to epicardium in children with recovered DCM compared to the healthy control. There was a significant positive correlation between different layer-specific myocardial strains and LV GLSS, LV ejection fraction, and LV peak systolic velocity. Left ventricular layer-specific myocardial strain can be a promising tool for early identifications of LV dysfunction in children with DCM. Subtle cardiac dysfunction is present in patients with recovered DCM, so long-term follow-up is recommended in these patients.


Assessment of Lewis negative phenotype as a risk factor for multivessel disease in patients with acute coronary syndrome.
Acute coronary syndrome is a manifestation of coronary artery disease caused by decreased blood flow to the heart musculature resulting in ischaemia and infarction of the heart. The Lewis (Le) blood group system comprise mainly Lewis a & b antigens which are secreted in plasma and are expressed on red cells, platelets and endothelium. This study assesses the risk of multivessel disease in acute coronary patients with lewis negative (a- b-) phenotype. The study included 183 patients diagnosed with acute coronary syndrome and who underwent coronary angiography to detect stenosis of the coronary vessels. The severity of the disease was classified based upon the number of vessels stenosed and their blood sample was phenotyped for Lewis antigens. The patients' risk factors, GRACE score and management were included for the study and multivariate logistic regression was carried out for analysis. The prevalence of Lewis (a- b-) was 27.4% and there was a significant association with multivessel disease (P<0.05). However, there was no association of lewis (a- b-) with any of the risk factors causing coronary disease. The adjusted odds ratio of triple vessel disease in lewis (a- b-) was 2.6, female gender was 0.6 and patients with diabetes mellitus was 3.1, respectively. The GRACE score showed a significant association with ABO blood group (P<0.05) but not with lewis (a- b-). Lewis negative patients are more likely to develop triple vessel disease compared to other lewis blood groups. This warrants further studies to investigate the link between lewis system and atherothrombosis.


Trends in COVID-19 vaccination receipt and intention to vaccinate, United States, April to August, 2021.
To assess trends in and factors associated with COVID-19 vaccination coverage, data from the Household Pulse Survey were analyzed. From April to August 2021, vaccination coverage with at least 1 dose increased from 70%-82%, while vaccination intent increased from 82%-86%, with the highest increase among the most vulnerable groups. More efforts are needed to boost confidence in vaccines and to encourage all eligible people to be fully vaccinated.


Angiotensin II activates the ouabain-insensitive Na+-ATPase from renal proximal tubules through a G-protein.
Angiotensin II (AG II) stimulates the ouabain-insensitive, furosemide- sensitive Na+-ATPase present in the basolateral membrane of pig renal proximal tubules in a dose dependent manner. Maximum effect was obtained with 10-8 M AG II, which corresponded to an activity 134% higher than control. Half of the maximum effect was observed between 10-11 M and 10-10 M, corresponding to physiological hormone levels. Saralasin, an AG II peptide analogue receptor antagonist, abolished the phenomenon, demonstrating that AG II interacts with specific sites in pig proximal tubules. The AG II stimulatory effect was also prevented by dithiothreitol (DTT), a reducing compound, and by 10 nM losartan, a non-peptide antagonist highly specific for AT1 receptors, characterizing AG II binding to AT1 receptors. GTPgammaS, a non-hydrolysable GTP analogue, increased by 159% the enzyme activity as compared to the control values. The simultaneous addition of 10-5 M GTPgammaS and 10-8 M AG II did not have additive effects. Furthermore, the stimulatory action of AG II was completely abolished by 0.1 microM GDPbetaS, a non-hydrolysable GDP analogue. Two microgram ml-1 pertussis toxin, an inhibitor of Gi-protein, did not modulate the AG II stimulatory effect. On the other hand, the Na+-ATPase activity was enhanced 100% in the presence of cholera toxin and 85% in the presence of both AG II and cholera toxin. Taken together, these data suggest that AG II activates the Na+-ATPase activity through AT1 receptors coupled to a pertussis-insensitive and cholera-sensitive G-protein.


Genetic and epigenetic alteration of the programmed cell death 1 in rheumatoid arthritis.
Rheumatoid arthritis (RA) is an autoimmune disease where both genetics and epigenetics are contributing factors. In order to discover genetic and epigenetic associations with RA and its phenotypes, we analysed RNA expression, DNA variations and DNA methylation of programmed cell death 1 (PDCD1) in a cohort of RA patients and healthy controls. RA patients (n = 206) and healthy controls (n = 234) were included for analysis of PDCD1 expression, PDCD1 polymorphisms and PDCD1 methylation. Differences in continuous variables between groups were compared by applying t tests. Associations between phenotypes and genotypes were evaluated with contingency tables. Sensitivity analyses were conducted to confirm the robustness of results, considering potential confounding factors and different treatment response definitions. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated. Higher expression of PDCD1 was found in RA compared to controls (P < 0.001), with similar PDCD1 polymorphisms in RA and controls. rs36084323 decreased inadequate response to conventional synthetic disease-modifying antirheumatic drugs (OR = 0.37, 95% CI = 0.19-0.72, P = 0.003), and rs41386349 increased rheumatoid factor seropositivity (OR = 11.89, 95% CI = 1.57-89.87, P = 0.003). Sensitivity analysis adjusting for further potential confounders and using different treatment response definition indicated similar results. Additionally, DNA methylation change at regulatory region of PDCD1 was detected in RA (P = 0.036). Altogether, this was the first study to suggest genetic and epigenetic changes of PDCD1 in RA subsets and RA. Independent prospective cohorts are awaited to address the implications of these genetic and epigenetic changes in disease pathogenesis and phenotypes of RA.


Does air pollutant exposure impact disease severity or outcomes in chronic rhinosinusitis?
Poor air quality increases the risk of developing chronic rhinosinusitis (CRS) and other airway diseases. However, there are limited data on air pollutants and CRS-specific disease severity. We assessed the impact of air pollutants on sinonasal-specific and general quality-of-life (QOL) measures in a multi-institutional cohort of patients with CRS. Participants with CRS were prospectively enrolled in a cross-sectional study and self-selected continued appropriate medical therapy or endoscopic sinus surgery (ESS). The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility value scores were recorded. Patient exposure to air pollutants was determined using residence zip codes. Unadjusted group differences were compared, and correlation coefficients were evaluated to identify the magnitude of bivariate association. A total of 486 patients were enrolled and followed for a mean of 6.9 (standard deviation [SD] ± 2.3) months. Pollutant exposure did not significantly correlate with baseline SNOT-22 or SF-6D scores. Revision ESS was associated with higher median fine particulate matter (PM2.5; Δ = 0.12, [95% confidence interval {CI}: 0.003, 0.234]; p = 0.006) compared with primary surgery. PM2.5, PM10, and nitrogen dioxide concentrations (μg/m3 ) did not correlate with change in total SNOT-22 or SF-6D scores after treatment. Nevertheless, sulfur dioxide (SNOT-22: ρ = -0.121 [95% CI: -0.210, -0.030]; p = 0.007; SF-6D: ρ = 0.095 [95% CI: 0.002, 0.186]; p = 0.04) and carbon monoxide (SNOT-22: ρ = -0.141 [95% CI: -0.230, 0.050]; p = 0.002) exposure did correlate with these outcome measures. Air pollutants may contribute, at least in part, to disease severity in CRS; future investigation is needed to further elucidate the nature of this relationship.


pPKC α regulates through integrin β 1 human gingival fibroblasts/Streptococcus mitis adhesion in response to HEMA.
To investigate in coculture of human gingival fibroblasts (HGFs) and Streptococcus mitis, the molecular mechanisms driving the response to 2-hydroxyethyl methacrylate (HEMA) in terms of eukaryotic/prokaryotic cell adhesion, signal transduction and apoptosis. The clinical strain S. mitis DS12, cultured in Trypticase soy broth was added to HGFs, obtained from fragments of healthy marginal gingival tissue and cultured in DMEM, treated with 3 mmol L(-1) 2-hydroxyethyl methacrylate (HEMA) for 48 h and processed for microscopic, western blotting and flow cytometric analyses. 2-hydroxyethyl methacrylate (HEMA) treatment increased the adhesion between S. mitis and HGFs, which seemed to be mediated by the PKC α/integrin β 1 signalling system, improved by the presence of saliva. It also reduced the viability and the adhesion of HGFs to polypropylene substrate in terms of procollagen I and MMP3 expression. The presence of saliva and S. mitis reduced the number of necrotic HGFs and upregulated the expression of both procollagen I and MMP3. These results shed more light on the biological and molecular events occurring in vitro in a coculture model that mimics the environment of the oral cavity with HEMA treatment. The key role played by oral bacteria and saliva in preventing inflammatory and toxic processes that occur in vivo in human gingival fibroblasts upon the release of dental material monomers is confirmed.


A Phase II study of intravenous exatecan administered daily for 5 days, every 3 weeks to patients with biliary tract cancers.
Exatecan is a hexacyclic topoisomerase-1 inhibitor that has broad in vitro and in vivo activity. A multicenter phase II study to determine the antitumor activity of exatecan was conducted in patients with advanced cholangiocarcinoma and gallbladder carcinoma. Patients with 0 to 1 prior chemotherapy regimens, adequate major organ function, and metastatic disease were eligible. Exatecan was administered at a dose of 0.5 mg/m2 IV over 30 minutes daily on days 1 through 5 every 21 days. The primary end point was overall response rate: complete response and partial response (PR). A Simon optimal 2-stage design was employed. Response was assessed every 6 weeks. Forty-two patients were enrolled. Two of 41 evaluated patients (4.9%) had a PR, 4 patients (9.8%) had a minor response, and 12 had stable disease. Twenty patients (51.2%) had progressive disease. The major toxicity was grade 3/4 neutropenia. The median overall survival was 7 months. The 6-month survival rate was 56.1% and the 12-month survival rate was 31.7%. Exatecan has minimal activity in advanced biliary tree cancers. Toxicity was predictable and manageable.


The split-cuff ureteral nipple reimplantation technique: reliable reflux prevention from bowel segments.
The split-cuff nipple ureteral implantation technique is described in 18 patients undergoing lower urinary tract reconstruction or supravesical diversion. This technique provides a simple and reliable antireflux mechanism into large and small bowel segments. No reflux or upper tract deterioration was seen initially, and only 1 case of mild reflux has occurred after 30 months of followup.


Toward dysfunctional connectivity: a review of neuroimaging findings in pediatric major depressive disorder.
Child and adolescent psychiatric neuroimaging research typically lags behind similar advances in adult disorders. While the pediatric depression imaging literature is less developed, a recent surge in interest has created the need for a synthetic review of this work. Major findings from pediatric volumetric and functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and resting state functional connectivity studies converge to implicate a corticolimbic network of key areas that work together to mediate the task of emotion regulation. Imaging the brain of children and adolescents with unipolar depression began with volumetric studies of isolated brain regions that served to identify key prefrontal, cingulate and limbic nodes of depression-related circuitry elucidated from more recent advances in DTI and functional connectivity imaging. Systematic review of these studies preliminarily suggests developmental differences between findings in youth and adults, including prodromal neurobiological features, along with some continuity across development.


Goal attainment scaling as a tool to enhance quality in community-based health promotion.
Goal attainment scaling (GAS) is an individual approach for measuring changes in clinical interventions. We adopted GAS as a tool for community-based health promotion to support practitioners in formulating and monitoring their intervention goals. Eleven regional health promotion networks were invited to set project-specific goals, following Kiresuk and Sherman's rules for goal setting. Follow-up interviews on goal attainment were conducted twenty-one months later. In addition, each network was interviewed on usage and applicability. In total, 35 goals were set. The expected outcomes were reached for the majority of projects. GAS has been proven to be a useful instrument for quality assurance as it helps with setting and monitoring goals and sub-goals.


Gut microbiota mediated the therapeutic efficiency of Simiao decoction in the treatment of gout arthritis mice.
Gut microbiota plays a significant role in the development and treatment of gouty arthritis. Simiao decoction has been shown to alleviate gouty arthritis by inhibiting inflammation, regulating NLRP3 inflammasome, and altering gut microbiota. However, there is no evidence to prove whether gut microbiota directly mediates the therapeutic efficiency of Simiao decoction in treating gout arthritis. In this study, fecal microbiota transplantation (FMT) was used to transfer the gut microbiota of gout arthritis mice treated with Simiao decoction or allopurinol to blank gout arthritis mice, in order to investigate whether FMT had therapeutic effects on gout arthritis. Both Simiao decoction and allopurinol effectively reduced the levels of serum uric acid, liver XOD activity, foot thickness, serum IL-1β, and G-CSF in gout arthritis mice. However, Simiao decoction also had additional benefits, including raising the pain threshold, reducing serum TNF-α and IL-6, alleviating gut inflammation, and repairing intestinal pathology, which were not observed with allopurinol treatment. Moreover, Simiao decoction had a greater impact on gut microbiota than allopurinol, as it was able to restore the abundance of phylum Proteobacteria and genus Helicobacter. After transplantation into gout arthritis mice, gut microbiota altered by Simiao decoction exhibited similar therapeutic effects to those of Simiao decoction, but gut microbiota altered by allopurinol showed no therapeutic effect. These findings demonstrates that Simiao decoction can alleviate gout arthritis symptoms by regulating gut microbiota.


Adiponectin gene polymorphisms and posttraumatic stress disorder symptoms among female rape survivors: an exploratory study.
Background: Rape is a common traumatic event which may result in the development of posttraumatic stress disorder (PTSD), yet few studies have investigated risk biomarkers in sexually traumatised individuals. Adiponectin is a novel cytokine within inflammatory and cardiometabolic pathways with evidence of involvement in PTSD. Objective: This prospective exploratory study in a sample of female rape survivors investigated the association of single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and posttraumatic stress symptom (PTSS) severity, and the interaction of these SNPs of interest with childhood trauma in modifying the association with PTSS severity. Method: The study involved 455 rape-exposed black South African women (mean age (SD), 25.3 years (±5.5)) recruited within 20 days of being raped. PTSS was assessed using the Davidson Trauma Scale (DTS) and childhood trauma was assessed using a modified version of the Childhood Trauma Scale-Short Form Questionnaire. Eight ADIPOQ SNPs (rs17300539, rs16861194, rs16861205, rs2241766, rs6444174, rs822395, rs1501299, rs1403697) were genotyped using KASP. Mixed linear regression models were used to test additive associations of ADIPOQ SNPs and PTSS severity at baseline, 3 and 6 months following rape. Results: The mean DTS score post-sexual assault was high (71.3 ± 31.5), with a decrease in PTSS severity shown over time for all genotypes. rs6444174TT genotype was inversely associated with baseline PTSS in the unadjusted model (β = -13.6, 95% CI [-25.1; -2.1], p = .021). However, no genotype was shown to be significantly associated with change in PTSS severity over time and therefore ADIPOQ SNP x childhood trauma interaction was not further investigated. Conclusion: None of the ADIPOQ SNPs selected for investigation in this population were shown to be associated with change in PTSS severity over a 6-month period and therefore their clinical utility as risk biomarkers for rape-related PTSD appears limited. These SNPs should be further investigated in possible gene-gene and gene-environment interactions.


Wavelet Analysis of the Temporal Dynamics of the Laser Speckle Contrast in Human Skin.
Spectral analysis of laser Doppler flowmetry (LDF) signals has been widely used in studies of physiological vascular function regulation. An alternative to LDF is the laser speckle contrast imaging method (LSCI), which is based on the same physical principle. In contrast to LDF, LSCI provides non-scanning full-field imaging of a relatively wide skin area and offers high spatial and temporal resolutions, which allows visualization of microvascular structure. This circumstance, together with a large number of works which had shown the effectiveness of temporal LSCI analysis, gave impetus to experimental studies of the relation between LDF and LSCI used to monitor the temporal dynamics of blood flow. Continuous wavelet transform was applied to construct a time-frequency representation of a signal. Analysis of 10 minute LDF and LSCI output signals recorded simultaneously revealed rather high correlation between oscillating components. It was demonstrated for the first time that the spectral energy of oscillations in the 0.01-2 Hz frequency range of temporal LSCI recordings carries the same information as the conventional LDF recordings and hence it reflects the same physiological vascular tone regulation mechanisms. The approach proposed can be used to investigate speckle pattern dynamics by LSCI in both normal and pathological conditions. The results of research on the influence of spatial binning and averaging on the spectral characteristics of perfusion monitored by LSCI are of considerable interest for the development of LSCI systems optimized to evaluate temporal dynamics.


Necrotizing fasciitis of the chest wall with a retropharyngeal abscess: case report and literature review.
We herein report a case of a diabetic 49-year-old woman with anterior chest wall necrotizing fasciitis that caused a retropharyngeal abscess and discuss the literature surrounding necrotizing soft tissue infections of the chest wall. The patient was treated with serial wound debridements, antibiotic therapy, and percutaneous drainage and serial irrigation of the retropharyngeal abscess with a silicone catheter. The resulting defect was grafted with a split thickness skin graft.


Characterization of free oligosaccharides from garden cress seed aqueous exudate using PGC LC-MS/MS and NMR spectroscopy.
Garden cress seeds produces mucilage that has found various food applications, however, there is little information on the free oligosaccharides (FOS) contents in these seeds. Herein, we explored the presence of FOS in cress seed aqueous exudate. PGC-LC MS/MS analysis indicated the presence of mainly hexose containing oligosaccharides such as raffinose, stachyose and verbascose belonging to raffinose family of oligosaccharides (RFOs). In addition, minor fraction of planteose, isomeric tri- and tetrasaccharides were also observed. Further, the structural confirmation of the abundant tri- and tetrasaccharide were obtained through 1D and 2D NMR analysis. Thus, the RFOs presence in cress seeds would enhance its bio-functionalities.


Mass balance of nitrogen, and estimates of COD, nitrogen and phosphorus used in microbial synthesis as a function of sludge retention time in a sequencing batch reactor system.
This study investigated characteristics of a sequencing batch reactor (SBR) system which was varied with respect to sludge retention time (SRT) (5.9, 8.2, 10.5, 12.2, and 16.2 days). The removal efficiencies of chemical oxygen demand (COD) were more than 90% under all SRT conditions, and the greatest efficiency (92.2%) occurred with a SRT of 16.2 days. As the SRT increased, the denitrification rate per mixed liquor suspended solids (MLSS) during the anoxic(I) period decreased significantly from 166.3 mg NO(X)(-)-N/g MLSS d to 68.8 mg NO(X)(-)-N/g MLSS d. As the SRT increased, the phosphorus removal efficiency decreased from 47.1% (SRT of 5.9 days) to 31.0% for a SRT of 16.2 days, because active phosphate release and uptake occurred under shorter SRT conditions. The mass balance of nitrogen (with respect to nitrogen in the influent) at a SRT of 16.2 days (the highest nitrogen removal efficiency) showed 14.9% of nitrogen was removed in clarified water effluent, 49.7% was removed by the sludge waste process and 33.3% was removed by denitrification. Nitrogen processing was well accounted for in the SBR system as the nitrogen mass balance was close to 100% (97.9%).


Combining prostrate-specific antigen and Gleason score increases the diagnostic power of endorectal coil magnetic resonance imaging in prostate cancer pathological stage.
The proper use of endorectal coil MRI (eMRI) images provide detailed information for the real extent of locally prostate cancer invasion and involvement of pelvic lymph nodes. This study evaluated the accuracy of endorectal coil magnetic resonance imaging (eMRI) results, combining the preoperative prostate-specific antigen (PSA), and the biopsy Gleason score to improve the diagnostic accuracy of prostate cancer (PCa) with organ-confined disease (OCD) or extracapsular extension (ECE)/seminal vesicle invasion (SVI). Between 2001 and 2007, 94 PCa patients received eMRI testing during presurgical evaluation and underwent radical prostatectomy. As a part of routine patient workup, serum PSA level and Gleason score after pathology examination were recorded. The eMRI images were used to help assess patient PCa staging status regarding OCD or ECE/SVI. These stage assessments as evaluated through the use of MRI were compared with the final specimen pathological stage after the patients underwent radical prostatectomy. Of the total 94 patients in our study, 65 had stage pT2, 12 had stage pT3a, and 17 had stage pT3b PCa. In patients with clinical stage T2 PCa, the Gleason score significantly improved the discriminative ability of eMRI to successfully predict PCa at the OCD stage. Otherwise, in cases of clinical stage T3 PCa, accurate determination of PSA levels significantly improved eMRI predictive ability to assess ECE or SVI staging. In clinical stage T2 PCa patients, integrating the biopsy Gleason score improved the discriminative ability to assess OCD PCa staging. Additionally, combining the preoperative PSA levels of clinical T3 prostate cancer cases with Gleason scores significantly improved the sensitivity and accuracy of eMRI diagnosis to distinguish ECE from SVI.


An example of burn prevention: the 'Urim' factory fire.
The blanket factory building at Kibbutz Urim in Israel was completely destroyed by a devastating fire. Forty-five of the 62 workers were injured, most of them very mildly, by inhalation of smoke. No skin burns were recorded. The preplanned fire evacuation programme that was routinely rehearsed and precisely carried out during the event prevented the grave results that could have followed such a disaster.


Quality of working life of employees in public healthcare organization in Finland: A cross-sectional study.
Work dissatisfaction, burnout and workforce shortage are major problems in healthcare globally, all of which are associated with QWL. Previous studies have found that the QWL of healthcare professionals is moderate or low. The aim was to describe the quality of working life (QWL) of employees working in public healthcare and describe the association between QWL and background variables. This study had a quantitative cross-sectional survey design. Data was collected from the employees of a Finnish healthcare organization in autumn 2021 using an online questionnaire (n = 837). Convenience sampling was used in the selection of the healthcare organization. The study was reported according to STROBE guidelines. The QWL was moderate, and the mean QWL index calculated from the questionnaire responses was 0.524. The QWL index was lowest in healthcare professionals and highest in upper management, with some dissatisfaction towards leadership noted.


Removal of selected endocrine disrupting chemicals and personal care products in surface waters and secondary wastewater by ozonation.
This study investigated the removal of parabens, N,N-diethyl-m-toluamide (DEET), and phthalates by ozonation. The second-order rate constants for the reaction between selected compounds with ozone at pH 7 were of (2.2 +/-0.2) X 10(6) to (2.9 +/-0.3) X 10(6) M 1/s for parabens, (2.1+/- 0.3) to (3.9 +/-0.5) M-1/s for phthalates, and (5.2 +/-0.3) M-1/s for DEET. The rate constants for the reaction between selected compounds with hydroxyl radical ranged from (2.49 +/-0.06) x 10(9) to (8.5 +/-0.2) x 10(9) M-1/s. Ozonation of selected compounds in secondary wastewater and surface waters revealed that ozone dose of 1 and 3 mg/L yielded greater than 99% depletion of parabens and greater than 92% DEET and phthalates, respectively. In addition, parabens were found to transform almost exclusively through the reaction with ozone, while DEET and phthalates were transformed almost entirely by hydroxyl radicals (.OH).


Haemophilus influenzae biofilm formation in chronic otitis media with effusion.
Otitis media with effusion (OME) is a highly prevalent disease in children, but the exact pathogenesis and role of bacteria are still not well understood. This study aimed to investigate the presence of otopathogenic bacteria in the middle ear effusion (MEE) and adenoid of children with chronic OME (COME), and to investigate in vivo whether these bacteria, especially Haemophilus influenzae, are organized as a biofilm in the middle ear fluid. MEE and adenoid samples were collected from 21 patients with COME. Extensive bacterial culturing and genotyping was performed on all middle ear and adenoid samples. Fluorescence in situ hybridization (FISH) and confocal laser scanning microscopy (CLSM) was used to visualize possible biofilm structures for a selection of middle ear effusion samples. 34 MEE samples were collected from 21 patients of which 64.7 % were culture positive for bacteria and 47.0 % were culture positive for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and/or Streptococcus pneumoniae. All 21 adenoid samples were culture positive for one or more of these four otopathogens. H. influenzae (35.3 %) and S. pneumoniae (76.2 %) were the most frequently cultured bacteria in the MEE and adenoid samples, respectively. The same bacterial species was found in MEE and adenoid for 84.6 % of the patients and in 81.2 % of the cases where the same species was found in more than one site it involved the same bacterial genotype. FISH and CLSM demonstrated the presence of H. influenzae specific biofilm structures in five of the eight culture positive MEEs that were tested, but in none of the two culture negative MEEs. The findings in this study indicate that the adenoid acts as a reservoir for bacteria in MEE and confirms that biofilms, in at least half of the cases consisting of H. influenzae, are indeed present in the MEE of children with COME. Biofilms may thus play a crucial role in the pathogenesis of COME, which is important in the understanding of this disease and the development of potential future treatment options.


Modulating effects of cholesterol feeding and simvastatin treatment on platelet-activating factor acetylhydrolase activity and lysophosphatidylcholine concentration.
Platelet-activating factor acetylhydrolyse (PAF-AH) is an enzyme that degrades PAF and bioactive oxidized lipids. However, it has been reported to be a risk factor for coronary heart disease. The present study examined the effects of cholesterol feeding and simvastatin treatment on plasma PAF-AH activity. Japanese White rabbits (n=22) were fed a diet containing 0.3% cholesterol and 3% corn oil for 1 month, and then divided into two groups that continued to receive this diet with (treated) or without (control) treatment with simvastatin (0.01%) for another 2 months. Cholesterol feeding increased and simvastatin treatment decreased apolipoprotein (apo) B-containing lipoprotein subfractions as characterized by capillary isotachophoresis, serum levels of total cholesterol, phospholipids, LDL-C, apoE, plasma and LDL-associated PAF-AH (LDL-PAF-AH) activities, and plasma lyso-PC concentration. Cholesterol feeding also increased apoB levels but decreased the LDL-PAF-AH/LDL-C ratio and did not change the plasma PAF-AH/lyso-PC ratio. Simvastatin treatment did not affect apoB levels and only slightly increased the LDL-PAF-AH/LDL-C ratio. Secretion of PAF-AH activity from monocyte-derived macrophages was increased by cholesterol feeding but not affected by simvastatin treatment. These results indicate that PAF-AH activity is increased by cholesterol feeding due to increased secretion of PAF-AH activity from macrophages and that PAF-AH activity is decreased by simvastatin due to increased removal of lipid and enzyme contents of LDL particles. Cholesterol elevation by cholesterol feeding and cholesterol-lowering by simvastatin modulate plasma PAF-AH activity by different mechanisms.


Expected Satiety: Application to Weight Management and Understanding Energy Selection in Humans.
Recent advances in the approaches used to quantify expectations of satiation and satiety have led to a better understanding of how humans select and consume food, and the associated links to energy intake regulation. When compared calorie for calorie some foods are expected to deliver several times more satiety than others, and multiple studies have demonstrated that people are able to discriminate between similar foods reliably and with considerable sensitivity. These findings have implications for the control of meal size and the design of foods that can be used to lower the energy density of diets. These methods and findings are discussed in terms of their implications for weight management. The current paper also highlights why expected satiety may also play an important role beyond energy selection, in moderating appetite sensations after a meal has been consumed, through memory for recent eating and the selection of foods across future meals.


A new long-proboscid genus of Pseudopolycentropodidae (Mecoptera) from the Middle Jurassic of China and its plant-host specializations.
We describe a new genus and species of Mecoptera with siphonate mouthparts, Sinopolycentropus rasnitsynigen. et sp. n., assigned to the family Pseudopolycentropodidae Handlirsch, 1925. The specimen was collected from late Middle Jurassic nonmarine strata of the Jiulongshan Formation in Inner Mongolia, northeastern China. The new material provides additional evidence for an early diversification of pseudopolycentropodids that was ongoing during the Middle Jurassic. This diversity also adds to the variety of known pseudopolycentropodids with tubular proboscides that apparently fed on ovulate fluids produced by Mesozoic gymnosperms.


Comparative studies with 15(R)-15-methylprostaglandin E2 (arbaprostil) in rat femoral arterial preparations in vivo and in vitro.
1. The vasodilator responses to 15(R)-15-methylprostaglandin E2 (arbaprostil), prostaglandin (PG) E2 and acetylcholine (ACh) administered into the femoral artery intra-arterial (i.a.) of anesthetized rats were attenuated by i.a. infusion of methylene blue, while that to nicardipine remained unaffected in the same dose-range of methylene blue. 2. The vasocontractor responses to arbaprostil and PGE2 in isolated femoral arterial strips were significantly potentiated by removal of the endothelium and the presence of NG-monomethyl L-arginine, while that to U-46619 remained unaffected under the same condition. 3. The present result indicates that the endothelium-dependent mechanism may play an important role in the vascular response to arbaprostil, like PGE2 and ACh.


Optimization of process parameters for drilled hole quality characteristics during cortical bone drilling using Taguchi method.
Orthopaedic surgery involves drilling of bones to get them fixed at their original position. The drilling process used in orthopaedic surgery is most likely to the mechanical drilling process and there is all likelihood that it may harm the already damaged bone, the surrounding bone tissue and nerves, and the peril is not limited at that. It is very much feared that the recovery of that part may be impeded so that it may not be able to sustain life long. To achieve sustainable orthopaedic surgery, a surgeon must try to control the drilling damage at the time of bone drilling. The area around the holes decides the life of bone joint and so, the contiguous area of drilled hole must be intact and retain its properties even after drilling. This study mainly focuses on optimization of drilling parameters like rotational speed, feed rate and the type of tool at three levels each used by Taguchi optimization for surface roughness and material removal rate. The confirmation experiments were also carried out and results found with the confidence interval. Scanning electrode microscopy (SEM) images assisted in getting the micro level information of bone damage.


Triangles and Family Engagement in Drug and Alcohol Addiction Treatment.
Despite the large number of studies that demonstrate the need for family involvement in addiction treatment, mental health professionals (MHPs) are often reluctant to collaborate with the affected family members (AFMs), while several times they enter-consciously or unconsciously-into a competitive relationship with the family of the person with addiction problems (PAPs). The present study presents the results of a thematic analysis of 42 vignettes provided by MHPs working in drug and alcohol addiction treatment. Participants' experiences were depicted by two overarching themes: the caring and the traumatizing triangle. Present findings suggest that MHPs' awareness of triadic influences and attempts to build alliances with AFMs supports PAPs' needs for reconciliation with AFMs and is supported by multidisciplinary need containment. In the attempt to collaborate with AFMs, MHPs need to avoid accepting the idealization of the PAPs and not to ally into the underestimation of the family, in order to resolve possible separation phenomena and to avoid therapeutic failure. Additionally, MHPs are called upon working out their own difficulties and possibly their prejudices about triangular interactions, so that the triangle MHPs-PAPs-AFMs can function therapeutically in a multidisciplinary context. Clinical supervision and Balint groups may support addiction professionals in these challenging tasks.


Nitric oxide inhibits a rise of ATP-introduced cytosolic free Ca2+ concentration and release from intracellular stored Ca2+.
The effects of ATP-introduced a rise in cytosolic free Ca2+ concentration and inhibition of nitric oxide were investigated. Measurement of free Ca2+ ([Ca2+]i) of cultured rat tail arterial smooth muscle cells using Fura-2/AM dual excitation wavelength spectrofluorometer. There are two components of [Ca2+]i can be evoked by ATP. One part is Ca2+ entry from Ca2+ channel and formed a plateau. The another part is a peak that released from Ca2+ store. Both of them can be inhibited by NO. The ATP induced [Ca2+]i rise that release Ca2+ from both Insp3 and ryanochine receptors and Ca2+ entry through calcium channels. The inhibition of NO on ATP induced [Ca2+]i rise that was mediated by cGMP.


Effects of auriculotherapy on weight and body mass index reduction in patients with overweight or obesity: Systematic review and meta-analysis.
Auriculotherapy is based on the stimulation of reflex points in the ear. However, little is known about its weight-reducing effects. The aim of the present systematic review and meta-analysis was to investigate the effects of auriculotherapy on weight and/or (BMI) reduction in overweight or patients with obesity. Twelve articles were selected for systematic review. Four randomized controlled trials (RCTs) investigating weight reduction and five investigating BMI reduction were selected for the meta-analyzes. The results revealed an association between auriculotherapy and weight reduction (WMD, 1.507; 95% CI, 0.606-2.407; p < 0.000). Auriculotherapy was also significantly associated with BMI reduction (WMD, 0.865; 95% CI, 0.533-1.196; p < 0.004). We found that auriculotherapy was effective in reducing weight and/or BMI in overweight or patients with obesity. However, the findings should be interpreted with caution due to heterogeneity.


Psychosocial factors and hospitalisations for COVID-19: Prospective cohort study of the general population.
To examine the association of a range of psychosocial factors with hospitalisation for COVID-19. Prospective cohort study. England. UK Biobank comprises around half a million people who were aged 40 to 69 years at study induction between 2006 and 2010 when information on psychosocial factors and covariates were captured. Hospitalisation for COVID-19 in England between 16th March and 26th April 2020 as provided by Public Health England. There were 908 hospitalisations for COVID-19 in an analytical sample of 431,051 people. In age- and sex-adjusted analyses, an elevated risk of COVID-19 was related to disadvantaged levels of education (odds ratio; 95% confidence interval: 2.05; 1.70, 2.47), income (2.00; 1.63, 2,47), area deprivation (2.20; 1.86, 2.59), occupation (1.39; 1.14, 1.69), psychological distress (1.58; 1.32, 1.89), mental health (1.50; 1.25, 1.79), neuroticism (1.19; 1.00, 1.42), and performance on two tests of cognitive function - verbal and numerical reasoning (2.66; 2.06, 3.34) and reaction speed (1.27; 1.08, 1.51). These associations were graded (p-value for trend ≤0.038) such that effects were apparent across the full psychosocial continua. After mutual adjustment for these characteristics plus ethnicity, comorbidity, and lifestyle factors, only the relationship between lower cognitive function as measured using the reasoning test and a doubling in the risk of the infection remained (1.98; 1.38, 2.85). A range of psychosocial factors revealed associations with hospitalisations for COVID-19 of which the relation with cognitive function was most robust to statistical adjustment.


Population Pharmacokinetics of Brigatinib in Healthy Volunteers and Patients With Cancer.
Brigatinib is an oral tyrosine kinase inhibitor approved in multiple countries for the treatment of patients with anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer who have progressed on or are intolerant to crizotinib. We report a population pharmacokinetic model-based analysis for brigatinib. Plasma concentration-time data were collected from 442 participants (105 healthy volunteers and 337 patients with cancer) who received single or multiple doses of oral brigatinib in one of five trials. Data were analyzed using non-linear mixed-effects modeling (NONMEM software version 7.3). Brigatinib plasma concentrations were best described by a three-compartment model with a transit compartment input (number of transit compartments = 2.35; mean transit time = 0.9 h). The final model included albumin as a covariate on apparent clearance. None of the additional covariates examined, including sex, age, race, body weight, mild or moderate renal impairment, total bilirubin, aspartate aminotransferase, and alanine aminotransferase, were found to meaningfully explain variability in apparent clearance, suggesting that no dose adjustment is required based on these covariates. Results from these population pharmacokinetic analyses informed the prescribing guidance for patients with mild or moderate renal impairment in the US Prescribing Information and the European Summary of Product Characteristics for brigatinib.


A model based on equations of kinetics to study nitrogen dioxide behavior within a plasma discharge reactor.
In this work, a zero-dimensional kinetics model is used to study the temporal behavior of different species such as charged particles, radicals and excited states inside a Dielectric Barrier Discharge plasma reactor. It is shown that, the reactor significantly reduces the concentration of nitrogen monoxide as an environmental pollutant. After a drastic increase, a decrease in the concentration of the NO2 molecules inside the reactor is seen. Nitrogen monoxide molecules with a very low concentration are produced inside the reactor and its quick conversion to other products is proved. The obtained results are compared with the existing experimental and simulation findings, whenever possible.


Integrated DNA, cDNA, and protein studies in Becker muscular dystrophy show high exception to the reading frame rule.
Becker muscular dystrophy (BMD) is a milder form of X-linked Duchenne muscular dystrophy (DMD). Here, we report a study of 75 patients with immunoblot and/or immunostaining findings of muscle biopsy consistent with BMD (abnormal dystrophin). We utilized multiplex ligation dependent probe amplification (MLPA) on genomic DNA (gDNA) to screen all 79 exons for both deletions and duplications. A total of 19 patients testing negative for MLPA mutations were tested for mRNA splicing abnormalities using cDNA-MLPA on muscle biopsy. Complete cDNA sequencing was done on MLPA-negative patients. We identified disease-causing mutations in 66 (88%) of the patients. Of the mutation-positive patients, 42 (64%) showed deletions of one or more exons, 14 (21%) showed duplications, and 10 (15%) showed various mutations detected by cDNA-MLPA and sequencing studies. We found a high rate of "exceptions" to the reading frame rule in this BMD series (out-of-frame BMD; 17/56 deletions/duplications; 30%). This was partly explained by the high incidence of 5' gene deletions in BMD patients (a region known to be a hotspot for exceptions), and due to complex splicing patterns in which a subset of transcripts showed deletions larger than gDNA (exon-skipping). Comparing our findings in BMD to previously published DMD data, BMD patients have higher proportions of duplications, a different distribution of mutations, and higher exception to the reading frame rule.


Occurrence of Escherichia coli and faecal coliforms in drinking water at source and household point-of-use in Rohingya camps, Bangladesh.
Safe water is essential for life but unsafe for human consumption if it is contaminated with pathogenic microorganisms. An acceptable quality of water supply (adequate, safe and accessible) must be ensured to all human beings for a healthy life. We collected and analyzed a total of 12,650 drinking water samples, for the presence of Escherichia coli and faecal coliforms, from a large habitation of the displaced Rohingya population comprising of about 1.16 million people living within 4 km2. We found that 28% (n = 893) water samples derived from tubewells were contaminated with faecal coliforms and 10.5% (n = 333) were contaminated with E. coli; also, 73.96% (n = 4644) samples from stored household sources (at point of use-POU) were found contaminated with faecal coliforms while 34.7% (n = 2179) were contaminated with E. coli. It was observed that a higher percentage of POU samples fall in the highest risk category than that of their corresponding sources. From our findings, it appears that secondary contamination could be a function of very high population density and could possibly occur during collection, transportation, and storage of water due to lack of knowledge of personal and domestic hygiene. Hence, awareness campaign is necessary, and the contaminated sources should be replaced. Further, the POU water should be treated by a suitable method.