Attention-guided joint learning CNN with noise robustness for bearing fault diagnosis and vibration signal denoising.
Mechanical system usually operates in harsh environments, and the monitored vibration signal faces substantial noise interference, which brings great challenges to the robust fault diagnosis. This paper proposes a novel attention-guided joint learning convolutional neural network (JL-CNN) for mechanical equipment condition monitoring. Fault diagnosis task (FD-Task) and signal denoising task (SD-Task) are integrated into an end-to-end CNN architecture, achieving good noise robustness through dual-task joint learning. JL-CNN mainly includes a joint feature encoding network and two attention-based encoder networks. This architecture allows FD-Task and SD-Task can achieve deep cooperation and mutual learning. The JL-CNN is evaluated on the wheelset bearing dataset and motor bearing dataset, which shows that JL-CNN has excellent fault diagnosis ability and signal denoising ability, and it has good performance under strong noise and unknown noise.


One-step fermentative production of poly(lactate-co-glycolate) from carbohydrates in Escherichia coli.
Poly(lactate-co-glycolate) (PLGA) is a widely used biodegradable and biocompatible synthetic polymer. Here we report one-step fermentative production of PLGA in engineered Escherichia coli harboring an evolved polyhydroxyalkanoate (PHA) synthase that polymerizes D-lactyl-CoA and glycolyl-CoA into PLGA. Introduction of the Dahms pathway enables production of glycolate from xylose. Deletion of ptsG enables simultaneous utilization of glucose and xylose. An evolved propionyl-CoA transferase converts D-lactate and glycolate to D-lactyl-CoA and glycolyl-CoA, respectively. Deletion of adhE, frdB, pflB and poxB prevents by-product formation. We also demonstrate modulation of the monomer fractions in PLGA by overexpressing ldhA and deleting dld to increase the proportion of D-lactate or by deleting aceB, glcB, glcD, glcE, glcF and glcG to increase the proportion of glycolate. Incorporation of 2-hydroxybutyrate is prevented by deleting ilvA or feeding strains with L-isoleucine. The utility of our approach for generating diverse forms of PLGA is shown by the production of copolymers containing 3-hydroxybutyrate, 4-hydroxybutyrate or 2-hydroxyisovalerate.


Expression of heat-shock protein 90 in glucocorticoid-sensitive and -resistant childhood acute lymphoblastic leukaemia.
Early reduction of leukaemic cells by chemotherapy is a strong predictor for treatment outcome in childhood acute lymphoblastic leukaemia (ALL). In ALL-(Berlin-Frankfurt-Münster) trials, early treatment response is assessed by the in vivo response to glucocorticoids (prednisone response, PR), the molecular background of which is unknown. The intracellular effects of glucocorticoids (GCs) are mediated by the glucocorticoid receptor (GR). In the absence of GC, the inactive GR resides within a multiprotein complex, consisting predominantly of the chaperone protein hsp90 (heat-shock protein 90). Until now, studies targeting GC resistance mainly focused on GR disorders and alterations of genes known to be associated with drug resistance. In addition, the GR multiprotein complex was associated with GC resistance in in vitro studies. We performed a case-control study for PR to investigate the association of in vivo GC resistance and hsp90 expression in childhood ALL. Hsp90 expression was assessed using a real-time PCR approach (Taqman technology) and Western blot technology. In this setting, we found no association of in vivo GC resistance and hsp90 expression. Therefore, we conclude that the expression of hsp90, the major component of the GR activating complex, is of minor importance for the in vivo GC resistance in childhood ALL.


Perinatal Outcomes of Singleton Live Births Following Preimplantation Genetic Testing for Chromosomal Structural Rearrangements in Single Frozen-Thawed Blastocyst Transfer Cycles: a Retrospective Cohort Study.
This study investigated whether singleton pregnancies conceived after preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) are associated with a higher risk of adverse perinatal outcomes than singleton pregnancies conceived after intracytoplasmic sperm injection (ICSI). We collected data on singleton live births after PGT-SR (n = 107) and ICSI (n = 585) in our hospital from January 2017 to August 2020. Multivariable analyses were used to adjust for maternal age, body mass index, gravidity and parity, paternal age, ovulatory disorder, and recurrent spontaneous abortion. The unadjusted results showed a significantly higher risk of hypertensive disorders of pregnancy (HDP) (odds ratio (OR) = 2.47; 95% confidence interval (CI): 1.10-5.54; P = 0.029) associated with PGT-SR singleton pregnancies than with ICSI singleton pregnancies. However, after adjusting for potential confounders, there were no longer any significant differences in the risk of HDP (adjusted OR = 2.24; 95% CI: 0.92-5.48; P = 0.077) between PGT-SR and ICSI singleton pregnancies. There were no significant differences between PGT-SR and ICSI singleton pregnancies in terms of gestational diabetes, preterm premature rupture of membranes, placenta previa, cesarean delivery, gestational age (weeks), preterm delivery (< 37 weeks), very preterm delivery (≥ 28 weeks and < 32 weeks), birth weight (g), low birth weight (< 2500 g), very low birth weight (< 1500 g), birth height (cm), birth defects, and 1-min and 5-min Apgar scores. In conclusion, for single frozen-thawed blastocyst cycles, there were no significant differences in adverse perinatal outcomes between PGT-SR and ICSI singleton pregnancies. However, due to the limited sample size, these conclusions need to be confirmed by further studies.


Conditional knockout mouse for tissue-specific disruption of the cyclooxygenase-2 (Cox-2) gene.
Cyclooxygenase-2 (Cox-2) modulates many normal functions, and appears to play a role in a wide variety of pathophysiologic conditions. Cox-2 gene expression is induced in many different cell types, in response to many distinct stimuli. We generated a conditional knockout mouse in which critical exons of the Cox-2 gene are flanked with loxP sites. Cox-2(flox/flox) mice appear normal and are fertile. Recombination at the loxP sites, loss of Cox-2 protein expression, and prevention of induced PGE2 accumulation are observed in Cox-2(flox/flox) mouse embryo fibroblasts following infection with an adenovirus expressing CRE recombinase. In vivo recombination at the Cox-2(flox) allele was demonstrated in the liver of Cox-2(flox/flox) mice following intravenous injection of adenovirus expressing CRE recombinase. Spatially and temporally restricted elimination of the Cox-2 gene in Cox-2(flox/flox) conditional knockout mice should provide a valuable tool to analyze the cell type-specific role of Cox-2 in many disease models.


Subclinical cardiovascular disease in HIV controller and long-term nonprogressor populations.
Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.


Celiac Trunk and Hepatic Arteries: Anatomical Variations of Liver Arterial Supply as Detected with Multidetector Computed Tomography in 1,520 Patients and its Clinical Importance.
Hepatic arterial variations are relatively common, but usually overlooked by radiologists, leading to iatrogenic complications or prolonging interventional or surgical procedures. Michels in 1966 classified hepatic arterial variations in 10 categories, based on a cadaveric study. Establishment of multidetector computed tomography (MDCT) provides useful anatomical information. The purpose of our study is to highlight these variations and to propose of a user-friendly algorithm when studying a CT examination. We studied 1,520 contrast-enhanced CTs (16-row MDCT system) during arterial phase and searched for hepatic arteries and celiac trunk (CTr) variations. CT images were postproccessed using multiplanar reconstruction, maximum intensity projection and volume rendering techniques in axial, sagittal, and coronal planes. Our results were organized according to Michels' classification. Normal anatomy was found in 72.89% of the cases and variations classified in Types II-X in 22.24%. However, 4.87% of the cases could not be classified in Michels' types. A single arterial variation was found in 22.89% of the cases and multiple arterial variations were found in 4.21% of the cases. We examined first the aorta for supernumerary branches and then checked the fissure between right and left liver lobe, following porta hepatis, and finally the CTr and superior mesenteric artery. Hepatic arteries and CTr variations are relatively common (27.11%) and should be identified by the radiologists when studying CTs as their recognition provides better surgical planning, preventing iatrogenic complications. Imaging in coronal plane was helpful for end branches, while sagittal plane was better for aortic branches. Clin. Anat., 33:1091-1101, 2020. © 2019 Wiley Periodicals, Inc.


Abiraterone acetate plus LHRH therapy versus abiraterone acetate while sparing LHRH therapy in patients with progressive, metastatic and chemotherapy-naïve, castration-resistant prostate cancer (SPARE): study protocol for a randomized controlled trial.
The value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Argumentation for cessation of LHRH therapy is the prolonged suppression of testosterone levels after the withdrawal of LHRH analogues and the fact that disease progression occurs despite castration levels of testosterone. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase (Cyp17)-inhibitor, abiraterone, which has the ability to further suppress testosterone serum levels over LHRH therapy alone, continuation of LHRH therapy seems to be negligible. However, the proven increase of luteinizing hormone levels after LHRH withdrawal, which is even further increased by abiraterone, may counteract the effects of abiraterone by the induction of enzymes of steroidogenesis. Therefore, cessation of LHRH therapy when starting treatment with abiraterone in CRPC may display an unpredictable hazard to the patients. This study will explore the role of continuation of LHRH therapy when starting treatment with abiraterone in patients with asymptomatic or mildly symptomatic, chemotherapy-naïve CPRC. The trial will assess radiographic progression-free survival after 12 months of treatment with abiraterone/prednisone in patients who will be randomized to receive continuing LHRH therapy versus LHRH withdrawal at the time of starting abiraterone therapy. This multicenter, prospective, randomized, exploratory phase-II trial will bring about new data regarding the efficacy and safety of abiraterone/prednisone treatment with or without continuation of LHRH therapy. In addition, further insight into the complex hormonal changes under treatment will be gained and the results of this trial may give rise to a larger phase-III trial to examine the possibility of withdrawing LHRH therapy in patients with CRPC. ClinicalTrials.gov, ID: NCT02077634 . Registered on 9 December 2013.


Design, synthesis and antifungal activities of novel triazole derivatives with selenium-containing hydrophobic side chains.
In this work, a series of novel 1,2,4-triazole derivatives with selenium-containing hydrophobic side chains were designed and synthesized based on the structure of lanosterol 14α-demethylase (CYP51). All compounds were characterized by HRMS, 1H NMR and 13C NMR. Then, their antifungal activities against eight human pathogenic fungi were evaluated in vitro by testing the minimal inhibitory concentrations. The results showed that nearly all tested compounds were found to be more potent against all tested fungal strains than control drug fluconazole. Further mechanism study demonstrated that the target compounds had fungal CYP51 inhibitory activity. Meanwhile, representative compounds revealed low cytotoxic effects toward mammalian cell lines. In addition, the docking results showed that the target compounds bound to Candida albicans CYP51 in a better pattern than fluconazole, especially in the narrow hydrophobic cleft. Overall, the novel 1,2,4-triazole derivatives with selenium-containing hydrophobic side chains can be further developed for the potential treatment of invasive fungal infections.


A step-by-step protocol for meiotic chromosome counts in flowering plants: A powerful and economical technique revisited.
Counting chromosomes is a fundamental botanical technique, yet it is often intimidating and increasingly sidestepped. Once mastered, the basic protocol can be applied to a broad range of taxa and research questions. It also reveals an aspect of the plant genome that is accessible with only the most basic of resources-access to a microscope with 1000× magnification is the most limiting factor. Here we provide a detailed protocol for choosing, staining, and squashing angiosperm pollen mother cells. The protocol is supplemented by figures and two demonstration videos. The protocol we provide will hopefully demystify and reinvigorate a powerful and once commonplace botanical technique that is available to researchers regardless of their location and resources.


Bi-directional semantic similarity for gene ontology to optimize biological and clinical analyses.
Semantic similarity analysis facilitates automated semantic explanations of biological and clinical data annotated by biomedical ontologies. Gene ontology (GO) has become one of the most important biomedical ontologies with a set of controlled vocabularies, providing rich semantic annotations for genes and molecular phenotypes for diseases. Current methods for measuring GO semantic similarities are limited to considering only the ancestor terms while neglecting the descendants. One can find many GO term pairs whose ancestors are identical but whose descendants are very different and vice versa. Moreover, the lower parts of GO trees are full of terms with more specific semantics. This study proposed a method of measuring semantic similarities between GO terms using the entire GO tree structure, including both the upper (ancestral) and the lower (descendant) parts. Comprehensive comparison studies were performed with well-known information content-based and graph structure-based semantic similarity measures with protein sequence similarities, gene expression-profile correlations, protein-protein interactions, and biological pathway analyses. The proposed bidirectional measure of semantic similarity outperformed other graph-based and information content-based methods.


Transglutaminase activity and N epsilon (gamma glutamyl) lysine isopeptide levels during cell growth: an enzymic and immunological study.
A monoclonal antibody (MAb) 81D1c2, which recognizes the N epsilon (gamma glutamyl) lysine isopeptide produced by the action of transglutaminase activity was prepared. Its reactivity towards the homologous isopeptide was about 3-fold greater than that with either N alpha (alpha glutamyl) lysine (a naturally occurring heterologous dipeptide) or N alpha (gamma glutamyl) lysine, another heterologous peptide not described so far in naturally occurring proteins. When used in an immunohistochemical study on cells in culture derived from human carcinoma of the larynx (HEp2) and from chicken embryo cells (CEC), both fixed in acetone, this MAb detected N epsilon (gamma glutamyl) lysine residues in the nucleus. The amount of N epsilon (gamma glutamyl) lysine isopeptides follows closely transglutaminase activity during the lag phase of growth of both CEC and HEp2 cells. However, during exponential growth, the 2 parameters decrease concomitantly in HEp2 cells, whereas in CEC, transglutaminase activity increases but isopeptide bond levels drop. Compared with other reported methods for measuring isopeptides, this immunohistological approach permits the localization and at least the semi-quantitative determination of N epsilon (gamma glutamyl) lysine in cells in situ.


A case of acute stent thrombosis during treatment with the thrombopoietin receptor agonist peptide--romiplostim.
Romiplostim is a thrombopoietin receptor agonist that increases platelet counts and restores platelet function in patients with chronic immune thrombocytopenia (ITP). Increase in platelet count and platelet activation has been associated with increased thromboembolic risk. The present case report describes an interesting case of acute stent thrombosis in a patient with chronic immune thrombocytopenic purpura (ITP) being treated with romiplostim.


Cancer inequalities in incidence and mortality in the State of São Paulo, Brazil 2001-17.
Cancer disparities exist between and within countries; we sought to compare cancer-specific incidence and mortality according to area-level socioeconomic status (SES) in the State of São Paulo, Brazil. Cancer cases diagnosed 2003-2017 in the Barretos region and 2001-2015 in the municipality of São Paulo were obtained from the respective cancer registries. Corresponding cancer deaths were obtained from a Brazilian public government database. Age-standardized rates for all cancer combined and the six most common cancers were calculated by SES quartiles. There were 14,628 cancer cases and 7513 cancer deaths in Barretos, and 472,712 corresponding cases and 194,705 deaths in São Paulo. A clear SES-cancer gradient was seen in São Paulo, with rates varying from 188.4 to 333.1 in low to high SES areas, respectively. There was a lesser social gradient for mortality, with rates in low to high SES areas ranging from 86.4 to 98.0 in Barretos, and from 99.2 to 100.1 in São Paulo. The magnitude of the incidence rates rose markedly with increasing SES in São Paulo city for colorectal, lung, female breast, and prostate cancer. Conversely, both cervical cancer incidence and mortality rose with lower levels of SES in both regions. A clear SES association was seen for cancers of the prostate, female breast, colorectum, and lung for São Paulo. This study offers a better understanding of the cancer incidence and mortality profile according to SES within a highly populated Brazilian state.


Interaction between the N-terminal SH3 domain of Nck-alpha and CD3-epsilon-derived peptides: non-canonical and canonical recognition motifs.
The first SH3 domain (SH3.1) of Nckalpha specifically recognizes the proline-rich region of CD3varepsilon, a subunit of the T cell receptor complex. We have solved the NMR structure of Nckalpha SH3.1 that shows the characteristic SH3 fold consisting of two antiparallel beta-sheets tightly packed against each other. According to chemical shift mapping analysis, a peptide encompassing residues 150-166 of CD3varepsilon binds at the canonical SH3 binding site. An exhaustive comparison with the structures of other SH3 domains able and unable to bind CD3varepsilon reveals that Nckalpha SH3.1 recognises a non-canonical PxxPxxDY motif that orientates at the binding site as a class II ligand. A positively charged residue (K/R) at position -2 relative to the WW sequence at the beginning of strand beta3 is crucial for PxxDY recognition. A 14-mer optimised Nckalpha SH3.1 ligand was found using a multi-substitution approach. Based on NMR data, this improved ligand binds Nckalpha SH3.1 through a PxxPxRDY motif that combines specific stabilising interactions corresponding to both canonical class II, PxxPx(K/R), and non-canonical PxxPxxDY motifs. This explains its higher capacity for Nckalpha SH3.1 binding relative to the wild type sequence.


Pharmacokinetic model of circulating covalent aggregates of insulin.
Covalent aggregates of insulin in blood of insulin-treated diabetic patients account for as much as 70% (mean 28 +/- 3.6%) of serum insulin immunoreactivity. These aggregates may originate in therapeutic insulin, because similar substances account for 0.1-3% of these preparations. Larger amounts in blood imply that aggregates accumulate as a result of delayed clearance. To test and quantify this speculation, we calculated the plasma kinetics of this material in four normal volunteers who received large intravenous doses (30 mU.kg-1.min-1) of beef-pork crystalline zinc insulin for 120 min. Insulin aggregate and monomer concentrations were measured in blood samples obtained at regular intervals throughout the infusion and during 4 h after discontinuation of insulin. Pharmacokinetic parameters were calculated from the data. Insulin aggregate and monomer serum t 1/2 were 63.6 +/- 6.9 and 34.3 +/- 2.8 min, respectively, and clearances were 101 +/- 10 and 232 +/- 47 ml/min. Volume of distribution (V beta) and volume at steady state (Vss) were 9.1 +/- 1.8 and 8.2 +/- 2.2 L for insulin aggregate and 11.6 +/- 2.8 and 12.2 +/- 3.6 L for insulin monomer, respectively. Mean residency time was 141 +/- 14 and 114 +/- 10 min for insulin aggregate and monomer, respectively [P less than .01 for all parameters except V beta (.014) and Vss (.012), aggregate vs. monomer]. Thus, in relation to insulin monomer, calculated pharmacokinetic parameters of the aggregate predict accumulation after insulin injection. Plasma t 1/2 of the aggregate was almost double that of monomeric insulin; total-body clearance and the corresponding volumes of distribution were smaller.


The Emerging Role of Peripheral Nerve Stimulation in Postoperative Analgesia.
Though peripheral nerve stimulation has long been utilized in the field of chronic pain management, its use in acute pain management in the postoperative period is relatively novel and warrants further consideration. In the postsurgical period, peripheral nerve stimulation may offer an additional low-risk, opioid-sparing analgesic option, which is particularly pertinent in the setting of the ongoing opioid epidemic, as inadequate postsurgical analgesia has been shown to increase the risk of developing persistent or chronic postsurgical pain. In this review, we discuss the current literature that illustrate the emerging role of peripheral nerve stimulation as an effective treatment modality in the postoperative period for the management of acute pain, as various studies have recently been conducted evaluating the feasibility of utilizing percutaneous peripheral nerve stimulation as an adjunct in postsurgical analgesia. Nonetheless, future studies are necessary to continue to elucidate the short- and long-term impacts of peripheral nerve stimulation use in acute postsurgical analgesia.


A profile of body mass index in a large rural Victorian obstetric cohort.
To report on the prevalence and implications of overweight and obesity in a rural maternity cohort. A retrospective 6-2013 cohort of 6138 pregnancies managed in a rural Victorian maternity service from 1 January 2005 to 31 December 2010. Maternal body mass index (BMI), prevalence of overweight and obesity, prevalence of pregnancy complications and their association with BMI class. A total of 65.6% of all women were overweight or obese. Only 32.7% of the women were of normal/healthy weight; 1.6% were underweight, 33.0% were overweight, 18.6% were obese class I, 8.3% obese class II and 5.7% were obese class III. Increased BMI was associated with increased rates of induction of labour, gestational diabetes mellitus, pregnancy-induced hypertension, operative vaginal deliveries, caesarean sections, invasive fetal monitoring, increased gestational age at delivery, increased birth weight, and increased maternal length of stay (P < 0.01 for all). Analysed separately, 60.5% of first-time mothers were overweight or obese. Almost two-thirds of this rural maternity cohort were overweight or obese; twice the level reported from metropolitan centres and higher than other Australian reports. The associations with complications are similar to those reported previously. This high rate of maternal overweight and obesity may have implications for rural maternity funding, outcomes and perinatal mortality rates.


Epidermal growth factor stimulates the growth of A431 tumors in athymic mice.
Growth of the human epidermoid carcinoma cell line A431 in vitro is stimulated by low concentrations of epidermal growth factor (EGF; 0.1-10 pM) and inhibited by high concentrations (0.1-10 nM). This cell also grows as a solid tumor in female athymic mice. Sustained high levels of EGF in vivo can be achieved by the administration of testosterone to female mice via a cholesterol-based pellet inserted subcutaneously. This chronic elevation of EGF levels (serum concentration = 90 ng/ml), however, does not affect growth of the tumor. In contrast, low levels of the growth factor (0.5 micrograms/g body wt by injection 5 times/week; serum concentration = 8.25 ng/ml) stimulate growth of the tumor. These data suggest that the mechanism(s) involved in the inhibition of A431 cell growth by EGF in vitro does not function in vivo and the physiologically significant effect of EGF in vivo is growth promotion.


Synergistic Ternary Composite (Carbon/Fe3 O4 @Graphene) with Hollow Microspherical and Robust Structure for Li-Ion Storage.
The electrode materials with hollow structure and/or graphene coating are expected to exhibit outstanding electrochemical performances in energy-storage systems. 2D graphene-wrapped hollow C/Fe3 O4 microspheres are rationally designed and fabricated by a novel facile and scalable strategy. The core@double-shell structure SPS@FeOOH@GO (SPS: sulfonated polystyrene, GO: graphene oxide) microspheres are first prepared through a simple one-pot approach and then transformed into C/Fe3 O4 @G (G: graphene) after calcination at 500 °C in Ar. During calcination, the Kirkendall effect resulting from the diffusion/reaction of SPS-derived carbon and FeOOH leads to the formation of hollow structure carbon with Fe3 O4 nanoparticles embedded in it. In the rationally constructed architecture of C/Fe3 O4 @G, the strongly coupled C/Fe3 O4 hollow microspheres are further anchored onto 2D graphene networks, achieving a strong synergetic effect between carbon, Fe3 O4 , and graphene. As an anode material of Li-ion batteries (LIBs), C/Fe3 O4 @G manifests a high reversible capacity, excellent rate behavior, and outstanding long-term cycling performance (1208 mAh g(-1) after 200 cycles at 100 mA g(-1) ).


Systematic review and meta-analysis of current evidence in endograft therapy vs medical treatment for uncomplicated type B aortic dissection.
Best medical therapy (BMT) should be recommended for treating uncomplicated Stanford type B aortic dissection (uSTBAD), whereas thoracic aortic endovascular repair (TEVAR) has been controversial for uSTBAD. In this paper, a meta-analysis was conducted on all available randomized controlled trials and observational studies that evaluated the relative benefits and harms of TEVAR and BMT for the management of patients suffering from uSTBAD. Primary endpoints consisted of early adverse events, long-term adverse events, and aortic remodeling. In addition, risk differences (RDs) or odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The random-effects model or the fixed-effects model was used in accordance with the 50% heterogeneity threshold. Seven observational studies and two randomized controlled studies from 11 articles that contained 15,066 patients with uSTBAD (1518 TEVARs) met the inclusion criteria. For early outcomes, no significant differences were found between the TEVAR group and the BMT group in aortic rupture, retrograde dissection, paraplegia/paraparesis, reintervention, aorta-related death, and all-cause death. In the long run, the TEVAR group was found to have a significantly lower incidence of adverse events, which included aortic rupture (OR, 0.26; 95% CI, 0.16-0.42; P < .05; heterogeneity: P = .90, I2 = 0%), reintervention (OR, 0.45; 95% CI, 0.26-0.75; P < .05; heterogeneity: P = .17, I2 = 41%), aorta-related death (OR, 0.27; 95% CI, 0.18-0.42; P < .05; heterogeneity: P = .61, I2 = 0%), and all-cause death (OR, 0.52; 95% CI, 0.42-0.66; P < .05; heterogeneity: P = .05, I2 = 53%) as compared with the BMT group. Moreover, in compared with BMT, TEVAR was found to significantly contribute to the complete thrombosis of thoracic false lumen (OR, 55.34; 95% CI, 34.32-89.21; P < .05; heterogeneity: P = .97, I2 = 0%), and aortic regression (true lumen expansion and false lumen shrinkage). Although early endovascular repair of uSTBAD does not outperform BMT, its implementation is found to be necessary to facilitate the long-term prognosis. Accordingly, if early TEVAR is to be deferred, close follow-up is critical to allow for timely reintervention.


Association between serum uric acid level and systemic lupus erythematosus kidney outcome: An observational study in Southern Chinese population and a meta-analysis.
The study aimed to explore the effect of serum uric acid (SUA) level on the progression of kidney function in systemic lupus erythematosus (SLE) patients. A total of 123 biopsy-proven lupus nephritis (LN) patients were included in this retrospective observational study. Cox proportional hazard regression analyses as well as restricted cubic spline analyses were performed to identify predictors of renal outcome in LN patients. We also performed a systematic review and meta-analysis for SUA and overall kidney outcomes in SLE patients. Based on the laboratory tests at renal biopsy, 72 (58.5%) of the 123 patients had hyperuricemia. The median (IQR) follow-up duration was 3.67 years (1.79-6.63 years), and a total of 110 (89.4%) patients experienced progression of LN. Increased serum uric acid level, whether analyzed as continuous or categorical variable, was associated with higher risk of LN progression in Cox proportional hazard regression model (hazard ratio [HR]: 1.003, 95% confidence interval [CI]: 1.001-1.005; HR: 1.780, 95% CI: 1.201-2.639, respectively). This relationship maintained in women (HR: 1.947, 95% CI: 1.234-3.074) but not men (HR: 2.189, 95% CI: 0.802-5.977). The meta-analysis showed a similar result that both continuous and categorical SUA were positively associated with the risk of kidney function progression in LN (weighted mean difference [WMD]: 1.73, 95% CI: 0.97-2.49; odds ratio [OR]: 1.55, 95% CI: 1.20-2.01, respectively). Our study found overall and especially in women that higher SUA in LN patients were associated with increased risk of renal progression. Meta-analysis yielded consistent results. Future studies are required to establish if uric acid can be used as a biomarker for risk assessment and/or as a novel therapeutic target in SLE.


Chitosan as matrix for bio-polymer dispersed liquid crystal systems.
The obtaining of bio-polymer dispersed liquid crystal (bio-PDLC) systems based on a chitosan polymer matrix is reported here for the first time. The new PDLC composites have been obtained by encapsulation of 4-cyano-4'-pentylbiphenyl (5CB) as low molecular weight liquid crystal into chitosan, and they have been characterized by polarized optical microscopy, differential scanning calorimetry, electron and transmission scanning microscopy, Raman and fluorescence spectroscopy. Submicrometric liquid crystalline droplets with uniform size distribution and density have been obtained for low liquid crystal content into the PDLCs. The droplets have a radial configuration being anchored into chitosan matrix by an interface ordering coupling phenomenon.


Imaging and elemental mapping of biological specimens with a dual-EDS dedicated scanning transmission electron microscope.
A dedicated analytical scanning transmission electron microscope (STEM) with dual energy dispersive spectroscopy (EDS) detectors has been designed for complementary high performance imaging as well as high sensitivity elemental analysis and mapping of biological structures. The performance of this new design, based on a Hitachi HD-2300A model, was evaluated using a variety of biological specimens. With three imaging detectors, both the surface and internal structure of cells can be examined simultaneously. The whole-cell elemental mapping, especially of heavier metal species that have low cross-section for electron energy loss spectroscopy (EELS), can be faithfully obtained. Optimization of STEM imaging conditions is applied to thick sections as well as thin sections of biological cells under low-dose conditions at room and cryogenic temperatures. Such multimodal capabilities applied to soft/biological structures usher a new era for analytical studies in biological systems.


Contamination of freshly slaughtered pig carcasses with human pathogenic Yersinia enterocolitica.
Evidence is presented for the extent of contamination of freshly slaughtered pig carscasses with human pathogenic Yersinia enterocolitica and shows the significance of faecal contamination as a source of infection. Swab samples collected from the rectum and the surface of a total of 1458 pig carcasses were examined for the presence of human pathogenic Y. enterocolitica. Y. enterocolitica, biovar IV, serogroup 0:3, were isolated from the rectum of 360 pigs (24.7%). The organism was isolated from carcass surfaces with varying frequencies depending on the evisceration technique. Manual evisceration was found to correspond with high frequencies of contamination: 26.3% on the medial hind limb and 12.9% on the split sternum. The use of a mechanised bung cutter was found to reduce the rate of contamination, especially when the bung cutter was used in connexion with enclosing the anus and rectum in a plastic bag to minimise faecal contamination. When carcasses were eviscerated in this way, it was possible to reduce carcass contamination to 1.9% on the medial hind limb, 1.0% in the pelvic duct, and 2.2% on the split sternum.


Ribonucleic acid synthesis in rat liver during fatty acid stimulated secretion of very low density lipoproteins.
Production of very low density lipoproteins by the liver depends on the cellular availability of fatty acids. It is stimulated by the uptake of free fatty acids from the plasma and by increased lipogenesis and is inhibited by actinomycin D, suggesting that RNA synthesis is involved in the regulation of apolipoprotein synthesis. This hypothesis has been investigated in rats in vivo and in isolated perfused livers with and without stimulation by fatty acid overload: [14C] orotate incorporation in liver polyribosomal RNA is 60 per cent greater in stimulated livers as compared to controls. This increase is primarily due to a higher incorporation in bound polysomes and in those containing at least six ribosomes and does not result from the inhibition of ribonuclease. RNase digestion of polysomal RNA (4.10(-10) M enzyme, 0 degrees C, 3 h) shows that there is twice as much radioactivity in the hydrolyzed RNA of stimulated livers as compared to controls. After partial purification of poly A-rich RNA by affinity chromatography, the mass yield and radioactivity are increased by 100 per cent in stimulated livers as compared to controls. In conclusion, de novo RNA synthesis seems to be necessary for fatty acid stimulation of VLDL production.


Enhancing the durable performance of LiMn2O4 at high-rate and elevated temperature by nickel-magnesium dual doping.
Various nickel and magnesium dual-doped LiNixMg0.08Mn1.92-xO4 (x ≤ 0.15) were synthesized via a modified solid-state combustion method. All as-prepared samples show typical spinel phase with a well-defined polyhedron morphology. The Ni-Mg dual-doping obviously decreases the lattice parameter that gives rise to the lattice contraction. Owing to the synergistic merits of metal ions co-doping, the optimized LiNi0.03Mg0.08Mn1.89O4 delivers high initial capacity of 115.9 and 92.9 mAh·g-1, whilst retains 77.1 and 69.7 mAh·g-1 after 1000 cycles at 1 C and high current rate of 20 C, respectively. Even at 10 C and 55 °C, the LiNi0.03Mg0.08Mn1.89O4 also has a discharge capacity of 92.2 mAh·g-1 and endures 500 cycles long-term life. Such excellent results are contributed to the fast Li+ diffusion and robust structure stability. The anatomical analysis of the 1000 long-cycled LiNi0.03Mg0.08Mn1.89O4 electrode further demonstrates the stable spinel structure via the mitigation of Jahn-Teller effect. Hence, the Ni-Mg co-doping can be a potential strategy to improve the high-rate capability and long cycle properties of cathode materials.


Dynamic behavior of large DNA molecules in an aqueous solution toward the understanding of pulsed-field electrophoresis.
Conformational dynamics of large DNA molecules have been monitored by use of a fluorescence microscopy. The time-trace of the movement has been quantitatively analyzed with Fourier transformation.


Environmental epidemiologic issues and minority health.
There exist great differences in morbidity and mortality across racial, cultural, and socioeconomic groups. Certain factors, like limited access to health care, are known to contribute to these differences. The contribution of other factors, like disparities in exposure to environmental hazards, is largely unknown as to the effect on minority groups' morbidity and mortality. This article describes select environmental hazards faced by minorities, such as lead toxicity in children, proximity to hazardous waste sites, and consumption of food contaminated with toxic substances, as well as the role of epidemiologists in documenting adverse health effects and participation in interventions to prevent them.


COVID-19 vaccine hesitancy: The effects of combining direct and indirect online opinion cues on psychological reactance to health campaigns.
This study aims to examine whether and how user-generated comments and reaction emojis on COVID-19 vaccine-promoting Facebook posts induce psychological reactance to posts and vaccine hesitancy in audiences of the posts. An online experiment including 465 American adults showed that, compared with COVID-19 vaccine promotion posts accompanied by pro-vaccine comments, those accompanied by anti-vaccine comments provoked greater reactance in audiences through the mediating effects of bandwagon perception and the presumed influence of the posts on others. Greater reactance, in turn, increased audiences' COVID-19 vaccine hesitancy. Additionally, reaction emojis altered the comments' effects such that pro-vaccine comments triggered less reactance than anti-vaccine comments when the pro-vaccine comments were accompanied by agreement emojis (i.e., "like" and "love"); whereas there was no significant difference between pro-vaccine comments and anti-vaccine comments in reactance when the pro-vaccine comments were accompanied by rejection emojis (i.e., "angry" and "sad"). Furthermore, audiences' pre-existing attitudes did not affect the effects of opinion cues on their' reactance and vaccine hesitancy.


Altered gene expression and possible immunodeficiency in cases of sudden infant death syndrome.
A large number of studies have tried to uncover a genetic predisposition for sudden infant death syndrome (SIDS), but there is still uncertainty concerning the pathogenesis of these deaths. The purpose of this study was to investigate mRNA gene expression in SIDS cases and controls, in order to uncover genes that are differentially expressed in the two groups. Tissue from brain, heart, and liver from 15 SIDS cases and 15 controls were included in the study, and mRNA expression was determined using the Illumina whole genome gene expression DASL HT assay. Seventeen genes showed significantly altered expression compared to controls, after correction for multiple testing. Three genes involved in the immune system were of particular interest, including the downregulation of MyD88 in tissue from SIDS brains, as well as the downregulation of the genes encoding CCL3 and UNC13 in the liver. These findings indicate that there is an altered expression of genes involved in the inflammatory process in a proportion of SIDS cases, which further strengthen the hypothesis that impaired immune response play a role in this syndrome.


Clinical predictors and survival outcome of patients receiving suboptimal neoadjuvant chemotherapy and radical cystectomy for muscle-invasive bladder cancer: a single-center experience.
To investigate the prevalence of and factors' association with receiving suboptimal neoadjuvant chemotherapy (NAC) and its impact on survival outcomes in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy (RC). We reviewed 1119 patients treated with NAC and/or RC for cT2-cT4N0M0 BC. Patients were segregated into three groups: (i) suboptimal NAC (received < 3 cycles of cisplatin-based NAC or non-cisplatin-based regimen), (ii) optimal NAC and (iii) no NAC. Clinical characteristics were compared among groups. Logistic regression analyses tested the association between clinical variables and the odds of receiving suboptimal NAC. To adjust for potential baseline confounders, propensity score matching was performed. Pathologic outcomes were compared between groups and Cox regression analyses tested the risk factors associated with recurrence, overall (OM) and cancer-specific mortality (CSM). Before matching, 84/315 (26.6%) patients received a suboptimal NAC regimen. Lower general health status and impaired renal functions were the most significant factors associated with the administration of a suboptimal NAC. After matching, the optimal NAC group achieved higher rates of complete pathological response as compared to the suboptimal group (p = 0.03). Suboptimal NAC (HR 1.77; p = 0.015) and no NAC (HR 1.52; p = 0.03) were both associated with higher risk of recurrence and OM (HR 1.71; p = 0.02 and HR 1.61; p = 0.02) as compared to optimal NAC. One out of four MIBC patients received a suboptimal NAC regimen before RC. Receiving a suboptimal NAC regimen was associated with worse disease recurrence and survival outcomes following surgery, as compared to an optimal NAC regimen.


[4 + 2] Cyclocondensation reactions of tungsten-dihydropyridine complexes and the generation of tri- and tetrasubstituted piperidines.
A new method for the preparation of functionalized piperidines is described in which various dihydropyridine (DHP) complexes of {TpW(NO)(PMe(3))} that are derived from pyridine-borane undergo [4 + 2] cyclocondensation with enones, enals, nitrosobenzene, and several isocyanates to form [2.2.2] bicyclic species. In several cases the diazabicyclooctene products derived from DHP complexes and isocyanates can be further elaborated into novel syn-2,5-disubstituted and 2,3,6-trisubstituted piperidinamides.


Effectiveness of early onset of rehabilitation on the postural stability after anterior cruciate ligament reconstruction.
The objective of this study was to evaluate the early onset of rehabilitation on restoring the postural stability of patients after anterior cruciate ligament reconstruction (ACLR) at the 3rd postoperative month. Forty patients after ACLR and twenty healthy controls took part in the investigation. The patients were divided into two groups, depending on the start of their proprioceptive rehabilitation program: an experimental group - on the 5th day after the surgery and a control group - on around the 30th postoperative day. Postural stability was investigated by static posturographic tests on stable and foam surfaces with open and closed eyes. The patients from the experimental group showed lower amplitudes and velocities of the postural sways than the patients from the control group at the 3rd postoperative month. We found that the early start of the proprioceptive rehabilitation affects more the amplitude than the velocity of the postural sway which remains significantly high in both directions compared to the conventional rehabilitation. The early start of the rehabilitation has a beneficial role in the recovery of the postural stability in the 3rd postoperative month, especially in more challenging conditions for keeping the equilibrium, which contributes to the minimizes the risk of a second anterior cruciate ligament injury after patients' return to their usual sport and daily activities routine.


Spatial distribution of visual pigment and dopamine in the bullfrog retina.
Visual pigments and a neurotransmitter, dopamine, were quantitatively investigated in the retina of adult bullfrog, Rana catesbeiana. The adult bullfrog (body length 15-16 cm, body weight 375 +/- 52 g, n = 10) had 21.4 +/- 4.2 nmol visual pigment and 209 +/- 28 pmol dopamine in retinal areas of 266 +/- 27 mm2. Greater pigment densities were recorded in a semicircular band around the optic disc, extending to the nasal and temporal peripheries of the ventral retina. The area with the highest concentration of visual pigment was found in the middle of the dorsal retina, 3-4 mm dorsal to the optic disc. A high concentration of vitamin A2-based pigment was found in the dorsal quarter of the retina (porphyropsin zone); the zone extended up to the most ventral part along peripheral regions of the retina. There was also a band with higher dopamine concentrations although it was not so prominent as that of the visual pigment; the highest concentration of dopamine was found in the area immediately dorsotemporal to the optic disc. Fluorescence micrography indicated that the distribution pattern of catecholamine-containing amacrine cells paralleled that of the dopamine content. The topographic map of dopamine was slightly different from that of visual pigment in the bullfrog retina.


Intravenous rt-PA: a tenth anniversary reflection.
Clinical trials with rt-PA for treating AIS began 20 years ago in 1987, and the pivotal NINDS rt-PA Stroke Study was completed and published in 1995 with FDA approval in 1996, about 10 years ago. A large number of articles emanated from that study and have established the efficacy and generalizability of this treatment. Here we summarize the background of how the NINDS trial was developed and carried out and its main findings. The NINDS rt-PA Stroke Study resulted from preclincal and pilot studies and paralleled similar studies carried out around the world. Its positive results, compared with the other trials, probably were due to the early time window for treatment and well-organized clinical and statistical centers. Many controversies have surrounded its use since its approval. As a result of the NINDS rt-PA Stroke Study, many new approaches to thrombolytic therapy are under evaluation. The results of the NINDS rt-PA Stroke Study have affected the management of patients with acute stroke worldwide.


Masseter muscle adaptation following surgical correction of vertical maxillary excess.
This study was designed to examine the adaptive response of the human masseter muscle following surgical correction of abnormal facial form. Biopsies of the deep surface of the anterior superficial masseter muscle were obtained from five patients demonstrating vertical maxillary excess (VME), one at the time of corrective surgery, and a second at a long-term postoperative time interval (mean, 8 months). Control biopsies were also obtained from five individuals (three cadavers and two patients) with normal dentofacial morphology. A standard regimen of histologic and histochemical staining was used to classify individual muscle fibers as either type 1, type 2, or intermediate. In both VME patients and normal subjects type 1 fibers predominated, with the control group displaying a higher percentage (50% vs. 43%). On the average, type 1 fibers also had the largest areas. Following surgery there was an increase in type 2 fibers (30% vs. 52%). Two patients receiving maxillary surgery only exhibited either no change in mean fiber area or only a slight increase. The three remaining patients who underwent concomitant maxillary and mandibular surgery all showed a significant decrease in mean fiber area. Two persons in the latter group also showed features consistent with a denervation-reinnervation process. The results of this study indicate that the human masseter responds to surgical manipulation of the jaws in a histochemically demonstrable manner, with the nature and magnitude of the response associated with the particular surgical procedure(s) performed.


Germplasm resources and secondary metabolism regulation in Reishi mushroom (Ganoderma lucidum).
Ganoderma lucidum is a valuable medical macrofungus with a myriad of diverse secondary metabolites, in which triterpenoids are the major constituents. This paper introduced the germplasm resources of genus Ganoderma from textual research, its distribution and identification at the molecular level. Also we overviewed G. lucidum in the components, the biological activities and biosynthetic pathways of ganoderic acid, aiming to provide scientific evidence for the development and utilization of G. lucidum germplasm resources and the biosynthesis of ganoderic acid.


Co/La modified Ti/PbO2 anodes for chloramphenicol degradation: Catalytic performance and reaction mechanism.
Chloramphenicol (CAP) is widely used in daily life, and its abuse hurts human health, so a suitable method is needed to solve the problem. In this study, the Ti/PbO2 electrodes prepared by the electroplating method were characterized. The CAP degradation effect and mechanism were investigated. It was shown that the electrode surface had a dense plating with a characteristic peak of β-PbO2 as the active component. The electrode had an oxygen precipitation potential of 1.695 V and a corrosion potential of 0.553 V, and a long service life (505.4 d). The degradation of CAP at Ti/PbO2 electrode followed a first-order kinetic reaction. The optimal degradation conditions (current density of 12.97 mA cm-2, electrolyte concentration of 50 mM, and solution pH of 6.38) were obtained by the response surface curve method. The degradation rate of CAP was 99.0% at 60 min. The results showed that the reactive groups leading to CAP degradation were mainly ·OH and SO42-, and only a tiny portion of CAP was directly oxidized on the electrode surface. The addition of Cl- favored the degradation of CAP, but reduced the mineralization rate. LC-MS analysis showed that ·OH mainly attacked the asymmetric centers (C1, C2) of weakly bound hydrogen atoms, resulting in underwent addition and substitution reactions. CAP was converted into two substances with m/z = 306 and m/z = 165. Finally, inorganic substances such as CO2 and H2O were generated. This study provided a new idea for preparing Ti/PbO2 electrode with high performance and the safe and efficient degradation of CAP.


Morphological factors influencing transepithelial permeability: a model for the resistance of the zonula occludens.
Epithelial cells are joined at their apical surfaces by zonulae occludentes. Claude and Goodenough (1973) demonstrated a correlation between the structure of the zonula occludens as seen in freeze-fracture preparations and the passive electrical permeability of several simple epithelia. In epithelia with high transepithelial resistance, the zonula occludens consisted of many strands. In epithelia with low transepithelial resistance the zonula occludens was much reduced, sometimes consisting of only one strand. Evidence is reviewed here that indicates that in a number of simple epithelia the structure of the zonula occludens is largely responsible for the magnitude of transepithelial conductance. An equation is derived relating transepithelial junctional resistance to the number of junctional strands: R = RminP-N where R is the transepithelial resistance of the zonula occludens, Rmin is the minimum resistance of the junction (as when there are no strands in the zonula occludens), p is the probability a given strand is "open" and n is the number of strands in the junction. Using published experimental values of R and n for different epithelia, the calculated value of p was found to be as high as 0.4, which suggests that the strands in the zonula occludens are remarkably labile. Other morphological parameters relevant to transepithelial permeability are also considered, such as the width and depth of the intercelllar spaces, and the size of the epithelial cells themselves.


Unraveling galectin-1 as a novel therapeutic target for cancer.
Galectins belong to a family of carbohydrate-binding proteins with an affinity for β-galactosides. Galectin-1 is differentially expressed by various normal and pathologic tissues and displays a wide range of biological activities. In oncology, galectin-1 plays a pivotal role in tumor growth and in the multistep process of invasion, angiogenesis, and metastasis. Evidence indicates that galectin-1 exerts a variety of functions at different steps of tumor progression. Moreover, it has been demonstrated that galectin-1 cellular localization and galectin-1 binding partners depend on tumor localization and stage. Recently, galectin-1 overexpression has been extensively documented in several tumor types and/or in the stroma of cancer cells. Its expression is thought to reflect tumor aggressiveness in several tumor types. Galectin-1 has been identified as a promising drug target using synthetic and natural inhibitors. Preclinical data suggest that galectin-1 inhibition may lead to direct antiproliferative effects in cancer cells as well as antiangiogenic effects in tumors. We provide an up-to-date overview of available data on the role of galectin-1 in different molecular and biochemical pathways involved in human malignancies. One of the major challenges faced in targeting galectin-1 is the translation of current knowledge into the design and development of effective galectin-1 inhibitors in cancer therapy.


Endometrial microbial colonization and plasma cell endometritis after spontaneous or indicated preterm versus term delivery.
This study was undertaken to determine whether endometrial microbial colonization or plasma cell endometritis is increased after spontaneous versus indicated preterm delivery or a spontaneous term delivery. Postpartum, endometrial specimens were obtained after a spontaneous (mean 83, +/- 17.6 days) or indicated (mean 83, +/- 16.7 days) preterm delivery before 34 weeks' gestation and after a spontaneous term delivery (mean 82, +/- 15.7 days; P=.980). Cultures for aerobic and anaerobic bacteria, Trichomonas vaginalis, and genital mycoplasmas were performed. Histologic endometritis was defined as the presence of plasma cells. The study population (n=820) was 71% black, 29% white, 69% unmarried, and 31% had less than 12 years of education. Endometrial cultures were positive for at least 1 microorganism in 82% of the women. No significant difference in positive endometrial cultures were observed among women after a spontaneous versus an indicated preterm delivery (85% vs 79%, P=.102), or a spontaneous preterm versus a spontaneous term delivery (85% vs 81%, P=.123). Plasma cell endometritis was present in 39% of 506 specimens sufficient for histologic examination and was also similar in the three groups (P=.160). Microbial colonization of the endometrium and plasma cell endometritis are similar 3 months after spontaneous or indicated preterm or term births. Therefore, chronic infection and inflammation of the endometrium (documented at 3 months postpartum) do not appear to be risk factors for subsequent delivery in women with a prior spontaneous delivery less than 34 weeks' gestation.


Overexpression of CD45RA isoforms in carriers of the C77G mutation leads to hyporeactivity of CD4+CD25highFoxp3+ regulatory T cells.
Disorders in regulatory T-cell (T(reg)) function can result in the breakdown of immunological self-tolerance. Thus, the identification of mechanisms controlling the activity of T(reg) is of great relevance. We used T(reg) from individuals carrying the C77G polymorphism as models to study the role of CD45 molecules in humans. C77G prevents splicing of CD45 exon A thereby leading to an aberrant expression pattern of CD45 isoforms in affected individuals. Resting and in vitro expanded/activated CD4(+)CD25(high)Foxp3(+) T(reg) from carriers of C77G strongly expressed CD45RA isoforms whereas these isoforms were almost absent in cells from individuals with wild-type CD45. C77G T(reg) showed diminished upregulation of activation markers, lower phosphorylation of p56(lck)(Y505) and a reduced proliferative potential when stimulated with anti-TcR or anti-TcR plus CD28 mAb suggesting decreased responsiveness to activating stimuli. In addition, the capacity to suppress proliferation of conventional CD4(+) T cells was impaired in C77G T(reg). Furthermore, microarray studies revealed distinct gene expression patterns in T(reg) from C77G carriers. These data suggest that the changes in CD45 isoform combination resulting from the C77G mutation alter the responsiveness of T(reg) to TcR-mediated signaling. Targeting CD45 isoform expression might be a useful approach to modulate T(reg) function.


Differential effects of pertussis toxin and lithium on muscarinic responses in the atria and ileum: evidence for receptor heterogeneity.
Pretreatment with pertussin toxin was shown to inhibit selectively muscarinic responses in the atria, but have no effect on responses in the ileum. The converse was true when the animals were pretreated with lithium. These data are consistent with the hypothesis that muscarinic receptors in the atria are coupled to an inhibition of adenylate cyclase, whilst those in the ileum are coupled to inositol phospholipid hydrolysis and indicate differences in the muscarinic receptors in these two tissues.


Phosphorus removal coupled to bioenergy production by three cyanobacterial isolates in a biofilm dynamic growth system.
In the present study a closed incubator, designed for biofilm growth on artificial substrata, was used to grow three isolates of biofilm-forming heterocytous cyanobacteria using an artificial wastewater secondary effluent as the culture medium. We evaluated biofilm efficiency in removing phosphorus, by simulating biofilm-based tertiary wastewater treatment and coupled this process with biodiesel production from the developed biomass. The three strains were able to grow in the synthetic medium and remove phosphorus in percentages, between 6 and 43%, which varied between strains and also among each strain according to the biofilm growth phase. Calothrix sp. biofilm turned out to be a good candidate for tertiary treatment, showing phosphorus reducing capacity (during the exponential biofilm growth) at the regulatory level for the treated effluent water being discharged into natural water systems. Besides phosphorus removal, the three cyanobacterial biofilms produced high quality lipids, whose profile showed promising chemical stability and combustion behavior. Further integration of the proposed processes could include the integration of oil extracted from these cyanobacterial biofilms with microalgal oil known for high monounsaturated fatty acids content, in order to enhance biodiesel cold flow characteristics.


WITHDRAWN: To wear or not to wear? Adherence to face mask use during the COVID-19 and Spanish influenza pandemics.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.


Evaluation of benefits and harms of adaptive screening schedules for lung cancer: A microsimulation study.
Although lung cancer screening (LCS) has been proven effective in reducing lung cancer mortality, it is associated with some potential harms, such as false positives and invasive follow-up procedures. Determining the time to next screen based on individual risk could reduce harms while maintaining health gains. Here, we evaluate the benefits and harms of LCS strategies with adaptive schedules, and compare these with those from non-adaptive strategies. We extended the Lee and Zelen risk threshold method to select screening schedules based on individual's lung cancer risk and life expectancy (adaptive schedules). We compared the health benefits and harms of these adaptive schedules with regular (non-adaptive) schedules (annual, biennial and triennial) using a validated lung cancer microsimulation model. Outcomes include lung cancer deaths (LCD) averted, life years gained (LYG), discounted quality adjusted life years (QALYs) gained, and false positives per LCD averted. We also explored the impact of varying screening-related disutilities. In comparison to standard regular screening recommendations, risk-dependent adaptive screening reduced screening harms while maintaining a similar level of health benefits. The net gains and the balance of benefits and harms from LCS with efficient adaptive schedules were improved compared to those from regular screening, especially when the screening-related disutilities are high. Adaptive screening schedules can reduce the associated harms of screening while maintaining its associated lung cancer mortality reductions and years of life gained. Our study identifies individually tailored schedules that optimize the screening benefit/harm trade-offs.


FruHis significantly increases the anti-benign prostatic hyperplasia effect of lycopene: A double-blinded randomized controlled clinical trial.
For decades, lycopene was considered the main compound of tomato protecting benign prostatic hyperplasia (BPH). Recent animal studies suggest that a newly discovered compound "FruHis" boosts lycopene for its action. This study aimed to determine whether FruHis enhances the action of lycopene to modify the laboratory parameters and clinical outcomes of patients with BPH. Current study was conducted on 52 BPH patients, who were randomly assigned into four groups of treatments: lycopene plus FruHis (n = 11, 25 mg/day lycopene and 10 mg/day FruHis), lycopene (n = 12, 25 mg/day lycopene), FruHis (n = 12, 10 mg/day FruHis), and placebo (n = 13). Patients received these supplements for 8 weeks. FruHis intake strengthened the reducing effects of lycopene on insulin-like growth factor-1 (IGF-1) (-54.47 ± 28.36 ng/mL in the lycopene + FruHis group vs. -30.24 ± 46.69 ng/mL in the lycopene group), total prostate-specific antigen (TPSA) (-1.49 ± 4.78 ng/mL in the lycopene + FruHis group vs. -0.64 ± 2.02 ng/mL in the lycopene group), and symptom score (-4.45 ± 4.03 in the lycopene + FruHis group vs. -1.66 ± 5.41 in the lycopene group) in BPH patients. Such findings were also seen for body mass index (BMI) and waist circumference (WC). However, except for IGF-1, these reductions were not statistically significant compared with the placebo, and the intakes of lycopene and FruHis alone, however, were clinically important. Such effects of lycopene and FruHis were not seen for free PSA (FPSA) and FPSA/TPSA ratio. Despite the non-significant effects of lycopene and FruHis, it seems that FruHis intake strengthens the beneficial effects of lycopene on IGF-1, TPSA, and symptom scores among BPH patients. [www.irct.ir], identifier [IRCT20190522043669N1].


Serial assessment of mitral regurgitation by pulsed Doppler echocardiography in patients undergoing balloon aortic valvuloplasty.
Mitral regurgitation was serially assessed by pulsed Doppler echocardiography in 144 patients undergoing balloon aortic valvuloplasty for symptomatic aortic stenosis. Regurgitant scores of 0, 1, 2 and 3 were assigned to pulsed Doppler patterns corresponding to no, mild, moderate and severe mitral regurgitation, respectively. Before balloon aortic valvuloplasty, mitral regurgitant score correlated significantly (p less than 0.005) but weakly with aortic valve area (r = -0.24), left ventricular ejection fraction (r = -0.34) and left ventricular systolic pressure (r = 0.23). There was no significant correlation between mitral regurgitation and either mean catheterization or mean Doppler aortic valve gradient. Balloon aortic valvuloplasty produced significant decreases in both catheterization and Doppler mean transvalvular aortic valve gradients (56 +/- 19 to 31 +/- 12 and 60 +/- 19 to 48 +/- 16 mm Hg, respectively; both p less than 0.0001) and a significant increase (p less than 0.0001) in aortic valve area assessed by catheterization (0.6 +/- 0.2 to 0.9 +/- 0.3 cm2). Left ventricular ejection fraction did not change, but cardiac output increased (p less than 0.001) and pulmonary capillary wedge pressure decreased (p less than 0.0001). Pulsed Doppler findings of mitral regurgitation were present in 102 of the 144 patients. Eighty-eight patients had a score compatible with mild or more severe degrees of mitral regurgitation, and 49 had a score indicative of moderate or severe valvular insufficiency. In the entire group of 144 patients, mitral regurgitant score decreased significantly from 1.1 +/- 1.0 to 1.0 +/- 1.0 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Ventral tegmental area α6β2 nicotinic acetylcholine receptors modulate phasic dopamine release in the nucleus accumbens core.
Phasic dopamine (DA) signaling underlies reward learning. Cholinergic and glutamatergic inputs into the ventral tegmental area (VTA) are crucial for modulating burst firing activity and subsequent phasic DA release in the nucleus accumbens (NAc), but the specific VTA nicotinic receptor subtypes that regulate phasic DA release have not been identified. The goal was to determine the role of VTA N-methyl-D-aspartate receptors (NMDARs) and specific subtypes of nicotinic acetylcholine receptors (nAChRs) in regulating phasic DA release in the NAc core. Fast-scan cyclic voltammetry in anesthetized rats was combined with intra-VTA micro-infusion to evaluate the ability of glutamatergic and cholinergic drugs to modulate stimulated phasic DA release in the NAc core. VTA NMDAR blockade with AP-5 decreased, while VTA NMDAR activation with NMDA increased NAc peak phasic DA release. Intra-VTA administration of the nonspecific nAChR antagonist mecamylamine produced a persistent decrease in phasic DA release. Infusion of the α6-selective antagonist α-conotoxin MII (α-ctx MII) produced a robust, but transient decrease in phasic DA, whereas infusion of selective doses of either the α4β2-selective antagonist, dihydro-beta-erythroidine, or the α7 antagonist, methyllycaconitine, had no effect. Co-infusion of AP-5 and α-ctx MII produced a similar phasic DA decrease as either drug alone, with no additive effect. The results suggest that VTA α6β2 nAChRs, but not α4β2 or α7 nAChRs, regulate phasic DA release in the NAc core and that VTA α6β2 nAChRs and NMDA receptors act at a common site or target to regulate NAc phasic DA signaling.


Chronic exposure to the parasite Enteromyxum leei (Myxozoa: Myxosporea) modulates the immune response and the expression of growth, redox and immune relevant genes in gilthead sea bream, Sparus aurata L.
The myxosporean parasite Enteromyxum leei invades the intestine of gilthead sea bream producing a slow-progressing disease, which may end in the death of fish. The present work aimed to better know the host immune response and the underlying molecular mechanisms, which may help to understand why some individuals seem to be refractory to the disease. Three main aspects involved in fish health and welfare (immune, growth and redox status) were studied in fish exposed to E. leei-contaminated effluent, in comparison with control animals (not exposed to the disease). After chronic exposure (113days), prevalence of infection was 67.8%. Among exposed fish, parasitized and non-parasitized fish exhibited clear differences in some of the measured innate immune factors (respiratory burst, serum peroxidases, lysozyme and complement), and in the expression of immune, antioxidant and GH-related genes. The respiratory burst of parasitized fish was significantly higher, and serum peroxidases and lysozyme were significantly decreased both in parasitized and non-parasitized fish. The gene expression of GHR-I, GHR-II, IGF-I and IGF-II was measured in head kidney (HK) samples, and that of interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, alpha-2M, GR, GPx-1 and GRP-75 was measured in intestine and HK samples, by rtqPCR. Parasitized fish exhibited a down-regulation of IL-1beta, TNF-alpha and GPx-1 in the intestine, and GHR-I and IGF-I were also down regulated in HK. alpha-2M and GRP-75 were over-expressed in the intestine of parasitized animals. Non-parasitized fish had increased transcripts of GHR-I and IGF-I with respect to control animals, which could furnish their immunocytes with an advantage to combat the parasite. The expression of GHR-II and IGF-II was not altered by the parasite challenge.


Attenuation of high sweet solution preference by mood stabilizers: a possible mouse model for the increased reward-seeking domain of mania.
The lack of appropriate animal models for bipolar disorder (BPD) is a major factor hindering the research of its pathophysiology and the development of new drug treatments. In line with the notion that BPD might represent a heterogeneous group of disorders, it was suggested that models for specific domains of BPD should be developed and then integrated. The present study tested sweet solution preference as a rodent model for increased reward seeking, a central component of manic behavior and a possible endophenotype of the disorder. The study identified that Black Swiss mice show high baseline saccharin preference compared with C57bl/6, CBA/J and A/J strains. Sweet solution preference in Black Swiss mice was therefore evaluated across a number of saccharin concentrations, with or without treatment with the mood stabilizers lithium and valproate and the antidepressant imipramine. Results indicated that the structurally dissimilar mood stabilizers lithium and valproate, but not the antidepressant imipramine, reduce sweet solution preference. However, different dosing schedules were needed for the two drugs to induce this effect. These findings support the face and the predictive validity of the sweet solution preference test as an animal model for the elevated reward-seeking domain of mania. As such, this test might be well integrated into a battery of models for different domains of BPD. Such a battery can be effectively utilized to screen new treatments, to distinguish between specific effects of different drugs, and to explore the mechanisms underlying BPD.


Rapid Cancer Fluorescence Imaging Using A γ-Glutamyltranspeptidase-Specific Probe For Primary Lung Cancer.
We set out to examine the activity of γ-glutamyltranspeptidase (GGT) in lung cancer and the validity of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) for intraoperative imaging of primary lung cancer. GGT activities and mRNA expression levels of GGT1 (one of the GGT subtypes) in five human lung cancer cell lines were examined by fluorescence imaging and quantitative reverse transcription polymerase chain reaction. In vivo imaging of an orthotopic A549 xenograft model in nude mice was performed to confirm its applicability to intraoperative imaging. Furthermore, ex vivo imaging of 73 specimens from lung cancer patients were performed and analyzed to calculate the sensitivity/specificity of gGlu-HMRG for lung cancer diagnosis. GGT activities and mRNA expression levels of GGT1 are diverse depending on cell type; A549, H441, and H460 showed relatively high GGT activities and expression levels, whereas H82 and H226 showed lower values. In the in vivo mouse model study, tiny pleural dissemination and hilar/mediastinal lymph node metastasis (less than 1 mm in diameter) were clearly detected 15 minutes after topical application of gGlu-HMRG. In the ex vivo study of specimens from patients, the sensitivity and specificity of gGlu-HMRG were calculated to be 43.8% (32/73) and 84.9% (62/73), respectively. When limited to female patients, never smokers, and adenocarcinomas, these values were 78.9% (15/19) and 73.7% (14/19), respectively. Although GGT activity of lung cancer cells vary, gGlu-HMRG can serve as an intraoperative imaging tool to detect small foci of lung cancer when such cells have sufficient GGT activity.


Awareness of gestational diabetes mellitus among females in Jeddah, Saudi Arabia - A cross-sectional study.
This study aimed to assess the awareness about gestational diabetes mellitus (GDM) among married females in Jeddah, Saudi Arabia. A cross-sectional study was done on all women in reproductive age and an electronic questionnaire was used. Data about participants' demographics, parity, BMI, pregnancy, family and personal history of chronic diseases, gestational diabetes were collected. Their knowledge about effect of gestational diabetes on mother and on neonatal outcomes and their source of information about GDM were assessed. The mean age of the participants was 37.99 ± 9.44 years and 77.8% of them had poor knowledge about GDM and 6.1% had good knowledge. Multipara women with a university education had a significantly higher mean knowledge level and the most common source of participants' knowledge about GDM was social media. Females' knowledge about GDM was significantly low in Jeddah. Health education campaigns and mass media education are urgent to increase their awareness about GDM. Health care practitioners should focus on popularizing GDM and raising awareness of its consequences.


Ulnar nerve and cubital tunnel ultrasound in ulnar neuropathy at the elbow.
To determine the accuracy of the ultrasonographic measurement of ulnar nerve to cubital tunnel area for diagnosis of ulnar neuropathy at the elbow. Patients with confirmed ulnar neuropathy at the elbow and normative, healthy volunteers were evaluated with high-resolution ultrasound. The cross-sectional areas (CSAs) of the ulnar nerve and cubital tunnel were measured with the elbow extended and flexed, and results from the 2 groups were compared. Electromyography laboratory and radiology department of a tertiary care center. Twenty-seven patients with ulnar neuropathy at the elbow and 20 controls. Not applicable. The ratio of ulnar nerve to cubital tunnel CSA with the elbow flexed. The ulnar nerve, with the elbow flexed, was larger in those with ulnar neuropathy at the elbow, and this group also had larger cubital tunnels than did controls. In those with ulnar neuropathy at the elbow, the ratio of the ulnar nerve to cubital tunnel was .31, and in the controls it was .32, which was not significantly different (P=.89). The ratio of ulnar nerve to cubital tunnel did not differentiate those with ulnar neuropathy at the elbow from controls.


Interobserver variability among expert readers quantifying plaque volume and plaque characteristics on coronary CT angiography: a CLARIFY trial sub-study.
The difference between expert level (L3) reader and artificial intelligence (AI) performance for quantifying coronary plaque and plaque components is unknown. This study evaluates the interobserver variability among expert readers for quantifying the volume of coronary plaque and plaque components on coronary computed tomographic angiography (CCTA) using an artificial intelligence enabled quantitative CCTA analysis software as a reference (AI-QCT). This study uses CCTA imaging obtained from 232 patients enrolled in the CLARIFY (CT EvaLuation by ARtificial Intelligence For Atherosclerosis, Stenosis and Vascular MorphologY) study. Readers quantified overall plaque volume and the % breakdown of noncalcified plaque (NCP) and calcified plaque (CP) on a per vessel basis. Readers categorized high risk plaque (HRP) based on the presence of low-attenuation-noncalcified plaque (LA-NCP) and positive remodeling (PR; ≥1.10). All CCTAs were analyzed by an FDA-cleared software service that performs AI-driven plaque characterization and quantification (AI-QCT) for comparison to L3 readers. Reader generated analyses were compared among readers and to AI-QCT generated analyses. When evaluating plaque volume on a per vessel basis, expert readers achieved moderate to high interobserver consistency with an intra-class correlation coefficient of 0.78 for a single reader score and 0.91 for mean scores. There was a moderate trend between readers 1, 2, and 3 and AI with spearman coefficients of 0.70, 0.68 and 0.74, respectively. There was high discordance between readers and AI plaque component analyses. When quantifying %NCP v. %CP, readers 1, 2, and 3 achieved a weighted kappa coefficient of 0.23, 0.34 and 0.24, respectively, compared to AI with a spearman coefficient of 0.38, 0.51, and 0.60, respectively. The intra-class correlation coefficient among readers for plaque composition assessment was 0.68. With respect to HRP, readers 1, 2, and 3 achieved a weighted kappa coefficient of 0.22, 0.26, and 0.17, respectively, and a spearman coefficient of 0.36, 0.35, and 0.44, respectively. Expert readers performed moderately well quantifying total plaque volumes with high consistency. However, there was both significant interobserver variability and high discordance with AI-QCT when quantifying plaque composition.


Magnetically controlled graphene field-effect transistor biosensor for highly sensitive detection of cardiac troponin I.
Herein, we have constructed a magnetic graphene field-effect transistor biosensor (MGFETs) for highly sensitive detection of cardiac troponin I (CTNI). Graphene films transferred to ITO conductive glass as conductive channels. CTNI aptamer was immobilized onto the graphene film via 1-pyrene-butanoic acid succinimidyl ester (PBASE) to capture CTNI. Magnetic nanobeads (MBs) modified with CTNI antibody were added to the reaction chamber to form an aptamer/CTNI/antibody/magnetic nanobeads sandwich-type complex. We found that the magnetic force exerted on the complex leads to an impedance change of the graphene film. The reason for this result is that the magnetic field exerts an influence on the MBs, causing CTNI aptamer strand to bend, resulting in a change in the distance between the double conductive layers of the graphene film surface and the test solution. With periodic sampling integration, different concentrations of CTNI can be detected with high sensitivity. Due to the stringent recognition capability and high affinity between the CTNI aptamer and CTNI, MGFETs have the potential to detect various types of proteins. Furthermore, MGFETs also have the potential to be utilized for the detection of DNA or specific cells in the future.


Efficiency of the intestinal bacteria in the degradation of the toxic pesticide, chlorpyrifos.
Chlorpyrifos (CP) is the most commonly used pesticide throughout the world. Its widespread use in agriculture and its potential toxicity to humans from ingestion of CP contaminated food have raised concerns about its risk to health. Human intestinal microflora has the ability to degrade pesticides, but the exact mechanisms involved and the metabolite end-products formed are not well understood. The primary objective of this work was to analyse the in vitro degradation of CP by five model intestinal bacteria namely Lactobacillus lactis, L. fermentum, L. plantarum, Escherichia coli and Enterococcus faecalis. Plate assay results revealed that L. lactis, E. coli and L. fermentum could grow with high concentrations of CP (>1,400 μg/mL), whereas E. faecalis and L. plantarum could grow with concentrations as low as 400 and 100 μg/mL, respectively. The best three CP degraders were therefore used in further experiments. The degradation of CP-induced organophosphorous phosphatase (OPP) production and that OPP concentration were higher in the supernatant (extracellular) rather than inside the cells by factor of up to 28. L. fermentum degraded 70 % CP with 3,5,6-trichloro-2-pyridinol (TCP) detected as the end product. L.lactis degraded up to 61 % CP with chlorpyrifos oxon detected as the end product, whereas E.coli degraded a lesser concentration (16 %) to chlorpyrifos-oxon and diethylphosphate.


Reduction of intrafraction pancreas motion using an abdominal corset compatible with proton therapy and MRI.
Motion mitigation is of crucial importance in particle therapy (PT) of patients with abdominal tumors to ensure high-precision irradiation. Magnetic resonance imaging (MRI) is an excellent modality for target volume delineation and motion estimation of mobile soft-tissue tumors. Thus, the aims of this study were to develop an MRI- and PT-compatible abdominal compression device, to investigate its effect on pancreas motion reduction, and to evaluate patient tolerability and acceptance. In a prospective clinical study, 16 patients with abdominal tumors received an individualized polyethylene-based abdominal corset. Pancreas motion was analyzed using time- and phase resolved MRI scans (orthogonal 2D-cine and 4D MRI) with and without compression by the corset. The pancreas was manually segmented in each MRI data set and the population-averaged center-of-mass motion in inferior-superior (IS), anterior-posterior (AP) and left-right (LR) directions was determined. A questionnaire was developed to investigate the level of patient acceptance of the corset, which the patients completed after acquisition of the planning computed tomography (CT) and MRI scans. The corset was found to reduce pancreas motion predominantly in IS direction by on average 47 % - 51 % as found in the 2D-cine and 4D MRI data, respectively, while motion in the AP and LR direction was not significantly reduced. Most patients reported no discomfort when wearing the corset. An MRI- and PT-compatible individualized abdominal corset was presented, which substantially reduced breathing-induced pancreas motion and can be safely applied with no additional discomfort for the patients. The corset has been successfully integrated into our in-house clinical workflow for PT of tumors of the upper abdomen.


Quantitative analysis of the exercise tolerance test for determining the severity of coronary artery disease.
Results were compiled from the literature on the use of the exercise tolerance test to identify patients with severe coronary artery disease. Pooled estimates of sensitivity and specificity were derived for the ability of the exercise tolerance test to identify three-vessel or left main coronary artery disease. There was great variability among the studies examined in the estimated sensitivity and specificity of a given criterion for severe coronary artery disease. This variability could not be explained by reported variations in study design. The findings suggest that the accuracy of the exercise tolerance test and other tests cannot be properly interpreted without much greater detail presented in the literature on patient selection and test administration.


Nonequilibrium isotope exchange reveals a catalytically significant enzyme-phosphate complex in the ATP hydrolysis pathway of the AAA(+) ATPase magnesium chelatase.
Magnesium chelatase is an AAA(+) ATPase that catalyzes the first committed step in chlorophyll biosynthesis. Using nonequilibrium isotope exchange, we show that the ATP hydrolysis reaction proceeds via an enzyme-phosphate complex. Exchange from radiolabeled phosphate to ATP was not observed, offering no support for an enzyme-ADP complex.


In-vitro anti-inflammatory activity, free radical (DPPH) scavenging, and ferric reducing ability (FRAP) of Sargassum cristaefolium lipid-soluble fraction and putative identification of bioactive compounds using UHPLC-ESI-ORBITRAP-MS/MS.
Sargassum brown seaweed is well-known to contain several bioactive compounds which exhibit various biological activities, including anti-inflammatory and antioxidant activity. Lipophilic extracts and fractions of Sargassum were reported to possess promising anti-inflammatory activity. This study, therefore, aims to evaluate the anti-inflammatory and antioxidant activity of Sargassum cristaefolium crude lipid extract and its fractions. The brown seaweed was obtained from Awur Bay, Jepara - Indonesia. Crude lipid fractionation was performed using normal phase column chromatography, and three different fractions (dichloromethane, acetone, methanol) were produced. The results showed that treatment of acetone fraction exerted strongest nitric oxide inhibition in lipopolysaccharide-induced RAW 264.7 cells, both in pre-incubated and co-incubated cell culture models. This outcome was in accordance with its 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and ferric reducing antioxidant power (FRAP). Metabolite profiling of lipid fractions was performed by ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry, while the orthogonal projection to latent structures analysis was conducted to determine some features with significant correlation to the bioactivity. There were 14 feature candidates considered from both positive and negative ionization mode datasets. Seven out of them were putatively identified as pheophytin a (1), all-trans fucoxanthin (2), 132-hydroxy-pheophytin a (3), pheophorbide a (4), 1-hexadecanoyl-2-(9Z-octadecenoyl)-3-O-β-D-galactosyl-sn-glycerol (6), 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-3-O-β-D-galactosyl-sn-glycerol (10), and 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-3-O-β-D-galactosyl-sn glycerol (12).


Systolic coronary flow reversal and abnormal diastolic flow patterns in patients with aortic stenosis: assessment with an intracoronary Doppler catheter.
Decreased left ventricular coronary flow reserve has been reported in patients with normal coronary arteries and left ventricular hypertrophy in association with aortic stenosis. However, phasic coronary flow characteristics have not been analyzed in detail in similar patients. The purpose of this study is to assess phasic coronary flow characteristics and their relation to hemodynamic parameters in patients with aortic stenosis. Coronary flow velocities were recorded in the left anterior descending artery with a 20 MHz Doppler catheter in nine patients with aortic stenosis and nine control subjects with normal coronary arteries. Patient aortic valve area ranged from 0.34 to 0.51 cm2. Flow reversal was observed in systole in all patients with aortic stenosis, and time velocity integrals of systolic flow were significantly smaller in patients with aortic stenosis than in controls (-0.3 +/- 2.3 vs 4.0 +/- 1.1 cm, p < 0.01). The time to peak diastolic velocity corrected by square root R-R interval was prolonged and the velocity half-time from peak diastolic velocity corrected by square root R-R interval was shorter in patients with aortic stenosis than in controls (5.3 +/- 1.1 vs 4.0 +/- 0.5, p < 0.01, 8.0 +/- 2.6 vs 13.0 +/- 3.3, p < 0.01, respectively). Peak velocity and time velocity integral of flow reversal showed significant correlations with mean pressure gradient across the aortic valve (y = 1.3x + 37.3, r = 0.72, p = 0.03, y = 11.3x + 41.2, r = 0.81, p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Enterohepatic Shunt-Driven Cholemia Predisposes to Liver Cancer.
Pathogenesis of hepatocellular carcinoma (HCC), which kills millions annually, is poorly understood. Identification of risk factors and modifiable determinants and mechanistic understanding of how they impact HCC are urgently needed. We sought early prognostic indicators of HCC in C57BL/6 mice, which we found were prone to developing this disease when fed a fermentable fiber-enriched diet. Such markers were used to phenotype and interrogate stages of HCC development. Their human relevance was tested using serum collected prospectively from an HCC/case-control cohort. HCC proneness in mice was dictated by the presence of congenitally present portosystemic shunt (PSS), which resulted in markedly elevated serum bile acids (BAs). Approximately 10% of mice from various sources exhibited PSS/cholemia, but lacked an overt phenotype when fed standard chow. However, PSS/cholemic mice fed compositionally defined diets, developed BA- and cyclooxygenase-dependent liver injury, which was exacerbated and uniformly progressed to HCC when diets were enriched with the fermentable fiber inulin. Such progression to cholestatic HCC associated with exacerbated cholemia and an immunosuppressive milieu, both of which were required in that HCC was prevented by impeding BA biosynthesis or neutralizing interleukin-10 or programmed death protein 1. Analysis of human sera revealed that elevated BA was associated with future development of HCC. PSS is relatively common in C57BL/6 mice and causes silent cholemia, which predisposes to liver injury and HCC, particularly when fed a fermentable fiber-enriched diet. Incidence of silent PSS/cholemia in humans awaits investigation. Regardless, measuring serum BA may aid HCC risk assessment, potentially alerting select individuals to consider dietary or BA interventions.


NRF2 in Cardiovascular Diseases: a Ray of Hope!
Heart failure is a worldwide pandemic influencing 26 million individuals worldwide and is expanding. Imbalanced redox homeostasis in cardiac cells alters the structure and function of the cells, which leads to contractile dysfunction, myocardial hypertrophy, and fibrosis in chronic heart failure. Various targets and agents acting on these such as siRNA, miRNA, interleukin-1, opioids, vasodilators, and SGLT2 inhibitors are being evaluated for heart failure, and nuclear factor erythroid 2-related factor 2 (NRF2) is one of them. NRF2 is a master transcription factor which is expressed in most of the tissues and exhibits a major role in amplification of the antioxidant pathways associated with the enzymes present in myocardium. Increased ROS generation and PI3K-Akt signaling can activate the receptor NRF2. Various in vitro and in vivo and few clinical studies suggested NRF2 may possess a potential for targeting oxidative stress-induced cardiovascular diseases including heart failures. All these studies collectively propose that upregulation of NRF2 will attenuate the increase in hemodynamic stress and provide beneficial role in cardiovascular diseases. The current review shall familiarize readers about the regulations and functions of NRF2. We have also discussed the current evidences suggesting beneficial role of NRF2 activators in heart failure. Graphical abstract.


Extended dual antiplatelet therapy for Asian patients with acute coronary syndrome: expert recommendations.
Recently, new evidence from large scale trials and updated guidelines have emerged on the risks and benefits of extended dual antiplatelet therapy (DAPT) for patients with acute coronary syndrome (ACS). To discuss, clarify and advise on the application of the evidences and guidelines on individual patient selection for extended DAPT, with regard to balancing risk factors, particularly in Asian populations. A total of 14 local cardiologists from Hong Kong with extensive experience in cardiology and cardiac interventions convened in a series of 3 advisory board meetings from October 2016 to September 2017, which included reviews of new evidence in the literature and discussions of the latest clinical trends, using an anonymous, electronic voting system for arriving at consensuses. Recommendations were produced for the following nine risk factors: old age (>65), chronic kidney disease (CKD), diabetes mellitus (DM), recurrent myocardial infarction (MI), multi-vessel disease (MVD), multiple stents, bioresorbable vascular scaffold (BVS) stent, left main stenting and peripheral artery disease (PAD). Strong ischaemic risk factors include DM, recurrent MI, MVD and/or >3 stents; less-strong ischaemic factors include CKD, left main stenting, BVS stent and PAD. Old age can be an unclear risk factor due to variations in physical fitness even among patients of identical age. The strengths and limitations of the results were acknowledged. ACS patients with ischaemic risk factors could be considered for extended DAPT beyond 12 months, while balancing the risk of bleeding.


A case of refractory Kawasaki disease complicated by peripheral ischemia.
Kawasaki disease (KD), an acute systemic vasculitis that primarily affects infants and young children, is occasionally refractory to initial high-dose intravenous immunoglobulin (IVIG). Some patients with KD develop peripheral gangrene as a fatal complication, though this is rare. There has been no case reported in the literature of complicated peripheral gangrene that completely resolved without sequelae. Recently, we encountered a patient with KD which was refractory to IVIG, later developing peripheral gangrene. For the treatment of a peripheral gangrene dexamethasone, methotrexate, and an anticoagulant were administered, resulting in resolution of the gangrenous lesions without sequelae. Early diagnosis and treatment can reduce permanent sequelae and mortality from refractory KD complicated by peripheral ischemia.


DNA damage response-related proteins in gastric cancer: ATM, Chk2 and p53 expression and their prognostic value.
The aims of this study were to assess expressions of the DNA damage response (DDR)-related proteins and to investigate their clinical significances in gastric carcinoma. Two independent cohorts, a training set (n=524) and validation set (n=394), of gastric cancer patients were enrolled. Ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (Chk2), and p53 expressions were examined by immunohistochemistry using tissue microarray. ATM loss, Chk2 loss, and p53 positivity were observed in 21.8, 14.1, and 36.1% of the training set, and in 17.3, 12.2, and 35.8% of the validation set, respectively. In the training set, the aberrant expressions of ATM, Chk2, or p53 were significantly associated with an advanced TNM stage and poor disease-specific survival. This association was verified in the validation set. Chk2 positivity and p53 negativity were significantly related to a prolonged disease-specific survival. Also, patients with nonaberrant expressional levels of all 3 DDR-related proteins had a more favorable outcome than others. Multivariate analyses showed that Chk2 loss and at least 1 aberrant DDR-related protein remained as independent prognostic factors of poor disease-specific survival. This study elucidated the prognostic implications of DDR-related proteins, and suggests that their aberrant expressions play critical roles in the development and progression of gastric cancer.


Conscience, tolerance, and pluralism in health care.
Increasingly, physicians are being asked to provide technical services that many (in some cases, most) believe are morally wrong or inconsistent with their beliefs about the meaning and purposes of medicine. This controversy has sparked persistent debate over whether practitioners should be permitted to decline participation in a variety of legal practices, most notably physician-assisted suicide and abortion. These debates have become heavily politicized, and some of the key words and phrases are being used without a clear understanding of their meaning. In this essay, I endeavor, firstly, to clarify the meaning of some of these terms: conscience, conscientious action, professional judgment, conscientious objection, conscience clauses, civil disobedience, and tolerance. I argue that use of the term conscientious objection to describe these refusals by health care professionals is mistaken and confusing. Secondly, relying on a proper understanding of the moral and technical character of medical judgment, the optimal deference that the state and markets ought to have toward professions, and general principles of Lockean tolerance for a diversity of practices and persons in a flourishing, pluralistic, democratic society, I offer a defense of tolerance with respect to the deeply held convictions of physicians and other health care professionals who hold minority views on contested but legal medical practices.


Binding of linker histones to the core nucleosome.
Binding of chicken erythrocyte linker histones H1/H5 to the core nucleosome has been studied. Histones H1/H5 bind very efficiently to the isolated core nucleosome in vitro. The binding of linker histones to the core nucleosome is associated with aggregation of the particles. Approximately one molecule of linker histone binds per core nucleosome in the aggregates, irrespective of the concentration of the linker histones and the salt used. Histone H5 shows greater binding affinity to the core nucleosome as compared to H1. The carboxyl-terminal fragment of the linker histones binds strongly to the core nucleosome while the binding of the central globular domain is weak. Each core nucleosome is capable of binding two molecules of carboxyl-terminal fragment of linker histone. The core nucleosome containing one molecule of carboxyl-terminal fragment of linker histone requires higher salt concentration for aggregation while the core nucleosome containing two molecules of carboxyl-terminal fragment of linker histone can self-associate even at lower salt concentrations. On the basis of these results we are proposing a novel mechanism for the condensation of chromatin by linker histones and other related phenomena.