Branched Arylalkenes from Cinnamates: Selectivity Inversion in Heck Reactions by Carboxylates as Deciduous Directing Groups.
A decarboxylative Mizoroki-Heck coupling of aryl halides with cinnamic acids has been developed in which the carboxylate group directs the arylation into its β-position before being tracelessly removed through protodecarboxylation. In the presence of a copper/palladium catalyst, both electron-rich and electron-deficient aryl bromides and chlorides bearing numerous functionalities were successfully coupled with broadly available cinnamates, with selective formation of 1,1-disubstituted alkenes. This reaction concept, in which the carboxylate acts as a deciduous directing group, ideally complements traditional 1,2-selective Heck reactions of styrenes.


Direct observation of sn adatoms dynamical fluctuations at the Sn/Ge(111) surface.
The well-known low-temperature phase transition sqrt[3]xsqrt[3] to 3x3 for the 1/3 monolayer of Sn adatoms on the Ge(111) surface has been studied by scanning tunneling microscopy. The STM tip was used as a probe to record the tunneling current as a function of time on top of the Sn adatoms. The presence of steps on the current-time curves allowed the detection of fluctuating Sn atoms along the direction vertical to the substrate. We discuss the effect of temperature and surface defects on the frequency of the motion, finding consistency with the dynamical fluctuations model.


Soft-tissue vibration and damping response to footwear changes across a wide range of anthropometrics in running.
Different factors were shown to alter the vibration characteristics of soft-tissue compartments during running. Changing pre-heel strike muscle activation or changing footwear conditions represents two possibilities to influence the vibration response via frequency shift or altered damping. Associated with the study of muscle pre-tuning is the difficulty in quantifying clean experimental data for the acceleration of soft-tissue compartments and muscle activities in heterogeneous populations. The purpose of this study was to determine the vibration and pre-tuning response to footwear across a wide range of participants during running and establish and describe groups formed according to the damping coefficient. 32 subjects were used for further analysis. The subjects ran at a self-selected speed (5 min) on a treadmill in two different shoes (soft & hard), while soft-tissue accelerations and muscle activation at the gastrocnemius medialis were quantified. Damping coefficients, total muscle intensity and dominant vibration frequencies were determined. Anthropometrics and skinfold measurements of the lower limbs were obtained. According to the damping coefficient response to the footwear intervention, three groups were formed, with most runners (n = 20) showing less damping in the hard shoe. Total muscle intensity, anthropometrics, and dominant vibration frequency across footwear were not different for these three groups. Most runners (84.4%) used the strategy of adjusting the damping coefficients significantly when switching footwear. Despite damping being the preferred adjustment to changes in footwear, muscle pre-tuning might not be the only mechanism to influence damping as previously suggested. Future studies should focus on the subject-specific composition of soft-tissue compartments to elucidate their contribution to vibrations.


An R package for Survival-based Gene Set Enrichment Analysis.
Functional enrichment analysis is usually used to assess the effects of experimental differences. However, researchers sometimes want to understand the relationship between transcriptomic variation and health outcomes like survival. Therefore, we suggest the use of Survival-based Gene Set Enrichment Analysis (SGSEA) to help determine biological functions associated with a disease's survival. We developed an R package and corresponding Shiny App called SGSEA for this analysis and presented a study of kidney renal clear cell carcinoma (KIRC) to demonstrate the approach. In Gene Set Enrichment Analysis (GSEA), the log-fold change in expression between treatments is used to rank genes, to determine if a biological function has a non-random distribution of altered gene expression. SGSEA is a variation of GSEA using the hazard ratio instead of a log fold change. Our study shows that pathways enriched with genes whose increased transcription is associated with mortality (NES > 0, adjusted p-value < 0.15) have previously been linked to KIRC survival, helping to demonstrate the value of this approach. This approach allows researchers to quickly identify disease variant pathways for further research and provides supplementary information to standard GSEA, all within a single R package or through using the convenient app.


Selective, Spontaneous One-Way Oil-Transport Fabrics and Their Novel Use for Gauging Liquid Surface Tension.
Thin porous materials that can spontaneously transport oil fluids just in a single direction have great potential for making energy-saving functional membranes. However, there is little data for the preparation and functionalities of this smart material. Here, we report a novel method to prepare one-way oil-transport fabrics and their application in detecting liquid surface tension. This functional fabric was prepared by a two-step coating process to apply flowerlike ZnO nanorods, fluorinated decyl polyhedral oligomeric silsesquioxanes, and hydrolyzed fluorinated alkylsilane on a fabric substrate. Upon one-sided UV irradiation, the coated fabric shows a one-way transport feature that allows oil fluid transport automatically from the unirradiated side to the UV-irradiated surface, but it stops fluid transport in the opposite direction. The fabric still maintains high superhydrophobicity after UV treatment. The one-way fluid transport takes place only for the oil fluids with a specific surface tension value, and the fluid selectivity is dependent on the UV treatment time. Changing the UV irradiation time from 6 to 30 h broadened the one-way transport for fluids with surface tension from around 22.3 mN/m to a range of 22.3-56.7 mN/m. We further proved that this selective one-way oil transport can be used to estimate the surface tension of a liquid simply by observing its transport feature on a series of fabrics with different one-way oil-transport selectivities. To our knowledge, this is the first example to use one-way fluid-transport materials for testing the liquid surface tension. It may open up further theoretical studies and the development of novel fluid sensors.


Overexpression of HSD17B4 exerts tumor suppressive function in adrenocortical carcinoma and is not associated with hormone excess.
Adrenocortical carcinoma (ACC) is characterized with excessive hormone production. We therefore investigated expression of hormone-related genes in ACC. We queried status of 14 key genes directly involved in adrenal hormone production and found HSD17B4 expression was upregulated in 39% of ACC cases on top of all queried genes. Overexpression of HSD17B4 was significantly associate with a normo-hormonal phenotype. Constitutive HSD17B4 expression was higher in ACC cell line NCI-H295R than in adrenocortical small cell carcinoma cell line SW13. NCI-H295R cells with HSD17B4-knockdown (KD) demonstrated significantly inhibited proliferation, increased apoptosis, and increased cell cycle arrest. Enrichment analysis for mRNA expression in ACC samples with or without HSD17B4 overexpression showed significant change in p53 pathway. Replenish of HSD17B4 in SW13 cells and knockdown of HSD17B4 in H295R cells confirmed alterations in MDM4, ATR, and IE24 with alterations more contrasting in H295R cells. HSD17B4-KD inhibited cell invasion, migration and anchorage independent growth of NCI-H295R cells, but not of SW13 cells. Clinical and genetic data of ACC samples were reproduced from the ACC dataset of The Cancer Genome Atlas (TCGA) database using cBioPortal. Genes participating in adrenal hormone production were queried. Association between gene status and hormone release were studied and in vitro assays using RNA interference were carried out. Overexpression of HSD17B4 exerted tumor suppressive function in adrenocortical carcinoma and was not related to hormone excess. Crosstalk between HSD17B4 and p53 warrants further investigation.


In Situ Constructing of Rigid-Soft Coupling Solid-Electrolyte Interphase on Silicon Electrode toward High-Performance Lithium Ion Batteries.
The application of Si anodes is hindered by some critical issues such as large volume changes of bare Si and fragile solid-electrolyte interface (SEI), resulting in low coulombic efficiency and rapid capacity decay. Herein, a multifunctional SEI film with high content of LiF is in situ constructed via the surface grafting of carbon-fluorine functionalized groups on silicon nanoparticles (SiNPs) during cycling. Mechanical study demonstrates that the incorporation of LiF with high modulus and unbroken carbon-fluorine groups with highly elastic guarantee the rigid-soft coupling SEI film on Si electrode. Furthermore, it is demonstrated that the rigid-soft coupling SEI film can effectively accommodate the volume expansion of Si nanoparticles during lithiation process, with the electrode expanding rate of only 114.16% after 100 cycles (263.87% for bare Si without surface modification). Afterward, with the aid of well-designed rigid-soft coupling SEI, the initial Coulomb efficiency of 89.8% is achieved, showing a reversible capacity of 1477 mAh g-1 after 200 cycles at 1.2 A g-1 . This work provides a simple and efficient solution that can potentially facilitate the practical application of Si anodes.


Two Treatment Cases of Severe Fever and Thrombocytopenia Syndrome with Oral Ribavirin and Plasma Exchange.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease. The primary symptoms associated with SFTS are fever, thrombocytopenia, leukopenia, nausea, and vomiting. Disease progression shows high mortality rate accompanied with multiple organ failure, bleeding tendency, and altered mentality. However, only supportive care has been the basis for the treatment of SFTS. We are reporting two patients who showed central nervous system manifestation, but cured them with ribavirin together with plasma exchange in an early state. The first case is a 60-year-old male, who was admitted to the hospital with a 7-day history of fever, chills, and thrombocytopenia. He was treated with empirical antibiotics; however, he experienced persistent high fever and an altered mentality has occurred. On hospital day 6, the SFTS virus (SFTSV) result from a real-time reverse transcription-polymerase chain reaction (RT-PCR) was confirmed positive. Therefore, ribavirin (30 mg/kg as initial loading dose, 15 mg/kg qid for 4 days and then 7.5 mg/kg qid as maintenance dose) was administered orally for 11 days and plasma exchange was performed for 5 days. The clinical outcome has improved. The second case is a 48-year-old male, who was admitted to the hospital with a 10-day history of fever, chills, myalgia, diarrhea, and thrombocytopenia. He was treated with empirical antibiotics. On hospital day 3, ribavirin (30 mg/kg as initial loading dose, 15 mg/kg qid as maintenance dose) was administered orally for 4 days and plasma exchange was performed for 4 days due to his high fever and altered mentality after a positive SFTSV result from a real-time RT-PCR. The patient had a successful recovery.


[Auricular arteriovenous fistula: a case report and therapeutic approach].
A case of arteriovenous fistula (AVF) arising in the auricle was presented together with its treatment. A 20-year-old man with an AVF on the right auricle was successfully treated with superselective embolization followed by ligation of the arteries supplying the fistula. The lesion underwent considerable regression within a follow-up period of five months and no complications were encountered. Small AVFs existing among several vessels can be satisfactorily treated by embolization and ligation of the vessels instead of extensive resection of the lesion.


Political influence.
SENIOR NURSES in Northern Ireland are to be trained in political influencing to help them understand better the political landscape of the country, and how they can help to shape policy on behalf of nurses and nursing.


Cutting Edge: Dual TCRα Expression Poses an Autoimmune Hazard by Limiting Regulatory T Cell Generation.
Despite accounting for 10-30% of the T cell population in mice and humans, the role of dual TCR-expressing T cells in immunity remains poorly understood. It has been hypothesized that dual TCR T cells pose an autoimmune hazard by allowing self-reactive TCRs to escape thymic selection. We revisited this hypothesis using the NOD murine model of type 1 diabetes. We bred NOD mice hemizygous at both TCRα and β (TCRα+/- β+/-) loci, rendering them incapable of producing dual TCR T cells. We found that the lack of dual TCRα expression skewed the insulin-specific thymocyte population toward greater regulatory T (Treg) cell commitment, resulting in a more tolerogenic Treg to conventional T cell ratio and protection from diabetes. These data support a novel hypothesis by which dual TCR expression can promote autoimmunity by limiting agonist selection of self-reactive thymocytes into the Treg cell lineage.


Trilacunary heteropolytungstates functionalized by organometallic ruthenium(II), [(RuC6H6)2XW9O34]6- (X = Si, Ge).
The benzene-Ru(II)-supported trilacunary heteropolytungstates [(RuC6H6)2XW9O34]6- (X = Si, 1; Ge, 2) have been synthesized and characterized by multinuclear solution NMR (183W, 13C, 1H, 29Si), UV-vis and IR spectroscopy, electrochemistry, and elemental analysis. Single-crystal X-ray analysis was carried out on Rb2Na4[(RuC6H6)2SiW9O34].21H2O (RbNa-1), which crystallizes in the triclinic system, space group P, with a = 11.9415(2) A, b = 13.3123(2) A, c = 19.4927(4) A, alpha = 96.6460(10) degrees , beta = 95.1570(10) degrees , gamma = 98.2560(10) degrees , and Z = 2 and on Cs2Na4[(RuC6H6)2GeW9O34].19.5H2O (CsNa-2), which crystallizes also in the triclinic system, space group P, with a = 11.930(4) A, b = 13.353(4) A, c = 19.586(6) A, alpha = 95.982(5) degrees , beta = 95.414(6) degrees , gamma = 98.142(5) degrees , and Z = 2. The novel polyanion structure consists of two (RuC6H6) units linked to a trilacunary (XW9O34) Keggin fragment via Ru-O(W) and Ru-O(X) bonds resulting in an assembly with Cs symmetry. Polyanions 1 and 2 were synthesized by reaction of [RuC6H6Cl2]2 with [A-alpha-XW9O34]10- in aqueous buffer medium (pH 6.0). Both 1 and 2 are stable in solution as indicated by the expected 5-line pattern (2:1:2:2:2) in the 183W NMR and the expected (3C, 1H, and 29Si spectra. Descriptions of the respective electrochemical behaviors of the W centers and the Ru centers in 1 and 2 are given in media where these processes are clearly defined. In a pH = 3 acetate medium, the cyclic voltammetry of the W centers shows the known fingerprint of the trilacunary alpha-[XW9O34]n- (X = Ge, Si) moieties. The presence of the (RuC6H6) substituents imparts a good stability to these fragments in solution. Stepwise oxidation of the Ru centers was suspected in pH = 5 acetate medium, but only the first step was well-separated from a large current composite wave. The stepwise oxidation was finally observed clearly in a DMF-water (90/10 v/v) mixture and shows two well-behaved Ru oxidation processes. A short comparison is made with DMSO-bearing Ru polyoxometalates.


Synthesis and antiproliferative evaluation of amide-containing anthraquinone, xanthone, and carbazole.
Certain amide-containing anthraquinone, xanthone, and carbazole derivatives have been synthesized and evaluated in vitro for their antiproliferative activities against a panel of human cancer cell lines including nasopharyngeal carcinoma (NPC-TW01), lung carcinoma (NCI-H661), and leukemia (Jurkat). Among them, 2-(9,10-dioxo-9,10-dihydroanthracen-2-yloxy)-N-(naphthalen-2-yl)acetamide (13) was the most active against NPC-TW01 with an IC50 value of 2.62 µM while its xanthone and dibenzofuran counterparts, 14 and 15, were inactive with an IC50 value of 16.10 and 11.09 µM, respectively. Studies on NPC-TW01 cell cycle distribution revealed that compound 13 inhibited proliferation of NPC-TW01 by the alteration of cell division and the accumulation of cells in G0/G1 phase.


GlycA, a Nuclear Magnetic Resonance Spectroscopy Measure for Protein Glycosylation, is a Viable Biomarker for Disease Activity in IBD.
Glycoprotein acetylation [GlycA] is a novel nuclear magnetic resonance [NMR] biomarker, measured in serum or plasma, that summarizes the signals originating from glycan groups of certain acute-phase glycoproteins. This biomarker has been shown to be robustly associated with cardiovascular and short-term all-cause mortality, and with disease severity in several inflammatory conditions. We investigated GlycA levels in a cohort of healthy individuals [HCs], patients with Crohn's disease [CD] and patients with ulcerative colitis [UC] prior to and after therapeutic control of inflammation. Serum samples of 10 HCs, 37 CD patients and 21 UC patients before and after biologic therapy were subjected to high-throughput NMR analysis by Nightingale Health Ltd. Paired C-reactive protein [CRP] and fecal calprotectin [fCal] measurements were used to characterize baseline differences, treatment effects and post-treatment association with endoscopic response [50% SES-CD decrease at Week 24] and mucosal healing [SES-CD ≤ 2 for CD, Mayo endoscopic score ≤ 1 for UC]. GlycA levels were significantly higher in patients with active inflammamtory bowel disease [IBD] compared with those in healthy controls, and accurately reflected the mucosal recovery to a 'healthy' state in both CD and UC patients achieving mucosal healing. In CD patients who experienced an endoscopic response without achieving full mucosal healing, GlycA levels also decreased but did not normalize to HC levels. Overall, GlycA correlated well with CRP and fCal, and accurately tracked disease activity in CRP-negative patients [<5 mg/dL]. GlycA holds promise as a viable serological biomarker for disease activity in IBD, even in patients without elevated CRP, and should therefore be tested in large prospective cohorts.


Lengthened callus activated by axial shortening. Histological and cytomorphometrical analysis.
The tibiae of rabbits were lengthened by 10 mm in 2 weeks, then approximately one half of the limbs were shortened by 2 mm in 3 days, and left for 3 days. Histological and cytomorphometrical findings of the calluses in both groups were compared. In the shortened callus, marked histologic changes were observed in the central mesenchymal cell layer where the number of the osteoblasts increased 4 fold, and massive primitive fiber bone formation took place. Cartilaginous tissue did not seem to respond to the axial shortening stress.


Effectiveness of Drug Treatments for Lowering Uric Acid on Renal Function in Patients With Chronic Kidney Disease and Hyperuricemia: A Network Meta-Analysis of Randomized Controlled Trials.
Background: Hyperuricemia is very common in patients with chronic kidney disease (CKD); the role of hyperuricemia in the occurrence and progression of kidney disease remains an interesting and unresolved issue for nephrologists, and whether urate-lowering therapy (ULT) is warranted in CKD patients is still in controversy. To summarize and compare the clinical outcomes and adverse events (AEs) of three common ULT drugs, we performed a systematic review and network meta-analysis of randomized clinical trials (RCTs). Method: PubMed, MEDLINE, Clinical Trials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials electronic databases were searched. The network meta-analysis was performed using the "gemtc 0.8-7" and its dependent packages in R software. The primary outcome was the change of renal function and uric acid; creatinine, proteinuria, blood pressure, and adverse events were assessed as the secondary outcomes. Results: 16 RCTs involving 1,943 patients were included in the final network analysis. Febuxostat, allopurinol, and benzbromarone were not found to exert superior effects over placebo upon renoprotective effect. With respect to lowering urate, the three drugs showed to be statistically superior to placebo, while febuxostat could better lower urate than allopurinol (MD: -1.547; 95% CrI: -2.473 to -0.626). It is also indicated that febuxostat was superior to placebo at controlling blood pressure, while no differences were observed when allopurinol and benzbromarone were compared to placebo. These results are stable in subgroup analysis. Conclusion: There is insufficient evidence to support the renoprotective effects of the three urate-lowering agents in CKD patients with hyperuricemia; febuxostat shows a tendency to be superior to allopurinol on lowering the decline of eGFR and increment of proteinturia, but the difference does not reach a statistical significance. Regarding its urate-lowering effect, febuxostat appears to be a satisfactory alternative to allopurinol and benzbromarone, and can control blood pressure better.


[Treatment and clinical analysis of laryngeal function preserving surgery in hypopharyngeal carcinoma].
To evaluate the therapeutic effect and the prognosis of the laryngeal function preserving surgery (LFPS) and total laryngectomy in hypopharyngeal carcinoma. Ninety-three cases of laryngopharynx carcinoma were retrospectively analyzed from September 1974 to September 2006. Among which 57 cases were primary pyriform sinus cancer, 20 cases were postero-cricoid cancer and 16 cases were postero-pharyngeal wall cancer. 53 cases were treated by LFPS, and 40 cases were treated by total laryngectomy. The treatment effectiveness, complication, survival rate and repair materials were analysed. Adopting Kaplan-Meier survival analysis, the 3-year survival rates were 69.9% and 5-year survival rates were 43.0%. The 3-year survival rates of LFPS and Non-LFPS were 73.6% and 67.5%, and the 5-year survival rates of LFPS and Non-LFPS were 49.1% and 32. 5%. There was no significant difference between the two groups (chi2 = 2.566, P > 0.05). Single element analysis indicated survival rates concerned with T-stage (chi2 = 9.764, P < 0.05), neck lymphatic transfer (chi2 = 10.472, P < 0.01) and the degree of pathological differentiation (chi2 = 25.894, P < 0.01). Cox regression analysis suggested that T-stage, the degree of pathological differentiation and whether going through the surgical operation were the independent element of the patient's prognosis. There was no significant difference between LFPS and No-LFPS in the neoplasms location, complication, neoplasms residuum and neoplasms recurrence. LFPS did not affect the survival rates and LFPS was feasible. LFPS can increase the living quality of laryngopharynx carcinoma patients.


Development and characterization of antioxidant bilayer film based on poly lactic acid-bitter vetch (Vicia ervilia) seed protein incorporated with Pistacia terebinthus extract for active food packaging.
This study focuses on designing an active bilayer food package film based on polylactic acid (PLA) and bitter vetch seed protein incorporated with Pistacia terebinthus extract (PTE). The effect of PTE on the physicochemical, barrier, structural, mechanical, and antioxidant properties of the active film was determined. Moisture content, water solubility, and water vapor permeability (WVP) of the active films indicated that the addition of PTE increased its suitability for food packaging. FE-SEM micrographs illustrated that the resulting films had a smooth and dense surface, describing a continuous network of protein molecules within the film structure. FTIR analysis displayed the physical interaction between PTE and the film polymer. XRD revealed an increase in the crystallinity of the active films. The resulting active film had a low migration rate (<7%) of phenolic compounds into fatty food simulant. Notably, the addition of PTE significantly (P ≤ 0.05) decreased the tensile strength and Young's modulus (from 15.13 and 315.98 MPa to 14.07 and 254.07 MPa, respectively). Concurrently, there was an increase in the elongation at break of the active films (from 23.19 to 75.60%), indicating higher flexibility compared to control films. Additionally, the incorporation of PTE improved the thermal properties of active films. The antioxidant capacity of the designed films was measured based on their DPPH radical scavenging activity, revealing that the antioxidant capacity of the control film increased from 44.65% to 59.72% in the active film containing 15% PTE. In conclusion, the prepared bilayer film can effectively be used as an active food package for sensitive foods to oxidation.


Two proteins for the price of one: Structural studies of the dual-destiny protein preproalbumin with sunflower trypsin inhibitor-1.
Seed storage proteins are both an important source of nutrition for humans and essential for seedling establishment. Interestingly, unusual napin-type 2S seed storage albumin precursors in sunflowers contain a sequence that is released as a macrocyclic peptide during post-translational processing. The mechanism by which such peptides emerge from linear precursor proteins has received increased attention; however, the structural characterization of intact precursor proteins has been limited. Here, we report the 3D NMR structure of the Helianthus annuus PawS1 (preproalbumin with sunflower trypsin inhibitor-1) and provide new insights into the processing of this remarkable dual-destiny protein. In seeds, PawS1 is matured by asparaginyl endopeptidases (AEPs) into the cyclic peptide SFTI-1 (sunflower trypsin inhibitor-1) and a heterodimeric 2S albumin. The structure of PawS1 revealed that SFTI-1 and the albumin are independently folded into well-defined domains separated by a flexible linker. PawS1 was cleaved in vitro with recombinant sunflower HaAEP1 and in situ using a sunflower seed extract in a way that resembled the expected in vivo cleavages. Recombinant HaAEP1 cleaved PawS1 at multiple positions, and in situ, its flexible linker was removed, yielding fully mature heterodimeric albumin. Liberation and cyclization of SFTI-1, however, was inefficient, suggesting that specific seed conditions or components may be required for in vivo biosynthesis of SFTI-1. In summary, this study has revealed the 3D structure of a macrocyclic precursor protein and provided important mechanistic insights into the maturation of sunflower proalbumins into an albumin and a macrocyclic peptide.


Postoperative infections in asymptomatic HIV-seropositive orthopedic trauma patients.
In a retrospective study of 476 surgical orthopedic trauma patients, we compared postoperative infection rates between individuals seropositive for the human immunodeficiency virus (HIV) and with no associated clinical symptoms with HIV-seronegative patients. Overall, the surgical postoperative infection rate was 16.7% in seropositive patients and 5.4% in the seronegative group (Chi-square, p = 0.035). When open fractures were considered separately, the seropositive group had a 55.6% infection rate compared with 11.3% in the seronegative group (Fisher's exact test, p = 0.004). Similarly, seropositive patients also had significantly increased rates of postoperative non-wound infections and complications (Chi-square p < 0.001). Asymptomatic HIV-seropositive orthopedic trauma patients are at significantly higher risk for postoperative infections than their seronegative counterparts. For HIV-seropositive patients with open fractures, this risk is especially pronounced.


[Evaluation of the diagnosis and treatment of cesarean scar pregnancy induced in the second trimester: a national multicenter retrospective study].
Objective: To study the risk factors of adverse pregnancy outcomes for induced abortion of cesarean scar pregnancy in midtrimester. Methods: A national multicenter retrospective study was conducted. A total of 154 singletons pregnant women with cesarean scar pregnancy during the second trimester induced abortion by various reasons in 12 tertiary A hospitals were selected, their pregnant outcomes were observed and the risk factors of serious adverse outcomes were analyzed with univariate and multivariate logstic regression; the role of ultrasound and MRI in predicting placenta accreta and severe adverse outcomes was evaluated, the effectiveness of uterine artery embolization (UAE) in preventing hemorrhage in pregnant women with and without placenta accreta was compared. Results: Among 154 subjects, the rate of placenta accreta was 42.2% (65/154), the rate of postpartum hemorrhage≥1 000 ml was 39.0% (60/154), the rate of hysterectomy was 14.9% (23/154), the rate of uterine rupture was 0.6% (1/154). The risk factor of postpartum hemorrhage≥1 000 ml and hysterectomy was placenta accreta (P<0.01). For each increase in the number of parity, the risk of placenta accreta increased 2.385 times (95%CI: 1.046-5.439; P=0.039); and the risk of placenta accreta decreased with increasing ultrasound measurement of scar myometrium thickness (OR=0.033, 95%CI: 0.001-0.762; P=0.033). The amount of postpartum hemorrhage and hysterectomy rate in the group with placenta accreta diagnosed by ultrasound combined with MRI were not significantly different from those in the group with placenta accreta diagnosed by ultrasound only or MRI only (all P>0.05). For pregnant women with placenta accreta, there were no significant difference in the amount of bleeding and hysterectomy rate between the UAE group [median: 1 300 ml; 34% (16/47)] and the non-embolization group (all P>0.05); in pregnant women without placenta accreta, the amount of bleeding in the UAE group was lower than that in the non-embolization group (median: 100 vs 600 ml; P<0.01), but there was no significant difference in hysterectomy rate [2% (1/56) vs 9% (3/33); P>0.05]. Conclusions: (1) Placenta accreta is the only risk factor of postpartum hemorrhage≥1 000 ml with hysterectomy for induced abortion of cesarean scar pregnancy in midtrimester; multi-parity and ultrasound measurement of scar myometrium thickness are risk factors for placenta accreta. (2) The technique of using ultrasound and MRI in predicting placenta accreta of cesarean scar pregnancy needs to be improved. (3) It is necessary to discuss of UAE in preventing postpartum hemorrhage for induced abortion of cesarean scar pregnancy in midtrimester.


Risk factors and myocardial infarction in patients with obstructive sleep apnea: impact of beta2-adrenergic receptor polymorphisms.
The increased sympathetic nervous activity in patients with obstructive sleep apnea (OSA) is largely responsible for the high prevalence of arterial hypertension, and it is suggested to adversely affect triglyceride and high-density lipoprotein (HDL) cholesterol levels in these patients. The functionally relevant polymorphisms of the beta2-adrenergic receptor (Arg-47Cys/Arg16Gly and Gln27Glu) have been shown to exert modifying effects on these risk factors in previous studies, but results are inconsistent. We investigated a group of 429 patients (55 +/- 10.7 years; 361 men, 68 women) with moderate to severe obstructive sleep apnea (apnea/hypopnea index (AHI) 29.1 +/- 23.1/h) and, on average, a high cardiovascular risk profile (body mass index 31.1 +/- 5.6, with hypertension in 60.1%, dyslipidemia in 49.2%, and diabetes in 17.2% of patients). We typed the beta2-adrenergic receptor polymorphisms and investigated the five most frequent haplotypes for their modifying effects on OSA-induced changes in blood pressure, heart rate, and lipid levels. The prevalence of cardiovascular risk factors and coronary heart disease (n = 55, 12.8%) and survived myocardial infarction (n = 27, 6.3%) were compared between the genotypes and haplotypes. Multivariate linear/logistic regressions revealed a significant and independent (from BMI, age, sex, presence of diabetes, use of antidiabetic, lipid-lowering, and antihypertensive medication) influence of AHI on daytime systolic and diastolic blood pressure, heart rate, prevalence of hypertension, and triglyceride and HDL levels. The beta2-adrenergic receptor genotypes and haplotypes showed no modifying effects on these relationships or on the prevalence of dyslipidemia, diabetes, and coronary heart disease, yet, for all three polymorphisms, heterozygous carriers had a significantly lower relative risk for myocardial infarction (Arg-47Cys: n = 195, odds ratio (OR) = 0.32, P = 0.012; Arg16Gly: n = 197, OR = 0.39, P = 0.031; Gln27Glu: OR = 0.37, P = 0.023). Carriers of the most frequent haplotype (n = 113) (haplotype 1; heterozygous for all three polymorphisms) showed a five-fold lower prevalence of survived myocardial infarction (OR = 0.21, P = 0.023). Our study showed no significant modifying effect of the functionally relevant beta2-adrenergic receptor polymorphisms on OSA-induced blood pressure, heart rate, or lipid changes. Nevertheless, heterozygosity of these polymorphisms is associated with a lower prevalence of survived myocardial infarction in this group with, on average, a high cardiovascular risk profile.


The activation of mTOR is required for monocyte pro-inflammatory response in patients with coronary artery disease.
Nuclear factor-κB (NF-κB) is a key regulator of systematic inflammation in atherosclerosis (AS). The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, has emerged as an important regulator of chronic inflammation. However, the relationship between mTOR and NF-κB remains poorly defined. The aim of the present study was to investigate the role of mTOR in the pro-inflammatory pathway of human monocytes (HMCs) in patients with coronary artery disease (CAD) and to determine the interaction between mTOR and NF-κB signalling in the inflammatory state. HMCs were isolated from fasting blood samples of 68 patients with CAD and 59 subjects without CAD (non-CAD) to test the activity of NF-κB, p65 nuclear translocation and mTOR phosphorylation, which were all significantly elevated in the CAD group compared with those in the non-CAD group. The concentrations of serum interleukin (IL)-6 and tumour necrosis factor (TNF)-α were higher in the CAD group than in the non-CAD group. In an in vitro experiment, HMCs isolated from non-CAD subjects were used as culture model and were treated with sera extracted from CAD patients (CAD sera) or non-CAD subjects (con sera). CAD sera induced time-dependent phosphorylation of mTOR, aberrant NF-κB activation, as well as up-regulation of inflammatory factors. Moreover, inhibition of mTOR by pharmacological or genetic means abolished the CAD sera-triggered NF-κB activation and pro-inflammatory response. Furthermore, lipid-lowering drug statins partly blocked the CAD sera-activated mTOR and pro-inflammatory response. Our results show that CAD patients are in the pro-inflammatory state with increased NF-κB binding activity and enhanced mTOR phosphorylation. We also found that the activation of mTOR is required for the pro-inflammatory response via NF-κB-dependent pathway in HMCs, which unveils the underlying mechanism of AS and potential strategies to attenuate AS in clinical practice.


Amorphous/Nanocrystalline High-Entropy CoCrFeNiTix Thin Films with Low Thermal Coefficient of Resistivity Obtained via Magnetron Deposition.
High-entropy alloys are promising materials for novel thin-film resistors since they have high resistivity and a low-temperature coefficient of resistivity (TCR). In this work, a new high-entropy thin-film CoCrFeNiTix was deposited on a Si/SiO2 substrate by means of magnetron sputtering of the multi-component target produced by hot pressing of the powder mixture. The samples possessed a thickness of 130-230 nm and an amorphous atomic structure with nanocrystallite traces. This structure persisted after being annealed up to 400 °C, which was confirmed using X-ray and electron diffraction. The film had a single-phase structure with a smooth surface and a uniform distribution of all elements. The obtained film served for microresistor elaboration, which was produced using the lithography technique and tested in a temperature range from -60 °C up to 200 °C. Resistivity at room temperature was estimated as 2.37 μOhm·m. The results have demonstrated that TCR depends on temperature according to the simple linear law in a range from -60 °C up to 130 °C, changing its value from -78 ppm/°C at low temperatures to -6.6 ppm/°C at 130 °C. Such characteristics show the possibility of using these high-entropy alloy films for resistive elements in contemporary and future micro-electronic devices.


Novel microsatellite marker development from the unassembled genome sequence data of the marbled flounder Pseudopleuronectes yokohamae.
Various genome-scale data have been increasingly published in diverged species, but they can be reused for other purposes by re-analyzing in other ways. As a case study to utilize the published genome data, we developed microsatellite markers from the genome sequence data (assembled contigs and unassembled reads) of the marbled flounder Pseudopleuronectes yokohamae. No microsatellites were identified in the contig sequences, whereas the computer software found 781,773 sequences containing microsatellites with di- to hexa-nucleotide motif in the unassembled reads. For 86,732 unique sequences among them, a total of 331,368 primer pairs were designed. Screening based on PCR amplification, polymorphisms and accurate genotyping resulted in sixteen primer sets, which were later characterized using 45 samples collected in Onagawa Bay, Miyagi, Japan. The presence of null alleles was suggested at four loci in the studied population but no evidence of allelic dropout was found. The observed number of alleles and heterozygosity was 2-20 and 0-0.88889, respectively, indicating polymorphisms and usefulness for population genetic analyses of this species. In addition, a large number of the microsatellite primers developed in this study are potentially applicable also for kinship estimation, individual fingerprint and linkage map construction.


[Health beliefs for the control of arterial hypertension].
Health beliefs can interfere with the adherence to arterial hypertension therapy. The aim of this descriptive-exploratory study that adopted the Model of Health Beliefs as a theoretical reference was to estimate percentages of health beliefs about the benefits of prevention and control measures of arterial hypertension and to identify the social-demographic factors associated with these beliefs. The study was conducted in a Health Center in the city of Salvador, with 106 adults self-declared as black, and with a medical diagnosis of arterial hypertension. For the interviews we used a "Scale of Health Beliefs" about 13 behaviors related to disease prevention and control measures. The data analysis was based on percentage rates, frequency of cases and scores and the social-demographic factors associated to these beliefs were analyzed based on the prevalence rate. The global analysis showed predominance in the category "beliefs about benefits" for 12 behaviors. Men and women realized different benefits from these behaviors. The socio-economically less favored strata, young adults and individuals living without a partner tended to perceive less benefits from the prevention and control measures of arterial hypertension.


FLAVI: An Amino Acid Substitution Model for Flaviviruses.
Amino acid substitution models represent substitution rates among amino acids during the evolution. The models play an important role in analyzing protein sequences, especially inferring phylogenies. The rapid evolution of flaviviruses is expanding the threat in public health. A number of models have been estimated for some viruses, however, they are unable to properly represent amino acid substitution patterns of flaviviruses. In this study, we collected protein sequences from the flavivirus genus to specifically estimate an amino acid substitution model, called FLAVI, for flaviviruses. Experiments showed that the collected dataset was sufficient to estimate a stable model. More importantly, the FLAVI model was remarkably better than other existing models in analyzing flavivirus protein sequences. We recommend researchers to use the FLAVI model when studying protein sequences of flaviviruses or closely related viruses.


Faunistic studies of the tribe Brachinini (Carabidae: Coleoptera) from northern Pakistan.
A faunistic study of the tribe Brachinini from northern Pakistan was carried out including extensive fieldwork collections and specimens housed in the Insect Repository, Pakistan Museum of Natural History, Islamabad and the National Insect Museum, National Agricultural Research Centre, Islamabad. Ten species belonging to three genera were identified from the study area, including four new records for Pakistan, Brachinus (Brachinus) ejaculans Fischer Von Waldheim, 1828, Brachinus (Neobrachinus) pallidipes Reitter, 1919, Pheropsophus (Stenaptinus) consularis (Schmidt-Goebel, 1846) and Pheropsophus (Stenaptinus) lineifrons Chaudoir, 1850. A key for these species is provided. A new combination is proposed for Brachinus (Brachynolomus) pallidipes Reitter, 1919, namely Brachinus (Neobrachinus) pallidipes Reitter, 1919, comb. nov.


M/F ratios of four different closing loops: 3D analysis using the finite element method (FEM).
It has been claimed that the opus loop is capable of delivering a constant and optimum M/F ratio without the need for gable bends. To compare the forces, moments and moment/force (M/F) ratios of the opus loop, L-loop, T-loop and vertical helical closing loop (VHC loop) in a segmented arch with the finite element method (FEM). The FEM was used to compare 3D models of closing loops in rectangular (0.016 x 0.022 inch) stainless steel wire. The L-, T- and VHC loops were designed with and without preactivation bends. The opus loop had no preactivation bends. The T-Loops were 10 mm in height and 10 mm in length. The horizontal and vertical forces, the moments and the M/F ratios at the alpha and beta ends were recorded at 0, 0. 1, 0.4, 0.7 and 1 mm intervals. The highest horizontal and vertical forces were produced by the L-loop (with and without preactivation bends) and in most cases the lowest forces were produced by the VHC loop. Loops with preactivation bends produced marked changes in the M/F ratio and loops without preactivation bends low, but relatively constant, M/F ratios over the full range of activation. Of the loops modelled without preactivation bends the opus and T-loop had the highest M/F ratios (7.20 - 7.67 mm at the anterior ends). Stainless steel opus and T-loops without preactivation bends had constant M/F ratios, but both loops failed to deliver the optimum M/F ratio of 10:1.


The T309G murine double minute 2 gene polymorphism is an independent prognostic factor for patients with renal cell carcinoma.
The purpose of this study was to evaluate the association of the T309G MDM2 gene polymorphism with renal cell carcinoma (RCC) risk, pathology, and cancer-specific survival (CSS). T309G MDM2 was genotyped in 449 Caucasians, including 240 with RCC and 209 cancer-free controls. The T309G MDM2 genotype was TT in 174 (38.8%), GT in 214 (47.7%), and GG in 61 (13.6%) subjects, without any significant differences between cases and controls on both univariable (p=0.58) and multivariable logistic regression (each p>0.25). Furthermore, T309G MDM2 was not linked with T stage (p=0.75), N stage (p=0.37), M stage (p=0.94), grade (p=0.21), and subtype (p=0.55). There was, however, a statistically significant association of T309G MDM2 with CSS (p=0.022): patients with TT had significantly worse survival than GG/GT (p=0.009), while those with GT and GG had similar outcomes (p=0.92). The 5-year survival rate for patients with TT, GT, and GG was 69.5%, 84.5%, and 89.7%, respectively. On the multivariable analysis, T309G was identified as an independent prognostic factor. The T309G MDM2 polymorphism is an independent prognostic factor for patients with RCC, with the TT genotype being associated with worse prognosis. In this study, there were no significant associations with RCC risk and pathology.


Lack of sexual behavior disclosure may distort STI testing outcomes.
Men who have sex with men (MSM) globally have a high burden of curable sexually transmitted infections (STIs). MSM do not frequently receive rectal STI testing because of several barriers, such as not being out (disclosure of sexual behavior). We evaluate whether Chinese MSM select an STI test (rectal vs urethral) appropriate for their sexual behavior (insertive and/or receptive), and the interactions with being out. This was a secondary analysis of data from a cross sectional MSM survey conducted at a multisite randomized controlled trial (RCT) (December 2018 to January 2019) around uptake of gonorrhea and chlamydia testing among Chinese MSM (N = 431). We collected socio demographics, relevant medical and sexual history, and disclosure of sexual behavior (outness). We estimated the decision to test and test choice, and the extent to which disclosure plays a role in decision making. Among 431 MSM, mean age was 28 years (SD = 7.10) and 65% were out to someone. MSM who indicated versatile sexual behavior and were out to someone had a 26.8% (95%CI = 6.1, 47.5) increased likelihood for selecting the rectal test vs the ure thral test, compared to those versatile and not out. Versatile MSM out to their health provider outside of the study context had a 29.4% (95%CI = 6.3, 52.6) greater likelihood for selecting the rectal STI test vs the urethral test, compared to versatile MSM not out to their health provider. Sexual behavior and outness may affect gonorrhea and chlamydia testing provision. Apart from clinicians, community based efforts may reduce stigma based barriers to testing.


Check list and geographical distribution of phlebotomine sandflies in China.
A total of 42 species of sandflies, included in five genera, have been recorded from 31 of 32 provinces, municipalities and autonomous regions of China (excluding Heilongjiang Province). Five species, namely Phlebotomus alexandri, P. chinensis, P. longiductus, P. sichuanensis and P. smirnovi (syn. P. wui), are known to be vectors of human leishmaniasis. A list of these 42 phlebotomines is given, and their geographical distributions in China are described.


The effects of remelting on the mechanical properties of a nickel base partial denture casting alloy.
Three series of tensile test pieces were produced using a nickel base partial denture casting alloy. For the first series induction heating was employed, for the second a resistance crucible, and for the third, an oxy-acetylene torch. In each series the same metal was cast sequentially a number of times and all test pieces so produced were subjected to mechanical testing. The mechanical properties were found to vary according to both the number of times the alloy was cast and the method of heating used to render the alloy molten.


Crystal Diagnostics Xpress S Kit for the Rapid Detection of Salmonella spp. in Selected Food Matrixes.
The Crystal Diagnostics (CDx) Xpress S Kit is a rapid-screening assay for Salmonella spp. in whole raw tomatoes, whole chicken carcasses, raw ground beef, raw beef trim, and whole liquid pasteurized eggs with citric acid when present at levels of 1 CFU/portion size. The Xpress S system comprises an automatic CDx Xpress Reader and a single-use CDx BioCassette that incorporates antibody-coupled microspheres and liquid crystal for the selective identification of the intended microbe. In internal evaluations, the CDx Xpress S Kit detected all 142 Salmonella strains tested, including non-enterica subspecies, and excluded all non-Salmonella species assayed. Method-developer studies, as well as a third-party evaluation, demonstrated that 15 h single-stage enrichment permits rapid detection equivalent to the U.S. Department of Agriculture and U.S. Food and Drug Administration reference methods. The results demonstrate that the CDx Xpress S Kit is one of the fastest, most sensitive, and most accurate methods for detecting Salmonella in food matrixes.


Helpfulness of mental health day care: client and staff views.
Seventeen clients of a mental health day service were interviewed regarding their treatment experiences. Content analysis of this information was undertaken, and the clients then rank-ordered the reported aspects of treatment from most to least helpful. Staff undertook a similar procedure to enable clients' views to be placed in context. Both clients and staff reported counselling as the most helpful aspect of treatment. Clients and staff disagreed as to the relative helpfulness of medical and group aspects of treatment. Clients reported medical treatment as the second most helpful aspect, and staff reported groups and the planned approach to care second. Social contact with other clients was reported to be just as helpful as organized group therapy by clients. Clients identified that just having somewhere to go to meet people was very helpful. Communication difficulties between staff and clients were evident with regard to the planned approach to care, discharge planning, and group activities. The ability of clients to evaluate their treatment experiences differentially is highlighted.


Whether and how will using social media induce social anxiety? The correlational and causal evidence from Chinese society.
Prior literature has well established the relationship between social media use and social anxiety, but little attention has been paid to the underlying mechanisms. Additionally, the causal evidence concerning the effect of social media use on social anxiety is scarce. Given that, two studies were conducted to examine the effect of social media use on social anxiety and the underlying mechanisms. In Study 1, with 470 undergraduates as participants, we applied the questionnaire survey to investigate the relationship between social media use and social anxiety. The results showed that higher social media use intensity was significantly related to higher social anxiety, and social media use was related to social anxiety via two possible mediation paths: (1) social media use → upward social comparison → social anxiety, (2) and social media use → upward social comparison → self-esteem → social anxiety. In Study 2, with 180 undergraduates as participants, we conducted a lab experiment, in which participants were assigned to the experimental (exposed to the content that undergraduates frequently access on social media) or control (exposed to landscape documentaries) condition, and then measured their upward social comparison, self-esteem and social anxiety. The results showed that participants in the experimental condition reported higher social anxiety than those in the control condition, demonstrating the causality between social media exposure and social anxiety. The subsequent mediation analysis basically replicated the findings of Study 1. That is, upward social comparison played the mediating role between social media exposure and social anxiety, and upward social comparison and self-esteem played the chain-mediating role between them. The current research firstly demonstrated the causality between social media use and social anxiety in Chinese society, and also revealed the mediating mechanisms between them, which would deepen our understanding of how social media use will increase social anxiety.


ETB receptor dependent alteration in aortic responses to ET-1 in the cardiomyopathic hamster.
The aim of this study was to verify whether an alteration in the aortic endothelin-1 (ET-1) response takes place in UM-X7.1 cardiomyopathic hamsters. Our results showed that ET-1 (10(-12) - 10(-5) mol/L) induces dose-dependent sustained increases in tension in the intact and endothelium denuded aortas from both normal and cardiomyopathic hamsters. The EC50 values of ET-1 of both intact and endothelium denuded aortas of normal hamsters were similar (2.2 x 10(-9) mol/L and 1.8 x 10(-9) mol/L, respectively). However, in cardiomyopathic hamsters, the EC50 of ET-1 in intact aortas was higher (1.5 x 10(-8) mol/L) than that of the endothelium denuded preparations (2.7 x 10(-9) mol/L). The EC50 of ET-1 in normal and cardiomyopathic hamster denuded aortas were similar. However, the EC50 of ET-1 in intact aortas of cardiomyopathic hamster was higher (1.5 x 10(-8) mol/L) than that of normal hamsters (2.2 x 10(-9) mol/L). Pre-treatment with the ETA receptor antagonist ABT-627 (10(-5)mol/L) of intact and endothelium denuded aortas from both normal and cardiomyopathic hamsters significantly prevented ET-1 (10(-7) mol/L) from inducing an increase in tension. Pre-treatment with the ETB receptor antagonist A-192621 (10(-5) mol/L) had no effect on the ET-1-induced increase in tension in endothelium denuded aortas of both normal and cardiomyopathic hamsters, as well as in intact preparations of normal animals. However, blockade of the ETB receptors in intact aortas of cardiomyopathic hamsters significantly (p < 0.001) potentiated the ET-1-induced increase in tension. In summary, an attenuation of the contraction response to ET-1 was found in UM-X7.1 cardiomyopathic hamsters when compared with normal age-matched hamsters. This alteration of the ET-1 effect in the aortas of cardiomyopathic hamsters seems to be dependent on the presence of the endothelium and could be due, in part, to an increase in the contribution of endothelial ETB receptors to relaxation, which in turn acts as a physiological depressor of ET-1 vasoconstriction. Our results suggest that an increase in the endothelium ETB receptor density may play a role in the development of hypotension in UM-X7.1 cardiomyopathic hamsters.


[Analysis of malaria epidemic situation and control in Hubei Province from 1974 to 2015].
To analyze the malaria control measures and epidemic trend in Hubei Province from 1974 to 2015, so as to provide the evidence for malaria elimination path analysis. The malaria control data in Hubei Province from 1974 to 2015 were collected and analyzed retrospectively by descriptive epidemiological methods. The epidemic process of malaria in Hubei Province was divided into four stages. From 1974 to 1979, it was high prevalence state of malaria, and the average annual incidence was 174.47/10 000. From 1980 to 1999, the main control strategies were to control the infection source and mosquitoes, and the average annual incidence was 17.30/10 000, significantly downward. From 2000 to 2009, through the surveillance of infection sources and controlling malaria outbreaks and strengthening the floating population management, the average annual incidence was 0.42/10 000. After 2010, followed by the elimination phase of malaria, the incidence continued to decline. In 2013, there was no local infection for the first time. The difference of average annual incidence among above-mentioned stages was statistically significant (χ2 = 1 254.36, P < 0.05). The malaria epidemic process in Hubei Provincial experienced the high epidemic stage, sharply drop stage, low incidence phase and the elimination phase. However, the natural factors affecting malaria still exist. Therefore, strengthening the control of imported malaria and surveillance should be the main task in the process of eliminating malaria in the future.


Oxidized low density lipoprotein induces apoptosis in cultured human umbilical vein endothelial cells by common and unique mechanisms.
Oxidized low density lipoprotein (oxLDL) induces apoptosis in vascular cells. To elucidate the mechanisms involved in this apoptosis, we studied the apoptosis-inducing activity in lipid fractions of oxLDL and the roles of two common mechanisms, ceramide generation and the activation of caspases, in apoptosis in human umbilical vein endothelial cells treated with oxLDL. We also studied the effects of antioxidants and cholesterol. oxLDL induced endothelial apoptosis in a time- and dose-dependent fashion. Apoptosis-inducing activity was recovered in the neutral lipid fraction of oxLDL. Various oxysterols in this fraction induced endothelial apoptosis. Neither the phospholipid fraction nor its component lysophosphatidylcholine induced apoptosis. oxLDL induced ceramide accumulation temporarily at 15 min in a dose-dependent fashion. Two inhibitors of acid sphinogomyelinase inhibited both the increase in ceramide and the apoptosis induced by oxLDL. Furthermore, a membrane-permeable ceramide (C2-ceramide) induced endothelial apoptosis. These findings demonstrated that ceramide generation by acid sphingomyelinase is indispensable for the endothelial apoptosis induced by oxLDL. Inhibitors of both caspase-1 and caspase-3 inhibited the apoptosis, suggesting that oxLDL induced apoptosis by activating these cysteine proteases. The antioxidants butylated hydroxytoluene and superoxide dismutase but not catalase inhibited the apoptosis induced by oxLDL or 25-hydroxycholesterol. This suggests not only that superoxide plays an important role but also that a critical interaction between oxLDL and the cell takes place on the outer surface of the membrane, because superoxide dismutase is not membrane-permeable. Exogenous cholesterol also inhibited the apoptosis. Our study demonstrated that neutral lipids in oxLDL induce endothelial apoptosis by activating membrane sphingomyelinase in a superoxide-dependent manner, as well as by activating caspases.


Pan-ebolavirus and Pan-filovirus Mouse Monoclonal Antibodies: Protection against Ebola and Sudan Viruses.
The unprecedented 2014-2015 Ebola virus disease (EVD) outbreak in West Africa has highlighted the need for effective therapeutics against filoviruses. Monoclonal antibody (MAb) cocktails have shown great potential as EVD therapeutics; however, the existing protective MAbs are virus species specific. Here we report the development of pan-ebolavirus and pan-filovirus antibodies generated by repeated immunization of mice with filovirus glycoproteins engineered to drive the B cell responses toward conserved epitopes. Multiple pan-ebolavirus antibodies were identified that react to the Ebola, Sudan, Bundibugyo, and Reston viruses. A pan-filovirus antibody that was reactive to the receptor binding regions of all filovirus glycoproteins was also identified. Significant postexposure efficacy of several MAbs, including a novel antibody cocktail, was demonstrated. For the first time, we report cross-neutralization and in vivo protection against two highly divergent filovirus species, i.e., Ebola virus and Sudan virus, with a single antibody. Competition studies indicate that this antibody targets a previously unrecognized conserved neutralizing epitope that involves the glycan cap. Mechanistic studies indicated that, besides neutralization, innate immune cell effector functions may play a role in the antiviral activity of the antibodies. Our findings further suggest critical novel epitopes that can be utilized to design effective cocktails for broad protection against multiple filovirus species. Filoviruses represent a major public health threat in Africa and an emerging global concern. Largely driven by the U.S. biodefense funding programs and reinforced by the 2014 outbreaks, current immunotherapeutics are primarily focused on a single filovirus species called Ebola virus (EBOV) (formerly Zaire Ebola virus). However, other filoviruses including Sudan, Bundibugyo, and Marburg viruses have caused human outbreaks with mortality rates as high as 90%. Thus, cross-protective immunotherapeutics are urgently needed. Here, we describe monoclonal antibodies with cross-reactivity to several filoviruses, including the first report of a cross-neutralizing antibody that exhibits protection against Ebola virus and Sudan virus in mice. Our results further describe a novel combination of antibodies with enhanced protective efficacy. These results form a basis for further development of effective immunotherapeutics against filoviruses for human use. Understanding the cross-protective epitopes are also important for rational design of pan-ebolavirus and pan-filovirus vaccines.


A novel folic acid-conjugated TiO₂-SiO₂ photosensitizer for cancer targeting in photodynamic therapy.
In this paper, a novel folic acid-conjugated silica-coated titanium dioxide (TiO2-SiO2) photosensitizer was synthesized and characterized using various analytical instruments. The photosensitizer was further assessed with regards to its photoreactivity, cellular and hemocompatibility, cell internalization, and phototoxicity. Conjugating folic acid with TiO2-SiO2 has shown a significantly improved compatibility of the nanoparticles with the mouse fibroblast cells (L929) at 24 h. An improved compatibility with the human nasopharyngeal epidermoid cancer (KB) cells was also demonstrated, but to a slightly reduced degree. Enhanced cell internalization was well demonstrated in the TiO2-SiO2 folate nanoparticles. Upon exposure to UV light, TiO2-SiO2 folate nanoparticles maintained a high level photodynamic reactivity and yielded a 38-43% photo-killing of KB cells. The photo-killing effect increased with increasing dosage in the investigated concentration range of 50-100 μg ml(-1).


THE "DARK SIDE" OF DEEP VEIN THROMBOSIS--CASE REPORT.
Venous thromboembolism (VTE) is an increasingly common cause of morbidity and mortality in cancer patients. In various malignancies the incidence of thrombosis ranges from 5% to 60%, that is four times higher in cancer patients compared to the general population. Large retrospective studies have shown that in men the tumors which are most commonly associated with VTE are lung cancer and pancreatic cancer and, in women cancer of the genital area, pancreas, colon and rectum. Thromboembolic events may often occur before the cancer diagnosis. We present the case of a 41-year-old female patient with a history of genital cancer which was surgically treated and who is now admitted for clinical signs of ileofemoral deep vein thrombosis (DVT) of the left leg. The diagnosis was confirmed by laboratory data and Doppler ultrasound and the patient received anticoagulant treatment. Given the history of the patient, abdominal and pelvic ultrasound and computer tomography (CT) were performed to detect the cause who predisposed to the thrombotic event. These confirmed the ovarian cancer, this time on the right side, and the presence of hepatic and pulmonary metastasis. This case highlights the importance of screening for a cause of the thromboembolic event in patients, especially in those who have a history of a neoplasia.


Polymyxin-B and vancomycin-associated acute kidney injury in critically ill patients.
This study aims to investigate renal toxicities of Polymyxin B and Vancomycin among critically ill patients and risk factors for acute kidney injury (AKI). This is a cross-sectional study conducted with patients admitted to an intensive care unit (ICU) of a tertiary hospital in Brazil. Patients were divided into two groups: those who used association of Polymyxin B + Vancomycin (Group I) and those who used only Polymyxin B (Group II). Risk factors for AKI were also analyzed. A total of 115 patients were included. Mean age was 59.2 ± 16.1 years, and 52.2% were males. Group I presented higher GFR (117.1 ± 70.5 vs. 91.5 ± 50 ml/min/1.73 m², p = 0.02) as well as lower creatinine (0.9 ± 0.82 vs. 1.0 ± 0.59 mg/dL, p = 0.014) and urea (51.8 ± 23.7 vs. 94.5 ± 4.9 mg/dL, p = 0.006) than group II on admission. Group I also manifested significantly higher incidence of AKI than group II (62.7% vs. 28.5%, p = 0.005), even when stratified according to RIFLE criteria ('Risk' 33.9% vs. 10.7%; 'Injury' 10.2% vs. 8.9%; 'Failure' 18.6% vs. 8.9%; p = 0.03). Accumulated Polymyxin B dose > 10 million IU was an independent predictor for AKI (OR = 2.72, 95% CI = 1.13-6.51, p = 0.024). Although patients who received Polymyxin B plus vancomycin had more favorable clinical profile and higher previous GFR, they presented a higher AKI incidence than those patients who received Polymyxin B alone. Cumulative Polymyxin B dose > 10 million IU was independently associated to AKI.


Neutrophilia, gelatinase release and microvascular leakage induced by human mast cell tryptase in a mouse model: Lack of a role of protease-activated receptor 2 (PAR2).
Tryptase, the most abundant protease of the human mast cell, has been implicated as a key mediator of allergic inflammation that acts through activation of PAR2. To investigate the contribution of PAR2 in the pro-inflammatory actions mediated by tryptase in a mice model. We have injected recombinant human βII-tryptase into the peritoneum of PAR2-deficient and wild-type C57BL/6 mice. After 6, 12 and 24 hours, mice were killed, peritoneal lavage performed and inflammatory changes investigated. Tryptase stimulated an increase in neutrophil numbers in the peritoneum, but responses did not differ between PAR2-deficient and wild-type mice. Heat inactivation of tryptase or pre-incubation with a selective tryptase inhibitor reduced neutrophilia, but neutrophil accumulation was not elicited with a peptide agonist of PAR2 (SLIGRL-NH2 ). Zymography indicated that tryptase stimulated the release of matrix metalloproteinases (MMP) 2 and 9 in the peritoneum of both mouse strains. Studies involving immunomagnetic isolation of neutrophils suggested that neutrophils represent the major cellular source of tryptase-induced MMP2 and MMP9. At 24 hours after tryptase injection, there was increased microvascular leakage as indicated by high levels of albumin in peritoneal lavage fluid, and this appeared to be partially abolished by heat-inactivating tryptase or addition of a protease inhibitor. There was no corresponding increase in levels of histamine or total protein. The extent of tryptase-induced microvascular leakage or gelatinase release into the peritoneum did not differ between PAR2-deficient and wild-type mice. Our findings indicate that tryptase is a potent stimulus for neutrophil accumulation, MMP release and microvascular leakage. Although these actions required an intact catalytic site, the primary mechanism of tryptase in vivo would appear to involve processes independent of PAR2.


Effects of n-butanol production on metabolism and the photosystem in Synecococcus elongatus PCC 7942 based on metabolic flux and target proteome analyses.
Although n-butanol (BuOH) is an ideal fuel because of its superior physical properties, it has toxicity to microbes. Previously, a Synechococcus elongatus PCC 7942 derivative strain that produces BuOH from CO2 was developed by introducing six heterologous genes (BUOH-SE strain). To identify the bottleneck in BuOH production, the effects of BuOH production and its toxicity on central metabolism and the photosystem were investigated. Parental (WT) and BUOH-SE strains were cultured under autotrophic conditions. Consistent with the results of a previous study, BuOH production was observed only in the BUOH-SE strain. Isotopically non-stationary 13C-metabolic flux analysis revealed that the CO2 fixation rate was much larger than the BuOH production rate in the BUOH-SE strain (1.70 vs 0.03 mmol gDCW-1 h-1), implying that the carbon flow for BuOH biosynthesis was less affected by the entire flux distribution. No large difference was observed in the flux of metabolism between the WT and BUOH-SE strains. Contrastingly, in the photosystem, the chlorophyll content and maximum O2 evolution rate per dry cell weight of the BUOH-SE strain were decreased to 81% and 43% of the WT strain, respectively. Target proteome analysis revealed that the amounts of some proteins related to antennae (ApcA, ApcD, ApcE, and CpcC), photosystem II (PsbB, PsbU, and Psb28-2), and cytochrome b6f complex (PetB and PetC) in photosystems decreased in the BUOH-SE strain. The activation of photosynthesis would be a novel approach for further enhancing BuOH production in S. elongatus PCC 7942.


Novel measure of the weigh distribution balance on the brain network: graph complexity applied to schizophrenia.
The aim of this study was to assess brain complexity dynamics in schizophrenia (SCH) patients during an auditory oddball task. For this task, we applied a novel graph measure based on the balance of the node weights distribution. Previous studies applied complexity parameters that were strongly dependent on network topology. This could bias the results, as well as making correction techniques, such as surrogating process, necessary. In the present study, we applied a novel graph complexity measure derived from the information theory: Shannon Graph Complexity (SGC). Complexity patterns from electroencephalographic recordings of 20 healthy controls and 20 SCH patients during an auditory oddball task were analyzed. Results showed a significantly more pronounced decrease of SGC for controls than for SCH patients during the cognitive task. These findings suggest an important change in the brain configuration towards a more balanced network, mainly in the connections related to long-range interactions. Since these changes are significantly more pronounced in controls, a deficit in the neural network reorganization can be associated with SCH. In addition, an accuracy of 72.5% was obtained using a receiver operating characteristic curve with a leave-one-out cross-validation procedure. The independence of network topology has been demonstrated by the novel complexity measure proposed in this study, therefore, it complements traditional graph measures as a means to characterize brain networks.


The mechanism of uptake of cobalt ions by Neurospora crassa.
Uptake of Co(2+) by 3-day-old mycelia of Neurospora crassa involves cell-surface binding as well as transport into the intracellular space. The surface binding is rapid and accounts for 30-40% of the total Co(2+) uptake. Transport of Co(2+) occurs at a rate of 40mug/h per 100mg dry wt. Surface binding and overall uptake show different temperature dependence. Metabolic inhibitors such as azide, dinitrophenol and fluoride depress transport of Co(2+). The overall uptake of Co(2+) exhibits a high K(m) value and hence the concentration mechanism is one of low ;affinity' for the metal. The uptake of Co(2+) varies linearly with pH in the range pH3 to pH6. Mg(2+) inhibits both surface binding and transport of Co(2+). It is suggested that the system that transports Mg(2+) is also involved in Co(2+) uptake by N. crassa.


Evaluation of the single-dose pharmacokinetics of bilastine in subjects with various degrees of renal insufficiency.
Bilastine is a novel second-generation H1 antihistamine, which has not shown sedative or cardiotoxic effects in clinical trials and in post-marketing experience so far, developed for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It has recently been granted marketing authorization for these therapeutic indications in adults and adolescents at a once-daily oral dose of 20 mg in several European countries. This study was conducted to determine the pharmacokinetics of bilastine at a single oral dose of 20 mg in renally impaired subjects. The need for a dose adjustment in patients with renal insufficiency was assessed by comparing the exposure to bilastine in these subjects with the estimated exposure of a dose corresponding to the safety margin. The study was an open-label, single-dose, parallel-group study of the pharmacokinetics and safety of a single dose of bilastine. The study was conducted as an in-patient setting at a clinical pharmacology facility. A total of 24 male or female subjects aged 18-80 years were to be enrolled in four groups of six subjects each. The groups were as follows: (1) healthy [glomerular filtration rate (GFR) >80 mL/min/1.73 m(2)]; (2) mild renal insufficiency (GFR 50-80 mL/min/1.73 m(2)); (3) moderate renal insufficiency (GFR 30-50 mL/min/1.73 m(2)); and (4) severe renal insufficiency (GFR ≤30 mL/min/1.73 m(2)). A single 20 mg bilastine tablet was administered in a fasted state. Blood and urine samples were collected from pre-dose up to 72 h post-dose for bilastine pharmacokinetic analysis. Pharmacokinetic results were summarized using appropriate descriptive statistics. There was a clear trend of increasing area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C(max)) through the groups 1-4. The mean AUC from time zero to infinity (AUC(∞)) ranged from 737.4 to 1708.5 ng·h/mL in healthy subjects and severely impaired subjects, respectively. No significant differences among groups in median time to reach Cmax (tmax) or in the mean terminal disposition rate constants for bilastine were found. Renal and plasma clearance paralleled GFR. In all groups of renally impaired subjects the corresponding 90 % confidence interval of both AUC(∞) and AUC from time zero to time of last measurable plasma concentration (AUC(last)) were not within the 0.8-1.25 interval, indicating that bioequivalence between groups could not be demonstrated. The majority of bilastine was excreted within the first 12 h, and elimination was essentially complete by 72 h. An oral dose of bilastine (20 mg) was well-tolerated in renal insufficiency, despite the increase in exposure. The oral plasma clearance to renal clearance ratio [(CL(P)/F)/CL(R)] was approximately equal in the different groups, suggesting that renal excretion was the main elimination route for bilastine, and no alternative elimination routes were used even in severe renal insufficiency. Although exposure to bilastine was higher in renally impaired subjects, it remained well within the safety margins, thus allowing the conclusion that a 20-mg daily dose can be safely administered to subjects with different degrees of renal insufficiency without the need for dose adjustments.


Epitope-specific antibody response to the surface antigen of duck hepatitis B virus in infected ducks.
In order to investigate the immune response to duck hepatitis B virus (DHBV) infection, newly hatched DHBV DNA negative ducklings were injected with infectious serum of sufficiently low DHBV-DNA titer to allow clearance of viremia. Of 20 injected ducklings, 13 (65%) became viremic. Of these, 6 (46%) cleared virus from the serum 3 to 22 weeks postinjection. The convalescent sera of these 6 animals were tested for an epitope-specific antibody response in a highly specific competitive inhibition assay using a panel of monoclonal antibodies against duck hepatitis B surface antigen (DHBsAg) that had been well-characterized. All 6 animals recovering from DHBV infection developed antibodies to epitopes on the preS and S proteins of DHBV. Antibody responses were highly variable with marked differences between animals in the extent and specificity of the antibody response. The humoral response to DHBsAg was prolonged in some animals but transient in others. No antibody to preS or S was detected in either preimmune sera or sera of control animals from an uninfected flock. Infected animals that did not clear viremia also remained antibody negative. The humoral responses to neutralizing preS epitopes III and V were weak but antibodies to two immunodominant epitopes on the preS region (II and B) were present in all 6 animals. The humoral response to the two epitopes in the S region was transient and of lower titer when compared to the two immunodominant preS epitopes. The two immunodominant preS epitopes may play an important role in clearance of DHBV infection in ducks.


Prevalence of high-risk human papillomavirus and abnormal pap smears in female sex workers compared to the general population in Antwerp, Belgium.
Although female sex workers (FSWs) are a well-known high-risk group for Human Papillomavirus (HPV) infections, few tailored intervention programmes for HPV have been established worldwide. The lack of reliable data on the prevalence of HPV and related cervical lesions hampers the establishment of evidence-based intervention programmes. The objectives of this study were to describe the prevalence of high-risk Human Papillomavirus (hrHPV) infections and abnormal pap smears in FSWs compared to a control group in Antwerp, Belgium. HPV genotyping and cytology data were analysed from routine Pap smear tests that were collected from both FSWs and the general population (1334 samples for each group) between June 2006 and June 2010. Within the laboratory database, all FSWs were matched 1:1 for age and testing date to determine the ORs of hrHPV genotypes, DNA and cytology outcome. The prevalence of hrHPV DNA in FSWs was 41.7 % compared to 19.8 % in the age-matched controls with an overall OR of 2.8 (95 % CI: 2.3-3.4). Significant differences were observed in all age groups, and the most significant differences were observed in the cohort under 21 years of age (prevalence of 64.4 % in FSWs versus 14.8 % in controls; OR 10.3 (95 % CI: 5.0-21.2). Significantly more cervical lesions were observed in FSWs, particularly in the 17- to 21-year old age group (OR for LSIL or HSIL: 10.3 (95 % CI: 3.2-33.8). In both groups, HPV 16 was the most prevalent at 12.1 and 6.6 % in the FSW and control groups, respectively. HPV 18 was the 8(th) and 7(th) most frequent genotype at 5.0 and 2.5 % in the FSW and control groups, respectively. FSWs have a significantly higher prevalence of hrHPV and more abnormal Pap smears than does the general population in Antwerp, Belgium. The hrHPV prevalence in FSWs is similar to that reported in the literature. The need for tailored intervention programmes should be investigated further.


Why business models matter.
"Business model" was one of the great buzz-words of the Internet boom. A company didn't need a strategy, a special competence, or even any customers--all it needed was a Web-based business model that promised wild profits in some distant, ill-defined future. Many people--investors, entrepreneurs, and executives alike--fell for the fantasy and got burned. And as the inevitable counterreaction played out, the concept of the business model fell out of fashion nearly as quickly as the .com appendage itself. That's a shame. As Joan Magretta explains, a good business model remains essential to every successful organization, whether it's a new venture or an established player. To help managers apply the concept successfully, she defines what a business model is and how it complements a smart competitive strategy. Business models are, at heart, stories that explain how enterprises work. Like a good story, a robust business model contains precisely delineated characters, plausible motivations, and a plot that turns on an insight about value. It answers certain questions: Who is the customer? How do we make money? What underlying economic logic explains how we can deliver value to customers at an appropriate cost? Every viable organization is built on a sound business model, but a business model isn't a strategy, even though many people use the terms interchangeably. Business models describe, as a system, how the pieces of a business fit together. But they don't factor in one critical dimension of performance: competition. That's the job of strategy. Illustrated with examples from companies like American Express, EuroDisney, WalMart, and Dell Computer, this article clarifies the concepts of business models and strategy, which are fundamental to every company's performance.


Rapidly and Repeatedly Reprogrammable Liquid Crystalline Elastomer via a Shape Memory Mechanism.
Realization of muscle-like actuation for a liquid crystal elastomer (LCE) requires mesogen alignment, which is typically achieved/fixed chemically during the synthesis. Post-synthesis regulation of the alignment in a convenient and repeatable manner is highly desirable yet challenging. Here, a dual-phase LCE network is designed and synthesized with a crystalline melting transition above a liquid crystalline transition. The crystalline phase can serve as an "alignment frame" to fix any mechanical deformation via a shape memory mechanism, leading to corresponding mesogen alignment in the liquid crystalline phase. The alignment can be erased by melting, which can be the starting point for reprogramming. This strategy that relies on a physical shape memory transition for mesogen alignment permits repeated reprogramming in a timescale of seconds, in stark contrast to typical methods. It further leads to unusual versatility in designing 3D printed LCE with unlimited programmable actuation modes.


Analytic density-functional self-consistent-field theory of diblock copolymers near patterned surfaces.
Analytical solutions are derived for the density profiles and the free energies of compressible diblock copolymer melts (or incompressible copolymer solutions) near patterned surfaces. The density-functional self-consistent-field theory is employed along with a Gaussian chain model for bonding constraints and a random mixing approximation for nonbonded interactions. An analytical solution is rendered possible by expanding the chain distribution function around an inhomogeneous reference state with a nontrivial analytical solution, by retaining the linear terms, and by requiring consistency with the homopolymer limit. The density profiles are determined by both real and complex roots of a sixth-degree polynomial that may easily be obtained by solving a generalized eigenvalue problem. This analytical formulation enables one to efficiently explore the large nine-dimensional parameter space and can serve as a first approximation to computationally intensive studies with more detailed models. Illustrative computations are provided for uniform and patterned surfaces above the order-disorder transition. The results are consistent with the previous self-consistent-field calculations in that lamellar ordering appears near the surface above the order-disorder transition and the lamella order perpendicular or parallel to the surface depending on the commensurability between the periods of the surface pattern and the density oscillations.


Turing structuring with multiple nanotwins to engineer efficient and stable catalysts for hydrogen evolution reaction.
Low-dimensional nanocrystals with controllable defects or strain modifications are newly emerging active electrocatalysts for hydrogen-energy conversion and utilization; however, a crucial challenge remains in insufficient stability due to spontaneous structural degradation and strain relaxation. Here we report a Turing structuring strategy to activate and stabilize superthin metal nanosheets by incorporating high-density nanotwins. Turing configuration, realized by constrained orientation attachment of nanograins, yields intrinsically stable nanotwin network and straining effects, which synergistically reduce the energy barrier of water dissociation and optimize the hydrogen adsorption free energy for hydrogen evolution reaction. Turing PtNiNb nanocatalyst achieves 23.5 and 3.1 times increase in mass activity and stability index, respectively, compared against commercial 20% Pt/C. The Turing PtNiNb-based anion-exchange-membrane water electrolyser with a low Pt mass loading of 0.05 mg cm-2 demonstrates at least 500 h stability at 1000 mA cm-2, disclosing the stable catalysis. Besides, this new paradigm can be extended to Ir/Pd/Ag-based nanocatalysts, illustrating the universality of Turing-type catalysts.


New acute peritoneal dialysis technique: wire-guide insertion and long-term indwelling of peritoneal catheter.
This paper presents the application of wire-guide insertion of peritoneal dialysis catheter. 30 patients who required acute peritoneal dialysis were treated using a total of 37 peritoneal catheters with the wire-guide method. The catheters were left in place as long as possible (periods totalling 644 days in all). The complication of insertion was minor bleeding with blood-tinged dialysate that tended to clear spontaneously in a few days. Leakage occurred in 17 indwelling catheters but did not occur on the days of insertion. There were 3 episodes of clinical peritonitis, so the infection rate was 1 episode every 7 patient-months. This technique is safer and simpler, i.e. the incidence of peritonitis is lower in long-term indwelling catheters, and so it will contribute to the wider and earlier utilization of peritoneal dialysis.


Role of NPY for vasoregulation in the splanchnic circulation during portal hypertension.
Vascular dysfunction in the splanchnic circulation during portal hypertension is characterized by enhanced NO-mediated vasorelaxation and vascular hyporeactivity to norepinephrine that lead to arterial vasodilation. NPY most likely counteracts both of these key features. Firstly, NPY appears to inhibit Ach- and PNS-induced vasorelaxation in mesenteric arteries. This effect is more pronounced in portal hypertensive rats as compared to control, and most likely reflects the inhibition of increased e- and nNOS-derived NO-synthesis during portal hypertensive conditions. Secondly, NPY sensitizes the mesenteric vasculature to alpha(1)-adrenergic vasoconstriction. Most importantly, in portal hypertensive rats but not in sham rats NPY markedly augments vascular contractility and thereby corrects vascular hyporeactivity. Both actions of NPY increase vascular tone and may well act synergistically in the splanchnic circulation during portal hypertension. Moreover, the vasoconstrictive effects of NPY are most pronounced at particularly high levels of alpha(1)-adrenergic activity. Therefore, it appears that NPY becomes increasingly important for optimizing adrenergic vasoconstriction at particularly high adrenergic drive and also for playing a predominant role for vascular homeostasis. Cirrhotic patients present with elevated circulating plasma levels of NPY, which appears to be independent from the severity of liver dysfunction and to correlate with portal pressure. This finding indicates enhanced NPY release during portal hypertension that may represent a compensatory mechanism aimed at counterbalancing arterial vasodilation by restoring the efficacy of endogenous catecholamines and inhibiting vasodilative drive in the splanchnic circulation.


Prevalence of hyperhomocysteinemia in normal healthy Thai subjects.
The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B12 status. The elevations of plasma homocysteine concentration are associated with an increased risk of vascular disease. The primary goals of this study were to identify plasma homocysteine concentrations in Thai residents and to test for differences in homocysteine levels among sex and age categories. The authors measured plasma total homocysteine concentrations in 3,345 Shinawatra employees (1,133 males, 2,212 females aged between 20-65 years) by using fluorescence polarization immunoassay (FPIA) method. The mean plasma homocysteine concentrations of males and females were 11.495 and 8.547 micromol/L respectively. Plasma homocysteine concentrations were significantly lower in females than in males (p < 0.0001). The age-specific plasma homocysteine levels were lower in females than in males for each group, but the levels of each group was not significantly different both in males and females. When more than 12 micromol/L was used as the cut-off value, it was found that 33.6 per cent of males and 6.69 per cent of females were classified as hyperhomocysteinemia subjects. The authors concluded that the prevalence of hyperhomocysteinemia in Thai males is more common than in females. Further investigation should be done to clarify the association between serum folate, vitamin B12, vitamin B6 concentrations and plasma homocysteine concentration.


Determinants of organophosphate esters exposure in pregnant women from East China.
Organophosphate esters (OPEs) have been broadly used in various industrial and consumer products, resulting in global distribution and human exposure. Gestational exposure to OPEs may adversely affect the health of both pregnant women and their offspring. To better understand OPE exposure in pregnant women, our study determined eight urinary metabolites of major OPEs in pregnant women (n = 733) recruited at 12-16 weeks of gestation from Shanghai, China, and explored the determinants of OPE exposure among various sociodemographic characteristics, lifestyles, and dietary factors. Urinary metabolites of OPEs, including bis (1,3-dichloro-2-propyl) phosphate (BDCPP), bis (2-chloroethyl) phosphate (BCEP), bis (1-chloro-2-propyl) phosphate (BCIPP), dicresyl phosphate (DCP), diphenyl phosphate (DPP), dibutyl phosphate (DBP), bis (2-ethylhexyl) phosphate (BEHP), and bis (2-butoxyethyl) phosphate (BBOEP), exhibited a detection rate ranging from 69.30% to 99.32%. Multivariate linear regression models indicated that pregnant women who were multiparous, had a higher family income per capita, worked in white-collar jobs, and took nutritional supplements such as milk powder and fish oil tended to have higher urinary OPE metabolite concentrations. Besides, independent of sociodemographic characteristics and lifestyle factors, consumption of more aquatic products, soy products, pork, and puffed food, as well as drinking of purified tap water versus tap water, were associated with increased urinary OPEs metabolite concentrations. Our study demonstrated that OPE exposure was ubiquitous in pregnant women from Shanghai, and provided new insights into the potential factors influencing OPE exposure during pregnancy.


Structural basis for the broad substrate specificity of fiddler crab collagenolytic serine protease 1.
Crab collagenolytic serine protease 1 efficiently cleaves peptide bonds directly C-terminal to basic, polar, and hydrophobic amino acids. The crystal structure of this enzyme complexed to the protein inhibitor ecotin at 2.5 A resolution reveals a large primary binding pocket punctuated on one wall by the side chain of aspartate-226. Removal or relocation of this negatively charged group by site-directed mutagenesis generates variant enzymes which retain very high activities toward selected substrates. Full retention of activity toward hydrophobic substrates in collagenase D226G is accompanied by a 10-100-fold reduction in k(cat)/Km toward basic residues. In contrast, restoration of the negative charge in a trypsin-like position in collagenase D226G/G189D regenerates nearly full activity toward basic substrates while introducing a 5-fold decrease in k(cat)/Km toward hydrophobic amino acids. These results imply that the collagenase S1 pocket has multiple distinct binding sites for different amino acid side chains, a suggestion supported by molecular modeling studies based on the crystal structure. The ease of specificity modification in the primary binding site of this serine protease parallels similar observations with the bacterial enzymes alpha-lytic protease and subtilisin, and stands in sharp distinction to the extensive mutagenesis required to alter specificity in trypsin.


The Influence of Ecological Factors on the Distribution and the Genetic Structure of Escherichia coli.
This review focuses on recent data concerning the ecological factors that determine the distribution of Escherichia coli and the genetic structures of naturally occurring E. coli populations. It summarizes some of the older literature concerning the dynamics of E. coli populations within a host and poses some questions that arise from our more recently acquired understanding of the factors affecting the genetic structures of E. coli populations. Multilocus enzyme electrophoresis (MLEE) studies indicate that E. coli, relative to other members of the family Enterobacteriaceae, exhibits a moderate degree of genetic diversity. The existence of subspecific structure in E. coli has for the most part been determined by largely neutral in its effects on the fitness of a strain. The consequences for E. coli of the transition between its primary and secondary habitats are of considerable practical significance for water quality assessment and disease transmission. E. coli causes a significant fraction of human bacterial disease and is responsible for two main types of disease in humans and domestic animals: diarrheal disease and extraintestinal infections. The observed distribution of strains from the different E. coli genetic groups indicates that they have different life history tactics and ecological niches. A and B1 strains appear to be generalists, as they can be recovered from any vertebrate group. Group B2 and D strains appear to be more specialized, as they are largely restricted to endothermic vertebrates.


Geometric similarity and heart weight scaling: an application of White's criterion of similarity.
Heart weight scaling among members of the primate tribe Papionini is analyzed in relation to the proposal that evolutionary size change may sometimes come about in such a way that geometric similarity is maintained across species. The results indicate that in terms of relative heart weight, the six species examined can be divided into two groups of geometric variants. Although these groupings do not conform to any hypothesized phylogenetic relationships, there is some evidence to support the associations based on shared patterns of ontogenetic development. An account is proposed for the differences between the two groups in terms of derived versus primitive patterns of relative heart weight growth.


Orotate phosphoribosyltransferase from Corynebacterium ammoniagenes lacking a conserved lysine.
The pyrE gene, encoding orotate phosphoribosyltransferase (OPRTase), was cloned by nested PCR and colony blotting from Corynebacterium ammoniagenes ATCC 6872, which is widely used in nucleotide production. Sequence analysis shows that there is a lack of an important conserved lysine (Lys 73 in Salmonella enterica serovar Typhimurium OPRTase) in the C. ammoniagenes OPRTase. This lysine has been considered to contribute to the initiation of catalysis. The enzyme was overexpressed and purified from a recombinant Escherichia coli strain. The molecular mass of the purified OPRTase was determined to be 45.4 +/- 1.5 kDa by gel filtration. Since the molecular mass for the subunit of the enzyme was 21.3 +/- 0.6 kDa, the native enzyme exists as a dimer. Divalent magnesium was necessary for the activity of the enzyme and can be substituted for by Mn2+ and Co2+. The optimal pH for the forward (phosphoribosyl transfer) reaction is 10.5 to 11.5, which is higher than that of other reported OPRTases, and the optimal pH for the reverse (pyrophosphorolysis) reaction is 5.5 to 6.5. The Km values for the four substrates were determined to be 33 microM for orotate, 64 microM for 5-phosphoribosyl-1-pyrophosphate (PRPP), 45 microM for orotidine-5-phosphate (OMP), and 36 microM for pyrophosphate. The Km value for OMP is much larger than those of other organisms. These differences may be due to the absence of Lys 73, which is present in the active sites of other OPRTases and is known to interact with OMP and PRPP.


Sparse Optical Flow Implementation Using a Neural Network for Low-Resolution Thermal Aerial Imaging.
This study is inspired by the widely used algorithm for real-time optical flow, the sparse Lucas-Kanade, by applying a feature extractor to decrease the computational requirement of optical flow based neural networks from real-world thermal aerial imagery. Although deep-learning-based algorithms have achieved state-of-the-art accuracy and have outperformed most traditional techniques, most of them cannot be implemented on a small multi-rotor UAV due to size and weight constraints on the platform. This challenge comes from the high computational cost of these techniques, with implementations requiring an integrated graphics processing unit with a powerful on-board computer to run in real time, resulting in a larger payload and consequently shorter flight time. For navigation applications that only require a 2D optical flow vector, a dense flow field computed from a deep learning neural network contains redundant information. A feature extractor based on the Shi-Tomasi technique was used to extract only appropriate features from thermal images to compute optical flow. The state-of-the-art RAFT-s model was trained with a full image and with our proposed alternative input, showing a substantial increase in speed while maintain its accuracy in the presence of high thermal contrast where features could be detected.


Electronic-Level View of O-O Bond Formation in Nature's Water Oxidizing Complex.
The crucial O-O bond forming step in the water oxidizing complex (WOC) of photosystem II is modeled using density functional theory calculations and compared with structural X-ray free electron laser (XFEL) determinations for the penultimate S3 state. Concerted electron flow between the Mn4O5 and Mn1O6 bonds of the complex and the nascent O-O bond is monitored using intrinsic bond orbital analysis along the reaction path. Concerted transfer to Mn1 and Mn4 of two electrons from the reactant oxos, O5 and O6, resulting in an unoccupied antibonding σ2p* orbital is the key to low barrier O-O bond formation. The potential energy surface for O-O bond formation shows a rather broad energy minimum for the oxo-oxo form ranging from 2.4-2.0 Å which may explain the relatively short O5-O6 bond distance reported in experimental structure studies. Alternatively the short O5-O6 bond distance may reflect a dynamic equilibrium model across the whole O-O potential energy surface.