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Legumes are a predominant source of isoflavones, termed phytoestrogens, that mimic 17β-estradiol (E2). Phytoalexins are inducible isoflavones produced in plants subjected to environmental stressors (e.g., UV, heat, or fungi). This study investigated estrogenic activity of snow and green peas elicited with Aspergillus sojae . Elicited extracts increased estrogenic activity and proliferation of breast cancer cells (MCF-7 or T47D) in a dose-dependent manner but exhibited antiestrogenic activity when combined with synthetic E2. HPLC analysis of elicited pea extracts identified (+)-pisatin as the primary phytoalexin, which was produced significantly ( p < 0.0001) more in snow pea compared to green pea. RNA sequencing results suggested potential functional effects on endothelial cells and tissue vascularization. Indeed, (+)-pisatin enhanced metrics of network assembly and maturation in a microphysiological model of bulk tissue vasculogenesis. Thus, context-dependent functional effects of (+)-pisatin and pharmacologically similar phytoestrogens on the entire tissue microenvironment should be considered in preclinical investigation as potential therapeutic agents.

Metal oxides are widely used in heterogeneous catalysis as supports to disperse catalytically active nanoparticles, isolated atomic sites, or even as catalysts themselves. Herein, we present a method to produce optically active metal oxide supports that exhibit size-dependent Mie resonances based on TiO 2 nanospheres with tunable size, crystalline phase composition, and optical properties. Mie resonant TiO 2 nanospheres were used as supports to disperse Au, Pt, and Pd nanoparticles. We have found up to a 50-fold enhancement of the electric field at the metal oxide/metal interface corresponding to wavelength-dependent multipolar resonances in the TiO 2 structure. Using Au/TiO 2 as a prototypical photocatalyst, we demonstrate broadband rate enhancements between 400 and 800 nm during CO oxidation, with a noticeable increase below 500 nm. This increased reactivity at higher photon energies is due to improved photon utilization and interband absorption in the gold that results in greater secondary electron generation through electron-electron scattering processes, thus leading to higher rates in conjunction with the Mie scattering TiO 2 support. This study not only highlights the potential of Mie resonant TiO 2 in broadband photocatalytic enhancements but also for developing various Mie resonant metal oxide supports, such as ZnO or Cu 2 O, which can improve photocatalytic performance for a number of critical reactions. As the chemical and energy industries move toward conversion technologies driven by renewable energy sources, the strategy of designing optical resonances into oxide supports that are already widely used could enable a straightforward adaptation of photochemical processing based on traditional heterogeneous catalysts.

Three cyclo-penta-dienylmolybdenum(II) propionyl complexes featuring tri-aryl-phosphine ligands with different para substituents, namely, dicarbon-yl(η 5 -cyclo-penta-dien-yl)propion-yl(tri-phenyl-phosphane-κ P )molybdenum(II), [Mo(C 5 H 5 )(C 3 H 5 O)(C 18 H 15 P)(CO) 2 ], ( 1 ), dicarbon-yl(η 5 -cyclo-penta-dien-yl)propion-yl[tris-(4-fluoro-phen-yl)phosphane-κ P ]molybdenum(II), [Mo(C 5 H 5 )(C 3 H 5 O)(C 18 H 12 F 3 P)(CO) 2 ], ( 2 ), and dicarbon-yl(η 5 -cyclo-penta-dien-yl)propion-yl[tris-(4-meth-oxy-phen-yl)phosphane-κ P ]molybdenum(II) dichloromethane solvate, [Mo(C 5 H 5 )(C 3 H 5 O)(C 21 H 21 O 3 P)(CO) 2 ]·CH 2 Cl 2 , ( 3 ), have been prepared from the corresponding ethyl complexes via phosphine-induced migratory insertion. These complexes exhibit four-legged piano-stool geom-etries with mol-ecular structures quite similar to each other and to related acetyl complexes. The extended structures of the three complexes differ somewhat, with the para substituent of the tri-aryl-phosphine of ( 2 ) (fluoro) or ( 3 ) (meth-oxy) engaging in non-classical C-H⋯F or C-H⋯O hydrogen-bonding inter-actions. The structure of ( 3 ) exhibits modest disorder in the position of one Cl atom of the di-chloro-methane solvent, which was modeled with two sites showing approximately equivalent occupancies [0.532 (15) and 0.478 (15)]., (© Whited et al. 2021.)

The multi-scale hierarchical structure of tooth enamel enables it to withstand a lifetime of damage without catastrophic failure. While many previous studies have investigated structure-function relationships in enamel, the effects of crystal misorientation on mechanical performance have not been assessed. To address this issue, in the present study, we review previously published polarization-dependent imaging contrast (PIC) maps of mouse and human enamel, and parrotfish enameloid, in which crystal orientations were measured and displayed in every 60-nm-pixel. By combining those previous results with the PIC maps of sheep enamel presented here we discovered that, in all enamel(oid)s, adjacent crystals are slightly misoriented, with misorientation angles in the 0°-30° range, and mean 2°-8°. Within this limited range, misorientation is positively correlated with literature hardness values, demonstrating an important structure-property relation, not previously identified. At greater misorientation angles 8°30°, this correlation is expected to reverse direction, but data from different non-enamel systems, with more diverse crystal misorientations, are required to determine if and where this occurs. STATEMENT OF SIGNIFICANCE: We identify a structure-function relationship in tooth enamels from different species: crystal misorientation correlates with hardness, contributing to the remarkable mechanical properties of enamel in diverse animals., Competing Interests: Declaration of Competing Interest The authors delcare no conflict of interest., (Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the safety and efficacy of elagolix vs. placebo and elagolix with low-dose E 2 /progestogen add-back therapy., Design: Proof-of-concept, dose-ranging, multiple-cohort study., Setting: Clinics., Patient(s): Premenopausal women with fibroids and heavy menstrual bleeding (menstrual blood loss [MBL] >80 mL per cycle)., Intervention(s): Three months' treatment with elagolix alone: 100 mg twice daily (BID), 200 mg BID, 300 mg BID, 400 mg once daily (QD), or 600 mg QD (all but the 600 mg QD arm were placebo controlled); or elagolix plus add-back therapy: 200 mg BID plus continuous low-dose E 2 0.5 mg/norethindrone acetate 0.1 mg or elagolix 300 mg BID plus E 2 1 mg continuously and cyclical P 200 mg., Main Outcome Measure(s): Least-squares mean percentage change in MBL; adverse events (AEs)., Result(s): Mean age was 41.8 years; 73.8% were black; mean baseline MBL was 267 mL. Of randomized women (elagolix alone, n = 160; placebo, n = 50; elagolix with add-back therapy, n = 61), 228 of 271 completed the 3-month treatment period. The MBL percentage change from baseline to last 28 days was significantly greater with elagolix alone (range, -72% to -98%; dose-dependent reduction was highest with 300 mg BID) vs. placebo (range, -8% to -41%); mean percentage changes with add-back regimens were -80% to -85%. Overall AEs were dose independent (elagolix alone, 70.0%-81.3%) but lower with placebo (56.0%) and add-back regimens (55.6%-70.6%). Hot flush was the most common AE (elagolix alone, 45.5%-62.5%; placebo, 12.0%; add-back regimens, 18.5%-26.5%)., Conclusion(s): Elagolix significantly reduced heavy menstrual bleeding in women with fibroids. Low-dose add-back regimens substantially reduced flushing., Clinical Trial Registration Number: NCT01441635., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Perthes-like hip deformities encompass variable proximal femoral abnormalities and associated acetabular dysplasia that can be reconstructed with contemporary hip preservation procedures. Nevertheless, the necessity and indications for surgical correction of associated acetabular dysplasia have not been established., Questions/purposes: We determined whether patient-specific factors (sex, age, BMI, previous surgery, hip pain and function) and/or structural deformity characteristics (radiographic parameters of acetabular morphology) were associated with our indications for acetabular reorientation in surgical reconstruction of Perthes-like hip deformities., Methods: We compared patient-specific characteristics and radiographic parameters of acetabular morphology in 94 patients (97 hips) with residual Perthes deformities who underwent joint preservation surgery without or with a periacetabular osteotomy (PAO) as part of the reconstruction., Results: Patient sex, BMI, preoperative Harris hip score, and previous hip surgery were not associated with our indications for a combined femoral and PAO procedure. Radiographic parameters associated with the indication for a PAO included the lateral center-edge angle, anterior center-edge angle, acetabular inclination, and acetabulum-head index. No or mild secondary osteoarthritis and joint congruency were associated with the indication for a PAO as part of the reconstruction., Conclusions: Contemporary hip preservation surgery for residual Perthes deformities covers a wide spectrum of procedures. We believe a PAO should be considered in the surgical treatment plan for symptomatic patients having radiographic parameters indicating acetabular dysplasia, no or mild secondary osteoarthritis, and adequate joint congruity., Level of Evidence: Level III, prognostic study. See Instructions for Authors for a complete description of levels of evidence.

This study's aim was to identify the effect of oscillation of torques in isometric tasks under identical mechanical conditions on the muscle synergies used. It was hypothesized that bi-functional muscles would play a lesser role in torque oscillation, because they would also generate an undesired oscillation. Thus, changes in muscle synergies were expected as a consequence of oscillation in torque generation. The effect of the trajectory of torque generation was investigated in dual-degrees-of-freedom submaximal isometric oscillation torque tasks at the elbow. The torques were flexion-extension and supination-pronation. Oscillation torques were compared with static torque generations at four torque positions during oscillation. Muscle activity was determined with surface electromyography. Compared with the static torque tasks, the oscillation tasks showed an overall increased muscle activity. The oscillation tasks, however, showed similar activity patterns and muscle synergies compared to the static composite tasks. It was found that the motor system is well able to control different orthogonal combinations of slow torque oscillations and constant torques by employing a single oscillating muscle synergy.

Objective: To compare the flavour and taste preferences of two acid-inhibitory therapies in children., Subjects and Setting: 104 (52 male and 52 female) healthy children aged 6-11 years participated in this phase IV single-centre, taste-test study after parental consent was obtained., Methods: Children were divided into two groups based upon age: group 1 included children aged 6-8 years and group 2 included children aged 9-11 years. Within each group an equal number of male and female subjects were recruited. Within each of the four strata defined by group and sex, an equal number of subjects were randomised to taste the strawberry-flavoured lansoprazole 15mg orally disintegrating tablet or the ranitidine 75mg/5mL peppermint-flavoured syrup samples in position 1. In group 1, the lansoprazole 15mg delayed-release orally disintegrating tablet was dispersed in 5mL of water, while in group 2, children gently rolled the tablet on the tongue until dissolution, before swallowing the particles. Children given the dose of lansoprazole dispersed in water (group 1) and the ranitidine dose (groups 1 and 2) were to taste it, swish it in their mouth for up to 10 seconds, and then swallow it. Children were given ambient temperature water and unsalted crackers to cleanse the palate during a 10-minute break between tastings., Main Outcome Measures: After each tasting, children rated their degree of liking on a five-point facial hedonic scale (5 = like very much, 1 = dislike very much). Product preference was recorded after the tasting of both samples., Results: Among group 1 and group 2 participants, 86.5% (45/52) and 90.4% (47/52) of children, respectively, 'liked' ('like a little' or 'like very much') the strawberry-flavoured lansoprazole orally disintegrating tablet. The proportion of children who 'liked' the peppermint-flavoured ranitidine syrup was lower than the proportion who liked lansoprazole, and the proportions were similar between the groups: 13.5% (7/52) in group 1 and 9.6% (5/52) in group 2. Children in both groups preferred the strawberry-flavoured lansoprazole delayed-release orally disintegrating tablet: 92% (95% CI 81.1, 97.8; p < 0.001) of those in group 1 and 98% (95% CI 89.7, 100.0; p < 0.001) of those in group 2., Conclusion: After tasting both products, >92% of children aged from 6-11 years preferred the strawberry-flavoured lansoprazole delayed-release orally disintegrating tablet, either dissolved in a small amount of water or allowed to dissolve on the tongue, over the peppermint-flavoured ranitidine syrup.

Hypertriglyceridemia is a common metabolic disorder with a major inherited component. In some individuals the condition is suspected to occur as a result of overproduction of apolipoprotein (apo)CIII, a major constituent of triglyceride-rich lipoproteins. Population studies have established an association with the apoCIII gene but the identify of the causal mutation remains unknown. In the present study we have examined a series of six 5' polymorphic nucleotides (G-935 to A, C-641 to A, G-630 to A, deletion of T-625, C-482 to T, and T-455 to C) that lie within the promoter region of the apoCIII gene for evidence of possible involvement in disease susceptibility. The polymorphic nucleotides at positions -455 and -482 reside within a negative insulin-response element. We show, in a community-based sample of 503 school children, that a DNA polymorphism (S2 allele) within the 3'-noncoding region of the apoCIII gene was associated with elevated apoCIII and triglyceride levels, but that the polymorphic nucleotides of the promoter were not. In addition, no obvious effect of any extended apoCIII promoter haplotype on plasma apoCIII or triglyceride levels, over and above that conferred by the presence of the S2 polymorphic nucleotide, was detected. These results demonstrate that none of the 5' apoCIII polymorphisms can account for the association of the apoCIII gene locus with hypertriglyceridemia and, moreover, owing to linkage disequilibrium, raise the possibility that the region conferring susceptibility maps downstream, rather than upstream, of the apoCIII gene promoter sequences.

A number of studies have reported that a variant allele (S2) of the apo AI/CIII/AIV complex is associated with high plasma lipid levels in some populations and furthermore that the frequency of this allele is 2-5-fold higher in patient groups with premature coronary heart disease compared to control groups. This study shows in the healthy "English" population that the S2 allele is associated with elevated plasma apo CIII levels but not with low apo AI levels. In addition, it shows that the allele is associated with elevated plasma levels of apo B in men. Regression analysis shows in both men and women that apo CIII levels are positively correlated with plasma triglyceride levels and moreover that they are a stronger predictor of this parameter than apo AI, B or AIV. Apo CIII levels are also an independent predictor of total plasma cholesterol and HDL-cholesterol levels in males and females, respectively. Together these data suggest that a genetic predisposition to develop elevated plasma levels of apo CIII, alone or in combination with elevated plasma apo AIV levels, is the primary defect responsible for the association of the S2 allele with hyperlipidemia and/or premature CHD.

Blood pressure on admission to hospital is a "stressed blood pressure" that will tend to exaggerate the prevalence of hypertension. Twelve per cent of patients admitted to Auckland Hospital did not have their blood pressure recorded. The number of blood pressure recordings was excessive in many untreated hypertensive patients admitted to Auckland Hospital. The physician tends to examine patients with high blood pressure in a predictable manner without regard to the severity of pressure recorded. The diagnosis of hypertension or kidney disease was recorded in the medical case summaries sent to the general practitioners in only 11% of patients whose admission blood pressure was raised. The blood pressure of many hypertensive patients was not communicated to the general practitioner; this information was given in 60% of treated and 39% of untreated hypertensive patients.

Death rates for cerebrovascular disease (stroke) in New Zealand are declining. To investigate the reasons for this decline and to measure the impact of stroke on a defined population, a register of new episodes of stroke was kept in the Auckland region for the year ending March 1982. All cases were followed for one year, with in-depth interviews at onset, one month and six months and a telephone follow-up at one year to establish dead or alive status. A total of 703 episodes were registered for 680 patients, 331 men and 349 women. The crude event rate for all those over 15 years was 228 and 220 per 100,000 for men and women, respectively. Age-adjusted event rates for all strokes were 28% higher for men than women and the age-adjusted event rates for Maoris were 44% higher than for non-Maoris. The case fatality rates were 23.1% at one week, 33.5% at one month, 43.5% at six months and 48.5% at one year. In comparison with other studies, case fatality rates are similar but the incidence rates appear to be lower.

Streptococcus suis is a zoonotic pathogen which causes meningitis, arthritis and septicaemia in pigs, and rarely meningitis or septicaemia in humans. This organism has recently been isolated from pigs in New Zealand, where it appears to be widely distributed in pig herds. This case is the first report of human infection in New Zealand.

The role of the immune response in pyelonephritis was investigated by manipulation of the host's immune capacity using the immunosuppressive drugs 6-mercaptopurine, cyclophosphamide and thiamphenicol. Treatment with 6-mercaptopurine depressed the humoral immune response but did not have an adverse effect on the course of renal infection. Thiamphenicol administration prevented the development of pathological lesions but this was due to the anti-bacterial activity of thiamphenicol and not to its immunosuppressive activity. Pyelonephritic animals treated with cyclophosphamide did not produce anti-bacterial antibody. Despite this, cyclophosphamide-treated animals were able to eliminate organisms more readily from the infected kidney than untreated animals with a normal humoral immune response. We believe that blocking of the phenomenon of immunological enhancement explains these unexpected results and that the immune response to renal infection may have an immunoenhancing role protecting the bacterial cell from otherwise effective host defence mechanisms.

A large population-based study of stroke is used to describe the pattern of management and the relative contribution of hospital care and community care in the year following an acute stroke episode. Two thirds of the 680 patients registered in the study were admitted to a public hospital during the acute stage of their illness, while almost one quarter of all patients were managed entirely at home. One month after the initial episode the majority of patients admitted to hospital had either died or had been discharged. Overall, four-fifths of the care during the first year after the onset of the stroke took place out of hospital, either at home or in private long-term institutions.

The objective of this study was to establish conditions whereby apoB secreted from HepG2 cells could be regulated over a wide range, and to determine whether changes of output were correlated with the level of apoB mRNA. The presence of oleate (complexed to 3% albumin at a molar ratio of 1.7:1) resulted in a 3.5-fold stimulation of apoB secretion that was apparent after only 3 h. Insulin halved the rate of apoB output and the inhibition was detectable within the physiological insulin range, but was not apparent until 12-16 h. Albumin in the culture medium had a dose-dependent inhibitory effect on apoB production. Overall, apoB secretion from HepG2 cells was modulated over a 7-fold range. However, when apoB mRNA was assayed by slot-blot hybridization, no change was detectable under any of the conditions that modulated apoB output. Quantitative solution hybridization was used to confirm that oleate did not affect the level of apoB mRNA. Kinetic analysis of the decay of [3H]uridine-labeled apoB mRNA showed that the half-life of apoB mRNA was 16 h. We conclude from these studies that the apoB gene is constitutively expressed in HepG2 cells and that the mechanism of acute regulation of apoB production by these cells must involve co- or post-translational processes.

To examine long-term trends in subarachnoid hemorrhage (SAH) mortality and morbidity, an analysis of routinely available information is presented for the 20 year period from 1959. To document the current incidence and case fatality of SAH, the results of a large scale community-based study in the Auckland region are presented. SAH mortality rates for both men and women, especially women, have declined since the mid-1970's. The decline appears to be real, and is most striking in the 45-64 year age groups. A corresponding decline in discharge rates from hospital has also occurred in these age groups. In contrast, cases fatality rates have remained stable at about 42% for the 20 year period under review. The community-based study identified 92 cases in a total population of 829,464 in a twelve month period. The age standardised incidence rates were 13.4 and 15.8 per 100,000 for men and women respectively. In the age group 25-35 years, the incidence rate was particularly high at 8.5/100,000. Case fatality at 28 days was 52%. A decline in incidence appears the most likely explanation for the overall decline in national mortality.

Antilymphocyte globulin (A.L.G.) was prepared by injecting fresh frozen splenic cells subcutaneously into horses. The IgG fraction of the serum was concentrated by a batch technique using diethylaminoethanol-Sephadex. Fourteen patients given this material by intramuscular injection after cadaveric renal transplants, in addition to azathioprine and prednisone, had less evidence of rejection compared with patients previously treated with azathioprine and prednisone only, despite a reduction of the mean daily prednisone dose from 65 to 45 mg. Toxicity, especially local reaction, fever, and hypotension, limited the amount of A.L.G. that was given.