Optimizing vascular access for patients receiving intravenous systemic therapy for early-stage breast cancer-a survey of oncology nurses and physicians.

Background: Despite advances in systemic therapy choices for patients with early-stage breast cancer, optimal practices for intravenous (IV) access remain unknown. That lack of knowledge holds particularly true for the use of central venous access devices (cvads) such as peripherally inserted central catheters (piccs) and implanted vascular access devices (ports). Methods: Using a survey of Canadian oncologists and oncology nurses responsible for the care of breast cancer patients, we evaluated current access practices, perceptions of complications, and perceptions of risk, and we estimated complication rates and evaluated perceived risk factors for lymphedema. Results: Survey responses were received from 25 physicians and 57 oncology nurses. Administration of trastuzumab or an anthracycline was associated with a higher likelihood of a cvad being recommended. Other factors associated with recommendation of a cvad included prior difficult IV access and a recommendation from the chemotherapy nurse. Although the complication rates perceived to be associated with the use of piccs and ports remained high, respondents felt that cvads might improve patient quality of life. Risk factors perceived to be associated with the risk of lymphedema were axillary lymph node dissection, radiation to the axilla, and line-associated infection. Factors known to be unrelated to lymphedema risk (specifically, blood draws and blood pressure measurement) continue to be perceived as posing a higher risk. Conclusions: Despite widespread use of chemotherapy for patients with breast cancer, the type of venous access used for treatment varies significantly, as do perceptions about the risks of cvad use and the risk for lymphedema development. Further prospective studies are needed to identify best-practice strategies.

Epigenetic variation in OPRM1 gene in opioid-exposed mother-infant dyads.

Neonatal abstinence syndrome (NAS) due to in-utero opioid exposure has significant variability of severity. Preliminary studies have suggested that epigenetic variation within the µ-opioid receptor (OPRM1) gene impacts NAS. We aimed to determine if DNA methylation in OPRM1 within opioid-exposed mother-infant dyads is associated with differences in NAS severity in an independent cohort. Full-term opioid-exposed newborns and their mothers (N = 68 pairs) were studied. A DNA sample was obtained and then assessed for level of DNA methylation at 20 CpG sites within the OPRM1 promoter region by next-generation sequencing. Infants were monitored for NAS and treated with replacement opioids according to institutional protocol. The association between DNA methylation level at each CpG site with NAS outcome measures was evaluated using linear and logistic regression models. Higher methylation levels within the infants at the -18 (11.4% vs 4.4%, P = .0001), -14 (46.1% vs 24.0%, P = .002) and +23 (26.3% vs 12.9%, P = .008) CpG sites were associated with higher rates of infant pharmacologic treatment. Higher levels of methylation within the mothers at the -169 (R = 0.43, P = .008), -152 (R = 0.40, P = .002) and +84 (R = 0.44, P = .006) sites were associated point-wise with longer infant length of stay. Maternal associations remained significant point-wise for -169 (ß = 0.07, P = .007) and on an experiment-wise level for +84 (ß = -0.10, P = .003) using regression models. These results suggest an association of higher levels of OPRM1 methylation at specific CpG sites and increased NAS severity, replicating prior findings. These findings have important implications for personalized treatment regimens for infants at high risk for severe NAS.

Diuretics for very low birth weight infants in the first 28 days: a survey of the U.S. neonatologists.

OBJECTIVE: The objective of this study was to describe factors influencing diuretic use by neonatologists caring for very low birth weight neonates. STUDY DESIGN: We surveyed 400 U.S. neonatologists. Respondents made therapeutic decisions in clinical scenarios involving very low birth weight infants at 7, 14 and 28 days of age. RESULT: Response rate was 39%. Diuretic therapy was chosen in 31% of scenario decisions, with pro re nata dosing selected early and regular dosing more common at later ages. Diuretic use was strongly associated with method of respiratory support, and was chosen less often by those also choosing fluid restriction and those concerned about patent ductus arteriosus risk. After adjusting for these factors, excessive weight gain, expected improvement in work of breathing and expected decrease in ventilator days were also associated with diuretic use. CONCLUSION: The extent of and expectations for diuretic therapy by neonatologists caring for very low birth weight neonates may exceed evidence for efficacy.

Effect of biotic elicitors on enrichment of antioxidant properties and induced isoflavones in soybean.

The antioxidant properties of methanolic extracts from soybean obtained with germination, wounding, and application of biotic elicitors were evaluated. Also, the relationship between observed antioxidant properties and compositional changes in isoflavone content was determined. The 2 biotic elicitors used in this study were the food-grade fungus Aspergillus sojae and A. sojae cell wall extract. Isoflavone content was determined by C(18) reverse phase high-performance chromatography coupled with a photodiode array detector. Antioxidant activities of the extracts were measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and beta-carotene cooxidation in a linoleate system. Higher antioxidant activities were observed in wounded and elicitor-treated extracts when compared with nonwounded control extracts. In addition, the phenolic content was higher in extracts from wounded and elicitor-treated soybean. Germination for 3 d slightly decreased total isoflavone content (-4.3%); however, wounding increased total isoflavone content (25.8%). The soybean extracts from seeds treated with A. sojae biotic elicitors had the highest total isoflavone contents (9.8 to 11.6 mg/g extract) and displayed the highest antioxidant activities in both the DPPH and beta-carotene assays. Also identified in the wounded and elicitor-treated extracts were the induced isoflavones glyceollins that contributed to the higher isoflavone contents observed.

Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn's disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density.

OBJECTIVES: Many patients with Crohn's disease (CD) have low bone mineral density (BMD) that may not be solely attributable to glucocorticoid use. We hypothesised that low BMD in patients with CD is associated with elevated circulating levels of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D). We further hypothesised that this was secondary to increased synthesis of 1,25(OH)(2)D by inflammatory cells in the intestine. The aim of this study was to examine the relationship between 1,25(OH)(2)D levels and BMD in patients with CD. METHODS: An IRB approved retrospective review of medical records from patients with CD (n = 138) or ulcerative colitis (UC, n = 29). Measurements of vitamin D metabolites and immunoreactive parathyroid hormone (iPTH) were carried out. BMD results were available for 88 CD and 20 UC patients. Immunohistochemistry or real time reverse transcription-polymerase chain reaction (RT-PCR) for the enzyme 1alpha-hydroxylase was performed on colonic biopsies from patients with CD (14) or UC (12) and normal colons (4). RESULTS: Inappropriately high levels of serum 1,25(OH)(2)D (>60 pg/ml) were observed in 42% of patients with CD compared with only 7% in UC, despite no differences in mean iPTH. Serum 1,25(OH)(2)D levels were higher in CD (57 pg/ml) versus UC (41 pg/ml) (p = 0.0001). In patients with CD, there was a negative correlation between 1,25(OH)(2)D levels and lumbar BMD (r = -0.301, p = 0.005) independent of therapeutic glucocorticoid use. 1,25(OH)(2)D levels also correlated with CD activity. Lastly, immunohistochemistry and RT-PCR demonstrated increased expression of intestinal 1alpha-hydroxylase in patients with CD. CONCLUSIONS: These data demonstrate that elevated 1,25(OH)(2)D is more common in CD than previously appreciated and is independently associated with low bone mineral density. The source of the active vitamin D may be the inflamed intestine. Treatment of the underlying inflammation may improve metabolic bone disease in this subgroup of patients.

Oil uptake properties of fried batters from rice flour.

Batters were prepared, using rice flour as the main component, and analyzed for their oil uptake properties during frying. Rice flour resisted oil absorption better but was less effective as a thickening agent than wheat flour. Of the rice components, increased amylose in the amylopectin/amylose ratio of the starch decreased the batter oil uptake, whereas increased protein content had the opposite effect. Various additives were introduced and investigated for their ability to develop viscosity and other desirable characteristics for the batter. As additives to the rice flour batters, phosphorylated starch and gelatinized rice flour enhanced both the thickening and oil-reducing capacities of the batter. Compared with values for batters from wheat flour, the percent batter oil uptake in the fried crust for the modified rice flour batters was decreased by up to 62%, and the percent total oil uptake for the whole coated drumstick was reduced by up to 59%.

An unlearned principle for controlling natural movements.

Recently, Gottlieb and colleagues discovered a linear relation between elbow and shoulder dynamic torque in natural pointing movements in the sagittal plane. The present study investigates if the process of learning to reach involves discovering this linearity principle. We inspected torque data from four infants who were learning to reach and grab a toy in front of them. In a longitudinal study, we collected data both in the period before and after they performed their first successful reaches. Torque profiles at the shoulder and elbow were typically multipeaked and became more and more biphasic toward the end of the first year of life. Torques at the shoulder and elbow were correlated tightly for movements in the prereaching period as well as for reaches later in the year. Furthermore, slopes of a regression of shoulder dynamic torque on elbow dynamic torque were remarkably constant at a value approximately 2.5-3.0. If linear synergy is used by the nervous system to reduce the controlled degrees of freedom, it will act as a strong constraint on the complex of possible coordination patterns for arm movement early in life. Natural reaching movements can capitalize on this constraint because it simplifies the process of learning to reach.

Initial hemocompatibility studies of titanium and zirconium alloys: prekallikrein activation, fibrinogen adsorption, and their correlation with surface electrochemical properties.

Two novel metal alloys, Ti-13Nb-13Zr and Zr-2.5Nb, have been engineered for applications in orthopedic implants because of their favorable mechanical properties, corrosion resistance, and compatibility with bone and tissue. These alloys also have the ability to form a hard, abrasion-resistant, ceramic surface layer upon oxidative heat treatment (diffusion hardening, DH). Previous studies have indicated that these and other ceramics cause limited hemolysis and exhibit remarkable structural integrity after extended exposure to physiological environments. Such observations suggest that DH Ti-13Nb-13Zr and ZrO2/Zr-2.5Nb could be used successfully as components in blood-contacting devices. Materials intended for such applications must possess properties that do not elicit adverse physiological responses, such as the initiation of the coagulation cascade or thrombus formation. In the present study measurements of prekallikrein activation, fibrinogen adsorption from diluted human plasma, and the strength of fibrinogen attachment as judged by residence-time experiments were performed to evaluate the potential hemocompatibility of these materials. The results of the prekallikrein activation and fibrinogen-retention studies correlated well with two electrochemical properties of the alloys, the open circuit potential and reciprocal polarization resistance. The results indicate that both the original and treated Ti and Zr alloys activate prekallikrein and adsorb as well as retain fibrinogen in amounts similar to other materials used as components of blood-contacting devices. On the basis of these studies, these alloys appear to be promising candidates for cardiovascular applications and merit further investigation.

Wear-resistant, hemocompatible Ti-Nb-Zr and Zr-Nb alloys to improve blood pump design and performance.

Over the past several years, we have developed novel titanium-niobium-zirconium (Ti-Nb-Zr) alloys to address the long-term performance needs of orthopedic implants. The unique properties of these alloys also render them promising candidates for blood pumps. These properties include excellent biocompatibility in combination with high strength and toughness, and low elastic modulus (low stiffness). Additionally, these metal alloys are readily hot or cold worked into complex shapes including wire, foil, tubing and bar. They are readily machined and polished, and they can be surface oxidized to form a hard, wear-resistant, low-friction ceramic surface layer. In this diffusion-hardened condition, oxygen also hardens the underlying metal to optimize the bone between the ceramic oxide surface and the tough metal substrate. Unlike metal surfaces, oxidative wear, which can alter surface energy, friction, and hemocompatibility, does not occur. Consequently, the combined benefits of a stable, wear-resistant, low-friction ceramic surface layer with the toughness, strength, formability, and thermal conductivity of metal may provide improvements in the design and performance of blood pumps and peripheral graft and percutaneous (power) components of the pump.

Pulmonary function abnormalities in Prader-Willi syndrome.

OBJECTIVE: To determine whether individuals with Prader-Willi syndrome (PWS) have abnormalities in pulmonary function as a result of thoracic muscle weakness. DESIGN: Testing of spirometry, flow-volume curves, lung volumes, and static respiratory pressures was performed in patients with PWS who are followed at the University of Connecticut. All tests were performed in triplicate on two or more occasions. Only reproducible tests were accepted. Established normative data were applied for all test results. RESULTS: A total of 18 male subjects (age, 17.9 +/- 10.2 years (mean +/- SD); range, 5-39 years) and 17 female subjects (age, 23.5 +/- 13.0 years; range, 5-54 years) completed the tests. Forced vital capacity and forced expiratory volume in 1 second were reduced; the forced expiratory volume in 1 second/forced vital capacity ratio was normal, total lung capacity was in the low normal range, and residual volume was elevated. Maximum inspiratory (PImax) and expiratory (PEmax) pressures were markedly reduced in 32 subjects tested. Fifteen subjects had PEmax values and 20 subjects had PImax values < 60 cm H2O, respectively. There was a linear correlation between forced expiratory volume in 1 second and both PImax and PEmax (r = 0.71; r = 0.62, respectively), and between forced vital capacity and both PEmax and PImax (r = 0.62 and r = 0.74, respectively). There was an inverse relationship between both PImax and PEmax, and residual volume (r = 0.47 and r = 0.72, respectively). CONCLUSION: Children and adults with PWS have restrictive ventilatory impairment primarily as a result of respiratory muscle weakness. Efforts to improve thoracic muscle strength may be useful in improving pulmonary function in individuals with PWS.

Electrochemical behavior of Ti-6Al-4V alloy in static biosimulating solutions.

The static general corrosion behavior of Ti-6Al-4V alloy specimens in three lactated Ringer's-based solutions was investigated using d.c. potentiodynamic, d.c. linear polarization resistance, and a.c. impedance techniques. A critical appraisal of the use of these techniques for the estimation of the corrosion rate of the material is presented. Whence it was shown that the presence of bovine serum in or decreasing the pH level of (to about 1) lactated Ringer's solution leads to an increase in the corrosion rate of the alloy (relative to that in lactated Ringer's solution, pH 6.25).

Protein synthesis inhibition by 8-oxo-12,13-epoxytrichothecenes.

The Fusarium mycotoxin, 4-deoxynivalenol, is an abundant, natural contaminant of corn and wheat. 8-Oxo-12,13-epoxytrichothecenes related to 4-deoxynivalenol were synthesized; they either lacked the 7-hydroxyl but contained a hydroxyl at C-4 (7-deoxynivalenol) or lacked substituents at C-3 and C-7 (3,7-dideoxynivalenol). The ability of these synthetic analogs and their acetylated derivatives to inhibit protein synthesis by cultured mammalian cells was compared to that of 4-deoxynivalenol. Whereas the 50% inhibitory dose (ID50) for murine erythroleukemia cells was about 1 microgram/ml for 4-deoxynivalenol and 3,7-dideoxynivalenol, all of the other analogs were at least 10-fold less potent. When tested at their ID50 dose, all of the 8-oxotrichothecenes, except 4-deoxynivalenol and 3,7-dideoxynivalenol, caused polysome 'run-off', indicating that, at this dose, they are inhibitors of polypeptide chain initiation. With 4-deoxynivalenol and 3,7-dideoxynivalenol, polysomes remained at control levels indicating that these toxins prevent polypeptide chain elongation. From these results and comparisons to previous studies of 8-oxo-12,13-epoxytrichothecenes (trichothecolone, trichothecin, nivalenol and fusarenone X), trichothecenes with substituents at both C-3 and C-4 predominantly inhibit polypeptide chain initiation, whereas those lacking one substituent at either site are inhibitors of chain elongation.

Hydrolysis by restriction endonucleases at their DNA recognition sequences substituted with mismatched base pairs.

Restriction endonucleases were tested for their ability to catalyze the cleavage of mismatch-containing recognition sites in DNA. These mismatched base pairs were T.G, U.G, or A.C in covalently closed, circular heteroduplexes prepared by in vitro extension of chemically synthesized oligonucleotide primers annealed to a bacteriophage M13-derived viral DNA. None of the restriction enzymes was able to completely cleave the mismatch-containing recognition sites under standard conditions. However, three of them, SmaI, SalI, and SstI, catalyzed partial digestion leading to an accumulation of DNA singly nicked at the mismatched recognition site. The ability of SmaI and SstI to partially cleave at a mismatch was shown to depend on the nature and position of the mismatch within the corresponding recognition site. In contrast, little or no digestion was obtained with AccI, HincII, HindIII, and KpnI at mismatch-containing sites. Therefore, in some cases a transition-type substitution in only one strand of a recognition site inhibits restriction endonuclease-catalyzed digestion at that site although in others partial digestion occurs.

Protein synthesis by mammalian cells treated with C-3-modified analogs of the 12,13-epoxytrichothecenes T-2 and T-2 tetraol.

Modification at the C-3 position of the trichothecenes T-2 and T-2 tetraol affected their ability to inhibit protein synthesis in African green monkey kidney (Vero) and mouse erythroleukemia cells. Replacement of the 3-hydroxyl of T-2 with hydrogen caused a 24-fold decrease in activity, whereas acetylation resulted in a 500-to 1,000-fold decrease. Protection of the 3-hydroxyl with a tetrahydropyranyl moiety gave an analog that was 37-fold more inhibitory to Vero than to mouse erythroleukemia cells; with the other analogs a similar effect on protein synthesis was found for both types of cells. The analogs obtained after alkaline hydrolysis were much less potent than the parent trichothecenes. The 3-tetrahydropyranyl-modified analog was equivalent in potency to T-2 tetraol, while the deoxygenated species was at least threefold less potent. All T-2 analogs caused some degree of polysome "runoff," thereby demonstrating that these species inhibit protein synthesis at the chain initiation stage when added at their 50% infective dose concentrations or lower. From these results, we suggest that the 3-hydroxyl moiety is essential for T-2 to exhibit such high activity on eucaryotic cell protein synthesis and that modification at the C-3 position decreases but does not eliminate this activity.