Dietary patterns and risk of systemic lupus erythematosus in women.

OBJECTIVE: Dietary intake is a complex exposure and a potential risk factor for systemic lupus erythematosus (SLE) due to its impact on lipid and glucose metabolism, oxidative stress, and the intestinal microbiome. We aimed to test whether a prudent dietary pattern is associated with a lower risk of SLE, and whether a Western dietary pattern is associated with a higher risk of SLE. METHODS: We prospectively investigated two dietary patterns and SLE risk among women in the Nurses' Health Study (NHS, 1984-2014) and Nurses' Health Study II (NHSII, 1991-2015). Food frequency questionnaires were completed every four years. Congruent with prior work in NHS and NHSII, we derived two separate dietary patterns (prudent and Western) using principal component analysis within each cohort. Incident SLE was confirmed by the American College of Rheumatology's 1997 criteria. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for SLE by dietary pattern quartiles using Cox models adjusted for time-varying covariates. Models were performed separately in each cohort and results were meta-analyzed. Stratified analyses tested the association of dietary patterns with anti-dsDNA positive SLE and anti-dsDNA negative SLE. RESULTS: We confirmed 82 NHS incident SLE cases and 98 NHSII SLE cases during 3,833,054 person-years of follow-up. A higher (healthier) prudent dietary pattern score was not associated with SLE risk (meta-analyzed HRQ4 versus Q1 0.84 [95% CI 0.51, 1.38]). Women with higher (less healthy) Western dietary pattern scores did not have a significantly increased risk for SLE (meta-analyzed HRQ4 versus Q1 1.35 [95% CI 0.77, 2.35]). Results were similar after further adjustment for body mass index. Incident anti-dsDNA positive SLE and anti-dsDNA negative SLE were not associated with either dietary pattern. CONCLUSION: We did not observe a relationship between prudent or Western dietary pattern score and risk of SLE.

The actin cytoskeleton is a suppressor of the endogenous skewing behaviour of Arabidopsis primary roots in microgravity.

Before plants can be effectively utilised as a component of enclosed life-support systems for space exploration, it is important to understand the molecular mechanisms by which they develop in microgravity. Using the Biological Research in Canisters (BRIC) hardware on board the second to the last flight of the Space Shuttle Discovery (STS-131 mission), we studied how microgravity impacts root growth in Arabidopsis thaliana. Ground-based studies showed that the actin cytoskeleton negatively regulates root gravity responses on Earth, leading us to hypothesise that actin might also be an important modulator of root growth behaviour in space. We investigated how microgravity impacted root growth of wild type (ecotype Columbia) and a mutant (act2-3) disrupted in a root-expressed vegetative actin isoform (ACTIN2). Roots of etiolated wild-type and act2-3 seedlings grown in space skewed vigorously toward the left, which was unexpected given the reduced directional cue provided by gravity. The left-handed directional root growth in space was more pronounced in act2-3 mutants than wild type. To quantify differences in root orientation of these two genotypes in space, we developed an algorithm where single root images were converted into binary images using computational edge detection methods. Binary images were processed with Fast Fourier Transformation (FFT), and histogram and entropy were used to determine spectral distribution, such that high entropy values corresponded to roots that deviated more strongly from linear orientation whereas low entropy values represented straight roots. We found that act2-3 roots had a statistically stronger skewing/coiling response than wild-type roots, but such differences were not apparent on Earth. Ultrastructural studies revealed that newly developed cell walls of space-grown act2-3 roots were more severely disrupted compared to space-grown wild type, and ground control wild-type and act2-3 roots. Collectively, our results provide evidence that, like root gravity responses on Earth, endogenous directional growth patterns of roots in microgravity are suppressed by the actin cytoskeleton. Modulation of root growth in space by actin could be facilitated in part through its impact on cell wall architecture.

Smoking association with influenza infection in renal transplant recipients.

We identified 22 cases of influenza infection among renal transplant recipients and matched them with 66 controls by influenza season to explore risk factors for influenza infection. Active cigarette smoking was associated with influenza infection in this population (adjusted odds ratio 13.1; 95% confidence interval 2.3-76; P = 0.004).

The deconstruction of magic: rereading, rethinking Erickson.

This article examines the case history writings of Milton Erickson as literary texts. A deconstructive analysis reveals that the modernist assumption of therapist as magical healer disguises the role clients play in their own change. Hypothetically constructed case transcripts contrasted with excerpts from Erickson (see Rossi, 1980) illustrate how the inclusion of client voice enriches understanding of therapeutic change.

Effects of continuous oral nicotine administration on brain nicotinic receptors and responsiveness to nicotine in C57Bl/6 mice.

The route of drug delivery is an important consideration in studies that evaluate the long-term bio-behavioral adaptations that occur in response to chronic drug administration. Continuous infusions (intravenous or subcutaneous) or intermittent intraperitoneal (or subcutaneous) injections are the most commonly utilized routes of chronic drug delivery in these studies. The purpose of the present study was to determine the effects of chronic oral nicotine exposure on sensitivity to nicotine and brain nicotinic cholinergic receptors in female C57Bl/6 mice. Mice were randomized to different treatment groups that received 2% saccharin, containing 0-200 microg/ml nicotine (free base). In preliminary experiments, radiotelemetry devices were implanted in the mice; consumption of the nicotine-containing drinking solution caused a significant increase in home-cage nocturnal (but not diurnal) activity and also altered circadian alterations in body temperature. Oral nicotine exposure resulted in dose-related elevations in plasma levels of cotinine, a primary nicotine metabolite. Continuous exposure (30 days) to oral nicotine (200 microg/ml) resulted in the expression of significant tolerance to the locomotor depressant and hypothermic actions of acute nicotine challenge. This tolerance was accompanied by a significant increase in brain nicotinic receptor number assessed by quantitative auto-radiography using [3H]-cytisine (alpha4 nAChr) and [125I]-alpha-bungarotoxin (alpha7 nAChr) as radioligands. These results suggest that chronic oral nicotine delivery to female C57Bl/6 mice results in behavioral and biochemical changes that resemble changes that occur following other routes of chronic nicotine delivery.

Lobeline and structurally simplified analogs exhibit differential agonist activity and sensitivity to antagonist blockade when compared to nicotine.

In the present study, lobeline and two structurally simplified analogs were evaluated for activity in muscarinic and nicotinic binding assays, a functional assay for nicotinic receptor activation (86Rb+ efflux from striatal synaptosomes) and an acetylcholinesterase (AChE) assay. Lobeline displaced [3H]cytisine binding to rat cortical membranes with a mean inhibition constant (KI) value of 16.0 nM, while the lobeline analogs CRM-I-13-1 and CRM-I-32-1 exhibited values of 15.0 and 5.4 microM, respectively. [3H]methylscopolamine was displaced by lobeline with a mean KI value of 37.0 microM while CRM-I-13-1 and CRM-I-32-1 exhibited values of 55.0 and 16.0 microM, respectively. While nicotine stimulated 86Rb+ efflux from striatal synaptosomes in a mecamylamine reversible manner at each concentration tested, lobeline slightly increased 86Rb+ efflux at lower concentrations and reduced efflux at higher concentrations. Further, none of the lobeline effects were reversed with mecamylamine. Although less potent, the two lobeline analogs exhibited a similar pattern of activity. These data may suggest that lobeline and structurally similar compounds bind with different subtype selectivity than nicotine, or exert their agonists effects through non-nicotinic mechanisms. All of the compounds tested were at least several hundred times less potent than physostigmine as AChE inhibitors. While some differences were apparent between the lobeline analog which contained the 2-keto-ethyl portion of lobeline and the analog which contained the phenyl 2-hydroxy-ethyl moiety, each compound was much less active than lobeline in most parameters assessed.

Mechanism of tetracycline-hydrochloride-induced pleurodesis. Tetracycline-hydrochloride-stimulated mesothelial cells produce a growth-factor-like activity for fibroblasts.

Intrapleural instillation of tetracycline hydrochloride (TCN) is an effective means of achieving pleural fibrosis. However, its mechanism of action remains unknown. To evaluate the hypothesis that TCN stimulates pleural mesothelial cells to release growth-factor-like activity for fibroblasts we performed the following experiments. Rat visceral pleural mesothelial cells were incubated with TCN at doses ranging from 0.01 microgram/ml to 100 mg/ml. The conditioned media (CM) were collected after incubation for 2 to 48 h. CM caused fibroblasts to increase incorporation of thymidine when compared with CM that was unexposed to TCN (p less than 0.05). This growth-factor-like activity continued to be produced by mesothelial cells for 48 h after removal of TCN from the medium. There was a dose-response relationship since increasing doses of TCN to as much as 1 mg/ml caused increasing production of growth-factor-like activity without mesothelial cell injury as measured by trypan blue exclusion. The growth factor activity was a competence-type activity. It coeluted with human PDGF at a molecular weight of 31,000. It was heat-stable (100 degrees C for 10 min) and sensitive to trypsin and papain but not to heat-inactivated trypsin. Addition of cycloheximide or actinomycin D inhibited its production. TCN did not have any direct effect on fibroblasts. Bleomycin CM did not contain growth-factor-like activity for fibroblasts. These data demonstrate that TCN stimulates mesothelial cells to release a growth-factor-like activity for fibroblasts. This phenomenon may play an important role in TCN-induced pleural fibrosis.

Mesothelial cell response to pleural injury: thrombin-induced proliferation and chemotaxis of rat pleural mesothelial cells.

Injury to the pleura ultimately results in either repair with fibrosis or repair without fibrosis and a reestablishment of the normal mesothelial monolayer. The role of the mesothelial cell, and of local mediators, in these repair processes remains essentially undefined. In order for repair without fibrosis to occur, mesothelial cells, in response to local mediators, must be capable of migration and/or proliferation to cover the injured and denuded mesothelium. We hypothesized that rat pleural mesothelial cells were capable of both chemotaxis and proliferation in response to thrombin. In an in vitro assay, mesothelial cells demonstrated directed migration in response to a known chemoattractant, formylmethionylleucylphenylalanine. In addition, mesothelial cells demonstrated chemotaxis in a dose-dependent manner in response to thrombin, with a maximal response at a concentration of 10(-8) M. Finally, this chemotaxis was blocked by a specific blocker of thrombin, antithrombin 3. Thrombin also stimulated mesothelial cell proliferation, which was measured both in a [3H]thymidine incorporation assay and by direct cell counts. Again, the response was dose dependent, with the maximal response at 10(-8) M causing the same amount of [3H]thymidine incorporation as 10% fetal bovine serum. As before, this response was completely blocked by antithrombin 3. These results demonstrate that mesothelial cells are capable of both chemotaxis and proliferation in response to thrombin. Thrombin may play an important role in the regulation of pleural repair without fibrosis and the re-establishment of the mesothelial monolayer.