Cross Sections for the Exclusive Photon Electroproduction on the Proton and Generalized Parton Distributions.

Unpolarized and beam-polarized fourfold cross sections (d^{4}σ/dQ^{2}dx_{B}dtdϕ) for the ep→e^{'}p^{'}γ reaction were measured using the CLAS detector and the 5.75-GeV polarized electron beam of the Jefferson Lab accelerator, for 110 (Q^{2},x_{B},t) bins over the widest phase space ever explored in the valence-quark region. Several models of generalized parton distributions (GPDs) describe the data well at most of our kinematics. This increases our confidence that we understand the GPD H, expected to be the dominant contributor to these observables. Through a leading-twist extraction of Compton form factors, these results support the model predictions of a larger nucleon size at lower quark-momentum fraction x_{B}.

Towards a resolution of the proton form factor problem: new electron and positron scattering data.

There is a significant discrepancy between the values of the proton electric form factor, G(E)(p), extracted using unpolarized and polarized electron scattering. Calculations predict that small two-photon exchange (TPE) contributions can significantly affect the extraction of G(E)(p) from the unpolarized electron-proton cross sections. We determined the TPE contribution by measuring the ratio of positron-proton to electron-proton elastic scattering cross sections using a simultaneous, tertiary electron-positron beam incident on a liquid hydrogen target and detecting the scattered particles in the Jefferson Lab CLAS detector. This novel technique allowed us to cover a wide range in virtual photon polarization (ϵ) and momentum transfer (Q(2)) simultaneously, as well as to cancel luminosity-related systematic errors. The cross section ratio increases with decreasing ϵ at Q(2)=1.45 GeV(2). This measurement is consistent with the size of the form factor discrepancy at Q(2)≈1.75 GeV(2) and with hadronic calculations including nucleon and Δ intermediate states, which have been shown to resolve the discrepancy up to 2-3 GeV(2).

Longitudinal target-spin asymmetries for deeply virtual compton scattering.

A measurement of the electroproduction of photons off protons in the deeply inelastic regime was performed at Jefferson Lab using a nearly 6 GeV electron beam, a longitudinally polarized proton target, and the CEBAF Large Acceptance Spectrometer. Target-spin asymmetries for ep→e^{'}p^{'}γ events, which arise from the interference of the deeply virtual Compton scattering and the Bethe-Heitler processes, were extracted over the widest kinematics in Q^{2}, x_{B}, t, and ϕ, for 166 four-dimensional bins. In the framework of generalized parton distributions, at leading twist the t dependence of these asymmetries provides insight into the spatial distribution of the axial charge of the proton, which appears to be concentrated in its center. These results also bring important and necessary constraints for the existing parametrizations of chiral-even generalized parton distributions.

Docosahexaenoic acid-enriched canola oil increases adiponectin concentrations: a randomized crossover controlled intervention trial.

BACKGROUND AND AIMS: Little is known about the effect of various dietary fatty acids on pro- and anti-inflammatory processes. We investigated the effect of 5 oils containing various amounts of alpha-linolenic acid (ALA), linoleic acid (LA), oleic acid (OA) and docosahexaenoic acid (DHA) on plasma inflammatory biomarkers and expression levels of key inflammatory genes and transcription factors in whole blood cells. METHODS AND RESULTS: In a randomized, crossover controlled nutrition intervention, 114 adult men and women with abdominal obesity and at least one other criterion for the metabolic syndrome consumed 5 experimental isoenergetic diets for 4 weeks each, separated by 4-week washout periods. Each diet provided 60 g/3000 kcal of different oils: 1) control corn/safflower oil blend (CornSaff; LA-rich), 2) flax/safflower oil blend (FlaxSaff; ALA-rich), 3) conventional canola oil (Canola; OA-rich), 4) high oleic canola oil (CanolaOleic; highest OA content), 5) DHA-enriched high oleic canola oil (CanolaDHA; OA- and DHA-rich). Gene expression in whole blood cells was assessed in a subset of 62 subjects. CanolaDHA increased plasma adiponectin concentrations compared with the control CornSaff oil treatment (+4.5%, P = 0.04) and FlaxSaff (+6.9%, P = 0.0008). CanolaDHA also reduced relative expression levels of interleukin (IL)1B compared with CornSaff and Canola (-11% and -13%, respectively, both P = 0.03). High-sensitivity C-reactive protein concentrations were lower after Canola than after FlaxSaff (-17.8%, P = 0.047). CONCLUSION: DHA-enriched canola oil exerts anti-inflammatory effects compared with polyunsaturated fatty acids from plant sources.

Strangeness suppression of qq creation observed in exclusive reactions.

We measured the ratios of electroproduction cross sections from a proton target for three exclusive meson-baryon final states: ΛK(+), pπ(0), and nπ(+), with the CLAS detector at Jefferson Lab. Using a simple model of quark hadronization, we extract qq creation probabilities for the first time in exclusive two-body production, in which only a single qq pair is created. We observe a sizable suppression of strange quark-antiquark pairs compared to nonstrange pairs, similar to that seen in high-energy production.

Nutrient displacement associated with walnut supplementation in men.

BACKGROUND: Dietary guidance issued by various global government agencies recommends nut consumption within the context of a healthy-eating pattern. Nuts are nutrient dense and may promote nutrient adequacy. As an energy-dense food, nuts must replace other foods in the diet to prevent an excess of calories. METHODS: We evaluated how recommending the inclusion of walnuts (75 g day(-1) ) in the diet affected energy and nutrient intake in men (45-75 years; mean body mass index = 27.6 kg m(-2) ; n = 19) at risk for developing prostate cancer. Guidance was provided about incorporating walnuts isocalorically in a healthy diet. Three-day food records and body weight were collected at baseline and after two 8-week diet periods (usual versus walnut supplement diets). RESULTS: Energy intake on the walnut supplement diet exceeded the usual diet, although body weight was maintained. Energy intake was lower on the actual walnut supplement diet than the calculated walnut diet [10,865 kJ (2595 kcal) versus 11,325 kJ (2705 kcal) per day, respectively] and contributed 23% less energy than 75 g of walnuts. Approximately, 86% and 85% of the total fat and saturated fatty acids from walnuts were not displaced, whereas the increase in fibre from the usual diet to the actual walnut supplement diet represented less than one-half (39%) of the fibre provided by 75 g of walnuts. Walnuts were substituted, in part, for other foods, and the nutrient profile of the diet was improved, however, the beneficial effect of walnuts on the diet quality was not optimized. CONCLUSIONS: Individuals do not optimally implement food-based guidance. Consequently, nutrition professionals play a key role in teaching the implementation of food-based recommendations.

Measurement of exclusive π(0) electroproduction structure functions and their relationship to transverse generalized parton distributions.

Exclusive π(0) electroproduction at a beam energy of 5.75 GeV has been measured with the Jefferson Lab CLAS spectrometer. Differential cross sections were measured at more than 1800 kinematic values in Q(2), x(B), t, and ϕ(π), in the Q(2) range from 1.0 to 4.6 GeV(2), -t up to 2 GeV(2), and x(B) from 0.1 to 0.58. Structure functions σ(T)+ϵσ(L), σ(TT), and σ(LT) were extracted as functions of t for each of 17 combinations of Q(2) and x(B). The data were compared directly with two handbag-based calculations including both longitudinal and transversity generalized parton distributions (GPDs). Inclusion of only longitudinal GPDs very strongly underestimates σ(T)+ϵσ(L) and fails to account for σ(TT) and σ(LT), while inclusion of transversity GPDs brings the calculations into substantially better agreement with the data. There is very strong sensitivity to the relative contributions of nucleon helicity-flip and helicity nonflip processes. The results confirm that exclusive π(0) electroproduction offers direct experimental access to the transversity GPDs.

Pregnancy and interferon tau regulate N-myc interactor in the ovine uterus.

In ruminants, interferon tau (IFNT) is synthesized and secreted by the mononuclear trophectoderm cells of the conceptus and maintains the corpus luteum and its secretion of progesterone for successful implantation and maintenance of pregnancy. In this study, we examined regulation of the expression of N-myc interactor (NMI) gene by IFNT in the ovine uterus based on results of microarray data from a study that compared gene expression by human 2fTGH and U3A (STAT1-null 2fTGH) cell lines in response to treatment with IFNT or vehicle. In the present study, semiquantitative reverse transcription-polymerase chain reaction analyses verified that IFNT stimulated expression of NMI mRNA in 2fTGH (ie, in a STAT1-dependent manner), but not in U3A (STAT1-null) cells. Furthermore, results of western blot analyses indicated that immunoreactive NMI proteins in 2fTGH and U3A cell lines increased in a time-dependent manner only in response to IFNT. In ovine endometria, steady-state levels of NMI mRNA increased between days 14 and 16 of pregnancy and then decreased slightly by day 20, but there was no effect of day of the estrous cycle. Expression of NMI mRNA was most abundant in endometrial stromal cells, glandular epithelium, and conceptus trophectoderm. Intrauterine infusion of IFNT in cyclic ewes increased expression of NMI in the endometrium. Expression of NMI in ovine and bovine uterine cell lines increased in response to IFNT. Collectively, the results of the present study indicate that IFNT regulates expression of NMI mRNA and protein in ovine endometria during pregnancy via a STAT1-dependent cell signaling pathway.

Are there gender differences in the prescribing of hypnotic medications for insomnia?

Gender differences in the prescribing patterns of general classes of medications for insomnia were examined. The classes of medications included: zopiclone, antidepressants, benzodiazepines, antihistamines and no medication. The sample comprised a sub-set of respondents from 2620 questionnaires of the Canadian Multicentre Sleep Database. Respondents for this database were contacted through physicians, announcements in the media and local pharmacies. The results indicated that gender alone was not associated with differential prescribing for insomnia, nor was gender associated with patterns of medication use such as frequency of taking medication, length of use, taking more or less medication than prescribed or attempts to stop taking medication. Demographic factors were included in the analysis and age and marital status were associated with different prescribing patterns for men and women with insomnia. It is possible that physicians refer to stereotypic expectations when prescribing hypnotics.

Effect of force direction on femoral fracture load for two types of loading conditions.

Identifying the loading conditions under which the femur is most likely to fracture may aid the prevention of hip fracture. This study quantified the effect of force direction on fracture load, a factor inherently associated with fracture risk. Finite element (FE) models of four femora were used to determine the force directions associated with the lowest fracture loads. Force directions were varied three-dimensionally for two types of loading, one representing impact from a fall and one similar to joint loading during daily activities (atraumatic loading). For the fall configuration, the force direction with lowest fracture load corresponded to an impact onto the posterolateral aspect of the greater trochanter. For atraumatic loading, the lowest fracture loads for the force directions analyzed occurred when posterior force components were relatively large or when posterior and lateral components were both small, similar to conditions while standing on one leg or climbing stairs. When both fall and atraumatic configurations are considered, the type of loading associated with greatest fracture risk, i.e., with the greatest applied force and lowest fracture load, is impact from a fall onto the posterolateral aspect of the greater trochanter. Therefore, evaluation of hip fracture risk and development of fracture prevention technologies should focus on this high-risk loading condition.

Cloning of the ovine estrogen receptor-alpha promoter and functional regulation by ovine interferon-tau.

Interferon-tau (IFNtau), the ruminant pregnancy recognition signal, inhibits transcription of the estrogen receptor alpha (ERalpha) gene in the endometrial lumenal epithelium of the sheep uterus, thereby abrogating production of luteolytic PGF(2alpha) pulses. The effects of IFNtau are mediated in part by IFN-stimulated response elements (ISREs) and IFN regulatory factor elements (IRFEs). The promoter/enhancer region of the ovine ERalpha gene was cloned, sequenced, and predicted to contain four IRFEs and one ISRE. Electrophoretic mobility shift assays indicated that the -2110 IRFE bound only IRF-1, whereas the -1877 IRFE and the -1284 ISRE were functional in binding IRF-1 and IRF-2. IFNtau inhibited transcriptional activity of the 2.7-kb ovine ERalpha promoter in transfection assays using ovine lumenal epithelium cells. Analyses of sequential 5'-deletion mutants of the ovine ERalpha promoter indicated that the effects of IFNtau may be mediated by IRFEs as well as other elements. Overexpression of ovine IRF-2, but not IRF-1, inhibited transcriptional activity of several regions of the ovine ERalpha promoter containing an IRFE or an ISRE as well as some, but not all, regions lacking these elements.

Function of tubulin binding proteins in vivo.

Overexpression of the beta-tubulin binding protein Rbl2p/cofactor A is lethal in yeast cells expressing a mutant alpha-tubulin, tub1-724, that produces unstable heterodimer. Here we use RBL2 overexpression to identify mutations in other genes that affect formation or stability of heterodimer. This approach identifies four genes-CIN1, CIN2, CIN4, and PAC2-as affecting heterodimer formation in vivo. The vertebrate homologues of two of these gene products-Cin1p/cofactor D and Pac2p/cofactor E-can catalyze exchange of tubulin polypeptides into preexisting heterodimer in vitro. Previous work suggests that both Cin2p or Cin4p act in concert with Cin1p in yeast, but no role for vertebrate homologues of either has been reported in the in vitro reaction. Results presented here demonstrate that these proteins can promote heterodimer formation in vivo. RBL2 overexpression in cin1 and pac2 mutant cells causes microtubule disassembly and enhanced formation of Rbl2p-beta-tubulin complex, as it does in the alpha-tubulin mutant that produces weakened heterodimer. Significantly, excess Cin1p/cofactor D suppresses the conditional phenotypes of that mutant alpha-tubulin. Although none of the four genes is essential for viability under normal conditions, they become essential under conditions where the levels of dissociated tubulin polypeptides increase. Therefore, these proteins may provide a salvage pathway for dissociated tubulin heterodimers and so rescue cells from the deleterious effects of free beta-tubulin.

Serum levels of soluble CD44 in primary Sjögren's syndrome.

OBJECTIVE: To determine whether elevated soluble CD44 (sCD44) levels serve as a marker of inflammation and lymphoproliferation in primary Sjögren's syndrome (SS). METHODS: We measured sCD44 levels by ELISA in serum samples from a cross section of healthy individuals and patients seen in a rheumatology clinic for evaluation of possible primary SS. RESULTS: Median serum levels of sCD44 were significantly higher in 48 healthy men compared to 52 healthy women (16 vs. 12 nmol/l; p = 0.0034). There was no relationship between serum levels of sCD44 and age or ethnic background. Slightly higher median levels of sCD44 were found in the serum of 37 women with primary SS compared to healthy women (14 vs. 12 nmol/l; p = 0.0402). However, these levels were comparable to those of 33 female patients without primary SS who were seen in the same clinic (p = 0.1233). CONCLUSION: Serum levels of sCD44 were slightly higher in female patients with primary SS compared to healthy women, but they are not likely to discriminate between patients with and without primary SS in a rheumatology practice.

Double-blind, randomized study of the effects of influenza vaccination on the specific antibody response and clinical course of patients with chronic fatigue syndrome.

OBJECTIVE: To determine whether influenza immunization is associated with early side effects, a deleterious impact on the illness course and depressed antibody response in patients with chronic fatigue syndrome (CFS). DESIGN: Prospective, randomized, double-blind, placebo controlled trial. CFS patients and healthy volunteers filled out a questionnaire on immunization side effects and had hemagglutination-inhibiting (HI) antibody titres measured pre- and three weeks after immunization. CFS patients completed symptom and function questionnaires before and during the six-week, postimmunization period. SETTING: Ambulatory care. POPULATION STUDIED: Convenience sample of 40 CFS patients fulfilling the Centers for Disease Control and Prevention criteria and 21 demographically matched healthy volunteers. INTERVENTIONS: CFS patients were randomly selected to receive commercially available whole virus influenza vaccine (n=19) or an injection of saline placebo (n=21). Healthy volunteers received vaccine only. MAIN RESULTS: As a group, immunized CFS patients had lower geometric mean HI antibody rises than healthy volunteers (P<0.001). However, there was no difference in the rates of fourfold titre rises, and immunization did achieve a probably protective titre (1:32 or greater) in most CFS patients. No difference could be detected between immunized and placebo CFS patients in immunization side effects, although CFS patients as a group reported four times as many side effects as healthy volunteers. Further, in the six weeks following immunization, placebo and immunized CFS patients did not demonstrate any differences in terms of functioning, symptom severity and sleep disturbance. CONCLUSIONS: In patients with CFS, influenza immunization is safe, not associated with any excess early reactions, and stimulates an immunizing response comparable with that of healthy volunteers.

A review of normal sleep and its disturbances in Parkinson's disease.

Patients with Parkinson's disease frequently report sleep disturbances which include difficulty initiating or maintaining sleep, parasomnias or excessive daytime sleepiness. The underlying causes include: normal aging, motor symptoms of the disease, antiparkinson drugs, comorbid psychiatric conditions, and concurrent illnesses. An accurate history from the patient and care-giver regarding previous sleep patterns and how they have changed, and the degree of impact these sleep disturbances have on patient's daily life is crucial for successful management. Apart from drug therapy, appropriate counselling and nonpharmacologic treatments have major roles in the overall management. This review summarizes the current concepts of (i) the pattern and function of normal sleep, and (ii) the nature, pathogenesis and management of sleep disturbances in Parkinson's disease.

Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy.

Seventy-five patients meeting international diagnostic criteria for narcolepsy enrolled in a 6-week, three-period, randomized, crossover, placebo-controlled trial. Patients received placebo, modafinil 200 mg, or modafinil 400 mg in divided doses (morning and noon). Evaluations occurred at baseline and at the end of each 2-week period. Compared with placebo, modafinil 200 and 400 mg significantly increased the mean sleep latency on the Maintenance of Wakefulness Test by 40% and 54%, with no significant difference between the two doses. Modafinil, 200 and 400 mg, also reduced the combined number of daytime sleep episodes and periods of severe sleepiness noted in sleep logs. The likelihood of falling asleep as measured by the Epworth Sleepiness Scale was equally reduced by both modafinil dose levels. There were no effects on nocturnal sleep initiation, maintenance, or architecture, nor were there any effects on sleep apnea or periodic leg movements. Neither dose interfered with the patients' ability to nap voluntarily during the day nor with their quantity or quality of nocturnal sleep. Modafinil produced no changes in blood pressure or heart rate in either normotensive or hypertensive patients. The only significant adverse effects were seen at the 400-mg dose, which was associated with more nausea and more nervousness than either placebo or the 200-mg dose. As little as a 200-mg daily dose of modafinil is therefore an effective and well-tolerated treatment of excessive daytime somnolence in narcoleptic persons.

Clinical, biochemical and pathological predictors of poor response to intravenous cyclophosphamide in patients with proliferative lupus nephritis.

BACKGROUND: Reports in the literature on the outcome of lupus nephritis (LN) treated with intravenous (i.v.) cyclophosphamide have varied considerably. Previous studies have suggested that less than 25% of patients with LN will progress to end stage renal failure (ESRD) after 5 years. In addition it has been reported that serum creatinine and chronic histologic changes on kidney biopsy are useful markers of renal prognosis. Whether treatment with cyclophosphamide alters the predictive value of these markers in LN patients is not clear. The aim of this study was to review our experience of treating a large cohort of patients with LN treated with i.v. cyclophosphamide and to identify biochemical and histological features at the time renal biopsy which predict outcome in these patients. DESIGN: We retrospectively reviewed our experience with 43 consecutive patients who met criteria for either World Health Organization (WHO) classification III (focal proliferative) or IV (diffuse proliferative) LN and were treated with monthly i.v. cyclophosphamide. Biochemical indices of renal function and lupus disease activity were recorded. Renal biopsies, performed within two months of commencing therapy, were reviewed by two experienced pathologists and classified according to WHO classification as well as activity and chronicity index. The primary outcome variable for the analysis was the development of ESRD. RESULTS: Patients were followed for a mean of 2 years after renal biopsy. The mean dose of cyclophosphamide received by patients was 8.3 g. One patient died during follow up and 22 (51%) progressed to ESRD. A higher serum creatinine (p = 0.003) and higher score for interstitial fibrosis (p = 0.001) were associated with shorter renal survival. There was no significant association between activity index or its components or in the total chronicity score and survival free from the need for dialysis. CONCLUSION: In our experience more than half of patients treated with i.v. cyclophosphamide for LN progress to ESRD and a high serum Cr and a high degree of interstitial fibrosis on renal biopsy before treatment are associated with a worse renal prognosis.

Lack of correlation between serum soluble Fas/APO-1 levels and autoimmune disease.

OBJECTIVE: To determine whether elevated soluble Fas/APO-1 (sFas/APO-1) levels are associated with either autoimmune disease or evidence of flares in autoimmune disease. METHODS: Thirty-seven serum samples were retrospectively obtained from normal controls and patients with laboratory evidence of autoimmune disease activity. These samples were assayed for sFas/APO-1 levels by an enzyme-linked immunosorbent assay, and hospital medical records were retrospectively reviewed for clinical and laboratory characteristics of the patients. RESULTS: Soluble Fas/APO-1 levels did not correlate with clinical diagnoses or laboratory abnormalities. The mean and range of sFas/APO-1 levels were similar in systemic lupus erythematosus patients (including those with active disease), patients with other autoimmune diseases, and normal controls. CONCLUSION: These data strongly suggest that measurement of sFas/APO-1 levels is unlikely to hold clinical value or play a role in the pathogenesis of autoimmune disease.

REM sleep abnormalities and psychiatry.

Since the 1950s, with the discovery of REM sleep and its relationship to dreaming, psychiatric sleep researchers have been interested in uncovering the complex relationship between disturbed sleep and psychiatric disorders. This paper reviews the alterations in REM sleep of relevance to psychiatry and indicates that continued developments in sleep research may assist in further understanding the neuropathophysiology of affective and other psychiatric illnesses.