MEG-guided analysis of 7T-MRI in patients with epilepsy.

PURPOSE: To study possible detection of structural abnormalities on 7T MRI that were not detected on 3T MRI and estimate the added value of MEG-guidance. For abnormalities found, analysis of convergence between clinical, MEG and 7T MRI localization of suspected epileptogenic foci. METHODS: In adult patients with well-documented localization-related epilepsy in whom a previous 3T MRI did not demonstrate an epileptogenic lesion but MEG indicated a plausible epileptogenic focus, 7T MRI was performed. Based on semiologic data, visual analysis of the 7T images was performed as well as based on prior MEG results. Correlation with other data from the patient charts, for as far as these were available, was analysed. To establish the level of concordance between the three observers the generalized or Fleiss kappa was calculated. RESULTS: In 3/19 patients abnormalities that, based on semiology, could plausibly represent an epileptogenic lesion were detected using 7T MRI. In an additional 3/19 an abnormality was detected after MEG-guidance. However, in these later cases there was no concordance among the three observers with regard to the presence of a structural abnormality. In one of these three cases intracranial recording was performed, proving the possible abnormality on 7T MRI to be the epileptogenic focus. CONCLUSIONS: In 32% of patients 7T MRI showed abnormalities that could indicate an epileptogenic lesion whereas previous 3T MRI did not, especially when visual inspection was guided by the presence of focal interictal MEG abnormalities.

Double-pionic fusion of nuclear systems and the "ABC" effect: approaching a puzzle by exclusive and kinematically complete measurements.

The ABC effect-a puzzling low-mass enhancement in the pipi invariant mass spectrum, first observed by Abashian, Booth, and Crowe-is well known from inclusive measurements of two-pion production in nuclear fusion reactions. Here we report on the first exclusive and kinematically complete measurements of the most basic double-pionic fusion reaction pn-->dpi;{0}pi;{0} at beam energies of 1.03 and 1.35 GeV. The measurements, which have been carried out at CELSIUS-WASA, reveal the ABC effect to be a (pipi)_{I=L=0} channel phenomenon associated with both a resonancelike energy dependence in the integral cross section and the formation of a DeltaDelta system in the intermediate state. A corresponding simple s-channel resonance ansatz provides a surprisingly good description of the data.

Hepatitis C patients' self-reported adherence to treatment with pegylated interferon and ribavirin.

BACKGROUND: Prior research on adherence to hepatitis C treatment has documented rates of dose reductions and early treatment discontinuation, but little is known about patients' dose-taking adherence. AIMS: To assess the prevalence of missed doses of pegylated interferon and ribavirin and examine the correlates of dose-taking adherence in clinic settings. METHODS: One hundred and eighty patients on treatment for hepatitis C (23% coinfected with HIV) completed a cross-sectional survey at the site of their hepatitis C care. RESULTS: Seven per cent of patients reported missing at least one injection of pegylated interferon in the last 4 weeks and 21% reported missing at least one dose of ribavirin in the last 7 days. Dose-taking adherence was not associated with HCV viral load. CONCLUSIONS: Self-reported dose non-adherence to hepatitis C treatment occurs frequently. Further studies of dose non-adherence (assessed by method other than self-report) and its relationship to HCV virological outcome are warranted.

Enhanced Cd2+ -selective root-tonoplast-transport in tobaccos expressing Arabidopsis cation exchangers.

Several Arabidopsis CAtion eXchangers (CAXs) encode tonoplast-localized transporters that appear to be major contributors to vacuolar accumulation/sequestration of cadmium (Cd(2+)), an undesirable pollutant ion that occurs in man largely as a result of dietary consumption of aerial tissues of food plants. But, ion-selectivity of individual CAX transporter types remains largely unknown. Here, we transformed Nicotiana tabacum with several CAX genes driven by the Cauliflower Mosaic Virus (CaMV) 35S promoter and monitored divalent cation transport in root-tonoplast vesicles from these plants in order to select particular CAX genes directing high Cd(2+) antiporter activity in root tonoplast. Comparison of seven different CAX genes indicated that all transported Cd(2+), Ca(2+), Zn(2+), and Mn(2+) to varying degrees, but that CAX4 and CAX2 had high Cd(2+) transport and selectivity in tonoplast vesicles. CAX4 driven by the CaMV 35S and FS3 [figwort mosaic virus (FMV)] promoters increased the magnitude and initial rate of Cd(2+)/H(+) exchange in root-tonoplast vesicles. Ion selectivity of transport in root-tonoplast vesicles isolated from FS3::CAX4-expressing plant lines having a range of gene expression was Cd(2+)>Zn(2+)>>Ca(2+)>>Mn(2+) and the ratios of maximal Cd(2+) (and Zn(2+)) versus maximal Ca(2+) and Mn(2+) transport were correlated with the levels of CAX4 expression. Root Cd accumulation in high CAX4 and CAX2 expressing lines was increased in seedlings grown with 0.02 muM Cd. These observations are consistent with a model in which expression of an Arabidopsis-gene-encoded, Cd(2+)-efficient antiporter in host plant roots results in greater root vacuole Cd(2+) transport activity, increased root Cd accumulation, and a shift in overall root tonoplast ion transport selectivity towards higher Cd(2+) selectivity. Results support a model in which certain CAX antiporters are somewhat more selective for particular divalent cations.

In-medium isovector piN amplitude from low-energy pion scattering.

Differential cross sections for elastic scattering of 21.5 MeV positive and negative pions by Si, Ca, Ni, and Zr have been measured as part of a study of the pion-nucleus potential across the threshold. The "anomalous" repulsion in the s-wave term was observed, as is the case with pionic atoms. The extra repulsion can be accounted for by a chiral-motivated model where the pion decay constant is modified in the medium. Unlike in pionic atoms, the anomaly cannot be removed by merely introducing an empirical on-shell energy dependence.

Correlates of HIV antiretroviral adherence in persons with serious mental illness.

Although several studies have examined the relationship between symptoms of depression or psychological distress and medication adherence, this is the first published study of HIV antiretroviral adherence and its correlates among persons diagnosed with serious mental illness. Forty-five of 47 (96%) participants completed a two-week study in which their adherence to antiretroviral medication was measured using electronic monitoring caps. Mean adherence (proportion of prescribed doses taken) was 66% (SD=34). There were several correlates (p<0.05) of adherence among background and medical characteristics, physical symptoms and side effects, cognitive and psychosocial functioning, and treatment-related attitudes and beliefs. However, in a forward stepwise regression, attendance at recent clinical appointments was the sole predictor that entered the model--accounting for 49% of the variance in adherence. Using attendance at recent clinic appointments as the criterion, adherence readiness (90+% adherence to antiretrovirals) was correctly determined for 72% of the sample. Although not sufficient to serve as the basis for treatment decision making, review of appointment-keeping records may provide clinicians with a simple, cost-effective method for predicting adherence to ongoing treatment, as well as for evaluating adherence readiness to inform the decision of whether to prescribe or defer treatment.

New approaches for studying and exploiting an old protuberance, the plant trichome.

BACKGROUND AND AIMS: Much recent study of plant trichomes has focused on various aspects of glandular secreting trichomes (GSTs) and differentiation of simple trichomes. This Botanical Briefing will highlight: research on various aspects of, and manipulation of glandular secreting trichomes; molecular aspects of the differentiation and development of simple trichomes of arabidopsis and cotton; how methods for manipulation of model systems used in the above work can be applied to expand our understanding of less studied surface structures of plants. SCOPE: The Briefing will cover: established and suggested roles of simple and glandular secreting trichomes; recent results regarding solute and ion movement in trichomes; methods for isolating trichomes; recent studies of trichome differentiation and development; attempts to modify metabolism in secreting trichomes; efforts to exploit trichomes for commercial and agronomic purposes.

Pill taking 'routinization': a critical factor to understanding episodic medication adherence.

This exploratory study examines the contextual factors that lead to episodic nonadherence to highly active antiretroviral therapy. Unlike global adherence that refers to the overall probability that a participant will take his or her medication over a given time period, episodic adherence refers to whether an individual took a particular dose (e.g., Saturday morning, 17 September). Semi-structured, qualitative interviews were conducted with a convenience sample of 27 consecutive participants enrolled in ongoing adherence trials who had missed at least one dose of antiretroviral medication during the past 2 days. A qualitative analysis revealed that routinization of pill regimens and factors associated with the participant's ability to maintain these routines (e.g., time of day of scheduled dose; location of participant at time of dose) play an important role in successful adherence. In addition, psychosocial factors such as psychological distress, substance abuse, and active and unpredictable social lives may act as barriers to adherence. Implications for adherence interventions are discussed.

Exclusive measurement of the pp --> pppi(+)pi(-) reaction near threshold.

The pp-->pp pi(+) pi(-) reaction has been measured exclusively near threshold at CELSIUS. The total cross sections are nearly an order of magnitude lower than expected from previous inclusive measurements. The differential cross sections reveal pp-->pp(*)(1440)-->pp sigma = pp(pi(+)pi(-))(I = l = 0) as the dominant process as well as significant contributions from p(*)-->Delta(++)pi(-)-->psigma. The observed anisotropy in the proton angular dependence is consistent with heavy-meson exchange. In the invariant mass spectra, no narrow structures of statistical relevance (3sigma) are found.

Correlates of adherence to combination antiretroviral therapy among members of HIV-positive mixed status couples.

This exploratory study assessed medication adherence and its correlates in HIV-positive members of HIV mixed status couples. Forty couples were interviewed; the HIV-positive participants consisted of 19 gay men, 14 heterosexual men and seven heterosexual women. Mean self-reported adherence (over the past three days) for the whole sample was 95%; the mean adherence rate for gay men (99%) was significantly higher (p < 0.05) than that of heterosexual men (94%) and heterosexual women (87%) based on a ranked transformation of the adherence score. In analyses involving measures rated by the HIV-positive partner, higher adherence was associated with more years of education, greater perceived treatment efficacy, stronger belief that combination therapy is a significant advancement in treatment, and greater knowledge of HIV treatments and consequences of poor adherence. Higher adherence was associated with the HIV-negative partner attributing less risk to unprotected anal/vaginal sex within the couple, while lower adherence was associated with a greater likelihood that the couple engaged in unprotected anal/vaginal sex in the last two months. A larger sample is needed to substantiate these findings.

Suppression of a P450 hydroxylase gene in plant trichome glands enhances natural-product-based aphid resistance.

Trichome glands on the surface of many higher plants produce and secrete exudates affecting insects, microbes, and herbivores. Metabolic engineering of gland exudation has potential for improving pest/disease resistance, and for facilitating molecular farming. We identified a cytochrome P450 hydroxylase gene specific to the trichome gland and used both antisense and sense co-suppression strategies to investigate its function. P450-suppressed transgenic tobacco plants showed a > or =41% decrease in the predominant exudate component, cembratriene-diol (CBT-diol), and a > or =19-fold increase in its precursor, cembratriene-ol (CBT-ol). Thus, the level of CBT-ol was raised from 0.2 to > or =4.3% of leaf dry weight. Exudate from antisense-expressing plants had higher aphidicidal activity, and transgenic plants with exudate containing high concentrations of CBT-ol showed greatly diminished aphid colonization responses. Our results demonstrate the feasibility of significantly modifying the natural-product chemical composition and aphid-interactive properties of gland exudates using metabolic engineering. The results also have implications for molecular farming.

Measuring medication adherence: are missed doses reported more accurately then perfect adherence?

Self-reports overestimate adherence compared to more objective measures such as electronic monitoring. However, self-report is the most feasible method for clinical settings; therefore, it is important to identify the context in which this method can provide an accurate assessment. To address whether self-reports are more accurate when missed doses are reported, we conducted a secondary analysis of data from a methodological study comparing multiple measures of adherence (including self-report and electronic monitoring) to a two-week placebo regimen mimicking HAART among 30 HIV-positive patients not on HAART. Results indicated a mean adherence of 85% and 62%, as measured by self-report and electronic monitoring, respectively. Self-report and electronic monitoring were not significantly correlated in the measurement of proportion of prescribed doses taken among the sub-group of 17 patients who reported missed doses (r = 0.22), nor among those who reported no missed doses, or the group as a whole. Using electronic monitoring as the validity criterion, these findings indicate that self-reports overestimate adherence even among patients who report missed doses.

Psychological and physical health correlates of body cell mass depletion among HIV+ men.

OBJECTIVE: To assess whether significant body cell mass depletion related to HIV is associated with declines in physical health and psychological well-being. METHODS: As part of a 2-year prospective HIV study, semiannual assessments included measures of body composition, psychological status, and physical health. RESULTS: As measured by bioelectric impedance analysis, 58 (31%) of 187 enrolled HIV+ men had significant body cell mass depletion at some point during the study, of who 23 subsequently lost at least an additional 5% of body cell mass in the 6 months between any two consecutive study visits. This additional body cell mass depletion was associated with significant increase in fatigue, global distress and depressive symptomatology, and reduced life satisfaction. CONCLUSION: These data illuminate the importance of monitoring body weight and body cell mass, and the need for awareness of the association between malnutrition, mental health, and quality of life.

Expression of arabidopsis CAX2 in tobacco. Altered metal accumulation and increased manganese tolerance.

Metal transport from the cytosol to the vacuole is thought to be an important component of ion tolerance and of a plant's potential for use in phytoremediation. The Arabidopsis antiporter CAX2 (calcium exchanger 2) may be a key mediator of this process. CAX2 expression in yeast suppressed both Ca(2+) and Mn(2+) growth defects. A peptide-specific antibody to the antiporter reacted with a 39-kD protein from plant vacuolar membranes. Tobacco (Nicotiana tabacum) plants expressing CAX2 accumulated more Ca(2+), Cd(2+), and Mn(2+) and were more tolerant to elevated Mn(2+) levels. Expression of CAX2 in tobacco increased Cd(2+) and Mn(2+) transport in isolated root tonoplast vesicles. These results suggest that CAX2 has a broad substrate range and modulation of this transporter may be an important component of future strategies to improve plant ion tolerance.

Prevalence of extradyadic sex in male couples of mixed HIV status and its relationship to psychological distress and relationship quality.

This study assessed the prevalence of extradyadic sex and the relationship between such activity and psychological distress and relationship quality in male couples of mixed HIV serostatus. Sixty-three couples were interviewed and had sufficient data for inclusion in all analyses. With regard to sexual activity during the year prior to being interviewed, 19 (30%) couples were monogamous, 18 (29%) described themselves as "open," 13 (21%) kept extradyadic sex a secret from their partners, and in 13 couples there was only partial knowledge of extradyadic sex. Though not statistically significant, monogamous and open couples consistently scored lower numerically on measures of psychological distress and higher on measures of relationship quality, compared to "partial knowledge" and "secretive" couples. When pooled, monogamous and open couples scored significantly higher on measures of dyadic consensus, affectional expression, dyadic satisfaction, and sexual satisfaction compared to the combined subgroup of partial knowledge and secretive couples.

Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial.

BACKGROUND: This report documents findings from a small placebo-controlled trial of dextroamphetamine for depression and fatigue in men with the human immunodeficiency virus (HIV). Dextroamphetamine offers the potential for rapid onset of effect and activation properties, both of which are important to persons with medical illness and an uncertain, but limited, life expectancy. METHOD: Primary inclusion criteria included the presence of a DSM-IV depressive disorder, debilitating fatigue, and no history of dependence on stimulants. The study consisted of a 2-week randomized, placebo-controlled trial, with the blind maintained until week 8 for responders, followed by open treatment through the completion of 6 months. RESULTS: Of 23 men who entered the study, 22 completed the 2-week trial. Intent-to-treat analysis indicated that 73% of patients (8/11) randomly assigned to dextroamphetamine reported significant improvement in mood and energy, compared with 25% (3/12) among placebo patients (Fisher exact test, p < .05). Both clinician- and self-administered measures indicated significantly improved mood, energy, and quality of life among patients taking dextroamphetamine. There was no evidence of the development of tolerance of, abuse of, or dependence on the medication. CONCLUSION: These results suggest that dextroamphetamine is a potentially effective, fast-acting antidepressant treatment for HIV patients with depression and debilitating fatigue.

Resilience and distress among amyotrophic lateral sclerosis patients and caregivers.

OBJECTIVES: The objectives of this study were to assess the prevalence of depressive disorders and symptoms and their correlates in patients with amyotrophic lateral sclerosis (ALS) and caregiver spouses and to identify dimensions of resilience as well as distress. METHODS: Fifty-six patients with ALS and 31 caregivers were interviewed on one occasion, and 20 patients were subsequently reinterviewed during a scheduled medical visit at an ALS center. Major measures included the Structured Clinical Interview for DSM-IV, the Beck Depression Inventory, the Schedule of Attitudes Toward Hastened Death, quality of life, spirituality, and degree of hopelessness. The ALS Functional Rating Scale, spirometry measures of forced vital capacity, and the Karnofsky Performance Index were used to assess physical status. RESULTS: Neither patients nor caregivers displayed significant psychopathology with respect to either current depressive disorders or scores on symptom scales. Depressive symptoms and psychological distress were not related to time since diagnosis, degree of disability, or illness progression during the period of observation. More interest in hastened death was associated with greater distress, but willingness to consider assisted suicide was not. Among caregivers, perceived caregiver burden was significantly associated with finding positive meaning in caregiving. Concordance between patient and caregiver distress was high, suggesting that attention to the mental health needs of caregivers may alleviate the patient's distress as well. CONCLUSIONS: Clinical depression or significant depressive symptomatology is not an inevitable or common outcome of life-threatening illness, even in the presence of major disability.

A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms.

BACKGROUND: The goal was to evaluate the efficacy of testosterone in alleviation of hypogonadal symptoms (diminished libido, depressed mood, low energy, and depleted muscle mass) in men with symptomatic human immunodeficiency virus illness. METHODS: Seventy-four patients were enrolled in a double-blind, placebo-controlled 6-week trial with bi-weekly testosterone injections, followed by 12 weeks of open-label maintenance treatment. Major outcome measures were Clinical Global Impressions Scale ratings for libido, mood, energy, and erectile function; Hamilton Depression Rating Scale scores, and Chalder Fatigue Scale scores. Body composition changes were assessed with bioelectric impedance analysis. RESULTS: Seventy men completed the 6-week trial. Response rates, defined as much or very much improved libido, were 74% (28/38) for patients randomized to testosterone, and 19% (6/32) for placebo-treated patients (P<.001). Of the 62 completers with fatigue at baseline, 59% (20/34) receiving testosterone and 25% (7/28) receiving placebo reported improved energy (P<.01). Among the 26 completers with an Axis I depressive disorder at baseline, 58% of the testosterone-treated patients reported improved mood compared with 14% of placebo-treated patients (Fisher exact test = .08). With testosterone treatment, average increase in muscle mass over 12 weeks was 1.6 kg for the whole group, and 2.2 kg for the 14 men with wasting at baseline. Improvement on all parameters was maintained during subsequent open-label treatment for up to 18 weeks. CONCLUSION: Testosterone is well tolerated and effective in the short-term treatment of symptoms of clinical hypogonadism in men with symptomatic human immunodeficiency virus illness, restoring libido and energy, alleviating depressed mood, and increasing muscle mass.

DHEA treatment for HIV+ patients: effects on mood, androgenic and anabolic parameters.

The goal of this pilot study was to evaluate the effect of dehydroepiandrosterone (DHEA) on depressed mood and fatigue in HIV+ men and women, unselected for baseline DHEA level. Secondary questions concerned treatment effects on libido and body cell mass, on serum testosterone levels, and elicitation of short-term side effects. Treatment consisted of an open-label 8-week trial using DHEA doses from 200 to 500 mg/day. Mood responders were maintained for another 4 weeks, then randomized to a double blind placebo controlled 4-week discontinuation trial. Forty-five patients, including six women, entered the trial. Of 32 week 8 completers, mood was much improved in 72%, and 81% were rated responders with respect to fatigue. Response on either parameter was unrelated to baseline serum DHEA level. Twenty-one patients entered the double blind discontinuation phase. No differences in relapse rate between placebo and DHEA groups were observed for either mood or fatigue. Body cell mass increased significantly by week 8, and this improvement was maintained throughout the double blind phase for patients in both treatment conditions. Libido increased significantly as well. DHEA therapy did not have an effect on CD4 cell count or on serum testosterone levels in men. In conclusion, DHEA may be a promising treatment for HIV+ patients with depressed mood and fatigue, although persistence of response even in placebo-treated patients during the discontinuation phase leaves unresolved questions. A parallel group double blind clinical trial is indicated as the next step to more clearly identify therapeutic efficacy.

Mode-locked Cr(2+):ZnSe laser.

We describe active mode locking of a Cr(2+):ZnSe laser operating near 2.5 mum. The laser produces 4.4-ps transform-limited Gaussian-shaped pulses and produces 82 mW of average power.