Accelerometers are often used to quantify the acceleration of the body in arbitrary units (counts) to measure physical activity (PA) and to estimate energy expenditure. The present study investigated whether the identification of types of PA with one accelerometer could improve the estimation of energy expenditure compared with activity counts. Total energy expenditure (TEE) of 15 subjects was measured with the use of double-labeled water. The physical activity level (PAL) was derived by dividing TEE by sleeping metabolic rate. Simultaneously, PA was measured with one accelerometer. Accelerometer output was processed to calculate activity counts per day (AC(D)) and to determine the daily duration of six types of common activities identified with a classification tree model. A daily metabolic value (MET(D)) was calculated as mean of the MET compendium value of each activity type weighed by the daily duration. TEE was predicted by AC(D) and body weight and by AC(D) and fat-free mass, with a standard error of estimate (SEE) of 1.47 MJ/day, and 1.2 MJ/day, respectively. The replacement in these models of AC(D) with MET(D) increased the explained variation in TEE by 9%, decreasing SEE by 0.14 MJ/day and 0.18 MJ/day, respectively. The correlation between PAL and MET(D) (R(2) = 51%) was higher than that between PAL and AC(D) (R(2) = 46%). We conclude that identification of activity types combined with MET intensity values improves the assessment of energy expenditure compared with activity counts. Future studies could develop models to objectively assess activity type and intensity to further increase accuracy of the energy expenditure estimation.

Ozone is a major gaseous pollutant that is known to have detrimental effects on plant growth and metabolism. We have investigated the effects of ozone on Arabidopsis thaliana growth and the pattern of expression of several stress-related genes. A. thaliana plants treated with either 150 or 300 parts per billion (ppb) ozone daily for 6 h exhibited reduced growth and leaf curling. Fresh and dry weights of ozone-treated plants were reduced 30 to 48% compared to ambient air controls. RNA blot analyses demonstrated that mRNA levels for glutathione S-transferase (GST), phenylalanine ammonia-lyase (PAL), a neutral peroxidase, and a cytosolic Cu/Zn superoxide dismutase (SOD) were higher in plants treated with 300 ppb ozone than in ambient air-treated controls. The mRNA levels of lipoxygenase and a catalase were not affected by ozone treatment. Of the transcripts examined, GST mRNA levels increased the most, showing a 26-fold induction 3 h after the initiation of ozone treatment. PAL mRNA was also rapidly induced, reaching 3-fold higher levels than controls within 3 h of ozone treatment. The neutral peroxidase and SOD mRNA levels rose more slowly, with both reaching maximum levels corresponding to 5-fold and 3-fold induction, respectively, approximately 12 h after ozone treatment. These studies indicate that ozone-induced expression of stress-related genes in A. thaliana provides an excellent model system for investigating the molecular and genetic basis of ozone-induced responses in plants.

The aim of this study was to evaluate the impact of a twice-weekly strength training intervention on perceptions of body image in 234 breast cancer survivors (112 with lymphedema) who participated in the Physical Activity and Lymphedema (PAL) trial. The study population included two hundred and thirty-four women randomly assigned to twice-weekly strength training or control group that completed the 32-item Body Image and Relationships Scale (BIRS) at baseline and 12 months. Percent change in baseline to 12-month BIRS total and subscale scores, upper and lower body strength, and general quality of life (QOL) were compared by intervention status. A series of multiple linear regression models including indicator variables for subgroups based on age, marital status, race, education, BMI, and strength change were used to examine differential intervention impact by subgroup. Strength and QOL variables were assessed as mediators of the intervention effect on BIRS.

RESULTS

Baseline BIRS scores were similar across intervention and lymphedema status. Significantly greater improvement in BIRS total score was observed from baseline to 12 months in treatment vs. control participants (12.0 vs. 2.0%; P < 0.0001). A differential impact of the intervention on the Strength and Health subscale was observed for older women (>50 years old) in the treatment group (P = 0.03). Significantly greater improvement was observed in bench and leg press among treatment group when compared to control group participants, regardless of lymphedema. Observed intervention effects were independent of observed strength and QOL changes. Twice-weekly strength training positively impacted self-perceptions of appearance, health, physical strength, sexuality, relationships, and social functioning. Evidence suggests the intervention was beneficial regardless of prior diagnosis of lymphedema. Strength and QOL improvements did not mediate the observed intervention effects.

Immunohistochemistry and image analysis were performed on sections from excessive dermal scar formation to investigate the potential of pericytes to differentiate into collagen-producing cells. Expression of the prolyl-4-hydroxylase beta-subunit (P-4-H) was used as a marker for collagen synthesis as the distribution of this protein was identical to the distribution of procollagen type I C-propeptide and similar to the distribution of cells expressing pro alpha 1(I) collagen mRNA. Double immunofluorescence stainings using combinations of monoclonal antibodies specific for activated pericytes in vivo (high molecular weight-melanoma associated antigen (HMW-MAA)), P-4-H, smooth muscle alpha-actin (SMA), endothelial cells (PAL-E), platelet-derived growth factor (PDGF) beta-receptor, and the integrin alpha 5 subunit were performed. Stained sections were analyzed by computerized image analysis allowing for a quantification of the degree of colocalization between pairs of antigens on the same tissue section. Four different subpopulations of HMW-MAA expressing cells were discerned. The first subpopulation corresponded to intramural pericytes, juxtapositioned to the endothelium, that expressed HMW-MAA, SMA, integrin alpha 5 subunit and the PDGF beta-receptor, but not P-4-H. The second subpopulation was partly dissociated from the microvascular wall and exhibited a similar antigen expression except for a decrease in expression of SMA. Cells in the third subpopulation were located in the perivascular space and expressed P-4-H, integrin alpha 5 subunit, the PDGF beta-receptor and, albeit less pronounced, HMW-MAA, but not SMA. The fourth subpopulation expressed integrin alpha 5 subunit, HMW-MAA and the PDGF beta-receptor, no expression of SMA and a strong expression of P-4-H. Moreover, an in vitro analysis of cells derived from isolated microvascular fragments from human dermis revealed a similar pattern of phenotypical change. Taken together the data suggest that a population of intramural pericytes migrate into the perivascular space and develop into collagen-synthesizing fibroblasts during fibrosis.

Convergent lines of evidence support a dual deficit model of stimulant withdrawal, where reductions in synaptic dopamine (DA) and 5-hydroxytryptamine (serotonin) (5-HT) contribute to dysphoria, drug craving, and relapse. Thus, we predicted that a nonamphetamine compound with substrate activity at DA and 5-HT transporters (i.e., a dual DA/5-HT releaser) would be an effective medication for treating stimulant addictions. Ideally, this type of medication would alleviate withdrawal symptoms, suppress cocaine self-administration, and lack side effects commonly associated with central nervous system stimulants. In the present work, more than 350 compounds were screened in vitro for activity as substrate-type releasing agents at DA, 5-HT, and norepinephrine transporters. These efforts identified PAL-287 (1-napthyl-2-aminopropane) as a nonamphetamine compound with potent substrate activity at biogenic amine transporters. In vivo microdialysis in rats demonstrated that PAL-287 (1-3 mg/kg i.v.) increased extracellular DA and 5-HT in frontal cortex, but effects on 5-HT were somewhat greater. PAL-287 induced substantially less locomotor stimulation than (+)-amphetamine, a drug that increases only extracellular DA. Administration of high-dose (+)-methamphetamine or (+/-)-3,4-methylenedioxymethamphetamine to rats produced long-lasting depletion of cortical 5-HT, whereas PAL-287 (18 mg/kg i.p. x 3) did not. PAL-287 displayed little or no reinforcing properties in rhesus monkeys trained to self-administer cocaine, yet PAL-287 produced a dose-dependent decrease in responding for cocaine when infused at a dose of 1.0 mg/kg/h. Collectively, the findings reported here demonstrate that nonamphetamine monoamine releasing agents such as PAL-287 might be promising candidate medications for the treatment of stimulant dependence.

To examine the mutagenic spectrum of 4,5',8-trimethylpsoralen (TMP) in Caenorhabditis elegans, we isolated mutations in the unc-22 and pal-1 genes following TMP mutagenesis and analyzed them for restriction fragment length polymorphisms by Southern blot. Eleven of 21 unc-22 mutations exhibited restriction fragment length polymorphisms, 8 of which were deletions of between 0.10 and 15 kb in length. Both of two pal-1 mutations were also small deletions within this size range. Comparison of our results with previous studies on mutagenesis by gamma-rays and x-rays suggests that the mutagenic spectrum of TMP may be similar. TMP should be useful in generating mutations that cause complete loss of function of single genes and that are likely to result in allele-specific DNA polymorphisms.

POP-1, a Tcf/Lef-1-like target of the convergent Wnt and MAP kinase (MAPK) signaling pathways, functions throughout Caenorhabditis elegans development to generate unequal daughters during asymmetric cell divisions. A particularly prominent such asymmetric division occurs when the EMS blastomere divides to produce MS, a mesoderm precursor, and E, the sole endoderm progenitor. POP-1 allows mesoderm development in the MS lineage by repressing the endoderm-promoting end-1 and end-3 genes. This repression is relieved in the E lineage by Wnt/MAPK signaling, which results in phosphorylation and export of POP-1 from the E nucleus. Here, we report that, in addition to repressing E development in MS, POP-1 also functions positively in endoderm development, in conjunction with the well-characterized endoderm-promoting SKN-1->>MED regulatory cascade. While removal of POP-1 alone results in derepression of endoderm development in the MS lineage, mutations in several genes that result in impenetrant loss of endoderm are strongly enhanced by loss of pop-1 function. A Lef-1-like binding site is essential for activation of an end-1 promoter fusion, suggesting that POP-1 may act directly on end-1. Thus, POP-1 may generate developmental asymmetry during many cell divisions in C. elegans by reiteratively switching from repressive and activating states. Furthermore, we report that the Caudal-like homeodomain protein PAL-1, whose role in early embryogenesis was thought to be exclusive specification of mesectodermal development in the lineage of the C blastomere, can act with POP-1 to activate endoderm specification in the absence of the SKN-1->>MED transcriptional input, accounting for the impenetrance of mutants lacking SKN-1 or MED-1,2 activity. We conclude that the combined action of several separate transcriptional regulatory inputs, including SKN-1, the MEDs, PAL-1, and the Wnt/MAPK-activated form of POP-1, are responsible for activating end gene transcription and endoderm development.

In Aspergillus nidulans, the regulation of gene expression in response to changes in ambient pH is mediated by the PacC zinc finger transcriptional regulator. At alkaline ambient pH, PacC is proteolytically processed to a functional form serving as an activator of alkaline-expressed genes and a repressor of acid-expressed genes. This activation of PacC occurs in response to a signal mediated by the products of the pal genes. Thus, the products of the palA, -B, -C, -F, -H, and -I genes constitute an alkaline ambient pH signal transduction pathway. How the pal signal transduction pathway senses ambient pH and transduces a signal to trigger PacC processing is a fascinating unresolved problem. We have cloned and sequenced the palB gene. The predicted palB gene product has similarity to the catalytic domain of the calpain family of calcium-activated cysteine proteases. We have shown, however, that the PalB protein does not catalyze the final step of proteolytic processing of PacC.

BACKGROUND

Nearsightedness (myopia) causes blurry vision when looking at distant objects. Highly nearsighted people are at greater risk of several vision-threatening problems such as retinal detachments, choroidal atrophy, cataracts and glaucoma. Interventions that have been explored to slow the progression of myopia include bifocal spectacles, cycloplegic drops, intraocular pressure-lowering drugs, muscarinic receptor antagonists and contact lenses. The purpose of this review was to systematically assess the effectiveness of strategies to control progression of myopia in children.

OBJECTIVE

To assess the effects of several types of interventions, including eye drops, undercorrection of nearsightedness, multifocal spectacles and contact lenses, on the progression of nearsightedness in myopic children younger than 18 years. We compared the interventions of interest with each other, to single vision lenses (SVLs) (spectacles), placebo or no treatment.

METHODS

We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 10), MEDLINE (January 1950 to October 2011), EMBASE (January 1980 to October 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (http://clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 11 October 2011. We also searched the reference lists and Science Citation Index for additional, potentially relevant studies.

METHODS

We included randomized controlled trials (RCTs) in which participants were treated with spectacles, contact lenses or pharmaceutical agents for the purpose of controlling progression of myopia. We excluded trials where participants were older than 18 years at baseline or participants had less than -0.25 diopters (D) spherical equivalent myopia.

METHODS

Two review authors independently extracted data and assessed the risk of bias for each included study. When possible, we analyzed data with the inverse variance method using a fixed-effect or random-effects model, depending on the number of studies and amount of heterogeneity detected.

RESULTS

We included 23 studies (4696 total participants) in this review, with 17 of these studies included in quantitative analysis. Since we only included RCTs in the review, the studies were generally at low risk of bias for selection bias. Undercorrection of myopia was found to increase myopia progression slightly in two studies; children who were undercorrected progressed on average 0.15 D (95% confidence interval (CI) -0.29 to 0.00) more than the fully corrected SVLs wearers at one year. Rigid gas permeable contact lenses (RGPCLs) were found to have no evidence of effect on myopic eye growth in two studies (no meta-analysis due to heterogeneity between studies). Progressive addition lenses (PALs), reported in four studies, and bifocal spectacles, reported in four studies, were found to yield a small slowing of myopia progression. For seven studies with quantitative data at one year, children wearing multifocal lenses, either PALs or bifocals, progressed on average 0.16 D (95% CI 0.07 to 0.25) less than children wearing SVLs. The largest positive effects for slowing myopia progression were exhibited by anti-muscarinic medications. At one year, children receiving pirenzepine gel (two studies), cyclopentolate eye drops (one study), or atropine eye drops (two studies) showed significantly less myopic progression compared with children receiving placebo (mean differences (MD) 0.31 (95% CI 0.17 to 0.44), 0.34 (95% CI 0.08 to 0.60), and 0.80 (95% CI 0.70 to 0.90), respectively).

CONCLUSIONS

The most likely effective treatment to slow myopia progression thus far is anti-muscarinic topical medication. However, side effects of these medications include light sensitivity and near blur. Also, they are not yet commercially available, so their use is limited and not practical. Further information is required for other methods of myopia control, such as the use of corneal reshaping contact lenses or bifocal soft contact lenses (BSCLs) with a distance center are promising, but currently no published randomized clinical trials exist.

To examine sources of variance in objectively measured physical activity and to determine the number of monitoring days needed to quantify physical activity patterns reliably, 394 Flemish adults (41.1 ± 9.9 years) were monitored during 7 days, using the SenseWear Armband. Differences between weekdays, Saturday and Sunday were examined with repeated measures ANOVA's. Variance components were estimated for subject, weekday and residual error using data from Mondays through Fridays and used to calculate the reliability of 1-5 monitoring weekdays. Saturday was more and Sunday less active than an average weekday. Inter-individual variability was the largest source of variance (54.4-67.9%) for physical activity level (PAL), energy expenditure, inactivity, light, moderate and total physical activity. Intra-individual variability accounted for 31.8-44.8% and weekday for 0.1-1.1% of total variance. Intra-individual variability was the largest source of variance for vigorous activity in both sexes and steps in women. At least, 3 monitoring weekdays were required to achieve a reliability of 0.80 for PAL, energy expenditure, inactivity, light, moderate and total physical activity. All 5 weekdays should be monitored to reach acceptable reliability for steps. Five weekdays resulted in a reliability of 0.58-0.60 for vigorous activity. Both Saturday and Sunday and at least 3 weekdays need to be monitored to obtain reliable measures of habitual physical activity.

During mammalian vascular development, endothelial cells form a complex array of vessels that differ markedly in structure and function, but the molecular basis for this vascular complexity is poorly understood. Recent insights into endothelial diversity have come from the identification of molecular markers expressed on distinct endothelial cell populations. One such marker, the PAL-E antibody, has been used for almost 20 years to distinguish blood and lymphatic vessels, but the identity of the protein recognized by PAL-E has been unknown. In the present study we have used protein purification and tandem mass spectrometry analysis of tryptic peptides to identify the PAL-E antigen as a secreted form of vimentin. Vimentin has been well characterized as an intracellular intermediate filament protein expressed broadly in mesenchymal cells. In contrast, PAL-E-reactive vimentin is secreted extracellularly, its synthesis is restricted to a distinct population of blood endothelial cells and activated macrophages, and PAL-E-reactive vimentin is found in circulating human blood. PAL-E-reactive vimentin does not arise from an endothelial cell-specific mRNA transcript but is the product of cell-specific posttranslational modification. The PAL-E antibody therefore defines secretion of vimentin as a molecular distinction among endothelial cells and exposes a novel, extracellular role for vimentin in the blood vasculature.

Most studies on the reduction of disease incidence in soil treated with Trichoderma asperellum have focused on microbial interactions rather than on plant responses. This study presents conclusive evidence for the induction of a systemic response against angular leaf spot of cucumber (Pseudomonas syringae pv. lachrymans) following application of T. asperellum to the root system. To ascertain that T. asperellum was the only microorganism present in the root milieu, plants were grown in an aseptic hydroponic growth system. Disease symptoms were reduced by as much as 80%, corresponding to a reduction of 2 orders of magnitude in bacterial cell densities in leaves of plants pretreated with T. asperellum. As revealed by electron microscopy, bacterial cell proliferation in these plants was halted. The protection afforded by the biocontrol agent was associated with the accumulation of mRNA of two defense genes: the phenylpropanoid pathway gene encoding phenylalanine ammonia lyase (PAL) and the lipoxygenase pathway gene encoding hydroxyperoxide lyase (HPL). This was further supported by the accumulation of secondary metabolites of a phenolic nature that showed an increase of up to sixfold in inhibition capacity of bacterial growth in vitro. The bulk of the antimicrobial activity was found in the acid-hydrolyzed extract containing the phenolics in their aglycone form. High-performance liquid chromatography analysis of phenolic compounds showed a marked change in their profile in the challenged, preelicited plants relative to that in challenged controls. The results suggest that similar to beneficial rhizobacteria, T. asperellum may activate separate metabolic pathways in cucumber that are involved in plant signaling and biosynthesis, eventually leading to the systemic accumulation of phytoalexins.

OBJECTIVE

Although peer-assisted learning (PAL) is widely employed throughout medical education, its effectiveness for training in technical procedures in skills laboratories has been subject to little systematic investigation. We conducted a prospective, randomised trial to evaluate the hypotheses that PAL is effective in technical skills training in a skills laboratory setting, and PAL is as effective as faculty staff-led training.

METHODS

Volunteer Year 3 medical students were randomly assigned to one of three groups. Two of these received regular skills training from either cross-year peer tutors or experienced faculty staff. Following training, both groups were assessed using an objective structured clinical examination (OSCE) (three stations assessing various injection techniques) which was video-recorded. Two independent video assessors scored the OSCEs using binary checklists and global ranking forms. A third student group was assessed prior to training and served as a control group.

RESULTS

A total of 89 students (mean age 23.0 +/- 0.2 years; 41 male, 48 female) agreed to participate in the trial. Confounding variables including prior training as a paramedic or previous experience in performing the technical procedures did not significantly differ between the three study groups. In the OSCE, PAL (58.1 +/- 1 binary points, 4.9 +/- 0.1 global ranking points) and faculty-led groups (58.3 +/- 1 binary points, 4.7 +/- 0.1 global ranking points) scored significantly higher than the control group (33.3 +/- 1 binary points, 2.7 +/- 0.1 global ranking points; all P < 0.0001). There was no significant difference between the PAL and faculty-led groups (P = 0.92 for binary checklists, P = 0.11 for global rankings).

CONCLUSIONS

Peer-assisted learning is a successful method for learning technical procedures in a skills laboratory setting and can be just as effective as the training provided by experienced faculty staff.

The use of palliative care programs and the number of trials assessing their effectiveness have increased.

To determine the association of palliative care with quality of life (QOL), symptom burden, survival, and other outcomes for people with life-limiting illness and for their caregivers.

MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL to July 2016.

Randomized clinical trials of palliative care interventions in adults with life-limiting illness.

Two reviewers independently extracted data. Narrative synthesis was conducted for all trials. Quality of life, symptom burden, and survival were analyzed using random-effects meta-analysis, with estimates of QOL translated to units of the Functional Assessment of Chronic Illness Therapy-palliative care scale (FACIT-Pal) instrument (range, 0-184 [worst-best]; minimal clinically important difference [MCID], 9 points); and symptom burden translated to the Edmonton Symptom Assessment Scale (ESAS) (range, 0-90 [best-worst]; MCID, 5.7 points).

Quality of life, symptom burden, survival, mood, advance care planning, site of death, health care satisfaction, resource utilization, and health care expenditures.

Forty-three RCTs provided data on 12 731 patients (mean age, 67 years) and 2479 caregivers. Thirty-five trials used usual care as the control, and 14 took place in the ambulatory setting. In the meta-analysis, palliative care was associated with statistically and clinically significant improvements in patient QOL at the 1- to 3-month follow-up (standardized mean difference, 0.46; 95% CI, 0.08 to 0.83; FACIT-Pal mean difference, 11.36] and symptom burden at the 1- to 3-month follow-up (standardized mean difference, -0.66; 95% CI, -1.25 to -0.07; ESAS mean difference, -10.30). When analyses were limited to trials at low risk of bias (n = 5), the association between palliative care and QOL was attenuated but remained statistically significant (standardized mean difference, 0.20; 95% CI, 0.06 to 0.34; FACIT-Pal mean difference, 4.94), whereas the association with symptom burden was not statistically significant (standardized mean difference, -0.21; 95% CI, -0.42 to 0.00; ESAS mean difference, -3.28). There was no association between palliative care and survival (hazard ratio, 0.90; 95% CI, 0.69 to 1.17). Palliative care was associated consistently with improvements in advance care planning, patient and caregiver satisfaction, and lower health care utilization. Evidence of associations with other outcomes was mixed.

In this meta-analysis, palliative care interventions were associated with improvements in patient QOL and symptom burden. Findings for caregiver outcomes were inconsistent. However, many associations were no longer significant when limited to trials at low risk of bias, and there was no significant association between palliative care and survival.

Decreased success at work and educational attainment by adulthood are of concern for children with ADHD given their widely documented academic difficulties; however there are few studies that have examined this empirically and even fewer that have studied predictors and individual variability of these outcomes. The current study compares young adults with and without a childhood diagnosis of ADHD on educational and occupational outcomes and the predictors of these outcomes. Participants were from the Pittsburgh ADHD Longitudinal Study (PALS), a prospective study with yearly data collection. Significant group differences were found for nearly all variables such that educational and occupational attainment was lower for adults with compared to adults without histories of childhood ADHD. Despite the mean difference, educational functioning was wide-ranging. High school academic achievement significantly predicted enrollment in post-high school education and academic and disciplinary problems mediated the relationship between childhood ADHD and post-high school education. Interestingly, ADHD diagnosis and disciplinary problems negatively predicted occupational status while enrollment in post-high school education was a positive predictor. Job loss was positively predicted by a higher rate of academic problems and diagnosis of ADHD. This study supports the need for interventions that target the child and adolescent predictors of later educational and occupational outcomes in addition to continuing treatment of ADHD in young adulthood targeting developmentally appropriate milestones, such as completing post-high school education and gaining and maintaining stable employment.

OBJECTIVE

The aim of this study was to test whether posterior fixed dental prostheses (FDPs) with zirconia frameworks exhibit similar survival rates and technical and biologic outcomes as those with metal frameworks.

METHODS

Fifty-nine patients in need of 76 FDPs replacing one to three posterior teeth (molars and premolars) were included in the study. The three- to five-unit FDPs were randomly assigned to 38 zirconia-ceramic and 38 metal-ceramic FDPs. At baseline, 6 months, and 1 to 3 years after cementation, the technical outcome of the reconstructions was examined using the United States Public Health Service (USPHS) criteria. The biologic outcome was analyzed at test (abutment) and control (contralateral) teeth by assessing: probing pocket depth (PPD), probing attachment level (PAL), plaque control record (PCR), bleeding on probing (BOP), and tooth vitality. Radiographs of the FDPs were made. Statistical analysis was performed by applying Kaplan-Meier, Pearson chi-square, Fisher exact, and Mann-Whitney U tests.

RESULTS

Fifty-three patients with 67 FDPs (36 zirconia-ceramic, 31 metal-ceramic) were examined after a mean observation period of 40.3 +/- 2.8 months. Six patients with 9 FDPs were lost to follow-up. The survival of both kinds of FDPs was 100%. No significant differences regarding the technical and biologic outcomes were found. Minor chipping of the veneering ceramic was found in 25% of the zirconia-ceramic and 19.4% of the metal-ceramic FDPs. Extended fracturing of the veneering ceramic occurred solely in zirconia-ceramic FDPs (C: 8.6%, D: 2.8% [USPHS criteria]). Few biologic complications were found. Both types of FDPs rendered the same mean values for the biologic parameters (mean PPD, PCR, and BOP for zirconia-ceramic FDPs = 2.4 +/- 0.3, 0.1 +/- 0.1, and 0.3 +/- 0.2, respectively; mean PPD, PCR, and BOP for metal-ceramic FDPs = 2.4 +/- 0.3, 0.1 +/- 0.1, and 0.3 +/- 0.2, respectively).

CONCLUSIONS

Zirconia-ceramic FDPs exhibited a similar survival rate to metal-ceramic FDPs at 3 years of function.

The DNA of the first northcentral United States human Lyme disease isolate, Borrellia burgdorferi NCH-1, was characterized and compared with the DNAs of nine other B. burgdorferi isolates. Strain NCH-1 was isolated in August 1989 from a human skin biopsy specimen. DNA was analyzed by pulsed-field gel electrophoresis and restriction endonuclease analysis. Contour-clamped homogeneous electric field pulsed-field gel electrophoresis of in situ-lysed cells was performed to compare the plasmid profiles of the various isolates. The plasmid profile of isolate NCH-1, which included five plasmids of approximately 69, 42, 38, 32, and 23 kb, could be distinguished from those of the other isolates examined. The DNA profile of NCH-1 was most similar to those of strain 297 (human cerebrospinal fluid isolate, Connecticut) and strain PAL (human erythema migrans isolate, New York) and most dissimilar from those of strain P/Gau (human erythema migrans isolate, Germany) and strain IPF (Ixodes persulcatus tick isolate, Japan). These results indicate that genetic diversity exists among B. burgdorferi strains isolated from different geographical areas.

OBJECTIVE

To identify the baseline psychological variables before receiving a Diabetes Prevention Program (DPP) lifestyle intervention that predict physical activity levels (PALs) at baseline, 1 year, and end of study (2 to 3 years after randomization).

METHODS

Of the final 293 DPP lifestyle participants randomized, 274 (94%) completed validated questionnaires at baseline assessing stage of change for PAL, exercise self-efficacy, perceived stress, depression, and anxiety.

METHODS

Correlations and stepwise multiple regression analyses.

RESULTS

At baseline, this subset was similar to the entire DPP lifestyle cohort: mean age was 52.5 years, 65% were women, and mean PAL was 15.7 metabolic equivalent hours per week. Higher levels of baseline leisure PAL correlated with greater readiness to change PAL (r=0.44, P<0.0001), higher exercise self-efficacy (r=0.18, P=0.002), and lower levels of perceived stress (r=-0.16, P=0.009), depression (r=-0.18, P=0.003), and anxiety (r=-0.14, P=0.03), with similar correlations at 1 year and end of study. In multivariate models, being a man, lower levels of depression, and lower body mass index were independent correlates of higher baseline leisure PAL; being a man, greater baseline exercise self-efficacy, and activity level were independent correlates of greater leisure PAL levels at 1 year and end of study. Greater readiness to change PAL at baseline was also an independent correlate of greater PAL at end of study.

CONCLUSIONS

In this representative sample of DPP lifestyle participants, being a man, lower body mass index, greater readiness for change in PAL, higher exercise self-efficacy, and lower perceived stress, depression, and anxiety scores correlated with higher levels of baseline PAL with similar patterns at 1 year and end of study. These findings may help determine which patients are most likely to increase PAL in lifestyle intervention programs.

An increasing number of epilepsy patients are afflicted with drug-resistant temporal lobe epilepsy (TLE) and require alternative therapeutic approaches. High-affinity glycine receptors (haGlyRs) are functionally adapted to tonic inhibition due to their response to hippocampal ambient glycine, and their synthesis is activity-dependent. Therefore, in our study, we scanned TLE hippocampectomies for expression of haGlyRs and characterized the effects mediated by these receptors using primary hippocampal neurons. Increased haGlyR expression occurred in TLE hippocampi obtained from patients with a severe course of disease. Furthermore, in TLE patients, haGlyR and potassium chloride cotransporter 2 (KCC2) expressions were inversely regulated. To examine this potential causal relationship with respect to TLE histopathology, we established a hippocampal cell culture system utilising tonic inhibition mediated by haGlyRs in response to hippocam-pal ambient glycine and in the context of a high Cl equilibrium potential, as is the case in TLE hippocampal neurons. We showed that hypoactive neurons increase their ratio between glutamatergic and GABAergic synapses, reduce their dendrite length and finally undergo excitotoxicity. Pharmacological dissection of the underlying processes revealed ionotropic glutamate and TrkB receptors as critical mediators between neuronal hypoactivity and the emergence of these TLE-characteristic histopathological signs. Moreover, our results indicate a beneficial role for KCC2, because decreasing the Cl- equilibrium potential by KCC2 expression also rescued hypoactive hippocampal neurons. Thus, our data support a causal relationship between increased haGlyR expression and the emergence of histopathological TLE-characteristic signs, and they establish a pathophysiological role for neuronal hypoactivity in the context of a high Cl- equilibrium potential.

In plants, chalcones are precursors for a large number of flavonoid-derived plant natural products and are converted to flavanones by chalcone isomerase or nonenzymatically. Chalcones are synthesized from tyrosine and phenylalanine via the phenylpropanoid pathway involving phenylalanine ammonia lyase (PAL), cinnamate-4-hydroxylase (C4H), 4-coumarate:coenzyme A ligase (4CL), and chalcone synthase (CHS). For the purpose of production of flavanones in Escherichia coli, three sets of an artificial gene cluster which contained three genes of heterologous origins--PAL from the yeast Rhodotorula rubra, 4CL from the actinomycete Streptomyces coelicolor A3(2), and CHS from the licorice plant Glycyrrhiza echinata--were constructed. The constructions of the three sets were done as follows: (i) PAL, 4CL, and CHS were placed in that order under the control of the T7 promoter (P(T7)) and the ribosome-binding sequence (RBS) in the pET vector, where the initiation codons of 4CL and CHS were overlapped with the termination codons of the preceding genes; (ii) the three genes were transcribed by a single P(T7) in front of PAL, and each of the three contained the RBS at appropriate positions; and (iii) all three genes contained both P(T7) and the RBS. These pathways bypassed C4H, a cytochrome P-450 hydroxylase, because the bacterial 4CL enzyme ligated coenzyme A to both cinnamic acid and 4-coumaric acid. E. coli cells containing the gene clusters produced two flavanones, pinocembrin from phenylalanine and naringenin from tyrosine, in addition to their precursors, cinnamic acid and 4-coumaric acid. Of the three sets, the third gene cluster conferred on the host the highest ability to produce the flavanones. This is a new metabolic engineering technique for the production in bacteria of a variety of compounds of plant and animal origin.

BACKGROUND

Age-related cognitive decline begins in mid-life and continues with advancing age. Leukocyte telomere length (LTL) shortens with age, and inflammation and oxidative stress enhance this process. Shorter LTL is associated with dementia.

METHODS

The relationship between cognitive function and LTL was investigated in a cross-sectional study of 382 women (mean age 50.6 years, range 19-78), not diagnosed with any form of dementia or cognitive impairment, from the TwinsUK cohort using six tests from the Cambridge neuropsychological test automated battery (CANTAB).

RESULTS

After adjusting for age and estimated prior intellectual ability, we observed significant correlations of LTL with episodic memory and associated learning (PAL, p=0.032), recognition memory for non-verbal patterns (DMS, p=0.007), and working memory capacity (SSP, p=0.003). In pairs of twins discordant for LTL the twin with longer telomeres also had significantly better DMS (p<0.05) and SSP (p<0.013) scores than their co-twin with shorter telomeres. The correlations between these two scores and LTL was significant both in women over the median mean age and in those below the median age, and remained significant after statistical adjustment for potential confounders.

CONCLUSIONS

Leukocyte telomere length correlates with a subset of measures of cognitive performance, suggesting that it might be a biomarker of cognitive aging in women before the onset of dementia.

BACKGROUND

Information about daily physical activity levels (PAL) in subjects with undiagnosed chronic obstructive pulmonary disease (COPD) is scarce. This study aims to assess PA and to investigate the associations between PA and clinical characteristics in subjects with newly diagnosed COPD.

METHODS

Fifty-nine subjects with a new spirometry-based diagnosis of mild (n=38) and moderate (n=21) COPD (63±6 years, 68% male) were matched with 65 smoking controls (62±7 years, 75% male). PA (daily steps, time spent in moderate-to-vigorous intense physical activities (MVPA) and PAL) was measured by accelerometry. Dyspnoea, complete pulmonary function tests, peripheral muscle strength and exercise capacity served as clinical characteristics.

RESULTS

PA was significantly lower in COPD versus smoking controls (7986±2648 vs 9765±3078 steps, 64 (27-120) vs 110 (55-164) min of MVPA, 1.49±0.21 vs 1.62±0.24 PAL respectively, all p<0.05). Subjects with COPD with either mild symptoms of dyspnoea (mMRC 1), those with lower diffusion capacity (T(L),co), low 6 min walking distance (6MWD) or low maximal oxygen uptake (VO(2) peak) had significantly lower PA. Multiple regression analysis identified 6 MWD and T(L),co as independent predictors of PA in COPD.

CONCLUSIONS

The reduction in PA starts early in the disease, even when subjects are not yet diagnosed with COPD. Inactivity is more pronounced in subjects with mild symptoms of dyspnoea, lower levels of diffusion capacity and exercise capacity.

OBJECTIVE

This study examines adolescent-specific practical problems associated with current practice parameters for diagnosing attention-deficit/hyperactivity disorder (ADHD) to inform recommendations for the diagnosis of ADHD in adolescents. Specifically, issues surrounding the use of self- versus informant ratings, diagnostic threshold, and retrospective reporting of childhood symptoms were addressed.

METHODS

Using data from the Pittsburgh ADHD Longitudinal Study (PALS), parent, teacher, and self-reports of symptoms and impairment were examined for 164 adolescents with a childhood diagnosis of ADHD (age M = 14.74 years) and 119 demographically similar non-ADHD controls (total N = 283).

RESULTS

Results indicated that 70% of the well-diagnosed childhood ADHD group continued to meet Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000) diagnostic criteria for ADHD in adolescence; however, an additional 17% possessed clinically significant impairment in adolescence but did not qualify for a current ADHD diagnosis. The optimal source of information was combined reports from the parent and a core academic teacher. Adolescents with ADHD met criteria for very few symptoms of hyperactivity/impulsivity, suggesting a need to revisit the diagnostic threshold for these items. Additionally, emphasis on impairment, rather than symptom threshold, improved identification of adolescents with a gold-standard childhood diagnosis of ADHD and persistent ADHD symptoms. Parent retrospective reports of baseline functioning, but not adolescent self-reports, were significantly correlated with reports collected at baseline in childhood.

CONCLUSIONS

Recommendations are offered for diagnosing ADHD in adolescence based on these findings.

Random mutagenesis methods only partially cover the mutational space and are constrained by DNA synthesis length limitations. Here we demonstrate programmed allelic series (PALS), a single-volume, site-directed mutagenesis approach using microarray-programmed oligonucleotides. We created libraries including nearly every missense mutation as singleton events for the yeast transcription factor Gal4 (99.9% coverage) and human tumor suppressor p53 (93.5%). PALS-based comprehensive missense mutational scans may aid structure-function studies, protein engineering, and the interpretation of variants identified by clinical sequencing.