Prostate specific antigen in a community-based sample of men without prostate cancer: Correlations with prostate volume, age, body mass index, and symptoms of prostatism

The correlation between both prostate specific antigen levels (PSA) and prostate specific antigen density (PSAD) and age, prostate volume parameters, body mass index, and the International Prostate Symptom Score (IPSS) were studied in a community‐based population. A sample of 502 men aged 55 through 74 years was evaluated, excluding those with a serum PSA above 10 ng/ml, those with biopsy proven prostate cancer, and those who had previously undergone a prostate operation. PSA and PSAD did not correlate with the body mass index. Weak correlations were found betwe

Control of anthocyanin and non-flavonoid compounds by anthocyanin-regulating MYB and bHLH transcription factors in Nicotiana benthamiana leaves

Coloration of plant organs such as fruit, leaves and flowers through anthocyanin production is governed by a combination of MYB and bHLH type transcription factors. In this study we introduced Rosea1 (ROS1, a MYB type) and Delila (DEL, a bHLH type), into Nicotiana benthamiana leaves by agroinfiltration. ROS1 and DEL form a pair of well-characterized transcription factors from Snapdragon (Antirrhinum majus), which specifically induce anthocyanin accumulation when expressed in tomato fruit. In N. benthamiana, robust induction of a single anthocyanin, delphinidin-3-rutinoside (D3R) was observed after expression of both ROS1 and DEL. Surprisingly in addition to D3R, a range of additional metabolites were also strongly and specifically up-regulated upon expression of ROS1 and DEL. Except for the D3R, these induced compounds were not derived from the flavonoid pathway. Most notable among these are nornicotine conjugates with butanoyl, hexanoyl and octanoyl hydrophobic moieties, and phenylpropanoid-polyamine conjugates such as caffeoyl-putrescine. The defensive properties of the induced molecules were addressed in bioassays using the tobacco specialist lepidopteran insect Manduca sexta. Our study showed that the effect of ROS1 and DEL expression in N. benthamiana leaves extends beyond the flavonoid pathway. Apparently the same transcription factor may regulate different secondary metabolite pathways in different plant species

Social cognition, emotion-regulation and social competence in classical galactosemia patients without intellectual disability

Objective: Classical galactosemia (CG) is an inborn error of galactose metabolism. Many CG-patients suffer from long-Term complications including poor cognitive functioning. There are indications of social dysfunction but limited evidence in the literature. Therefore, this study aims to improve our understanding of social competence in CG by investigating social cognition, neurocognition and emotion-regulation. Methods: A comprehensive (neuro)psychological test battery including self-and proxy questionnaires was administered to CG-patients without intellectual disability. Social cognition was assessed by facial emotion recognition, Theory of Mind and self-reported empathy. Standardized results were compared to normative data of the general population. Results: Data of 23 patients (aged 8-52) were included in the study. On a group-level, CG-patients reported satisfaction with social roles and no social dysfunction despite the self-report of lower social skills. They showed deficits on all aspects of social cognition on both performance tests (emotion-recognition and Theory of Mind) and self-report questionnaires (empathy). Adults had a lower social participation than the general population. Parents reported lower social functioning, less adaptive emotion-regulation and communication difficulties in their children. Individual differences in scores were present. Conclusion: This study shows that CG patients without intellectual disability are satisfied with their social competence, especially social functioning. Nevertheless, deficits in social cognition are present in a large proportion of CG-patients. Due to the large variability in scores and discrepancies between self-and proxy-report, an individually tailored, comprehensive neuropsychological assessment including social cognition is advised in all CG-patients. Treatment plans need to be customized to the individual patient.</p

Control of anthocyanin and non-flavonoid compounds by anthocyanin-regulating MYB and bHLH transcription factors in Nicotiana benthamiana leaves

Coloration of plant organs such as fruit, leaves and flowers through anthocyanin production is governed by a combination of MYB and bHLH type transcription factors (TFs). In this study we introduced Rosea1 (ROS1, a MYB type) and Delila (DEL, a bHLH type), into Nicotiana benthamiana leaves by agroinfiltration. ROS1 and DEL form a pair of well-characterized TFs from Snapdragon (Antirrhinum majus), which specifically induce anthocyanin accumulation when expressed in tomato fruit. In N. benthamiana, robust induction of a single anthocyanin, delphinidin-3-rutinoside (D3R) was observed after expression of both ROS1 and DEL. Surprisingly in addition to D3R, a range of additional metabolites were also strongly and specifically up-regulated upon expression of ROS1 and DEL. Except for the D3R, these induced compounds were not derived from the flavonoid pathway. Most notable among these are nornicotine conjugates with butanoyl, hexanoyl, and octanoyl hydrophobic moieties, and phenylpropanoid-polyamine conjugates such as caffeoyl putrescine. The defensive properties of the induced molecules were addressed in bioassays using the tobacco specialist lepidopteran insect Manduca sexta. Our study showed that the effect of ROS1 and DEL expression in N. benthamiana leaves extends beyond the flavonoid pathway. Apparently the same transcription factor may regulate different secondary metabolite pathways in different plant species

Rare Decays of \Lambda_b->\Lambda + \gamma and \Lambda_b ->\Lambda + l^{+} l^{-} in the Light-cone Sum Rules

Within the Standard Model, we investigate the weak decays of $\Lambda_b \to \Lambda + \gamma$ and $\Lambda_b \to \Lambda + l^{+} l^{-}$ with the light-cone sum rules approach. The higher twist distribution amplitudes of $\Lambda$ baryon to the leading conformal spin are included in the sum rules for transition form factors. Our results indicate that the higher twist distribution amplitudes almost have no influences on the transition form factors retaining the heavy quark spin symmetry, while such corrections can result in significant impacts on the form factors breaking the heavy quark spin symmetry. Two phenomenological models (COZ and FZOZ) for the wave function of $\Lambda$ baryon are also employed in the sum rules for a comparison, which can give rise to the form factors approximately 5 times larger than that in terms of conformal expansion. Utilizing the form factors calculated in LCSR, we then perform a careful study on the decay rate, polarization asymmetry and forward-backward asymmetry, with respect to the decays of $\Lambda_b \to \Lambda \gamma$, $\Lambda l^{+}l^{-}$.Comment: 38 pages, 15 figures, some typos are corrected and more references are adde

The Galactose Index measured in fibroblasts of GALT deficient patients distinguishes variant patients detected by newborn screening from patients with classical phenotypes

Background: The high variability in clinical outcome of patients with Classical Galactosemia (CG) is poorly understood and underlines the importance of prognostic biomarkers, which are currently lacking. The aim of this study was to investigate if residual galactose metabolism capacity is associated with clinical and biochemical outcomes in CG patients with varying geno- and phenotypes. Methods: Galactose Metabolite Profiling (GMP) was used to determine residual galactose metabolism in fibroblasts of CG patients. The association between the galactose index (GI) defined as the ratio of the measured metabolites [U13C]Gal-1-P/ [13C6]UDP-galactose, and both intellectual and neurological outcome and galactose-1-phosphate (Gal-1-P) levels was investigated. Results: GMP was performed in fibroblasts of 28 patients and 3 control subjects. The GI of the classical phenotype patients (n = 22) was significantly higher than the GI of four variant patients detected by newborn screening (NBS) (p = .002), two homozygous p.Ser135Leu patients (p = .022) and three controls (p = .006). In the classical phenotype patients, 13/18 (72%) had a poor intellectual outcome (IQ < 85) and 6/12 (50%) had a movement disorder. All the NBS detected variant patients (n = 4) had a normal intellectual outcome (IQ ≥ 85) and none of them has a movement disorder. In the classical phenotype patients, there was no significant difference in GI between patients with a poor and normal clinical outcome. The NBS detected variant patients had significantly lower GI levels and thus higher residual galactose metabolism than patients with classical phenotypes. There was a clear correlation between Gal-1-P levels in erythrocytes and the GI (p = .001). Conclusions: The GI was able to distinguish CG patients with varying geno- and phenotypes and correlated with Gal-1-P. The data of the NBS detected variant patients demonstrated that a higher residual galactose metabolism may result in a more favourable clinical outcome. Further research is needed to enable individual prognostication and treatment in all CG patients

Randomized controlled trial on the effect of 1-hour infusion of vincristine versus push injection on neuropathy in children with cancer (final analysis)

Introduction: Vincristine is an integral component of treatment for children with cancer. Its main dose-limiting side effect is vincristine-induced peripheral neuropathy (VIPN). The VINCA trial was a randomized controlled trial that explored the effect of 1-hour infusion compared with push injection of vincristine on the development of VIPN in children with cancer. The short-term outcomes (median follow-up 9 months) showed that there was no difference in VIPN between the randomization groups. However, 1-hour infusion was less toxic in children who also received azoles. We now report the results of the final analyses (median follow-up 20 months), which includes treatment outcome as a secondary objective (follow-up 3 years). Methods: VIPN was measured 1–7 times per participant using the Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric-modified total neuropathy score. Poisson mixed model and logistic generalized estimating equation analysis for repeated measures were performed.Results: Forty-five participants per randomization group were included. There was no significant effect of 1-hour infusion compared with push injection on VIPN. In participants receiving concurrent azoles, the total CTCAE score was significantly lower in the one-hour group (rate ratio 0.52, 95% confidence interval 0.33–0.80, p = 0.003). Four patients in the one-hour group and one patient in the push group relapsed. Two patients in the one-hour group died. Conclusion:1-hour infusion of vincristine is not protective against VIPN. However, in patients receiving concurrent azoles, 1-hour infusion may be less toxic. The difference in treatment outcome is most likely the result of differences in risk profile.</p