The influences of task repetition,napping, time of day,and instruction on the Sustained Attention to Response Task

Introduction: The Sustained Attention to Response Task (SART) helps to quantify vigilance impairments. Previous studies, in which five SART sessions on one day were administered, demonstrated worse performance during the first session than during the others. The present study comprises two experiments to identify a cause of this phenomenon. Method: Experiment 1, counting eighty healthy participants, assessed effects of repetition, napping, and time of day on SART performance through a between-groups design. The SART was performed twice in the morning or twice in the afternoon; half of the participants took a 20-minute nap before the second SART. A strong correlation between error count and reaction time (RT) suggested effects of test instruction. Participants gave equal weight to speed and accuracy in Experiment 1; therefore, results of 20 participants were compared to those of 20 additional participants who were told to prefer accuracy (Experiment 2). Results: The average SART error count in Experiment 1 was 10.1; the median RT was 280 ms. Neither repetition nor napping influenced error count or RT. Time of day did not influence error count, but RT was significantly longer for morning than for afternoon SARTs. The additional participants in Experiment 2 had a 49% lower error count and a 14% higher RT than the participants in Experiment 1. Error counts reduced by 50% from the first to the second session of Experiment 2, irrespective of napping or time of day. Conclusions: Preferring accuracy over speed was associated with a significantly lower error count. The data suggest that a worse performance in the first SART session only occurs when instructing participants to prefer accuracy, which is caused by repetition, not by napping or time of day. Note: We advise that participants are instructed to prefer accuracy over speed when performing the SART and that a full practice session is included.     

Comparative genomic hybridization reveals a specific pattern of chromosomal gains and losses during the genesis of colorectal tumors

Comparative genomic hybridization was used to screen the DNA extracted from histologically defined tissue sections from consecutive stages of colorectal carcinogenesis for chromosomal aberrations. No aberrations were detected in normal epithelium (n = 14). Gain of chromosome 7 occurred as a single event in low-grade adenomas (n = 14). In high-grade adenomas (n = 12), an overrepresentation of chromosomes 7 and 20 was present in 30% of the cases analyzed. The transition to colon carcinomas (n = 16) was characterized by the emergence of multiple chromosomal aberrations. Chromosomes 1, 13, and 20 and chromosome arms 7p and 8q were frequently gained, whereas chromosome 4 and chromosome arms 8p and 18q were recurrently underrepresented. The same tissue sections that were used for CGH were analyzed by means of DNA-ploidy measurements and immunohistochemical staining to quantify proliferative activity and p21/WAF-I and TP53 expression. We observed that crude aneuploidy and increased proliferative activity are early events in colorectal carcinogenesis, followed by TP53 overexpression and the acquisition of recurrent chromosomal gains and losses during the progression from high-grade adenomas to invasive carcinomas. Genes Chromosom Cancer (1996). © 1996 Wiley-Liss, Inc.     

Intranasal Delivery of a Methyllanthionine-Stabilized Galanin Receptor-2-Selective Agonist Reduces Acute Food Intake

The regulatory (neuro)peptide galanin is widely distributed in the central and peripheral nervous systems, where it mediates its effects via three G protein-coupled receptors (GAL_1-3R). Galanin has a vast diversity of biological functions, including modulation of feeding behavior. However, the clinical application of natural galanin is not practicable due to its rapid in vivo breakdown by peptidases and lack of receptor subtype specificity. Much effort has been put into the development of receptor-selective agonists and antagonists, and while receptor selectivity has been attained to some degree, most ligands show overlapping affinity. Therefore, we aimed to develop a novel ligand with specificity to a single galanin receptor subtype and increased stability. To achieve this, a lanthionine amino acid was enzymatically introduced into a galanin-related peptide. The residue’s subsequent cyclization created a conformational constraint which increased the peptide’s receptor specificity and proteolytic resistance. Further exchange of certain other amino acids resulted in a novel methyllanthionine-stabilized galanin receptor agonist, a G1pE-T3N-S6A-G12A-methyllanthionine[13–16]-galanin-(1–17) variant, termed M89b. M89b has exclusive specificity for GAL₂R and a prolonged half-life in serum. Intranasal application of M89b to unfasted rats significantly reduced acute 24 h food intake inducing a drop in body weight. Combined administration of M89b and M871, a selective GAL₂R antagonist, abolished the anorexigenic effect of M89b, indicating that the effect of M89b on food intake is indeed mediated by GAL₂R. This is the first demonstration of in vivo activity of an intranasally administered lanthipeptide. Consequently, M89b is a promising candidate for clinical application as a galanin-related peptide-based therapeutic.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01155-x.     

5-fluorouracil metabolite patterns in viable and necrotic tumor areas of murine colon carcinoma determined by 19F NMR spectroscopy

High-resolution ¹⁹F NMR spectroscopy at 9.4 T was used to study the difference in the metabolite pattern of 5-fluorouracil (5-FU) between viable and necrotic tissues of C38 murine colon tumors grown in C57BI/6 mice. Studies were performed on perchloric acid extracts of these tumor fractions after 5-FU treatment. The ¹⁹F nuclear magnetic resonance spectra exhibited resonances representing 5-FU, the catabolites α-fluoro-β-ureidopropionic acid and α-fluoro-β-alanine, as well as several fluoronucleotide anabolites. The absolute concentrations of anabolites and catabolites and the anabolite-to-catabolite ratio were significantly lower in the necrotic fraction than in the viable tumor fraction 50 min after administration of 5-FU, whereas the absolute concentration of 5-FU was the same. Therefore, in 5-FU metabolism studies with NMR spectroscopy, it is important to consider the necrotic contribution to the tumor volume.     

SUDEP („sudden unexpected death in epilepsy“) bei Kindern und Jugendlichen – Zahlen,Daten, Fakten

Clinical Epileptology - Das Thema SUDEP („sudden unexpected death in epilepsy“) ist in den letzten Jahren auch in Bezug auf Kinder und Jugendliche mit Epilepsie zunehmend in den Fokus...     

Transfer of Hexon‐ and Penton‐selected adenovirus‐specific T cells for refractory adenovirus infection after haploidentical stem cell transplantation

Adenovirus (HAdV) infections confer a high risk of morbidity and mortality for immunocompromised patients after stem cell transplantation (SCT). Treatment with standard antiviral drugs is of limited efficacy and associated with a high rate of adverse effects. HAdV‐specific T cells are crucial for sustained viral elimination and the efficacy of adoptive T‐cell therapy with donor‐derived HAdV‐specific T cells has been reported by several investigators. Here, we report our experience with the transfer of HAdV‐specific T cells specific for penton, which was recently identified as an immunodominant target of T cells, and hexon in a 14‐year‐old boy after T‐cell‐depleted haploidentical SCT for myelodysplastic syndrome (MDS). He developed severe HAdV‐associated enteritis complicated by acute graft‐versus‐host disease (GvHD). The patient received ten infusions of allogeneic HAdV‐specific T cells manufactured from the haploidentical stem cell donor using the CliniMacs Interferon‐γ (IFN‐γ) cytokine capture and immunomagnetic selection. Initially, T cells were generated against the immunodominant target hexon and in subsequent transfers dual antigen‐specific T cells against hexon and penton were applied. T‐cell transfers were scheduled individually tailored to current immunosuppressive treatment. Each transfer was followed by reduction of HAdV load in peripheral blood and clinical improvement. Importantly, T‐cell responses to both penton and hexon pools emerged in patient blood after repetitive transfers. Unfortunately, the patient experienced bacterial sepsis, and in this context, severe GvHD requiring intensive immunosuppression followed by secondary progression of HAdV infection. The patient succumbed to multiorgan failure 283 days after SCT. This case demonstrates the feasibility of HAdV‐specific T‐cell transfer even in the presence of immunosuppressive treatment. Targeting of multiple immunodominant viral proteins may prove valuable in patients with complicated HAdV infections.     

Effects of visual feedback therapy on postural control in bilateral standing after stroke: a systematic review.

OBJECTIVE: To establish whether bilateral standing with visual feedback therapy after stroke improves postural control compared with conventional therapy and to evaluate the generalization of the effects of visual feedback therapy on gait and gait-related activities. DESIGN: A systematic review. METHODS: A computer-aided literature search was performed. Randomized controlled trials and controlled clinical trials, comparing visual feedback therapy with conventional balance treatments were included up to April 2005. The methodological quality of each study was assessed with the the Physiotherapy Evidence Database scale. Depending on existing heterogeneity, studies with a common variable of outcome were pooled by calculating the summary effect-sizes using fixed or random effects models. RESULTS: Eight out of 78 studies, presenting 214 subjects, were included for qualitative and quantitative analysis. The methodological quality ranged from 3 to 6 points. The meta-analysis demonstrated non-significant summary effect-sizes in favour of visual feedback therapy for weight distribution and postural sway, as well as balance and gait performance, and gait speed. CONCLUSION: The additional value of visual feedback therapy in bilateral standing compared with conventional therapy shows no statistically significant effects on symmetry of weight distribution between paretic and non-paretic leg, postural sway in bilateral standing, gait and gait-related activities. Visual feedback therapy should not be favoured over conventional therapy. The question remains as to exactly how asymmetry in weight distribution while standing is related to balance control in patients with stroke.